Resistance Exercise Program in Cognitively Normal Older Adults: CERT-Based Exercise Protocol of the AGUEDA Randomized Controlled Trial.

OBJECTIVES: To provide a comprehensive CERT (Consensus on Exercise Reporting Template)-based description of the resistance exercise program implemented in the AGUEDA (Active Gains in brain Using Exercise During Aging) study, a randomized controlled trial investigating the effects of a 24-week supervised resistance exercise program on executive function and related brain structure and function in cognitively normal older adults. DESIGN AND PARTICIPANTS: 90 cognitively normal older adults aged 65 to 80 were randomized (1:1) to a: 1) resistance exercise group; or a 2) wait-list control group. Participants in the exercise group (n = 46) performed 180 min/week of resistance exercise (3 supervised sessions per week, 60 min/session) for 24 weeks. INTERVENTION: The exercise program consisted of a combination of upper and lower limb exercises using elastic bands and the participant's own body weight as the main resistance. The load and intensity were based on the resistance of the elastic bands (7 resistances), number of repetitions (individualized), motor complexity of exercises (3 levels), sets and rest (3 sets/60 sec rest), execution time (40-60 sec) and velocity (as fast as possible). SETTINGS: The maximum prescribed-target intensity was 70-80% of the participants' maximum rate of perceived exertion (7-8 RPE). Heart rate, sleep quality and feeling scale were recorded during all exercise sessions. Those in the wait-list control group (n = 44) were asked to maintain their usual lifestyle. The feasibility of AGUEDA project was evaluated by retention, adherence, adverse events and cost estimation on the exercise program. RESULTS AND CONCLUSIONS: This study details the exercise program of the AGUEDA trial, including well-described multi-language manuals and videos, which can be used by public health professionals, or general public who wish to implement a feasible and low-cost resistance exercise program. The AGUEDA exercise program seems to be feasible by the high retention (95.6%) and attendance rate (85.7%), very low serious adverse event (1%) and low economic cost (144.23 € /participant/24 weeks). We predict that a 24-week resistance exercise program will have positive effects on brain health in cognitively normal older adults.

Presentations and outcomes of interstitial lung disease and the anti-Ro52 autoantibody.

BACKGROUND: Distinct clinical presentations of interstitial lung disease (ILD) with the myositis-specific antibodies, including anti-synthetase antibodies, are well-recognized. However, the association between ILD and the myositis-associated antibodies, including anti-Ro52, is less established. Our objectives were to compare presenting phenotypes of patients with anti-Ro52 alone versus in combination with myositis-specific autoantibodies and to identify predictors of disease progression or death. METHODS: We performed a retrospective cohort study of 73 adults with ILD and a positive anti-Ro52 antibody. We report clinical features, treatment, and outcomes. RESULTS: The majority of patients with ILD and anti-Ro52 had no established connective tissue disease (78%), and one-third had no rheumatologic symptoms. Thirteen patients (17.8%) required ICU admission for respiratory failure, with 84.6% all-cause mortality. Of the 73 subjects, 85.7% had a negative SS-A, and 49.3% met criteria for idiopathic pneumonia with autoimmune features (IPAF). The 50 patients with anti-Ro52 alone were indistinguishable from patients with anti-Ro52 plus a myositis-specific autoantibody. ICU admission was associated with poor outcomes (HR 12.97, 95% CI 5.07-34.0, p < 0.0001), whereas rheumatologic symptoms or ANA > = 1:320 were associated with better outcomes (HR 0.4, 95% CI 0.16-0.97, p = 0.04, and HR 0.29, 95% CI 0.09-0.81, p = 0.03, respectively). CONCLUSIONS: Presentations of ILD with the anti-Ro52 antibody are heterogeneous, and outcomes are similar when compared to anti-Ro52 plus myositis-specific antibodies. Testing for anti-Ro52 may help to phenotype unclassifiable ILD patients, particularly as part of the serologic criteria for IPAF. Further research is needed to investigate treatment of ILD in the setting of anti-Ro52 positivity.

A sipometer for measuring motivation to consume and reward value of foods and beverages in humans: Description and proof of principle.

