Abstract Purpose Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the ...contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse. Methods A telephone survey was conducted at Group Health Cooperative and Kaiser Permanente of Northern California. We interviewed 1,334 patients on COT for noncancer pain who had no history of substance abuse. Patients were asked about 3 forms of opioid misuse: (1) self-medicating for symptoms other than pain, (2) self-increasing doses, and (3) giving to or getting opioids from others. Depression was evaluated by the 8-item Patient Health Questionnaire (PHQ-8). Results Compared with patients who were not depressed (PHQ-8 score 0 to 4), patients with moderate depression (PHQ-8 score 10 to 14) and severe depression (PHQ-8 score 15 or higher) were 1.8 and 2.4 times more likely, respectively, to misuse their opioid medications for non–pain symptoms. Patients with mild (PHQ-8 score 5 to 9), moderate, and severe depression were 1.9, 2.9, and 3.1 times more likely, respectively, to misuse their opioid medications by self-increasing their dose. There was no statistically significant association between depression and giving opioids to or getting them from others. Conclusion In patients with no substance abuse history, depressive symptoms are associated with increased rates of some forms of self-reported opioid misuse. Clinicians should be alert to the risk of patients with depressive symptoms using opioids to relieve these symptoms and thereby using more opioids than prescribed.
The formation of epicormic sprouts on the boles of trees is a phenomenon that has, until recently, been poorly understood. Renewed interest in the topic in the last two decades has led to significant ...advances in our knowledge of the subject, especially in regard to bud anatomy, morphology and ontogeny. There exists, however, no comprehensive synthesis of results from different disciplines across genera and geographical areas; this review seeks to fill that void and provide a comprehensive framework capable of guiding future research. A tree's potential for producing epicormic branches is dependent on the number of buds that are produced on a growing shoot, the development of those buds and associated meristems over time and the factors that promote sprout formation or bud death. Based on the descriptions of a limited number of researched species, we were able to describe four different developmental strategies for epicormics based on characteristics of meristem development. Control over epicormic bud dormancy is complex, but it is clear that the traditional view of auxin-mediated dormancy release is incomplete. Genetic control over epicormic development is yet to be empirically proven. Future research should focus on clarifying these physiological and genetic controls of epicormic bud development as well as developing more robust methods for tracking epicormics in ecological and silvicultural studies.
Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in ...white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.
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•Adipocytes transfer their mitochondria to macrophages in vivo•Mitochondria transfer from adipocytes to macrophages is decreased in obesity•Mitochondria uptake by macrophages is mediated by heparan sulfates•Mice that lack heparan sulfates on macrophages exhibit metabolic dysfunction
Brestoff et al. show that adipose-tissue-resident macrophages acquire mitochondria from neighboring adipocytes in a heparan-sulfate-dependent process that is impaired in obesity. Genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and exacerbates diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.
Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive ...shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. STATEMENT OF SIGNIFICANCE: Current treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential "off-the-shelf" surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects.
Accurate quantification of forest aboveground biomass (AGB) is the foundation to the responses of diverse forest ecosystems to the changing climate. Lidar-based statistical models have been used to ...accurately estimate AGB in large spatial extents, especially in boreal and temperate softwood forest ecosystems. However, the few available models for temperate hardwood and hardwood-dominated mixed forests are low in accuracy due both to the deliquescent growth form of hardwood trees and the strong site-to-site variations in height-diameter relationship. In this study, we established multiplicative nonlinear regression models that incorporated both lidar-derived metrics and soil-based site productivity classes (high and low productivity sites) to estimate aboveground biomass in temperate hardwood forests. The final optimized model had high accuracy (R2=0.81; RMSE=45.5Mgha−1) with reliable performance in ABG estimation by integrating relative height metrics at 75 and 70 percentiles (RH75 and RH70), canopy coverage and site productivity class. An optimized model that included an index of site productivity explained 14% more variance than the best-fit model without the term. Moreover, the relationship between AGB and lidar-based metrics was nonlinear on low productivity sites and nearly linear on high productivity sites, further indicating the importance of including direct or indirect measures of site productivity in lidar-based biomass models, particularly for those applied to temperate hardwood forests. Our new lidar-based model provides a potential framework to integrate lidar-based structural information and soil-based site productivity to improve AGB estimation in temperate hardwood forests.
•A new biomass estimation model is developed for temperate hardwood forests.•The variance of site quality has significant effects in biomass estimation models.•Height metrics have varied responses to biomass in high and low quality sites.•CHM provides better canopy coverage metrics than point cloud using leaf-off lidar.
This statement revises a previous statement on screening of preterm infants for retinopathy of prematurity (ROP) that was published in 2006. ROP is a pathologic process that occurs only in immature ...retinal tissue and can progress to a tractional retinal detachment, which can result in functional or complete blindness. Use of peripheral retinal ablative therapy by using laser photocoagulation for nearly 2 decades has resulted in a high probability of markedly decreasing the incidence of this poor visual outcome, but the sequential nature of ROP creates a requirement that at-risk preterm infants be examined at proper times and intervals to detect the changes of ROP before they become permanently destructive. This statement presents the attributes on which an effective program for detecting and treating ROP could be based, including the timing of initial examination and subsequent reexamination intervals.
