Four ways blue foods can help achieve food system ambitions across nations.

Blue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12 and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.

A 20-year retrospective review of global aquaculture.

The sustainability of aquaculture has been debated intensely since 2000, when a review on the net contribution of aquaculture to world fish supplies was published in Nature. This paper reviews the developments in global aquaculture from 1997 to 2017, incorporating all industry sub-sectors and highlighting the integration of aquaculture in the global food system. Inland aquaculture-especially in Asia-has contributed the most to global production volumes and food security. Major gains have also occurred in aquaculture feed efficiency and fish nutrition, lowering the fish-in-fish-out ratio for all fed species, although the dependence on marine ingredients persists and reliance on terrestrial ingredients has increased. The culture of both molluscs and seaweed is increasingly recognized for its ecosystem services; however, the quantification, valuation, and market development of these services remain rare. The potential for molluscs and seaweed to support global nutritional security is underexploited. Management of pathogens, parasites, and pests remains a sustainability challenge industry-wide, and the effects of climate change on aquaculture remain uncertain and difficult to validate. Pressure on the aquaculture industry to embrace comprehensive sustainability measures during this 20-year period have improved the governance, technology, siting, and management in many cases.

Author Correction: A 20-year retrospective review of global aquaculture.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03508-0.

Aquatic foods to nourish nations.

Despite contributing to healthy diets for billions of people, aquatic foods are often undervalued as a nutritional solution because their diversity is often reduced to the protein and energy value of a single food type ('seafood' or 'fish')1-4. Here we create a cohesive model that unites terrestrial foods with nearly 3,000 taxa of aquatic foods to understand the future impact of aquatic foods on human nutrition. We project two plausible futures to 2030: a baseline scenario with moderate growth in aquatic animal-source food (AASF) production, and a high-production scenario with a 15-million-tonne increased supply of AASFs over the business-as-usual scenario in 2030, driven largely by investment and innovation in aquaculture production. By comparing changes in AASF consumption between the scenarios, we elucidate geographic and demographic vulnerabilities and estimate health impacts from diet-related causes. Globally, we find that a high-production scenario will decrease AASF prices by 26% and increase their consumption, thereby reducing the consumption of red and processed meats that can lead to diet-related non-communicable diseases5,6 while also preventing approximately 166 million cases of inadequate micronutrient intake. This finding provides a broad evidentiary basis for policy makers and development stakeholders to capitalize on the potential of aquatic foods to reduce food and nutrition insecurity and tackle malnutrition in all its forms.

Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States.

BACKGROUND: In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route. METHODS: We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100. RESULTS: Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1). CONCLUSIONS: In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.).

Hyperarousal features in the sleep architecture of individuals with and without insomnia.

Sleep architecture encodes relevant information on the structure of sleep and has been used to assess hyperarousal in insomnia. This study investigated whether polysomnography-derived sleep architecture displays signs of hyperarousal in individuals with insomnia compared with individuals without insomnia. Data from Phase 3 clinical trials, private clinics and a cohort study were analysed. A comprehensive set of sleep architecture features previously associated with hyperarousal were retrospectively analysed focusing on sleep-wake transition probabilities, electroencephalographic spectra and sleep spindles, and enriched with a novel machine learning algorithm called the Wake Electroencephalographic Similarity Index. This analysis included 1710 individuals with insomnia and 1455 individuals without insomnia. Results indicate that individuals with insomnia had a higher likelihood of waking from all sleep stages, and showed increased relative alpha during Wake and N1 sleep and increased theta power during Wake when compared with individuals without insomnia. Relative delta power was decreased and Wake Electroencephalographic Similarity Index scores were elevated across all sleep stages except N3, suggesting more wake-like activity during these stages in individuals with insomnia. Additionally, sleep spindle density was decreased, and spindle dispersion was increased in individuals with insomnia. These findings suggest that insomnia is characterized by a dysfunction in sleep quality with a continuous hyperarousal, evidenced by changes in sleep-wake architecture.

Adolescent girls in aquaculture ecozones at risk of nutrient deficiency in Bangladesh development and validation of an integrated metric.

