Mineral tessellation in bone and the stenciling principle for extracellular matrix mineralization.

We review here the Stenciling Principle for extracellular matrix mineralization that describes a double-negative process (inhibition of inhibitors) that promotes mineralization in bone and other mineralized tissues, whereas the default condition of inhibition alone prevents mineralization elsewhere in soft connective tissues. The stenciling principle acts across multiple levels from the macroscale (skeleton/dentition vs soft connective tissues), to the microscale (for example, entheses, and the tooth attachment complex where the soft periodontal ligament is situated between mineralized tooth cementum and mineralized alveolar bone), and to the mesoscale (mineral tessellation). It relates to both small-molecule (e.g. pyrophosphate) and protein (e.g. osteopontin) inhibitors of mineralization, and promoters (enzymes, e.g. TNAP, PHEX) that degrade the inhibitors to permit and regulate mineralization. In this process, an organizational motif for bone mineral arises that we call crossfibrillar mineral tessellation where mineral formations - called tesselles - geometrically approximate prolate ellipsoids and traverse multiple collagen fibrils (laterally). Tesselle growth is directed by the structural anisotropy of collagen, being spatially restrained in the shorter transverse tesselle dimensions (averaging 1.6 × 0.8 × 0.8 µm, aspect ratio 2, length range 1.5-2.5 µm). Temporo-spatially, the tesselles abut in 3D (close ellipsoid packing) to fill the volume of lamellar bone extracellular matrix. Poorly mineralized interfacial gaps between adjacent tesselles remain discernable even in mature lamellar bone. Tessellation of a same, small basic unit to form larger structural assemblies results in numerous 3D interfaces, allows dissipation of critical stresses, and enables fail-safe cyclic deformations. Incomplete tessellation in osteomalacia/odontomalacia may explain why soft osteomalacic bones buckle and deform under loading.

Crossfibrillar mineral tessellation in normal and Hyp mouse bone as revealed by 3D FIB-SEM microscopy.

In bone, structural components such as mineral extend across length scales to provide essential biomechanical functions. Using X-ray micro-computed tomography (µCT), and focused ion beam scanning electron microscopy (FIB-SEM) in serial-surface-view mode, together with 3D reconstruction, entire mouse skeletons and small bone tissue volumes were examined in normal wildtype (WT) and mutant Hyp mice (an animal model for X-linked hypophosphatemia/XLH, a disease with severe hypomineralization of bone). 3D thickness maps of the skeletons showed pronounced irregular thickening and abnormalities of many skeletal elements in Hyp mice compared to WT mice. At the micro- and nanoscale, near the mineralization front in WT tibial bone volumes, mineralization foci grow as expanding prolate ellipsoids (tesselles) to abut and pack against one another to form a congruent and contiguous mineral tessellation pattern within collagen bundles that contributes to lamellar periodicity. In the osteomalacic Hyp mouse bone, mineralization foci form and begin initial ellipsoid growth within normally organized collagen assembly, but their growth trajectory aborts. Mineralization-inhibiting events in XLH/Hyp (low circulating serum phosphate, and increased matrix osteopontin) combine to result in decreased mineral ellipsoid tessellation - a defective mineral-packing organization that leaves discrete mineral volumes isolated in the extracellular matrix such that ellipsoid packing/tessellation is not achieved. Such a severely altered mineralization pattern invariably leads to abnormal compliance, other aberrant biomechanical properties, and altered remodeling of bone, all of which indubitably lead to macroscopic bone deformities and anomalous mechanical performance in XLH/Hyp. Also, we show the relationship of osteocytes and their cell processes to this mineralization pattern.

Posterior Distal Clavicle Beveling for Chronic Nonincarcerated Type IV Acromioclavicular Separations: Surgical Technique and Early Clinical Outcomes.

