Ecosystem restoration is integral to humanity's recovery from COVID-19.

COVID-19 has devastated global communities and economies. The pandemic has exposed socioeconomic disparities and weaknesses in health systems worldwide. Long-term health effects and economic recovery are major concerns. Ecosystem restoration-ie, the repair of ecosystems that have been degraded-relates directly to tackling the health and socioeconomic burdens of COVID-19, because stable and resilient ecosystems are fundamental determinants of health and socioeconomic stability. Here, we use COVID-19 as a case study, showing how ecosystem restoration can reduce the risk of infection and adverse sequelae and have an integral role in humanity's recovery from COVID-19. The next decade will be crucial for humanity's recovery from COVID-19 and for ecosystem repair. Indeed, in the absence of effective, large-scale restoration, 95% of the Earth's land could be degraded by 2050. The UN Decade on Ecosystem Restoration (2021-30) declaration reflects the growing urgency and scale at which we should repair ecosystems. Importantly, ecosystem restoration could also help to combat the health and socioeconomic issues that are associated with COVID-19, yet it is poorly integrated into current responses to the disease. Ecosystem restoration can be a core public health intervention and assist in COVID-19 recovery if it is closely integrated with socioeconomic, health, and environmental policies.

Coalescing expansile skeletal disease: Delineation of an extraordinary osteopathy involving the IFITM5 mutation of osteogenesis imperfecta type V.

In 2003, we briefly reported the remarkable osteopathy of a 12-year-old boy who at age two months began fracturing his limbs with subsequent hyperplastic callus formation and expansion and fusion of appendicular bones. By age ten years he had coalesced his lumbosacral spine, pelvis, femurs, and leg and foot bones as a single structure. Computed tomography of expanded bone revealed a thin cortical shell, diminished irregular trabeculae, and cystic areas. Histopathology featured foci of woven bone, densely packed osteocytes, cartilage, fibrovascular tissue, and massive fat deposition in the marrow space lacking hematogenous precursor cells. Bone turnover markers indicated accelerated remodeling and the few radiographically assessable appendicular bones improved during brief adherence to alendronate therapy. Following puberty, serum multiplex biomarker profiling confirmed accelerated bone turnover. At age 23 years, macrospecimens from leg amputation revealed ossification along capsular tissue together with hyaline cartilage degeneration. Concurrently, the life-long course of this same disorder was delineated in an unrelated woman until her death at age 51 years. Both patients demonstrated the radiographic hallmarks and harbored the heterozygous point mutation (c.-14C>T) in the 5'-UTR of IFITM5 associated with osteogenesis imperfecta type V (OI-V). Herein, we detail the clinical, radiological, histopathological, biochemical, and molecular findings and discuss the etiology and pathogenesis of this extraordinary osteopathy that we call coalescing expansile skeletal disease.

Global restoration opportunities in tropical rainforest landscapes.

Over 140 Mha of restoration commitments have been pledged across the global tropics, yet guidance is needed to identify those landscapes where implementation is likely to provide the greatest potential benefits and cost-effective outcomes. By overlaying seven recent, peer-reviewed spatial datasets as proxies for socioenvironmental benefits and feasibility of restoration, we identified restoration opportunities (areas with higher potential return of benefits and feasibility) in lowland tropical rainforest landscapes. We found restoration opportunities throughout the tropics. Areas scoring in the top 10% (i.e., restoration hotspots) are located largely within conservation hotspots (88%) and in countries committed to the Bonn Challenge (73%), a global effort to restore 350 Mha by 2030. However, restoration hotspots represented only a small portion (19.1%) of the Key Biodiversity Area network. Concentrating restoration investments in landscapes with high benefits and feasibility would maximize the potential to mitigate anthropogenic impacts and improve human well-being.

Anthropogenic ecosystem disturbance and the recovery debt.

