Laparoscopic sleeve gastrectomy is safe and effective in elderly patients: a comparative analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is gaining widespread popularity as a definitive bariatric operation that provides satisfactory and durable weight loss as well as comorbidity resolution. Although SG is being increasingly offered to patients of all ages, there is a paucity of reported outcomes in patients ≥62 years of age. The purpose of this study was to perform a comparative analysis of the outcomes of SG in patients >62 years versus a younger age group, with an emphasis on safety and efficacy. METHODS: A retrospective analysis was performed from a prospectively collected database on patients who underwent SG from 2007 to 2012. All patients who were ≥62 years old were compared to those <62 years. RESULTS: There were 182 patients who underwent SG, 17 of whom were ≥62 years old. There were no significant differences in demographics or comorbidity characteristics between the groups. The mean follow-up was 1 year. There was no 30-day mortality in either group. The percent excess weight loss for the younger age group was 44 ± 21 % and the older group was 44 ± 25 %. The percent total body weight loss was 22 ± 10 and 21 ± 10 %, respectively. Weight loss outcomes were maintained for up to 3 years. Comorbidity resolution and improvement rates were equivalent in both groups. CONCLUSIONS: SG is safe and effective in patients ≥62 years. Weight loss and the beneficial effects on comorbidities are equivalent among elderly and younger patients. SG should be offered to elderly patients who are deemed to be appropriate candidates.

Early endosomal abnormalities and cholinergic neuron degeneration in amyloid-ß protein precursor transgenic mice.

Early endosomal changes, a prominent pathology in neurons early in Alzheimer's disease, also occur in neurons and peripheral tissues in Down syndrome. While in Down syndrome models increased amyloid-ß protein precursor (AßPP) expression is known to be a necessary contributor on the trisomic background to this early endosomal pathology, increased AßPP alone has yet to be shown to be sufficient to drive early endosomal alterations in neurons. Comparing two AßPP transgenic mouse models, one that contains the AßPP Swedish K670N/M671L double mutation at the ß-cleavage site (APP23) and one that has the AßPP London V717I mutation near the γ-cleavage site (APPLd2), we show significantly altered early endosome morphology in fronto-parietal neurons as well as enlargement of early endosomes in basal forebrain cholinergic neurons of the medial septal nucleus in the APP23 model, which has the higher levels of AßPP ß-C-terminal fragment (ßCTF) accumulation. Early endosomal changes correlate with a marked loss of the cholinergic population, which is consistent with the known dependence of the large projection cholinergic cells on endosome-mediated retrograde neurotrophic transport. Our findings support the idea that increased expression of AßPP and AßPP metabolites in neurons is sufficient to drive early endosomal abnormalities in vivo, and that disruption of the endocytic system is likely to contribute to basal forebrain cholinergic vulnerability.

Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.

Sleep deprivation is a common problem of considerable health and economic impact in today's society. Sleep loss is associated with deleterious effects on cognitive functions such as memory and has a high comorbidity with many neurodegenerative and neuropsychiatric disorders. Therefore, it is crucial to understand the molecular basis of the effect of sleep deprivation in the brain. In this study, we combined genome-wide and traditional molecular biological approaches to determine the cellular and molecular impacts of sleep deprivation in the mouse hippocampus, a brain area crucial for many forms of memory. Microarray analysis examining the effects of 5 h of sleep deprivation on gene expression in the mouse hippocampus found 533 genes with altered expression. Bioinformatic analysis revealed that a prominent effect of sleep deprivation was to downregulate translation, potentially mediated through components of the insulin signaling pathway such as the mammalian target of rapamycin (mTOR), a key regulator of protein synthesis. Consistent with this analysis, sleep deprivation reduced levels of total and phosphorylated mTOR, and levels returned to baseline after 2.5 h of recovery sleep. Our findings represent the first genome-wide analysis of the effects of sleep deprivation on the mouse hippocampus, and they suggest that the detrimental effects of sleep deprivation may be mediated by reductions in protein synthesis via downregulation of mTOR. Because protein synthesis and mTOR activation are required for long-term memory formation, our study improves our understanding of the molecular mechanisms underlying the memory impairments induced by sleep deprivation.

Lipolytic function of adipocyte/endothelial cocultures.

The rising incidence of adipose-related disorders such as obesity has prompted increased interest in the in vitro development of functional human soft tissues to study the disease and treatment options. Further, soft tissues maintained in vitro with a capacity to resemble in vivo tissues in structure and metabolic function would help gain insight into mechanisms involved in adipose tissue development. In the current study, the metabolic potential of adipose/endothelial cocultures on three-dimensional silk fibroin scaffolds was studied. Endothelial contributions to adipose lipogenesis and lipolysis were the focus of the study. Triglyceride accumulation, adipogenic gene transcript expression, and basal lipolysis measurements demonstrated the ability of this coculture system to retain metabolic levels obtained in adipocyte monocultures. Additionally, basal lipolysis was stimulated in mono- and coculture systems to a similar extent at 1.6- and 1.9-fold over controls, respectively. The ability to maintain adipose functions in these cocultures represents a step forward in the development of a tissue-engineered adipose tissue system exhibiting both endothelial lumens and metabolic functions.

Adipogenic differentiation of human adipose-derived stem cells on 3D silk scaffolds.