PURPOSE: To describe the arthroscopic partial posterior distal clavicle beveling technique for treatment of chronic nonincarcerated type IV acromioclavicular (AC) separations and report clinical outcomes and return to sport. METHODS: All patients who underwent the arthroscopic partial distal clavicle beveling technique and met eligibility criteria were identified and retrospectively reviewed. Inclusion criteria included the clinical diagnosis of a chronic nonincarcerated type IV AC separation and a minimum follow-up period of 24 months. Subjects completed the American Shoulder Elbow Surgeons shoulder assessment and a study-designed questionnaire. Radiographic images and clinical charts were also reviewed. RESULTS: This study identified 15 consecutive patients with 2 lost to follow-up, resulting in inclusion of 13 subjects (9 males and 4 females). Dominant arm was involved in 77% of cases. Mean age at operation was 33.2 years (range, 19-56 years). The mean period between injury and operation was 12.5 months (range, 3-37 months), and follow-up was 48.5 months (range, 24-126 months). The mean preoperative ASES score was 46.6 ± 16.9 (range, 33-68), and the mean postoperative ASES score was 87.3 ± 17.4 (range, 50-100) (P < .0001). All 9 athletes in the study returned to competition with a mean recovery period of 2.3 months (range, 2 weeks to 4 months). Mean timeframe for return to work was 2 weeks (range, 1 day to 2 months). One subject underwent a subsequent coracoclavicular ligament reconstruction for continued pain. The mean satisfaction level was 4.3 out of 5, and 91% would choose to have the surgery again. One subject indicated dissatisfaction with shoulder appearance. CONCLUSIONS: The arthroscopic partial distal clavicle beveling procedure for nonincarcerated type IV AC separations resulted in a significant reduction in pain, improved daily function, and early return to sport. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Stream biomonitoring using macroinvertebrates around the globe: a comparison of large-scale programs.

Water quality agencies and scientists are increasingly adopting standardized sampling methodologies because of the challenges associated with interpreting data derived from dissimilar protocols. Here, we compare 13 protocols for monitoring streams from different regions and countries around the globe. Despite the spatially diverse range of countries assessed, many aspects of bioassessment structure and protocols were similar, thereby providing evidence of key characteristics that might be incorporated in a global sampling methodology. Similarities were found regarding sampler type, mesh size, sampling period, subsampling methods, and taxonomic resolution. Consistent field and laboratory methods are essential for merging data sets collected by multiple institutions to enable large-scale comparisons. We discuss the similarities and differences among protocols and present current trends and future recommendations for monitoring programs, especially for regions where large-scale protocols do not yet exist. We summarize the current state in one of these regions, Latin America, and comment on the possible development path for these techniques in this region. We conclude that several aspects of stream biomonitoring need additional performance evaluation (accuracy, precision, discriminatory power, relative costs), particularly when comparing targeted habitat (only the commonest habitat type) versus site-wide sampling (multiple habitat types), appropriate levels of sampling and processing effort, and standardized indicators to resolve dissimilarities among biomonitoring methods. Global issues such as climate change are creating an environment where there is an increasing need to have universally consistent data collection, processing and storage to enable large-scale trend analysis. Biomonitoring programs following standardized methods could aid international data sharing and interpretation.

Selecting a sensitive battery of bioassays to detect toxic effects of metals in effluents.

The use of bioassay batteries is necessary to evaluate toxic effects at various biological levels. The selection of bioassays without prior testing and determination of the most sensitive/suitable groups for each impact may allow the discharge of effluents that pose a threat to the environment. The present study tested and selected a battery of sensitive ecotoxicological bioassays for detecting toxic effects of metals. The sensitivities of six organisms were evaluated (algae Pseudokirchneriella subcapitata and Chlorella vulgaris, Cladocera Daphnia similis and Ceriodaphnia dubia, and fish Poecilia reticulata and Danio rerio) after exposure to 10 individual metal species deemed toxic to the aquatic environment (Ag+, Cd2+, Cu+, Cu2+, Cr3+, Cr6+, Pb2+, Ni2+, Zn2+, and Hg2+) and to real (steel-mill) and laboratory simulated effluents. In the bioassays, fish were the least sensitive; D. rerio showed no sensitivity to any of the effluents tested. P. subcapitata was a good bioindicator of Cr3+ toxicity, and D. similis was the most sensitive organism to Hg2+; but the toxic effect of effluents with higher levels of Hg2+ was better detected by C. dubia. The most sensitive battery of bioassays to detect low concentrations of dissolved metals in effluents was the 72-h chronic test with C. vulgaris and the 48-h acute test with C. dubia.

The 2023 Latin America report of the Lancet Countdown on health and climate change: the imperative for health-centred climate-resilient development.