Ecosystem recovery from anthropogenic disturbances, either without human intervention or assisted by ecological restoration, is increasingly occurring worldwide. As ecosystems progress through recovery, it is important to estimate any resulting deficit in biodiversity and functions. Here we use data from 3,035 sampling plots worldwide, to quantify the interim reduction of biodiversity and functions occurring during the recovery process (that is, the 'recovery debt'). Compared with reference levels, recovering ecosystems run annual deficits of 46-51% for organism abundance, 27-33% for species diversity, 32-42% for carbon cycling and 31-41% for nitrogen cycling. Our results are consistent across biomes but not across degrading factors. Our results suggest that recovering and restored ecosystems have less abundance, diversity and cycling of carbon and nitrogen than 'undisturbed' ecosystems, and that even if complete recovery is reached, an interim recovery debt will accumulate. Under such circumstances, increasing the quantity of less-functional ecosystems through ecological restoration and offsetting are inadequate alternatives to ecosystem protection.

Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity.

The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP-associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin-3). The effects of nutlin-3 on CDP osteotoxicity were studied using both pre- and post-operative treatment models. In both cases the addition of nutlin-3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01-0.001). In addition the combination of nutlin-3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri-operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1716-1724, 2016.

eHALOPH a Database of Salt-Tolerant Plants: Helping put Halophytes to Work.

eHALOPH (http://www.sussex.ac.uk/affiliates/halophytes/) is a database of salt-tolerant plants-halophytes. Records of plant species tolerant of salt concentrations of around 80 mM sodium chloride or more have been collected, along with data on plant type, life form, ecotypes, maximum salinity tolerated, the presence or absence of salt glands, photosynthetic pathway, antioxidants, secondary metabolites, compatible solutes, habitat, economic use and whether there are publications on germination, microbial interactions and mycorrhizal status, bioremediation and of molecular data. The database eHALOPH can be used in the analysis of traits associated with tolerance and for informing choice of species that might be used for saline agriculture, bioremediation or ecological restoration and rehabilitation of degraded wetlands or other areas.

A critique of the 'novel ecosystem' concept.

The 'novel ecosystem' concept has captured the attention of scientists, managers, and science journalists, and more recently of policymakers, before it has been subjected to the scrutiny and empirical validation inherent to science. Lack of rigorous scrutiny can lead to undesirable outcomes in ecosystem management, environmental law, and policy. Contrary to the contentions of its proponents, no explicit, irreversible ecological thresholds allow distinctions between 'novel ecosystems' and 'hybrid' or 'historic' ones. Further, there is no clear message as to what practitioners should do with a 'novel ecosystem'. In addition, ecosystems of many types are being conserved, or restored to trajectories within historical ranges of variation, despite severe degradation that could have led to their being pronounced 'novel'.

The economics of restoration: looking back and leaping forward.

Since the publication of the Millennium Ecosystem Assessment in 2005 there has been a surge of interest in ecological restoration (ER) to recover biodiversity, re-establish ecosystem functioning and connectivity, and reactivate the delivery of ecosystem services. In policy spheres, there have also been repeated calls for expansion of restoration efforts. In many countries, new legislation now requires some form of restoration and/or a form of offset investment. All of this will require major increases in financial allocations toward restoration science, technology, and implementation, and much more detailed valuation techniques. The economics of restoration is a new field emerging to support these needs. Our paper here starts with an analysis of the articles and reviews published on this broad subject from 1928 to 2012, as captured in the Scopus academic search platform. Our goal is to present and summarize what has been said and done in this area to date. Next, we map out one possible way forward, illustrated by examples and based on a coherent bundle of decision parameters related to the economics of ER and, more broadly, to the restoration of natural capital. The restoration of natural capital is defined as activities that integrate investment in, and replenishment of, natural capital stocks to improve the flows of ecosystem goods and services, and the preservation of biodiversity, while enhancing all aspects of human well-being. We give special attention to system dynamic approaches and other promising tools and techniques.

Cisplatin inhibits bone healing during distraction osteogenesis.

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non-cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five-dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five-dose CDP regimen were observed in TNFR1KO mice. The two-dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri-operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP.

Benefits of investing in ecosystem restoration.

