The Long‐Term Management of Obesity with Continuing Pharmacotherapy

Objective: Long‐term, possibly lifetime, use of medications for the management of obesity may be thought to be similar to the use of pharmacotherapy for other chronic diseases such as hypertension or diabetes. Because there have been no systematic studies of this extended use, the experience of eight patients who have used obesity medications in a sustaining manner was studied. Research Methods and Procedures: The clinical characteristics of eight adult patients, each of whom has experience with long‐term (more than 10 years) use of medications for weight loss and weight maintenance, were studied. Results: The clinical experience of these eight patients was analyzed. Each chose to sustain the use of weight management medications for more than 10 years because of perceived benefit, comfort, and the absence of significant side effects. There has been no evidence of the development of tolerance, addiction, or misuse and no adverse events related to the medication. The beneficial effects of the medication have not diminished with time. Discussion: The clinical characteristics of eight patients, each of whom has used obesity pharmacotherapy for more than 10 years, are described. The experience of these eight individuals cannot be generalized to the entire population of overweight or obese patients. It does suggest, however, that some patients respond successfully to this form of therapy and that they will derive value from it for the management of this disease. Efforts should be made to identify these patients, and consideration should be given to the use of chronic medications for the continuing management of obesity.     

Towards Long‐Term Photostability of Solid‐State Dye Sensitized Solar Cells

The solid‐state dye‐sensitized solar cell (DSSC) was introduced to overcome inherent manufacturing and instability issues of the electrolyte‐based DSSC and progress has been made to deliver high photovoltaic efficiencies at low cost. However, despite 15 years research and development, there still remains no clear demonstration of long‐term stability. Here, solid‐state DSSCs are subjected to the severe aging conditions of continuous illumination at an elevated temperature. A fast deterioration in performance is observed for devices encapsulated in the absence of oxygen. The photovoltaic performance recovers when re‐exposed to air. This reversible behavior is attributed to three related processes: i) the creation of light and oxygen sensitive electronic shunting paths between TiO₂ and the top metal electrode, ii) increased recombination at the TiO₂/organic interface, and iii) the creation of deep electron traps that reduce the photocurrent. The device deterioration is remedied by the formation of an insulating alumino‐silicate shell around the TiO₂ nanocrystals, which reduces interfacial recombination, and the introduction of an insulating mesoporous SiO₂ buffer layer between the top electrode and TiO₂, which acts as a permanent insulating barrier between the TiO₂ and the metal electrode, preventing shunting.     

Long‐Term Stability of Primary Rat Hepatocytes in Micropatterned Cocultures

Primary hepatocytes display functional and structural instability in standard monoculture systems. We have previously developed a model in which primary hepatocytes are organized in domains of empirically optimized dimensions and surrounded by murine embryonic fibroblasts (HepatoPac?). Here, we assess the long‐term phenotype of freshly isolated and cryopreserved rat hepatocytes in a 96‐well HepatoPac format. The viability, cell polarity (actin microfilaments, bile canaliculi), and functions (albumin, urea, Phase I/II enzymes, transporters) of fresh and cryopreserved rat hepatocytes were retained in HepatoPac at similar levels for at least 4 weeks as opposed to rapidly declining over 5 days in collagen/Matrigel? sandwich cultures. Pulse or continuous exposure of rat HepatoPac to GW‐7647, a selective agonist of PPARα, caused reproducible induction of CYP4A1 and 3‐hydroxy‐3‐methylglutaryl‐CoA synthase over 4 weeks. In conclusion, rat HepatoPac in a 96‐well format can be used for chronic dosing of highly functional hepatocytes and assessment of perturbed hepatocellular pathways. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:204‐212, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21469     