In 2023, a series of climatological and political events unfolded, partly driving forward the global climate and health agenda while simultaneously exposing important disparities and vulnerabilities to climate-related events. On the policy front, a significant step forward was marked by the inaugural Health Day at COP28, acknowledging the profound impacts of climate change on health. However, the first-ever Global Stocktake showed an important gap between the current progress and the targets outlined in the Paris Agreement, underscoring the urgent need for further and decisive action. From a Latin American perspective, some questions arise: How do we achieve the change that is needed? How to address the vulnerabilities to climate change in a region with long-standing social inequities? How do we promote intersectoral collaboration to face a complex problem such as climate change? The debate is still ongoing, and in many instances, it is just starting. The renamed regional centre Lancet Countdown Latin America (previously named Lancet Countdown South America) expanded its geographical scope adding Mexico and five Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, and Panama, as a response to the need for stronger collaboration in a region with significant social disparities, including research capacities and funding. The centre is an independent and multidisciplinary collaboration that tracks the links between health and climate change in Latin America, following the global Lancet Countdown's methodologies and five domains. The Lancet Countdown Latin America work hinges on the commitment of 23 regional academic institutions, United Nations agencies, and 34 researchers who generously contribute their time and expertise. Building from the first report, the 2023 report of the Lancet Countdown Latin America, presents 34 indicators that track the relationship between health and climate change up to 2022, aiming at providing evidence to public decision-making with the purpose of improving the health and wellbeing of Latin American populations and reducing social inequities through climate actions focusing on health. This report shows that Latin American populations continue to observe a growing exposure to changing climatic conditions. A warming trend has been observed across all countries in Latin America, with severe direct impacts. In 2022, people were exposed to ambient temperatures, on average, 0.38 °C higher than in 1986-2005, with Paraguay experiencing the highest anomaly (+1.9 °C), followed by Argentina (+1.2 °C) and Uruguay (+0.9 °C) (indicator 1.1.1). In 2013-2022, infants were exposed to 248% more heatwave days and people over 65 years old were exposed to 271% more heatwave days than in 1986-2005 (indicator 1.1.2). Also, compared to 1991-2000, in 2013-2022, there were 256 and 189 additional annual hours per person, during which ambient heat posed at least moderate and high risk of heat stress during light outdoor physical activity in Latin America, respectively (indicator 1.1.3). Finally, the region had a 140% increase in heat-related mortality from 2000-2009 to 2013-2022 (indicator 1.1.4). Changes in ecosystems have led to an increased risk of wildfires, exposing individuals to very or extremely high fire danger for more extended periods (indicator 1.2.1). Additionally, the transmission potential for dengue by Aedes aegypti mosquitoes has risen by 54% from 1951-1960 to 2013-2022 (indicator 1.3), which aligns with the recent outbreaks and increasing dengue cases observed across Latin America in recent months. Based on the 2023 report of the Lancet Countdown Latin America, there are three key messages that Latin America needs to further explore and advance for a health-centred climate-resilient development. Latin American countries require intersectoral public policies that simultaneously increase climate resilience, reduce social inequities, improve population health, and reduce greenhouse gas (GHG) emissions. The findings show that adaptation policies in Latin America remain weak, with a pressing need for robust vulnerability and adaptation (V&A) assessments to address climate risks effectively. Unfortunately, such assessments are scarce. Up to 2021, Brazil is the only country that has completed and officially reported a V&A to the 2021 Global Survey conducted by the World Health Organization (WHO). Argentina, Guatemala, and Panama have also conducted them, but they have not been reported (indicator 2.1.1). Similarly, efforts in developing and implementing Health National Adaptation Plans (HNAPs) are varied and limited in scope. Brazil, Chile, and Uruguay are the only countries that have an HNAP (indicator 2.1.2). Moreover, self-reported city-level climate change risk assessments are very limited in the region (indicator 2.1.3). The collaboration between meteorological and health sectors remains insufficient, with only Argentina, Brazil, Colombia, and Guatemala self-reporting some level of integration (indicator 2.2.1), hindering comprehensive responses to climate-related health risks in the region. Additionally, despite the urgent need for action, there has been minimal progress in increasing urban greenspaces across the region since 2015, with only Colombia, Nicaragua, and Venezuela showing slight improvements (indicator 2.2.2). Compounding these challenges is the decrease in funding for climate change adaptation projects in Latin America, as evidenced by the 16% drop in funds allocated by the Green Climate Fund (GCF) in 2022 compared to 2021. Alarmingly, none of the funds approved in 2022 were directed toward climate change and health projects, highlighting a critical gap in addressing health-related climate risks (indicator 2.2.3). From a vulnerability perspective, the Mosquito Risk Index (MoRI) indicates an overall decrease in severe mosquito-borne disease risk in the region due to improvements in water, sanitation, and hygiene (WASH) (indicator 2.3.1). Brazil and Paraguay were the only countries that showed an increase in this indicator. It is worth noting that significant temporal variation within and between countries still persists, suggesting inadequate preparedness for climate-related changes. Overall, population health is not solely determined by the health sector, nor are climate policies a sole responsibility of the environmental sector. More and stronger intersectoral collaboration is needed to pave development pathways that consider solid adaptation to climate change, greater reductions of GHG emissions, and that increase social equity and population health. These policies involve sectors such as finance, transport, energy, housing, health, and agriculture, requiring institutional structures and policy instruments that allow long-term intersectoral collaboration. Latin American countries need to accelerate an energy transition that prioritises people's health and wellbeing, reduces energy poverty and air pollution, and maximises health and economic gains. In Latin America, there is a notable disparity in energy transition, with electricity generation from coal increasing by an average of 2.6% from 1991-2000 to 2011-2020, posing a challenge to efforts aimed at phasing out coal (indicator 3.1.1). However, this percentage increase is conservative as it may not include all the fossil fuels for thermoelectric electricity generation, especially during climate-related events and when hydropower is affected (Panel 4). Yet, renewable energy sources have been growing, increasing by an average of 5.7% during the same period. Access to clean fuels for cooking remains a concern, with 46.3% of the rural population in Central America and 23.3% in South America lacking access to clean fuels in 2022 (indicator 3.1.2). It is crucial to highlight the concerning overreliance on fossil fuels, particularly liquefied petroleum gas (LPG), as a primary cooking fuel. A significant majority of Latin American populations, approximately 74.6%, rely on LPG for cooking. Transitioning to cleaner heating and cooking alternatives could also have a health benefit by reducing household air pollution-related mortality. Fossil fuels continue to dominate road transport energy in Latin America, accounting for 96%, although some South American countries are increasing the use of biofuels (indicator 3.1.3). Premature mortality attributable to fossil-fuel-derived PM2.5 has shown varied trends across countries, increasing by 3.9% from 2005 to 2020 across Latin America, which corresponds to 123.5 premature deaths per million people (indicator 3.2.1). The Latin American countries with the highest premature mortality rate attributable to PM2.5 in 2020 were Chile, Peru, Brazil, Colombia, Mexico, and Paraguay. Of the total premature deaths attributable to PM2.5 in 2020, 19.1% was from transport, 12.3% from households, 11.6% from industry, and 11% from agriculture. From emission and capture of GHG perspective, commodity-driven deforestation and expansion of agricultural land remain major contributors to tree cover loss in the region, accounting for around 80% of the total loss (indicator 3.3). Additionally, animal-based food production in Latin America contributes 85% to agricultural CO2 equivalent emissions, with Argentina, Brazil, Panama, Paraguay, and Uruguay ranking highest in per capita emissions (indicator 3.4.1). From a health perspective, in 2020, approximately 870,000 deaths were associated with imbalanced diets, of which 155,000 (18%) were linked to high intake of red and processed meat and dairy products (indicator 3.4.2). Energy transition in Latin America is still in its infancy, and as a result, millions of people are currently exposed to dangerous levels of air pollution and energy poverty (i.e., lack of access to essential energy sources or services). As shown in this report, the levels of air pollution, outdoors and indoors, are a significant problem in the wholeregion, with marked disparities between urban and rural areas. In 2022, Peru, Chile, Mexico, Guatemala, Colombia, El Salvador, Brazil, Uruguay, Honduras, Panama, and Nicaragua were in the top 100 most polluted countries globally. Transitioning to cleaner sources of energy, phasing out fossil fuels, and promoting better energy efficiency in the industrial and housing sectors are not only climate mitigation measures but also huge health and economic opportunities for more prosperous and healthy societies. Latin American countries need to increase climate finance through permanent fiscal commitments and multilateral development banks to pave climate-resilient development pathways. Climate change poses significant economic costs, with investments in mitigation and adaptation measures progressing slowly. In 2022, economic losses due to weather-related extreme events in Latin America were US$15.6 billion -an amount mainly driven by floods and landslides in Brazil-representing 0.28% of Latin America's Gross Domestic Product (GDP) (indicator 4.1.1). In contrast to high-income countries, most of these losses lack insurance coverage, imposing a substantial financial strain on affected families and governments. Heat-related mortality among individuals aged 65 and older in Latin America reached alarming levels, with losses exceeding the equivalent of the average income of 451,000 people annually (indicator 4.1.2). Moreover, the total potential income loss due to heat-related labour capacity reduction amounted to 1.34% of regional GDP, disproportionately affecting the agriculture and construction sectors (indicator 4.1.3). Additionally, the economic toll of premature mortality from air pollution was substantial, equivalent to a significant portion of regional GDP (0.61%) (indicator 4.1.4). On a positive note, clean energy investments in the region increased in 2022, surpassing fossil fuel investments. However, in 2020, all countries reviewed continued to offer net-negative carbon prices, revealing fossil fuel subsidies totalling US$23 billion. Venezuela had the highest net subsidies relative to current health expenditure (123%), followed by Argentina (10.5%), Bolivia (10.3%), Ecuador (8.3%), and Chile (5.6%) (indicator 4.2.1). Fossil fuel-based energy is today more expensive than renewable energy. Fossil fuel burning drives climate change and damages the environment on which people depend, and air pollution derived from the burning of fossil fuels causes seven million premature deaths each year worldwide, along with a substantial burden of disease. Transitioning to sustainable, zero-emission energy sources, fostering healthier food systems, and expediting adaptation efforts promise not only environmental benefits but also significant economic gains. However, to implement mitigation and adaptation policies that also improve social wellbeing and prosperity, stronger and solid financial systems are needed. Climate finance in Latin American countries is scarce and strongly depends on political cycles, which threatens adequate responses to the current and future challenges. Progress on the climate agenda is lagging behind the urgent pace required. While engagement with the intersection of health and climate change is increasing, government involvement remains inadequate. Newspaper coverage of health and climate change has been on the rise, peaking in 2022, yet the proportion of climate change articles discussing health has declined over time (indicator 5.1). Although there has been significant growth in the number of scientific papers focusing on Latin America, it still represents less than 4% of global publications on the subject (indicator 5.3). And, while health was mentioned by most Latin American countries at the UN General Debate in 2022, only a few addressed the intersection of health and climate change, indicating a lack of awareness at the governmental level (indicator 5.4). The 2023 Lancet Countdown Latin America report underscores the cascading and compounding health impacts of anthropogenic climate change, marked by increased exposure to heatwaves, wildfires, and vector-borne diseases. Specifically, for Latin America, the report emphasises three critical messages: the urgent action to implement intersectoral public policies that enhance climate resilience across the region; the pressing need to prioritise an energy transition that focuses on health co-benefits and wellbeing, and lastly, that need for increasing climate finance by committing to sustained fiscal efforts and engaging with multilateral development banks. By understanding the problems, addressing the gaps, and taking decisive action, Latin America can navigate the challenges of climate change, fostering a more sustainable and resilient future for its population. Spanish and Portuguese translated versions of this Summary can be found in Appendix B and C, respectively. The full translated report in Spanish is available in Appendix D.