Measures aimed at conservation or restoration of ecosystems are often seen as net-cost projects by governments and businesses because they are based on incomplete and often faulty cost-benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) of ecosystem restoration projects that had sufficient reliable data in 9 different biomes ranging from coral reefs to tropical forests. Costs included capital investment and maintenance of the restoration project, and benefits were based on the monetary value of the total bundle of ecosystem services provided by the restored ecosystem. Assuming restoration is always imperfect and benefits attain only 75% of the maximum value of the reference systems over 20 years, we calculated the net present value at the social discount rates of 2% and 8%. We also conducted 2 threshold cum sensitivity analyses. Benefit-cost ratios ranged from about 0.05:1 (coral reefs and coastal systems, worst-case scenario) to as much as 35:1 (grasslands, best-case scenario). Our results provide only partial estimates of benefits at one point in time and reflect the lower limit of the welfare benefits of ecosystem restoration because both scarcity of and demand for ecosystem services is increasing and new benefits of natural ecosystems and biological diversity are being discovered. Nonetheless, when accounting for even the incomplete range of known benefits through the use of static estimates that fail to capture rising values, the majority of the restoration projects we analyzed provided net benefits and should be considered not only as profitable but also as high-yielding investments. Beneficios de Invertir en la Restauración de Ecosistemas.

Interobserver variability using a commercially available system of archived digital radiography with integrated computer-assisted measurements for scoliosis Cobb angles.

BACKGROUND: The purpose of this study was to determine if digital enhancements could improve upon published and interobserver variability for Cobb angle measurements of idiopathic scoliosis using a commercially available PACS system. The study also sought to determine if experience of the observer affected overall variability and to evaluate the time required to measure Cobb angles using 3 different techniques. As the decision for scoliosis treatment requires serial radiographic measurements by 1 or more observers at different times, precise landmark identification and curve measurement should decrease variability and improve accuracy. METHODS: Fifty-four consecutive digital radiographs of 49 children with idiopathic scoliosis were collected and archived, yielding a total of 117 curves. Five observers, ranging from a PGY2 resident to a senior level faculty member, measured each radiograph in 3 different ways. Technique A involved measuring the curves as the image first appeared on the computer screen. Technique B consisted of 2 extra steps: enlarging the image until the spine filled the screen and using an edge enhancement tool. Technique C utilized the steps in B and further enlarging each vertebra to adjust each measurement. Each technique was timed for each observer. RESULTS: Technique C had the lowest variability that was significantly different from technique A. Technique B also had lower variability than technique A. The 2 observers with the greatest experience demonstrated the least intraobserver and interobserver variability. Techniques B and C decreased the variability of less experienced observers. The average time required for techniques A, B, and C was 25, 29, and 40 seconds, respectively. Confounding variables such as obesity did not affect the measurements, but curve location did, with thoracic curves causing greater variability for less experienced observers. DISCUSSION: The results demonstrate that less experienced observers using the relatively rapid technique A for digital radiographs are more likely to have clinically significant discrepancies in their measurements, which could affect treatment decisions. Taking 4 extra seconds using technique B significantly decreases variability and improves accuracy in the evaluation and management of scoliosis patients. LEVEL OF EVIDENCE: I (testing of previously developed diagnostic criteria).

Impacts of biological invasions: what's what and the way forward.

Study of the impacts of biological invasions, a pervasive component of global change, has generated remarkable understanding of the mechanisms and consequences of the spread of introduced populations. The growing field of invasion science, poised at a crossroads where ecology, social sciences, resource management, and public perception meet, is increasingly exposed to critical scrutiny from several perspectives. Although the rate of biological invasions, elucidation of their consequences, and knowledge about mitigation are growing rapidly, the very need for invasion science is disputed. Here, we highlight recent progress in understanding invasion impacts and management, and discuss the challenges that the discipline faces in its science and interactions with society.

Rosiglitazone disrupts endosteal bone formation during distraction osteogenesis by local adipocytic infiltration.