Loss of native foundation tree species to introduced pests profoundly alters the structure and function of many forest ecosystems. Recent advances to resurrect or prevent the loss of species by ...developing resistant hybrids hold promise, but uncertainty remains about the potential impacts of introducing a novel genotype on ecological processes, such as fire. A classic example of a non-native, pathogen-caused loss of a foundation species is American chestnut (Castanea dentata), a species now functionally extinct from the eastern US but undergoing experimental trials to resurrect the species with a putatively disease-resistant genotype. We compared the litter flammability among American chestnut, Chinese chestnut (C. mollisima), and a population of first intercross, third-generation backcrossed hybrid (BC₃F₂) using laboratory burning experiments. Litter flammability of American chestnut was consistently greater than Chinese chestnut, whereas the hybrid had an intermediate flammability or more closely resembled Chinese chestnut flammability by some measures. Greater flammability in American chestnut was associated with a longer leaf structure with greater curling when dry. American chestnut had flammability properties consistent with other pyrophytic species present in contemporary fire-prone ecosystems. The loss of American chestnut may have altered litter flammability of some eastern US forest ecosystems, a result more commonly associated with compositional changes in conjunction with fire exclusion and other disturbances. Resurrecting American chestnut with a hybrid genotype may mitigate this change in areas where less flammable species have replaced American chestnut. Resurrection of lost foundation species through introduction of resistant genotypes may represent a resounding ecological success story, but unanticipated changes to ecological processes, such as fire, should be considered.
A central event in Alzheimer's disease is the accumulation of amyloid β (Aβ) peptides generated by the proteolytic cleavage of the amyloid precursor protein (APP). APP overexpression leads to ...increased Aβ generation and Alzheimer's disease in humans and altered neuronal migration and increased long term depression in mice. Conversely, reduction of APP expression results in decreased Aβ levels in mice as well as impaired learning and memory and decreased numbers of dendritic spines. Together these findings indicate that therapeutic interventions that aim to restore APP and Aβ levels must do so within an ideal range. To better understand the effects of modulating APP levels, we explored the mechanisms regulating APP expression focusing on post-transcriptional regulation. Such regulation can be mediated by RNA regulatory elements such as guanine quadruplexes (G-quadruplexes), non-canonical structured RNA motifs that affect RNA stability and translation. Via a bioinformatics approach, we identified a candidate G-quadruplex within the APP mRNA in its 3'UTR (untranslated region) at residues 3008-3027 (NM_201414.2). This sequence exhibited characteristics of a parallel G-quadruplex structure as revealed by circular dichroism spectrophotometry. Further, as with other G-quadruplexes, the formation of this structure was dependent on the presence of potassium ions. This G-quadruplex has no apparent role in regulating transcription or mRNA stability as wild type and mutant constructs exhibited equivalent mRNA levels as determined by real time PCR. Instead, we demonstrate that this G-quadruplex negatively regulates APP protein expression using dual luciferase reporter and Western blot analysis. Taken together, our studies reveal post-transcriptional regulation by a 3'UTR G-quadruplex as a novel mechanism regulating APP expression.
Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient ...pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.
When a tree dies, it continues to play an important ecological role within forests. Coarse woody debris (CWD), including standing deadwood (SDW) and downed deadwood (DDW), is an important functional ...component of forest ecosystems, particularly for many dispersal-limited saproxylic taxa and for metapopulation dynamics across landscapes. Processes, such as natural disturbance or management, modify forest composition and structure, thereby influencing CWD abundance and distribution. Many studies have compared older forests to forests managed with even-aged silvicultural systems and observed a prolonged period of low CWD occurrence after harvesting. With fine-scale spatial data, our study compares the long-term impacts of light partial harvesting on the CWD structure of eastern deciduous hardwood forests. We mapped and inventoried DDW and SDW using variable radius plots based on a 10 m × 10 m grid throughout an unmanaged, structurally-complex relict forest and two nearby forests that were partially harvested over 46 years ago. The relict stand had significantly larger individual pieces and higher accumulations of DDW and SDW than both of the partially harvested stands. Connectivity of CWD was much higher in the relict stand, which had fewer, larger patches. Larger pieces and higher proportion of decay-resistant species (e.g. Quercus spp.) in the relict forest resulted in slower decomposition, greater accumulation and increased connectivity of CWD. Partial harvests, such that occur with selection forestry, are generally considered less disruptive of ecosystem services, but this study highlights the long-term impacts of even light partial harvests on CWD stocks and distribution. When planning harvesting events, forest managers should also consider alternative methods to ensure the sustainability of deadwood resources and function.
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