Attaching organic fibers to mineral: The case of the avian eggshell.

Bird eggs possess a mineralized eggshell with a soft underlying fibrous membrane. These dissimilar material layers successfully evolved a structural attachment to each other as a conserved avian reproduction strategy essential to avian embryonic development, growth, and hatching of the chick. To understand how organic membrane fibers attach to shell mineral (calcite), 3D multiscale imaging including X-ray and electron tomography coupled with deep learning-based feature segmentation was used to show how membrane fibers are organized and anchored into shell mineral. Whole fibers embed into mineral across the microscale, while fine mineral projections (granules/spikes) insert into fiber surfaces at the nanoscale, all of which provides considerable surface area and multiscale anchorage at the organic-inorganic interface between the fibrous membrane and the shell. Such a reciprocal anchorage system occurring at two different length scales between organic fibers and inorganic mineral provides a secure attachment mechanism for avian eggshell integrity across two dissimilar materials.

Mineral tessellation in mouse enthesis fibrocartilage, Achilles tendon, and Hyp calcifying enthesopathy: A shared 3D mineralization pattern.

The hallmark of enthesis architecture is the 3D compositional and structural gradient encompassing four tissue zones - tendon/ligament, uncalcified fibrocartilage, calcified fibrocartilage and bone. This functional gradient accommodates the large stiffness differential between calcified bone and uncalcified tendon/ligament. Here we analyze in 3D the organization of the mouse Achilles enthesis and mineralizing Achilles tendon in comparison to lamellar bone. We use correlative, multiscale high-resolution volume imaging methods including µCT with submicrometer resolution and FIB-SEM tomography (both with deep learning-based image segmentation), and TEM and SEM imaging, to describe ultrastructural features of physiologic, age-related and aberrant mineral patterning. We applied these approaches to murine wildtype (WT) Achilles enthesis tissues to describe in normal calcifying fibrocartilage a crossfibrillar mineral tessellation pattern similar to that observed in lamellar bone, but with greater variance in mineral tesselle morphology and size. We also examined Achilles enthesis structure in Hyp mice, a murine model for the inherited osteomalacic disease X-linked hypophosphatemia (XLH) with calcifying enthesopathy. In Achilles enthesis fibrocartilage of Hyp mice, we show defective crossfibrillar mineral tessellation similar to that which occurs in Hyp lamellar bone. At the cellular level in fibrocartilage, unlike in bone where enlarged osteocyte mineral lacunae are found as peri-osteocytic lesions, mineral lacunar volumes for fibrochondrocytes did not differ between WT and Hyp mice. While both WT and Hyp aged mice demonstrate Achilles tendon midsubstance ectopic mineralization, a consistently defective mineralization pattern was observed in Hyp mice. Strong immunostaining for osteopontin was observed at all mineralization sites examined in both WT and Hyp mice. Taken together, this new 3D ultrastructural information describes details of common mineralization trajectories for enthesis, tendon and bone, which in Hyp/XLH are defective.