New methods, derived from animal work, for measuring food reward value (i.e. reinforcing value of food), and motivation (i.e. strength of desire) to consume, in humans are described and validated. A sipping device (sipometer) was developed that permits access to a liquid food or beverage on two reward schedules: continuous reinforcement (CR) and progressively increasing time spent exerting pressure on a straw (PR-schedule). In addition, a pictorial scale showing a cup, from which the 'amount wanted' could be marked was used to pre-test potential consumption. Intake, time spent sipping, breakpoint, and pressure exerted were the main dependent variables measured. Three pilot experiments were conducted. In Experiment 1, participants (n=8) consumed yogurt shakes after a 1-h or 21-h food deprivation period on both schedules. In Experiment 2, participants (n=8) sham-consumed (i.e. spit out) sweet and non-sweet beverages, utilizing both schedules. In Experiment 3, sham-consuming sweet and non-sweet beverages on both schedules and working for shake on the PR schedule were repeated, after three nights of either habitual sleep or short sleep duration (n=7) in a crossover design. In Experiment 1, participants sipped longer after 21-h vs. 1-h of food deprivation (13±3.0 vs. 8.0±2.1s; p=0.04), on the PR schedule. In Experiment 2, sham-intake (p=0.01) and sipping time (p=0.04) were greater for sweet than non-sweet beverages on the PR schedule and a similar, though not conventionally significant, effect was observed for exerted pressure (p=0.09). In both Experiment 2 and Experiment 3 after habitual sleep, on the PR schedule, cumulative pressure difference between sweet and non-sweet beverage increased with difference in amount wanted in the taste test. In contrast, after short sleep participants were less willing to work for sweet taste as their wanting increased, suggesting that sleep deprivation raises desire, but lowers behavioral output. Taken together these results demonstrate that the sipometer and associated ratings are reliable and useful measures of motivation to consume and reward value in humans. Participants were more motivated to obtain access to sweet beverages, especially when these were better liked than to obtain access to non-sweet beverages.

Insulin receptor activation in the nucleus accumbens reflects nutritive value of a recently ingested meal.

With respect to feeding, insulin is typically thought of as a satiety hormone, acting in the hypothalamus to limit ingestive behavior. However, accumulating evidence suggests that insulin also has the ability to alter dopamine release in the striatum and influence food preferences. With increased access to high calorie foods, Western societies have a high prevalence of obesity, accompanied by insulin insensitivity. Little is known about how insulin is trafficked into the brain following food consumption and whether insulin insensitivity in the periphery is mirrored in the central nervous system. We investigated insulin receptor activation in the ventral striatum of rats receiving water or 16% glucose either orally or intragastrically. We also investigated whether glucose-induced insulin receptor activation was altered in food-restricted (FR) or diet-induced obesity (OB) rat models. Lastly, we examined whether insulin plays a significant role in flavor-nutrient preference learning. Glucose intake stimulated a rapid increase in insulin receptor activity in the ventral striatum of FR and ad libitum (AL) fed rats, but not OB rats. Similarly, both AL and FR, but not OB rats demonstrated significant flavor-nutrient preferences. However AL rats receiving brief inhibition of insulin activity during conditioning failed to acquire a significant flavor-nutrient preference. These findings suggest that impaired insulin receptor activation in the ventral striatum may result in inaccurate valuation of nutritive foods, which could lead to overconsumption of food or the selection of foods that don't accurately meet the body's current physiological needs.

Critical role of NMDA but not opioid receptors in the acquisition of fat-conditioned flavor preferences in rats.

Animals learn to prefer flavors associated with the intake of dietary fats such as corn oil (CO) solutions. We previously reported that fat-conditioned flavor preferences in rats were relatively unaffected by systemic treatment with dopamine D1 and D2 antagonsits. The present study examined whether systemic opioid (naltrexone, NTX) or NMDA (MK-801) receptor antagonists altered the acquisition and/or expression of CO-CFP. The CFP was produced by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in a 3.5% CO solution and another flavor (CS-, e.g., grape) in a 0.9% CO solution. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 d. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), NTX (0.1-5 mg/kg) or MK-801 (50-200 µg/kg). Rats displayed a robust CS+ preference following VEH treatment (85-88%) which was significantly though moderately attenuated by NTX (69-70%). The lower doses of MK-801 slightly reduced the CS+ preference; the high dose blocked the CS+ preference (49%) but also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH or NTX (0.1, 0.5, 1mg/kg) or MK-801 (100 µg/kg) 0.5h prior to 1-bottle training trials with CS+/3.5% CO and CS-/0.9% CO training solutions. Additional Limited VEH groups were trained with intakes limited to that of the NTX and MK-801 groups. Subsequent two-bottle CS+ vs. CS- tests were conducted without injections. Significant and persistent CS+ preferences were observed in VEH (77-84%) and Limited VEH (88%) groups. NTX treatment during training failed to block the acquisition of CO-CFP although the magnitude of the CS+ preference was reduced by 0.5 (70%) and 1.0 (72%) mg/kg doses relative to the Limited VEH treatment (88%). In contrast, MK-801 (100 µg/kg) treatment during training blocked the acquisition of the CO-CFP. These data suggest a critical role for NMDA, but not opioid receptor signaling in the acquisition of a fat conditioned flavor preferences, and at best limited involvement of NMDA and opioid receptors in the expression of a previously learned preference.