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial–embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, a trophectoderm spheroid‐based in vitro model mimicking the pre‐implantation human embryo is used to recapitulate important functional aspects of blastocyst implantation. Functionally, human endometrial EVs, derived from hormonally treated cells synchronous with implantation, are readily internalized by trophectoderm cells, regulating adhesive and invasive capacity of human trophectoderm spheroids. To gain molecular insights into mechanisms underpinning endometrial EV‐mediated enhancement of implantation, quantitative proteomics reveal critical alterations in trophectoderm cellular adhesion networks (cell adhesion molecule binding, cell–cell adhesion mediator activity, and cell adherens junctions) and metabolic and gene expression networks, and the soluble secretome from human trophectodermal spheroids. Importantly, transfer of endometrial EV cargo proteins to trophectoderm to mediate changes in trophectoderm function is demonstrated. This is highlighted by correlation among endometrial EVs, the trophectodermal proteome following EV uptake, and EV‐mediated trophectodermal cellular proteome, important for implantation. This work provides an understanding into molecular mechanisms of endometrial EV‐mediated regulation of human trophectoderm functions—fundamental in understanding human endometrium–embryo signaling during implantation.     

Targeting Parents Exclusively in the Treatment of Childhood Obesity: Long‐Term Results

Objective: To report the long‐term change in children's overweight following a family‐based health‐centered approach where only parents were targeted compared with a control intervention where only children were targeted. Research Methods and Procedures: Fifty of the 60 children who participated in the original study were located 7 years later, and their weight and height were measured. At the point of the 7‐year follow‐up, the children were 14 to 19 years of age. Repeated measure ANOVA was used to test differences between the groups in percent overweight at different time‐points. Results: Mean reduction in percent overweight was greater at all follow‐up points in children of the parent‐only group compared with those in the children‐only group (p < 0.05). Seven years after the program terminated, mean reduction in children's overweight was 29% in the parent‐only group vs. 20.2% in the children‐only group (p < 0.05). Discussion: Over the long term, treatment of childhood obesity with the parents as the exclusive agents of change was superior to the conventional approach.     

Long‐Term Outcomes of Venus Flytrap (Dionaea muscipula) Establishment

Determining the success or failure of rare plant establishment requires long‐term monitoring, but such monitoring is seldom conducted. A 2004 census of Venus flytrap populations created by seeding and transplanting was compared to a similar census in 2010. Of the 18 original populations, three were destroyed by logging operations, 12 decreased and three increased. Venus flytraps face several limitations keeping populations small. Consistent soil moisture and the presence of population remnants improved the long‐term management outcomes.     

The Value of Long‐Term Assessment of Restoration: Support from a Seagrass Investigation

The importance of judging success of restoration studies over extended time periods has been repeatedly voiced but convincing information to justify increased monitoring is generally unavailable. Building on Bell et al. (2008), we investigated the development of areal coverage of the seagrass, Halodule wrightii, as a metric for assessing the outcome of a restoration effort conducted near Tampa Bay, Florida, U.S.A., over 7 years, thereby expanding the timescale over which a subtropical seagrass restoration project was evaluated for success. In each of 12 plots, 500 planting units of H. wrightii were introduced in 2002, and the seagrass cover level documented annually through 2009. Although only low‐moderate levels of H. wrightii cover were recorded after 3 years, a rapid increase to high coverage levels was evident in many plots after 2006 and sustained through 2009. Plots that supported only low levels of seagrass cover initially remained poor performers, 4–7 years post‐planting. By 2008, substantial seagrass spillover, contiguous with over 75% of plots, was recorded. When both within‐plot coverage and spillover were considered, seagrass restoration success was attained 6 years after initiation. Our findings provide an example of comparatively longer‐term monitoring of a restoration effort leading to reversal of an earlier evaluation of project success. Moreover, unique information on H. wrightii temporal dynamics emerged from the 7 year study, further illustrating the value of long‐term assessment of restoration. Extending the duration of post‐planting surveys of seagrass coverage may address multiple needs as it advances the field of seagrass restoration .     

Long‐Term Weight Development in Women: A 15‐Year Follow‐up of the Effects of Pregnancy