The Lancet Countdown South America: increasing health opportunities by identifying the gaps in health and climate change research.

South America is experiencing the effects of climate change, including extreme weather events and changes in temperature and precipitation patterns. These effects interact with existing social vulnerabilities, exacerbating their impact on the health and wellbeing of populations. This viewpoint highlights four main messages from the series, which presented key gaps from five different perspectives of health and climate. First, there is an overall need for local analyses of priority topics to inform public policy, which include national and sub-national evidence to adequately strengthen responses and preparedness for climate change hazards and address relevant social vulnerabilities in South American countries. Second, research in health and climate is done in silos and the intersection is not clear in terms of responsibility and leadership; therefore, transdisciplinary research and action are key. Third, climate research, policies, and action need to be reflected in effective funding schemes, which until now are very limited. For adaptation and mitigation policies to be effective, they need a robust and long-term funding scheme. Finally, climate action is a big opportunity for healthier and more prosperous societies in South America, taking the advantage of strategic climate policies to face the challenges of climate change and tackle existing social inequities.

Analysis of individual versus group behavior of zebrafish: a model using pH sublethal effects.

An image analysis biomonitoring system was used to evaluate sublethal effects of pH on the mean swimming velocity of zebrafish. Responses to stress were tested comparing individual and group responses. Group analysis indicated no effect for all acid pH and for pH 9.0-9.5. Individual analysis indicated behavioral differences for most acid pH and higher than 9.5. Sensitivity to sublethal pH was best assessed when using individual analysis. Zebrafish decreased hyperactivity and increased hypoactivity with more acid or alkaline pH. Individual approach allowed to determine hyperactivity or hypoactivity and the species' thresholds of exposure, which is critical for the management of impairments.

Hierarchical organization of bone in three dimensions: A twist of twists.

Structural hierarchy of bone - observed across multiple scales and in three dimensions (3D) - is essential to its mechanical performance. While the mineralized extracellular matrix of bone consists predominantly of carbonate-substituted hydroxyapatite, type I collagen fibrils, water, and noncollagenous organic constituents (mainly proteins and small proteoglycans), it is largely the 3D arrangement of these inorganic and organic constituents at each length scale that endow bone with its exceptional mechanical properties. Focusing on recent volumetric imaging studies of bone at each of these scales - from the level of individual mineralized collagen fibrils to that of whole bones - this graphical review builds upon and re-emphasizes the original work of James Bell Pettigrew and D'Arcy Thompson who first described the ubiquity of spiral structure in Nature. Here we illustrate and discuss the omnipresence of twisted, curved, sinusoidal, coiled, spiraling, and braided motifs in bone in at least nine of its twelve hierarchical levels - a visualization undertaking that has not been possible until recently with advances in 3D imaging technologies (previous 2D imaging does not provide this information). From this perspective, we hypothesize that the twisting motif occurring across each hierarchical level of bone is directly linked to enhancement of function, rather than being simply an energetically favorable way to assemble mineralized matrix components. We propose that attentive consideration of twists in bone and the skeleton at different scales will likely develop, and will enhance our understanding of structure-function relationships in bone.

Towards a global framework for transport, health and health equity.

This study derives a generalised global framework for transport, health and health equity, based on a synthesis of 94 urban transport and health frameworks. The framework emphasises factors related to health equity, which are generally ignored in existing conceptual frameworks on the relationship between transport and health. While some factors such as travel behaviour were included in most reviewed frameworks, climate change and other macro-level factors were included in less than a quarter of frameworks, and health equity was included in less than 10%. We developed a framework that includes key framework components identified by a scoping review, as well as addressing important gaps. This framework can be utilized to inform work on transport, health and health equity by different agencies such as the World Health Organization. It can be used to guide health sector engagement with transport issues to lead to healthier and more equitable transport decision-making globally.