Roles of dopamine D1 and D2 receptors in the acquisition and expression of fat-conditioned flavor preferences in rats.

Sugars and fats elicit innate and learned flavor preferences with the latter mediated by flavor-flavor (orosensory) and flavor-nutrient (post-ingestive) processes. Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC), but not opioid antagonists blocked the acquisition and expression of flavor-flavor preferences conditioned by sugars. In addition, systemic D1, but not D2 or opioid antagonists blocked the acquisition of flavor-nutrient preferences conditioned by intragastric (IG) sugar infusions. Given that DA antagonists reduce fat intake, the present study examined whether systemic D1 or D2 antagonists altered the acquisition and/or expression of conditioned flavor preferences (CFP) produced by pairing one novel flavor (CS+, e.g., cherry) with a 3.5% corn oil (CO: fat) solution relative to another flavor (CS-, e.g., grape) paired with a 0.9% CO solution. In an expression study, food-restricted rats were trained to drink either flavored 3.5% or 0.9% CO solutions on alternate days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), SCH (50-800 nmol/kg) or RAC (50-800 nmol/kg). The rats displayed a robust CS+ preference following VEH treatment (87-88%) the expression of which was attenuated by treatment with moderate doses of RAC, and to a lesser degree, SCH. In an acquisition study, six groups of rats received VEH, SCH (25, 50, 200 nmol/kg) or RAC (50, 200 nmol/kg) 0.5 h prior to 1-bottle training trials with CS+ flavored 3.5% and CS- flavored 0.9% (CS-) CO solutions. A seventh Limited VEH group was trained with its training intakes limited to that of the SCH and RAC groups. Subsequent two-bottle tests were conducted with the CS+ and CS- flavors presented in 0.9% CO without injections. Significant and persistent CS+ preferences were observed in VEH (75-82%), Limited VEH (70-88%), SCH25 (75-84%), SCH50 (64-87%), SCH200 (78-91%) and RAC200 (74-91%) groups. In contrast, the group trained with RAC50 displayed a significant initial CS+ preference (76%) which declined over testing to 61%. These data indicate limited DA D1 and D2 receptor signaling involvement in the expression and acquisition of a fat-CFP relative to previous robust effects for sugar-CFP.

CD36 gene deletion reduces fat preference and intake but not post-oral fat conditioning in mice.

Several findings suggest the existence of a "fatty" taste, and the CD36 fatty acid translocase is a candidate taste receptor. The present study compared fat preference and acceptance in CD36 knockout (KO) and wild-type (WT) mice using nutritive (triglyceride and fatty acid) and nonnutritive (Sefa Soyate oil) emulsions. In two-bottle tests (24 h/day) naive KO mice, unlike WT mice, displayed little or no preference for dilute soybean oil, linoleic acid, or Sefa Soyate emulsions. At high concentrations (2.5-20%), KO mice developed significant soybean oil preferences, although they consumed less oil than WT mice. The postoral actions of fat likely conditioned these preferences. KO mice, like WT mice, learned to prefer a flavored solution paired with intragastric soybean oil infusions. These findings support CD36 mediation of a gustatory component to fat preference but demonstrate that it is not essential for fat-conditioned flavor preferences. The finding that oil-naive KO mice failed to prefer a nonnutritive oil, assumed to provide texture rather than taste cues, requires explanation. Finally, CD36 deletion decreased fat consumption and enhanced the ability of the mice to compensate for the calories provided by their optional fat intake.

Grafting of the peritonsillar fossa with an acellular dermal graft to reduce posttonsillectomy pain.