BACKGROUND: This study developed and validated an integrated metric that enhances understanding of linkages between agro-ecological and socio-economic factors that are important for explaining nutritional wellbeing in relation to fish consumption; especially among adolescent girls who are at risk of nutritional deficiency in Bangladesh. Currently, there is no metric that takes account of environmental, cultural and economic contexts when considering fish consumption and dietary health from a policy perspective. METHODS: The study was designed as a bi-seasonal survey, repeated in the same population of adolescent girls recruited during the dry and wet seasons. Sampling was stratified by five settings (four aqua-agroecological zones and one processing plant community), with 60 girls recruited in each. Associations between candidate predictors (salinity, diet diversity, religion, socio-economic status and women's autonomy score) and dependent variables representing nutritional outcomes (anthropometry, omega-3 index and micronutrient levels) were explored in multivariable regressions. The fitted model with its predictors was validated, and a risk score derived from responses to a few short questions on religion, salinity zone, female autonomy, diet diversity and tilapia consumption. RESULTS: The omega-3 index showed the clearest distinction between seasons, by salinity and religion. Higher female autonomy, religion (being Hindu rather than Muslim), geographical location (living in a high or mid-saline area), and a higher dietary diversity were the strongest predictors of whole blood omega-3 index. The c-index for the prognostic model was 0.83 and 0.76 in the wet and dry season respectively, indicating good predictive accuracy. There appeared to be a clear trend in risk scores differentiating between those 'chronically at risk' and those 'never at risk'. CONCLUSIONS: Observational data on different aquaculture-ecozones defined by salinity enabled us to establish linkages between seasonal fish intake, religion, diet diversity, female autonomy and nutritional wellbeing. The purpose of the metric is to reveal these specific linkages in practice. This tool should improve targeting of timely, preventative and cost-effective nutritional interventions to adolescent girls most at-risk from low omega-3 levels in communities where seafood is produced.

Who Benefits From Allowing the Physis to Grow in Slipped Capital Femoral Epiphysis?

BACKGROUND: The globally acknowledged treatment for mild to moderate slipped capital femoral epiphysis (SCFE) is single screw in situ fixation, also used for prophylactic contralateral fixation. The Free-Gliding Screw (FG; Pega Medical) is a 2-part free-extending screw system designed to allow the growth of the proximal femur. We aimed to analyze the relationship between skeletal maturity and potential growth of the proximal physis and remodeling of the femoral neck using this implant. MATERIALS AND METHODS: Females below 12 years and males below 14 years undergoing in situ fixation for stable SCFE or prophylactic fixation were treated using the implant. Three elements of the modified Oxford Bone (mOB 3 ) score were used to measure maturity (triradiate cartilage, head of the femur, and greater trochanter). Radiographs were analyzed immediately postoperatively and at a minimum of 2 years for a change in screw length, posterior-sloping angle, articulotrochanteric distance, α angle, and head-neck offset. RESULTS: The study group comprised 30 (F:M=12:18) of 39 hips treated with SCFE and 22 (F:M=13:9) of 29 hips managed prophylactically using the free-Gliding screw. In the therapeutic group, chronologic age was a less valuable predictor of future screw lengthening than mOB 3 . An mOB 3 of ≤13 predicted future growth of >6 mm but did not reach statistical significance ( P =0.07). Patients with open triradiates showed a mean screw lengthening of 6.6 mm compared with those with closed triradiates (4.0 mm), but this did not reach significance ( P =0.12). In those with mOB 3 ≤13, the α angle reduced significantly ( P <0.01) and the head-neck offset increased significantly, suggesting remodeling. There was no change in these parameters when mOB 3 ≥14. In the prophylactic group, change in screw length was significant with mOB 3 of ≤13 (mean=8.0 mm, P <0.05), as was the presence of an open triradiate cartilage (mean=7.7 mm, P <0.05). In both cohorts, posterior-sloping angle and articulotrochanteric distance did not change, indicating no slip progression in either treatment or prophylactic groups and minimal effect on the proximal physeal growth relative to the greater trochanter. CONCLUSIONS: Growing screw constructs can halt slip progression while allowing proximal femoral growth in young patients with SCFE. Ongoing growth is better when the implant is used for prophylactic fixation. The results in treated SCFE need to be expanded to demonstrate a clinically meaningful cut-off for significant growth, but SCFE patients with an open triradiate remodel significantly more than those where it is closed. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial.

Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.

Ensemble modeling of auditory streaming reveals potential sources of bistability across the perceptual hierarchy.