Advancing climate change health adaptation through implementation science.

To date, there are few examples of implementation science studies that help guide climate-related health adaptation. Implementation science is the study of methods to promote the adoption and integration of evidence-based tools, interventions, and policies into practice to improve population health. These studies can provide the needed empirical evidence to prioritise and inform implementation of health adaptation efforts. This Personal View discusses five case studies that deployed disease early warning systems around the world. These cases studies illustrate challenges to deploying early warning systems and guide recommendations for implementation science approaches to enhance future research. We propose theory-informed approaches to understand multilevel barriers, design strategies to overcome those barriers, and analyse the ability of those strategies to advance the uptake and scale-up of climate-related health interventions. These findings build upon previous theoretical work by grounding implementation science recommendations and guidance in the context of real-world practice, as detailed in the case studies.

Why a New Research Agenda on Green Spaces and Health Is Needed in Latin America: Results of a Systematic Review.

(1) Background: Increasing and improving green spaces have been suggested to enhance health and well-being through different mechanisms. Latin America is experiencing fast population and urbanization growth; with rising demand for interventions to improve public health and mitigate climate change. (2) Aim: This study aimed to review the epidemiological evidence on green spaces and health outcomes in Latin America. (3) Methods: A systematic literature review of green spaces and health outcomes was carried out for studies published in Latin America before 28 September 2020. A search strategy was designed to identify studies published in Medline via PubMed and LILACS. The search strategy included terms related to green spaces combined with keywords related to health and geographical location. No time limit for the publication was chosen. The search was limited to English, Spanish, Portuguese, and French published articles and humans' studies. (4) Findings: This systematic review found 19 epidemiological studies in Latin America related to green spaces and health outcomes. Nine studies were conducted in Brazil, six in Mexico, three in Colombia, and one in Chile. In terms of study design, 14 were cross-sectional studies, 3 ecological, and 2 cohort studies. The population included among the studies ranged from 120 persons to 103 million. The green space definition used among studies was green density or proximity (eight studies), green presence (five studies), green spaces index (four studies), and green space visit (two studies). The health outcomes included were mental health (six studies), overweight and obesity (three studies), quality of life (three studies), mortality (two studies), cardiorespiratory disease (one study), disability (one study), falls (one study), and life expectancy (one study). Eleven studies found a positive association between green spaces and health, and eight studies found no association. (5) Conclusion: This systematic review identified 19 epidemiological studies associating green spaces and health outcomes in Latin America. Most of the evidence suggests a positive association between green spaces and health in the region. However, most of the evidence was supported by cross-sectional studies. Prioritizing longitudinal studies with harmonized exposure and outcome definitions and including vulnerable and susceptible populations is needed in the region.

Kinetics and equilibrium study for the biosorption of lanthanum by Penicillium simplicissimum INCQS 40,211.

Lanthanum (La) is a light rare-earth element that plays an essential role in manufacturing technological products, clean technologies, medical products, electron cathodes, scintillators, fluorescent lamps, and fertilizers. This study is the first investigation of La3+ biosorption using inactive lyophilized biomass from Penicillium simplicissimum INCQS 40,211. The maximum sorption capacity (qmax) for P. simplicissimum was 7.81 mg g-1. La 3+ biosorption followed the Freundlich model, where the biosorption system possibly multilayer coverage of P. simplicissimum by lanthanum ions. The kinetic data for the adsorption process obeyed a pseudo-second-order (R 2 > 0.92), indicating chemical sorption. The results indicated that inactive lyophilized biomass from Penicillium simplicissimum INCQS 40211are an excellent candidate for removing light rare-earth elements from aquatic environments.

Genetic Ablation of Osteopontin in Osteomalacic Hyp Mice Partially Rescues the Deficient Mineralization Without Correcting Hypophosphatemia.