PURPOSE: Adult tonsillectomy is a common surgical procedure that is accompanied by masked postoperative pain. Analgesics are usually only partially effective, and the use of narcotics such as codeine is often poorly tolerated because of associated nausea. Because the pain associated with tonsillectomy is believed to arise from the large areas of exposed parapharyngeal muscle, we hypothesized that acellular dermal grafting of the peritonsillar fossa, providing biologic coverage to these areas, would result in a notable reduction of postoperative pain. MATERIALS AND METHODS: We did a double-blind, prospective study, with 10 adult patients undergoing electrodissection tonsillectomy concurrently with grafting of 1 peritonsillar fossa with an acellular dermal graft (ADG) (AlloDerm, LifeCell Corp, The Woodlands, TX), whereas the other side of the throat received no treatment and was designated as the control side. Patients were examined on postoperative days 1, 7, and 14, and completed pain questionnaires on postoperative days 1, 3, 5, 7, and 14. RESULTS: ADG grafting of the peritonsillar fossa resulted in a statistically significant reduction in pain (by approximately 50%) on postoperative days 1, 3, 5, and 7, compared with the control side. Two patients experienced partial graft sloughing within the first 10 postoperative days, but no other untoward effects such as bleeding, graft aspiration, or infection, were associated with ADG of the peritonsillar fossa. CONCLUSIONS: This study suggests that AlloDerm grafting of the peritonsillar fossa is a potentially useful, alternative means of reducing pain in the adult tonsillectomy patient and has potential use in reconstruction of oropharyngeal defects. Because of the cost of the graft, we suggest its use in selected difficult adult cases, but not as part of routine adult tonsillectomy.

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.

Endoscopic forehead lifting and contouring.

The concept of endoscopic foreheadplasty is based upon a sub- or supraperiosteal dissection of the parietal, occipital and frontal scalp, incision and release of the superior and lateral orbital periosteum, selective myotomies of the brow depressor muscles, and brow elevation into a desired position with fixation and healing. A significant limitation of this procedure appears to be the ability to predict the long-term forehead and brow elevation. We review the anatomy relevant to forehead rejuvenation surgery and present our surgical technique for permanent fixation endoscopic forehead lifting. We discuss the scientific rationale for permanent fixation to ensure long-term forehead and brow position and draw our conclusions based upon the results of animal and clinical studies that have been completed.

The multivectorial subperiosteal midface lift.

Traditional rejuvenation on the midface has been predicated on extension of laterally based rhytidectomy techniques. Recently, attempts to improve this area have been performed through brow access points and are directed superolaterally. Transblepharoplasty approaches have in the past focused on limited rejuvenation of the immediate periocular area. The technique described in this article is a method by which the multiple directions of midfacial aging can be reversed and corrected with greater safety and better visualization than previously described.

Augmentation of the cheeks, chin and pre-jowl sulcus, and nasolabial folds.

The demand for augmentation of central and lower facial features continues to increase. There are several safe and effective materials available for this purpose, and techniques have become highly refined. The relative strengths and weaknesses of silicone, expanded polytetrafluoroethylene (ePTFE), high-density polyethylene (HDPE), and merseline mesh are discussed for augmentation of the chin/pre-jowl sulcus and cheek. Materials for augmentation of the nasolabial folds (NLF) are also discussed. There are various forms of solid ePTFE that have been developed for soft tissue augmentation. These are particularly well suited for the NLF. Techniques for facial skeletal and soft tissue augmentation are presented.

Collagen, human collagen, and fat: the search for a three-dimensional soft tissue filler.

As the body ages, not only are the soft tissues of the face subject to gravity but they also may undergo progressive atrophy. Suspensory procedures may return the tissues to a more youthful position, but the atrophic changes are left uncorrected and produce an aged appearance. Three-dimensional (3-D) soft tissue fillers ideally would replace the bulk that was lost. Safety, persistence, and verisimilitude to the native tissues should be optimal in useful 3-D fillers. To date, no such material has been described, but there has been a resurgence in natural materials for this purpose. This article serves as an update on human-derived soft tissue fillers.

D1 but not D2 dopamine receptor antagonism blocks the acquisition of a flavor preference conditioned by intragastric carbohydrate infusions.