Perceptual bistability-the spontaneous, irregular fluctuation of perception between two interpretations of a stimulus-occurs when observing a large variety of ambiguous stimulus configurations. This phenomenon has the potential to serve as a tool for, among other things, understanding how function varies across individuals due to the large individual differences that manifest during perceptual bistability. Yet it remains difficult to interpret the functional processes at work, without knowing where bistability arises during perception. In this study we explore the hypothesis that bistability originates from multiple sources distributed across the perceptual hierarchy. We develop a hierarchical model of auditory processing comprised of three distinct levels: a Peripheral, tonotopic analysis, a Central analysis computing features found more centrally in the auditory system, and an Object analysis, where sounds are segmented into different streams. We model bistable perception within this system by applying adaptation, inhibition and noise into one or all of the three levels of the hierarchy. We evaluate a large ensemble of variations of this hierarchical model, where each model has a different configuration of adaptation, inhibition and noise. This approach avoids the assumption that a single configuration must be invoked to explain the data. Each model is evaluated based on its ability to replicate two hallmarks of bistability during auditory streaming: the selectivity of bistability to specific stimulus configurations, and the characteristic log-normal pattern of perceptual switches. Consistent with a distributed origin, a broad range of model parameters across this hierarchy lead to a plausible form of perceptual bistability.

Importance of early diagnosis for developmental dysplasia of the hip: A 5-year radiological outcome study comparing the effect of early and late diagnosis.

AIM: Australia utilises a selective ultrasound screening programme. The rate of late diagnosis of developmental dysplasia of the hip (DDH) in Australia is increasing. The aim of this study is to quantify the treatment required and compare the 5-year radiological outcomes between early and late diagnosis in children with DDH with frank dislocation. METHODS: We performed a case-matched control study of children with frank DDH dislocations from 2000 to 2010 comparing three groups: children with an early diagnosis successfully treated in a Pavlik harness (SP), children with an early diagnosis who failed Pavlik harness treatment (FP) and children with a late diagnosis (LD). Minimum follow-up was 4 years. RESULTS: A total of 115 hips were included. Patients in the LD group required significantly more open reductions (P < 0.001), acetabular osteotomies (P < 0.001) and femoral osteotomies (P < 0.001). LD was also associated with significantly higher rates of growth disturbance at 46.3%, compared to 20.6% in the FP group and 5% in the SP group (P < 0.001). Overall, there were excellent radiological outcomes in 58.5% of the LD group compared to 79.4% in the FP group and 100% in the SP group. CONCLUSION: In Australia, high rates of LD in DDH persist in the context of selective ultrasound screening. While good radiological outcomes are achievable, a significantly greater level of surgical intervention is required and this is associated with significantly higher rates of growth disturbance. Optimisation of screening in Australia is vital.

Safely Reducing the Incidence of Contralateral Slipped Capital Femoral Epiphysis: Results of a Prospectively Implemented Prophylactic Fixation Protocol Using the Posterior Sloping Angle.

BACKGROUND: Bilateral slipped capital femoral epiphysis (SCFE) is common. The management of the contralateral hip in unilateral SCFE remains controversial. The aim of this study was to report on the clinical outcomes using a posterior sloping angle (PSA) threshold of 14.5 degrees for prophylactic fixation in preventing contralateral SCFE. METHODS: Having previously established through a retrospective study that PSA was predictive of future slip, the authors put in place a protocol where patients with unilateral SCFE who had a PSA ≥14.5 degrees on the contralateral side were offered prophylactic fixation. Those with unilateral SCFE presenting between January 2008 and December 2018 with a minimum of 12-month follow-up were included. Patients with renal or endocrine disorders were excluded. Primary outcomes were the number of slips prevented, the number needed to treat, and the complication rate. RESULTS: Of the 219 patients who were included, 114 (52.1%) underwent prophylactic fixation.A PSA threshold of 14.5 degrees prevented 77% of subsequent slips with a number needed to treat of 2.4 in our population. There were no cases of chondrolysis, avascular necrosis, or periprosthetic fracture associated with prophylactic pinning. CONCLUSIONS: Prophylactic fixation using a PSA of 14.5 degrees is safe, decreases unnecessary intervention, and reduces 77% of subsequent SCFE. The PSA can increase over time and the authors recommend that the protocol be applied for the duration of follow-up. LEVEL OF EVIDENCE: Level III.

Systems-thinking approach to identify and assess feasibility of potential interventions to reduce antibiotic use in tilapia farming in Egypt.