PHEX is predominantly expressed by bone and tooth-forming cells, and its inactivating mutations in X-linked hypophosphatemia (XLH) lead to renal phosphate wasting and severe hypomineralization of bones and teeth. Also present in XLH are hallmark hypomineralized periosteocytic lesions (POLs, halos) that persist despite stable correction of serum phosphate (Pi ) that improves bulk bone mineralization. In XLH, mineralization-inhibiting osteopontin (OPN, a substrate for PHEX) accumulates in the extracellular matrix of bone. To investigate how OPN functions in Hyp mice (a model for XLH), double-null (Hyp;Opn-/- ) mice were generated. Undecalcified histomorphometry performed on lumbar vertebrae revealed that Hyp;Opn-/- mice had significantly reduced osteoid area/bone area (OV/BV) and osteoid thickness of trabecular bone as compared to Hyp mice, despite being as hypophosphatemic as Hyp littermate controls. However, tibias examined by synchrotron radiation micro-CT showed that mineral lacunar volumes remained abnormally enlarged in these double-null mice. When Hyp;Opn-/- mice were fed a high-Pi diet, serum Pi concentration increased, and OV/BV and osteoid thickness normalized, yet mineral lacunar area remained abnormally enlarged. Enpp1 and Ankh gene expression were increased in double-null mice fed a high-Pi diet, potentially indicating a role for elevated inhibitory pyrophosphate (PPi ) in the absence of OPN. To further investigate the persistence of POLs in Hyp mice despite stable correction of serum Pi , immunohistochemistry for OPN on Hyp mice fed a high-Pi diet showed elevated OPN in the osteocyte pericellular lacunar matrix as compared to Hyp mice fed a control diet. This suggests that POLs persisting in Hyp mice despite correction of serum Pi may be attributable to the well-known upregulation of mineralization-inhibiting OPN by Pi , and its accumulation in the osteocyte pericellular matrix. This study shows that OPN contributes to osteomalacia in Hyp mice, and that genetic ablation of OPN in Hyp mice improves the mineralization phenotype independent of systemic Pi -regulating factors. © 2020 American Society for Bone and Mineral Research.

Typical and atypical shoulder impingement syndrome: diagnosis, treatment, and pitfalls.

The cause of shoulder impingement syndrome usually is considered to be compression of the rotator cuff and subacromial bursa against the anterolateral aspect of the acromion. The typical symptom is anterolateral shoulder pain that worsens at night and with overhead activity. However, the pain may be caused by factors other than a hooked acromion. Atypical impingement syndrome most commonly results from an os acromiale, a subcoracoid disorder, acromioclavicular joint undersurface hypertrophy, a deconditioned rotator cuff, or scapular dyskinesis. The correct diagnosis is made through the patient history and physical examination, with appropriate diagnostic imaging. Nonsurgical treatment is successful for most types of impingement syndrome; if it is not successful, all structural causes of mechanical impingement must be corrected.

[A protocol for evaluating the probability of the recreational use of rivers and its application in risk analysis]. / Protocolo de avaliação da probabilidade de uso recreativo de rios e sua aplicação para análise de risco.

Contaminated waters constitute health risks not only due to direct consumption, but also in recreational use. Risk analysis strategies aim to reduce the instances of contaminations and must include the population's perceptions and willingness to assume risks. A rapid and simple method was developed to evaluate the probability of use of recreational waters. Interviews were conducted in municipalities with different ecological conditions, in order to define the factors used by people to decide to use, or otherwise, river waters. After analyzing the results, the "Índice de Probabilidade de Uso Recreativo de Águas (I-PURA)" was elaborated and tested. The index was then employed at 26 river locations representing five of the nine hydrographic regions of Rio de Janeiro state. The frequency of use, water contamination and a Habitat Assessment Visual Index (IAH) was also measured. The I-PURA was correlated with the frequency of use. Furthermore, the I-PURA was not correlated with IAH, showing that user perceptions are different from purely ecological aspects. This tool offers useful information for risk assessment and environmental management. Sites with a high probability of use, or observed use, that are highly contaminated should be prioritized for interventions.

Águas contaminadas representam um risco à saúde não somente pelo consumo direto, mas também pelo uso recreativo. Estratégias de análise de risco visam à redução dos casos de contaminação e devem incorporar as percepções e aceitação das pessoas em assumir riscos. Um método rápido e simplificado foi desenvolvido para avaliar a probabilidade do uso de águas recreativas. Foram realizadas entrevistas em municípios com condições ecológicas distintas, para elencar fatores que embasam a decisão das pessoas pelo uso dos rios. Em seguida, foi elaborado e realizado pré-teste do Índice de Probabilidade de Uso Recreativo de Águas (I-PURA) que, após ajuste, foi aplicado em 26 balneários de 5 das 9 regiões hidrográficas do estado do Rio de Janeiro. Foram medidas, ainda, a frequência de uso, a contaminação bacteriana da água e um índice de avaliação do habitat (IAH). O I-PURA foi correlacionado à frequência de uso, mas não com o IAH, evidenciando que a percepção dos usuários é diferente de aspectos puramente ecológicos. Este método contribui com a análise de risco e manejo dos recursos hídricos. Locais em que há alta probabilidade de uso, ou uso observado, e alta contaminação são estratégicos para intervenção.