Rosiglitazone (Rosi) is a drug in the thiazolidinedione class for treatment of type 2 diabetes mellitus (T2DM), which binds and activates PPARγ nuclear receptor in fat cells, sensitizing them to insulin. Despite proven antidiabetic efficacy, Rosi therapy may be associated with trabecular bone loss and an increased risk of fractures. To examine the potential side effects of Rosi treatment on bone formation, we delivered Rosi to mice using a combined model of distraction osteogenesis (DO) and type 2 diabetes mellitus (T2DM). DO provides a unique method to isolate the sequence of intramembranous bone formation, an important component of both fracture healing and bone homeostasis. Four groups of n=6 mice were used to compare the effects of Rosi on bone formation and cellular composition in both diabetic (Avy/a strain) and non-diabetic mice (a/a strain). New bone formation was examined by high resolution radiographs, micro-computed tomography, and histology. Precursor cells in the distraction gap were quantitated using immunohistochemical stains for proliferating cell nuclear antigen. Committed osteoblasts and adipocytes in the gap were identified and quantitated by immunostaining for osteocalcin and FABP4/aP2, respectively. The diabetic model developed obesity, hyperglycemia, hyperinsulinemia and insulin resistance, while the control littermates remained lean, normoglycemic and insulin sensitive. Rosi treatment decreased levels of non-fasted glucose and insulin and improved insulin sensitivity in the A(vy)/a mice, but had no effect in a/a mice, indicating antidiabetic efficacy of Rosi at the tested dose. Despite the diabetic, obese mice having twice the number of fat cells in their marrow than the non-diabetic mice, bone formation using DO was not adversely affected by the diabetes itself. However, Rosi treatment significantly diminished intramembranous endosteal bone formation, while increasing adipogenesis in and adjacent to the distraction gap up to 3.5- to 3.8-fold in both diabetic and non-diabetic models. This effect was independent of the anti-diabetic therapeutic response. These results raise the question of whether osteoblast precursors are inhibited in their development or actually converted to adipocytic phenotypes, possibly via marrow fat PPARγ nuclear receptor.

Rosiglitazone inhibits bone regeneration and causes significant accumulation of fat at sites of new bone formation.

Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma activators, and insulin sensitizers represent drugs used to treat hyperglycemia in diabetic patients. Type 2 diabetes mellitus (T2DM) is associated with a twofold increase in fracture risk, and TZDs use increases this risk by an additional twofold. In this study, we analyzed the effect of systemic administration of the TZD rosiglitazone on new bone formation in two in vivo models of bone repair, a model of drilled bone defect regeneration (BDR) and distraction osteogenesis (DO) and a model of extended bone formation. Rosiglitazone significantly inhibited new endosteal bone formation in both models. This effect was correlated with a significant accumulation of fat cells, specifically at sites of bone regeneration. The diminished bone regeneration in the DO model in rosiglitazone-treated animals was associated with a significant decrease in cell proliferation measured by the number of cells expressing proliferating cell nuclear antigen and neovascularization measured by both the number of vascular sinusoids and the number of cells producing proangiogenic vascular endothelial growth factor at the DO site. In summary, rosiglitazone decreased new bone formation in both BDR and DO models of bone repair by mechanisms which include both intrinsic changes in mesenchymal stem cell proliferation and differentiation and changes in the local environment supporting angiogenesis and new bone formation. These studies suggest that bone regeneration may be significantly compromised in T2DM patients on TZD therapy.

Distraction osteogenesis in TNF receptor 1 deficient mice is protected from chronic ethanol exposure.

Distraction osteogenesis (DO) is an orthopedic protocol, which induces direct new bone formation as a result of the stimulating effects of mechanical distraction. Chronic ethanol exposure has been demonstrated to inhibit bone formation in rodent models of DO. Further, it has been demonstrated that (1) tumor necrosis factor-α (TNF) blockers are protective against ethanol exposure and (2) recombinant mouse TNF (rmTNF) inhibits direct bone formation in ethanol naïve mice through TNF receptor 1 (TNFR1). These results suggest that the inhibitory effects are significantly mediated by TNF signaling. Therefore, we hypothesized that direct new bone formation in TNFR1 knockout (KO) mice would be protected from ethanol exposure. We used a unique model of mouse DO combined with liquid/chow diets to compare the effects of ethanol on both a strain of TNFR1 knockout (TNFR1 KO) mice and on mice of their C57BL/6 (B6) control strain. In the B6 study, and in concordance with previous work, both radiological and histological analyses of direct bone formation in the distraction gaps demonstrated significant osteoinhibition due to ethanol compared with chow- or pair-fed mice. In the TNFR1 KO study and in support of the hypothesis, both radiological and histological analyses of distraction gap bone formation demonstrated no significant differences between the ethanol, chow fed, or pair fed. We conclude that exogenous rmTNF and ethanol-induced endogenous TNF act to inhibit new bone formation during DO by signaling primarily through TNFR1.