Antibiotics are used in aquaculture to maintain the health and welfare of stocks; however, the emergence and selection of antibiotic resistance in bacteria poses threats to humans, animals and the environment. Mitigation of antibiotic resistance relies on understanding the flow of antibiotics, residues, resistant bacteria and resistance genes through interconnecting systems, so that potential solutions can be identified and issues around their implementation evaluated. Participatory systems-thinking can capture the deep complexity of a system while integrating stakeholder perspectives. In this present study, such an approach was applied to Nile tilapia (Oreochromis niloticus) production in the Nile Delta of Egypt, where disease events caused by antibiotic-resistant pathogens have been reported. A system map was co-produced with aquaculture stakeholders at a workshop in May 2018 and used to identify hotspots of antibiotic use, exposure and fate and to describe approaches that would promote fish health and thus reduce antibiotic use. Antibiotics are introduced into the aquaculture system via direct application for example in medicated feed, but residues may also be introduced into the system through agricultural drainage water, which is the primary source of water for most fish farms in Egypt. A follow-up survey of stakeholders assessed the perceived feasibility, advantages and disadvantages of potential interventions. Interventions that respondents felt could be implemented in the short-term to reduce antibiotic usage effectively included: more frequent water exchanges, regular monitoring of culture water quality parameters, improved storage conditions for feed, use of probiotics and greater access to farmer and service providers training programmes. Other potential interventions included greater access to suitable and rapid diagnostics, high quality feeds, improved biosecurity measures and genetically-improved fish, but these solutions were expected to be achieved as long-term goals, with cost being of one of the noted barriers to implementation. Identifying feasible and sustainable interventions that can be taken to reduce antibiotic use, and understanding implementation barriers, are important for addressing antibiotic resistance and ensuring the continued efficacy of antibiotics. This is vital to ensuring the productivity of the tilapia sector in Egypt. The approach taken in the present study provides a means to identify points in the system where the effectiveness of interventions can be evaluated and thus it may be applied to other food production systems to combat the problem of antibiotic resistance.

Modulation of spine fusion with BMP-2, MEK inhibitor (PD0325901), and zoledronic acid in a murine model of NF1 double inactivation.

BACKGROUND: Spine fusion is a common procedure for the treatment of severe scoliosis, a frequent and challenging deformity associated with Neurofibromatosis type 1 (NF1). Moreover, deficiencies in NF1-Ras-MEK signaling affect bone formation and resorption that in turn impacts on spine fusion outcomes. METHODS: In this study we describe a new model for AdCre virus induction of Nf1 deficiency in the spines of Nf1flox/flox mice. The virus is delivered locally to the mouse spine in a fusion procedure induced using BMP-2. Systemic adjunctive treatment with the MEK inhibitor (MEKi) PD0325901 and the bisphosphonate zoledronic acid (ZA) were next trialed in this model. RESULTS: AdCre delivery resulted in abundant fibrous tissue (Nf1null +393%, P < 0.001) and decreased marrow space (Nf1null -67%, P < 0.001) compared to controls. While this did not significantly impact on the bone volume of the fusion mass (Nf1null -14%, P = 0.999 n.s.), the presence of fibrous tissue was anticipated to impact on the quality of spine fusion. Multinucleated TRAP + cells were observed in the fibrous tissues seen in Nf1null spines. In Nf1null spines, MEKi increased bone volume (+194%, P < 0.001) whereas ZA increased bone density (+10%, P < 0.002) versus BMP-2 alone. Both MEKi and ZA decreased TRAP + cells in the fibrous tissue (MEKi -62%, P < 0.01; ZA -43%, P = 0.054). No adverse effects were seen with either MEKi or ZA treatment including weight loss or signs of illness or distress that led to premature euthanasia. CONCLUSIONS: These data not only support the utility of an AdCre-virus induced knockout spine model, but also support further investigation of MEKi and ZA as adjunctive therapies for improving BMP-2 induced spine fusion in the context of NF1.

COVID-19 impacts and adaptations in Asia and Africa's aquatic food value chains.

The COVID-19 pandemic is a shock affecting all areas of the global food system. We tracked the impacts of COVID-19 and associated policy responses on the availability and price of aquatic foods and production inputs during 2020, using a high frequency longitudinal survey of 768 respondents in Bangladesh, Egypt, India, Myanmar, Nigeria. We found the following: (1) Aquatic food value chains were severely disrupted but most effects on the availability and accessibility of aquatic foods and production inputs were short-lived. (2) Impacts on demand for aquatic foods, production inputs, and labor have been longer lasting than impacts on their supply. (3) Retail prices of aquatic foods spiked briefly during March-May 2020 but trended down thereafter, whereas prices of production inputs rose. These trends suggest a deepening 'squeeze' on the financial viability of producers and other value chain actors. (4) Survey respondents adapted to the challenges of COVID-19 by reducing production costs, sourcing alternative inputs, diversifying business activities, leveraging social capital, borrowing, seeking alternative employment, and reducing food consumption. Many of these coping strategies are likely to undermine well-being and longer-term resilience, but we also find some evidence of proactive strategies with potential to strengthen business performance. Global production of aquatic food likely contracted significantly in 2020. The importance of aquatic food value chains in supporting livelihoods and food and nutrition security in Asia and Africa makes their revitalization essential in the context of COVID-19 recovery efforts. We outline immediate and longer-term policies and interventions to support this goal.