Objective: The aim of this study was to evaluate how well prepregnancy BMI, gestational weight gain, and postpartum weight retention predict retention of weight 15 years later among parous women. Research Methods and Procedures: The Stockholm Pregnancy and Women's Nutrition (SPAWN) study is a long‐term follow‐up study of women who delivered children in 1984 to 1985 (n = 2342). The participants initially filled out questionnaires about their eating and exercise habits, social circumstances, etc. before, during, and at 1 year after pregnancy. Anthropometric data were also sampled. Fifteen years later, these women were invited to take part in the follow‐up study. Anthropometric measurements were collected, and similar questions were asked. Five hundred sixty‐three women participated in the SPAWN 15‐year follow‐up study. The sample was divided into groups to examine three presumably critical time periods: 1) overweight and normal weight before pregnancy; 2) low, intermediate, and high weight gainers during pregnancy; and 3) low, intermediate, and high weight retainers at 1 year after pregnancy. Results: The overweight women did not gain more weight during pregnancy or retain more weight at 1 year follow‐up. High weight gainers during pregnancy retained more weight at the 1‐year and the 15‐year follow‐ups. High weight retainers had gained more during pregnancy and retained it at the 15‐year follow‐up. Fifty‐six percent of the high weight gainers during pregnancy ended up in the high weight retainers group. Discussion: Women who are overweight before pregnancy do not have a higher risk of postpartum weight retention than normal weight women. Thus, it is not necessarily the initially overweight woman who should be the target or focus of weight control programs during or after pregnancy. Both high weight gainers and high weight retainers had higher BMI at the 15‐year follow‐up, although only 56% of the high weight gainers during pregnancy were also classified as high weight retainers at the 1‐year follow‐up. Weight retention at the end of the postpartum year predicts future overweight 15 years later.     

Time‐Continuous Phosphorus Flows in the Indian Agri‐Food Sector: Long‐Term Drivers and Management Options

Phosphorus (P) is a major agricultural nutrient and, in its mineable form, a potentially scarce resource. Countries with limited physical access to P should hence develop an effective national P governance. This requires analyses of trends and variations in P flows and stocks over time. Here, we present a long‐term P flow analysis for the Indian agri‐food sector from 1988 to 2011. Major P flows are imports of mineral P, fertilizer application, and uptake of animal fodder. The mineral P import dependency ratio is constant at around 93%. On average, 20% of P inputs to soils are lost through erosion. Key drivers of changes in P flows include population growth, dietary change, and agricultural intensification. To reduce its P fertilizer import dependence, India could, for example, substitute up to 19% of the presently applied mineral P if manure used as a household fuel were recycled, and up to 21% if P was fully recovered from wastewater and household waste. Comparing selected indicators for P use in agriculture with China and the European Union (EU) reveals that there are structural similarities, such as increasing fertilizer application rates and P accumulation in soils, with the first but large differences compared to the latter. The analyses highlight that in contrast to static indicators, the time‐continuous tracking of P flows provides substantial advantages, such as the identification of long‐term trends, drivers, and intervention options for sustainable P management, given that it allows for the interpretation of present indicators in the context of past trends and legacies.     

Dlx5 Is a Cell Autonomous Regulator of Chondrocyte Hypertrophy in Mice and Functionally Substitutes for Dlx6 during Endochondral Ossification

The axial and appendicular skeleton of vertebrates develops by endochondral ossification, in which skeletogenic tissue is initially cartilaginous and the differentiation of chondrocytes via the hypertrophic pathway precedes the differentiation of osteoblasts and the deposition of a definitive bone matrix. Results from both loss-of-function and misexpression studies have implicated the related homeobox genes Dlx5 and Dlx6 as partially redundant positive regulators of chondrocyte hypertrophy. However, experimental perturbations of Dlx expression have either not been cell type specific or have been done in the context of endogenous Dlx5 expression. Thus, it has not been possible to conclude whether the effects on chondrocyte differentiation are cell autonomous or whether they are mediated by Dlx expression in adjacent tissues, notably the perichondrium. To address this question we first engineered transgenic mice in which Dlx5 expression was specifically restricted to immature and differentiating chondrocytes and not the perichondrium. Col2a1-Dlx5 transgenic embryos and neonates displayed accelerated chondrocyte hypertrophy and mineralization throughout the endochondral skeleton. Furthermore, this transgene specifically rescued defects of chondrocyte differentiation characteristic of the Dlx5/6 null phenotype. Based on these results, we conclude that the role of Dlx5 in the hypertrophic pathway is cell autonomous. We further conclude that Dlx5 and Dlx6 are functionally equivalent in the endochondral skeleton, in that the requirement for Dlx5 and Dlx6 function during chondrocyte hypertrophy can be satisfied with Dlx5 alone.