The effects of dopamine D1 (SCH23390) and D2 (raclopride) receptor antagonists on the acquisition and expressions of flavor preferences conditioned by the postingestive actions of sucrose were investigated. Food-restricted rats were trained in one-bottle sessions to associate one flavored saccharin solution (CS+) with intragastric (i.g.) infusions of 16% sucrose, and another flavored saccharin solution (CS-) with water infusions. Flavor preferences were then measured in two-bottle tests. In Experiment 1A, rats that received the D2 antagonist (raclopride, 200 nmol/kg; RAC group) throughout training consumed less CS+ and CS- than did saline-treated Control rats; a saline-treated Yoked group had its intake limited to that of the RAC group. All three groups displayed CS+ preferences during two-bottle tests when treated with saline or raclopride, except at doses that greatly suppressed intake. Experiment 1B obtained similar results with rats treated with 400 nmol/kg raclopride throughout training. In Experiment 2, rats that received the D1 antagonist (SCH23390, 200 nmol/kg; SCH group) throughout training consumed less CS+ and CS- than did saline-treated Control rats; a saline-treated Yoked group had its intake limited to that of the SCH group. Unlike the Control and Yoked groups, the SCH group failed to prefer the CS+ to the CS- in two bottle tests. SCH23390 treatment during two-bottle testing did not block CS+ preference in the Control or Yoked groups, except at doses that greatly suppressed intake. We conclude that D1, but not D2, dopamine receptors are critically involved in the acquisition of a sucrose-conditioned flavor preference, and both receptor subtypes have a more limited role in the expression of this preference.

Flavor preferences conditioned by intragastric fructose and glucose: differences in reinforcement potency.

Many prior conditioning studies indicate that fructose, unlike glucose, has minimal postingestive reinforcing effects. Using a new training procedure, food-restricted rats were trained in alternate 20-h/day sessions with one flavored solution (CS+F) paired with intragastric (IG) infusions of 16% fructose and another flavor (CS-) paired with IG water. In subsequent two-bottle tests they showed a robust (85%) preference for the CS+F over the CS-. A third flavor (CS+G) was then paired with IG 16% glucose, and it was strongly preferred to the CS+F. When retrained 30 min/day with new flavors paired with IG fructose, glucose, or water the rats learned only a CS+G preference. When training was extended to 20 h/day, a CS+F preference developed. New rats trained 20 h/day with two-bottle access to CS+F and CS- paired with IG fructose and water failed to acquire a CS+F preference. Other rats rapidly developed a strong preference when trained with concurrent access to CS+G and CS- paired with IG glucose and water. These data indicate that both fructose and glucose generate postingestive reinforcing signals, but that the fructose signals are weaker and/or delayed relative to those produced by glucose.

Evaluation of acellular dermal graft (AlloDerm) sheet for soft tissue augmentation: a 1-year follow-up of clinical observations and histological findings.

OBJECTIVES: To evaluate and compare the long-term clinical persistence and histological appearance of subdermally implanted acellular dermal graft (AlloDerm) sheets and intradermal type I bovine collagen cross-linked with glutaraldehyde (Zyplast). PATIENTS: Ten adult patients (5 men and 5 women; average age, 46 years; age range, 37-59 years) not allergic to bovine collagen. METHODS: AlloDerm sheets were implanted surgically in a subdermal plane in one postauricular crease, and Zyplast was injected intradermally on the opposite side. AlloDerm and Zyplast implants were digitally photographed and their apparent volumes calculated at 1, 3, 6, 9, and 12 months after implantation. A specimen was removed at 3 and 12 months and examined histologically for collagen persistence, host tissue invasion, and inflammatory reaction. RESULTS: The apparent implant volume of the AlloDerm sheets decreased during the first 6 months and then stabilized over the next 6 months. By contrast, Zyplast was progressively absorbed, with complete loss of clinical effect by 6 months. Histological analysis of implanted AlloDerm sheets demonstrated progressive repopulation of the graft with minimal inflammation. CONCLUSIONS: AlloDerm sheets seem to provide stable soft tissue augmentation after an early period of resorption and are clearly superior to Zyplast injections for long-term, large-volume, soft tissue correction. Recommendations for clinical use include routine overcorrection, with subsequent augmentation delayed by at least 6 months.

Preoperative identification of psychiatric illness in aesthetic facial surgery patients.

The purpose of this study was to evaluate the preoperative use of a two-part standardized assessment program (Prime-MD, Biometrics Research Department, New York State Psychiatric Institute) to objectively detect psychiatric disorders in facial plastic surgery patients, and to compare its use to findings identified by the facial plastic surgeon. Seventy-five new patients requesting aesthetic facial surgery at two academic centers and two private practice locations were evaluated.