Dietary intervention rescues myopathy associated with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with complex symptomology. In addition to a predisposition to tumors, children with NF1 can present with reduced muscle mass, global muscle weakness, and impaired motor skills, which can have a significant impact on quality of life. Genetic mouse models have shown a lipid storage disease phenotype may underlie muscle weakness in NF1. Herein we confirm that biopsy specimens from six individuals with NF1 similarly manifest features of a lipid storage myopathy, with marked accumulation of intramyocellular lipid, fibrosis, and mononuclear cell infiltrates. Intramyocellular lipid was also correlated with reductions in neurofibromin protein expression by western analysis. An RNASeq profile of Nf1null muscle from a muscle-specific Nf1 knockout mouse (Nf1MyoD-/-) revealed alterations in genes associated with glucose regulation and cell signaling. Comparison by lipid mass spectrometry demonstrated that Nf1null muscle specimens were enriched for long chain fatty acid (LCFA) containing neutral lipids, such as cholesterol esters and triacylglycerides, suggesting fundamentally impaired LCFA metabolism. The subsequent generation of a limb-specific Nf1 knockout mouse (Nf1Prx1-/-) recapitulated all observed features of human NF1 myopathy, including lipid storage, fibrosis, and muscle weakness. Collectively, these insights led to the evaluation of a dietary intervention of reduced LCFAs, and enrichment of medium-chain fatty acids (MCFAs) with L-carnitine. Following 8-weeks of dietary treatment, Nf1Prx1-/- mice showed a 45% increase in maximal grip strength, and a 71% reduction in intramyocellular lipid staining compared with littermates fed standard chow. These data link NF1 deficiency to fundamental shifts in muscle metabolism, and provide strong proof of principal that a dietary intervention can ameliorate symptoms.

Pretreatment with Pamidronate Decreases Bone Formation but Increases Callus Bone Volume in a Rat Closed Fracture Model.

Clinical concerns have been raised over prior exposure to bisphosphonates impairing fracture healing. To model this, groups of male Wistar rats were assigned to saline control or treatment groups receiving 0.15 mg/kg (low dose), 0.5 mg/kg (medium dose), and 5 mg/kg (high dose) Pamidronate (PAM) twice weekly for 4 weeks. At this point, closed fractures were made using an Einhorn apparatus, and bisphosphonate dosing was continued until the experimental endpoint. Specimens were analyzed at 2 and 6 weeks (N = 8 per group per time point). Twice weekly PAM dosing was found to have no effect on early soft callus remodeling at 2 weeks post fracture. At this time point, the highest dose PAM group gave significant increases in bone volume (+ 10%, p < 0.05), bone mineral content (+ 30%, p < 0.01), and bone mineral density (+ 10%, p < 0.01). This PAM dosing regimen showed more substantive effects on hard callus at 6 weeks post fracture, with PAM treatment groups showing + 46-79% increased bone volume. Dynamic bone labeling showed reduced calcein signal in the PAM-treated calluses (38-63%, p < 0.01) and reduced MAR (32-49%, p < 0.01), suggesting a compensatory reduction in bone anabolism. These data support the concept that bisphosphonates lead to profound decreases in bone turnover in fracture repair, however, this does not affect soft callus remodeling.

Opportunity for marine fisheries reform in China.

China's 13th Five-Year Plan, launched in March 2016, provides a sound policy platform for the protection of marine ecosystems and the restoration of capture fisheries within China's exclusive economic zone. What distinguishes China among many other countries striving for marine fisheries reform is its size-accounting for almost one-fifth of global catch volume-and the unique cultural context of its economic and resource management. In this paper, we trace the history of Chinese government priorities, policies, and outcomes related to marine fisheries since the 1978 Economic Reform, and examine how the current leadership's agenda for "ecological civilization" could successfully transform marine resource management in the coming years. We show how China, like many other countries, has experienced a decline in the average trophic level of its capture fisheries during the past few decades, and how its policy design, implementation, and enforcement have influenced the status of its wild fish stocks. To reverse the trend in declining fish stocks, the government is introducing a series of new programs for sustainable fisheries and aquaculture, with greater traceability and accountability in marine resource management and area controls on coastal development. As impressive as these new plans are on paper, we conclude that serious institutional reforms will be needed to achieve a true paradigm shift in marine fisheries management in China. In particular, we recommend new institutions for science-based fisheries management, secure fishing access, policy consistency across provinces, educational programs for fisheries managers, and increasing public access to scientific data.