Current treatment modalities for soft tissue defects due to various pathologies and trauma include autologous grafting and the use of commercially available fillers. However, these treatment methods are associated with a number of limitations, such as donor site morbidity and volume loss over time. As such, improved therapeutic options are needed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue with an appropriate structure and function. The recent advances in the derivation and characterization of hASCs have led to numerous studies of soft tissue reconstruction. In this chapter, we discuss methods in which our laboratory has used hASCs and silk scaffolds for adipose tissue engineering. The use of naturally occurring and clinically acceptable materials such as silk protein for tissue-engineering applications poses advantages with respect to biocompatibility and mechanical and biological properties.

Effects of hyperinsulinemia on lipolytic function of three-dimensional adipocyte/endothelial co-cultures.

The increased incidence of both type 2 diabetes mellitus and obesity has prompted the need to develop physiologically relevant adipose tissue models for controlled study of both normal and diseased adipose functions. Insulin resistance, characteristic of both type 2 diabetes mellitus and obesity, is often preceded by hyperinsulinemia. We propose here a three-dimensional (3D) co-culture adipose tissue model to study the effects of high insulin exposure, which enabled the study of physiological cell responses to hyperinsulinemic conditions. Two-dimensional adipocyte studies were initially conducted to establish a baseline control in which insulin levels were established. Adipocytes and endothelial cells were subsequently co-cultured on 3D porous silk fibroin scaffolds in normal or high insulin concentrations, and their physiological responses were assessed with respect to lipogenesis and lipolysis. High insulin levels stimulated both an increase in triglyceride accumulation and a decrease in lipolysis levels compared to that of normal insulin conditions. In contrast, adipocyte monocultures did not exhibit any differences between insulin levels. The ability of this 3D system to elicit physiological responses to hyperinsulinemia in co-culture serves as a significant step forward in adipose tissue engineering. The development of physiologically relevant 3D in vitro adipose tissue models presents promise for the study of disease mechanisms as well as in assessing therapeutic treatments.

Adipose tissue engineering for soft tissue regeneration.

Current treatment modalities for soft tissue defects caused by various pathologies and trauma include autologous grafting and commercially available fillers. However, these treatment methods present a number of challenges and limitations, such as donor-site morbidity and volume loss over time. As such, improved therapeutic modalities need to be developed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue in both structure and function. Recently, a number of studies have been designed to explore various methods to engineer human adipose tissue. This review will focus on these developments in the area of adipose tissue engineering for soft tissue replacement. The physiology of adipose tissue and current surgical therapies used to replace lost tissue volume, specifically in breast tissue, are introduced, and current biomaterials, cell sources, and tissue culture strategies are discussed. We discuss future areas of study in adipose tissue engineering.

In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice.

The metabolism of the amyloid precursor protein (APP) and tau are central to the pathobiology of Alzheimer's disease (AD). We have examined the in vivo turnover of APP, secreted APP (sAPP), Abeta and tau in the wild-type and Tg2576 mouse brain using cycloheximide to block protein synthesis. In spite of overexpression of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain more slowly, particularly in the Tg2576 model where the half-life of both the endogenous murine and transgene-derived human sAPP is nearly doubled compared to wild-type mice. The important Abeta degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Abeta40 and Abeta42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. The cytoskeletal-associated protein tau was found to be highly stable in both wild-type and Tg2576 mice. Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a beta-amyloid depositing, APP overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may represent a neuroprotective response.

Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model.

Individuals with Down syndrome develop beta-amyloid deposition characteristic of early-onset Alzheimer's disease (AD) in mid-life, presumably because of an extra copy of the chromosome 21-located amyloid precursor protein (App) gene. App mRNA and APP metabolite levels were assessed in the brains of Ts65Dn mice, a mouse model of Down syndrome, using quantitative PCR, western blot analysis, immunoprecipitation, and ELISAs. In spite of the additional App gene copy, App mRNA, APP holoprotein, and all APP metabolite levels in the brains of 4-month-old trisomic mice were not increased compared with the levels seen in diploid littermate controls. However starting at 10 months of age, brain APP levels were increased proportional to the App gene dosage imbalance reflecting increased App message levels in Ts65Dn mice. Similar to APP levels, soluble amino-terminal fragments of APP (sAPPalpha and sAPPbeta) were increased in Ts65Dn mice compared with diploid mice at 12 months but not at 4 months of age. Brain levels of both Abeta40 and Abeta42 were not increased in Ts65Dn mice compared with diploid mice at all ages examined. Therefore, multiple mechanisms contribute to the regulation towards diploid levels of APP metabolites in the Ts65Dn mouse brain.

Bone marrow: orchestrated cells, cytokines, and growth factors for bone regeneration.

Bone regeneration requires an orchestrated interaction between various cells and other biological components. The synthesis of bone matrix with the release of cellular cytokines and growth factors facilitates and regulates cell growth. This leads to the maturation of bone that can support functional implants. Bone-marrow aspirate is a rich source of cells, cytokines, and growth factors needed for bone formation. Harvesting the marrow from the anterior iliac crest is a simple, safe, and cost-effective procedure. Mixing it with a resorbable scaffold and transplanting it to a site can predictably enhance bone regeneration. This article explores the anatomy of the bone marrow and describes the necessary elements for successful bone grafts, such as cells, bone matrix, and cellular regulators (both soluble and insoluble).