Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice.

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.

Surgical Anti-Reflux Options Beyond Fundoplication.

PURPOSE OF REVIEW: This paper provides an overview of current and future surgical interventions available for the management of gastroesophageal reflux disease (GERD) beyond the well established and recognized fundoplication. Review the current indications and outcomes of these surgical procedures. RECENT FINDINGS: Fundoplication has been a cornerstone of the surgical management of GERD. However, other effective surgical options exist and can be considered based on prior interventions as well as patient, anatomical or other factors. These options are intended to address some of the shortcomings or potential complications of fundoplication such as symptom recurrence, dysphagia, or gas bloating, for example. Alternative procedures to fundoplication include magnetic sphincter augmentation, electrical stimulation and Roux-en-Y gastric bypass. The indication for surgical management remains failure of or inability to tolerate medical therapy.

A New Preclinical Paradigm for Testing Anti-Aging Therapeutics.

Testing drugs for anti-aging effects has historically been conducted in mouse life-span studies, but are costly and time consuming, and more importantly, difficult to recapitulate in humans. In addition, life-span studies in mice are not well suited to testing drug combinations that target multiple factors involved in aging. Additional paradigms for testing therapeutics aimed at slowing aging are needed. A new paradigm, designated as the Geropathology Grading Platform (GGP), is based on a standardized set of guidelines developed to detect the presence or absence of low-impact histopathological lesions and to determine the level of severity of high-impact lesions in organs from aged mice. The GGP generates a numerical score for each age-related lesion in an organ, summed for total lesions, and averaged over multiple mice to obtain a composite lesion score (CLS). Preliminary studies show that the platform generates CLSs that increase with the age of mice in an organ-dependent manner. The CLSs are sensitive enough to detect changes elicited by interventions that extend mouse life span, and thus help validate the GGP as a novel tool to measure biological aging. While currently optimized for mice, the GGP could be adapted to any preclinical animal model.

The effect of exposure to a single vowel on talker normalization for vowels.

The current work investigated the role of single vowels in talker normalization. Following initial training to identify six talkers from the isolated vowel /i/, participants were asked to identify vowels in three different conditions. In the blocked-talker conditions, the vowels were blocked by talker. In the mixed-talker conditions, vowels from all six talkers were presented in random order. The precursor mixed-talker conditions were identical to the mixed-talker conditions except that participants were provided with either a sample vowel or just the written name of a talker before target-vowel presentation. In experiment 1, the precursor vowel was always spoken by the same talker as the target vowel. Identification accuracy did not differ significantly for the blocked and precursor mixed-talker conditions and both were better than the pure mixed-talker condition. In experiment 2, half of the trials had a precursor spoken by the same talker as the target and half had a different talker. For the same-talker precursor condition, the results replicated those in experiment 1. In the different-talker precursor, no benefit was observed relative to the pure-mixed condition. In experiment 3, only the written name was presented as a precursor and no benefits were observed relative to the pure-mixed condition.

Does mechanical filtration of intraoperative cell salvage effectively remove titanium debris generated during instrumented spinal surgery? An in vitro analysis.

BACKGROUND CONTEXT: Instrumented fusion of the spine is a surgery commonly performed to stabilize vertebrae causing pain and to correct anatomic deformities. Such surgery can create substantial blood loss. Autotransfusion is a means to limit homologous blood transfusion in this setting. However, a dilemma is created when the high-speed drill used for bone removal comes in contact with implanted titanium spinal hardware. A clinician at this point is forced to decide between two options: to discontinue autotransfusion to avoid the potential transfusion of titanium fragments while risking blood loss and the need for homologous transfusion or to continue autotransfusion while risking transfusion of titanium fragments back into circulation. PURPOSE: To conclusively identify whether titanium fragments created by a high-speed drill are able to pass through standard autotransfusion microaggregate blood filters. STUDY DESIGN: A positive and negatively controlled experiment with blinded sample analysis. OUTCOMES MEASURES: The presence or absence of titanium alloy on a filter with detection by energy-dispersive X-ray spectroscopy (EDX). METHODS: A mock autotransfusion setup was devised for in vitro filtering. Six investigational and two control experiments were conducted. Titanium fragments generated by a high-speed drill were aspirated with saline and filtered with standard autotransfusion reservoirs and microaggregate blood filters. A final filter with a 1-µm pore size was placed distal to the blood filters. After filtration was complete, this final filter was analyzed using EDX. RESULTS: The presence of titanium was confirmed by EDX on five of six investigational filters. The positive and negative control filters were analyzed by EDX and tested positive and negative, respectively, for titanium. CONCLUSIONS: Standard 40 µm reservoir and blood microaggregate filters do not eliminate the smallest fragments of titanium generated by contact between a high-speed drill and a titanium hardware. The mass of titanium able to elude filtration is very small. The impact of transfusing blood contaminated with such a small mass of titanium is not known.

Increased response time of primed associates following an "episodic" hypnotic amnesia suggestion: a case of unconscious volition.

Following a hypnotic amnesia suggestion, highly hypnotically suggestible subjects may experience amnesia for events. Is there a failure to retrieve the material concerned from autobiographical (episodic) memory, or is it retrieved but blocked from consciousness? Highly hypnotically suggestible subjects produced free-associates to a list of concrete nouns. They were then given an amnesia suggestion for that episode followed by another free association list, which included 15 critical words that had been previously presented. If episodic retrieval for the first trial had been blocked, the responses on the second trial should still have been at least as fast as for the first trial. With semantic priming, they should be faster. In fact, they were on average half a second slower. This suggests that the material had been retrieved but blocked from consciousness. A goal-oriented information processing framework is outlined to interpret these and related data.

Single high-dose oral vitamin D3 (stoss) therapy--a solution to vitamin D deficiency in children with cystic fibrosis?

OBJECTIVES: To determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (<75 nmol/L). STUDY DESIGN: Retrospective chart review of 142 paediatric CF patients from 2007 till 2011. RESULTS: Thirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p=0.001; 81.54 ± 24.6 nmol/L, p=0.001; 92.18 ± 36.5 nmol/L, p=0.008 and 64.6 ± 20.0 nmol/L, p=0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p=0.038). CONCLUSION: Stoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.

The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

BACKGROUND: Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. METHODS: Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. RESULTS: Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. CONCLUSIONS: VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Laparoscopic diaphragmatic pacer placement--a potential new treatment for ALS patients: a brief description of the device and anesthetic issues.

The Diaphragm Pacing Stimulator (DPS) has been used to treat ventilatory insufficiency in quadriplegic patients. The FDA approved a trial using the DPS in patients with amyotrophic lateral sclerosis (ALS). Three patients with advanced ALS, who underwent laparoscopic diaphragmatic pacer placement, and their general anesthetic management, are presented.

Methamphetamine use following bariatric surgery in an adolescent.

Bariatric surgery is increasingly popular as a therapeutic strategy for morbidly obese adolescents. Adolescence represents a sensitive period of psychosocial development, and children with considerable weight loss may experience greater peer acceptance, accompanied by both positive and negative influences. Substance abuse exists as one of these negative influences. We present the case of an adolescent bariatric surgical patient who abused methamphetamines in the postoperative period, with consequent nutritional instability. A concerted effort must be made in the preoperative assessment of adolescent bariatric patients to delineate a history of illicit drug use, including abuse of diet pills and stimulants. Excessive postoperative weight loss or micronutrient supplementation non-compliance should raise a suspicion of stimulant use and appropriate screening tests should be performed. The consequent appetite suppression may manifest with signs of malnutrition such as bradycardia, hypotension, and weakness. Inpatient nutritional rehabilitation and psychiatric assessment should be considered.