Making way: Developing national legal and policy frameworks for pastoral mobility

Mobility is a vital strategy employed by pastoralists to capitalize on the scarce availability of resources in variable environments, making pastoralism economically feasible and environmentally sustainable. Through mobility, pastoralists can produce animal-sourced products that provide food and income security to populations in the world’s rangelands. Such a practice also provides a range of benefits to the environment while fostering the capacity to adapt to changing social and natural environments. With a few exceptions, policies have largely not kept up with new scholarship and development discourse that acknowledges the importance of mobility to pastoralism. There is a lag in and resistance to legislating in favor of mobility. The overall objective of this handbook is to guide the development of legal and policy frameworks for securing mobility for various pastoral production systems and practices. This handbook calls for the legal recognition and securing of pastoral mobility as a way of safeguarding and facilitating a continuous stream of economic and social benefits for pastoralists, countries, and the environment. It facilitates a deeper understanding of pastoral mobility through examples and case studies drawn from various parts of the world and identifies considerations to be borne in mind when legislating for mobility.Peer reviewe

Role of appetitive phenotype trajectory groups on child body weight during a family-based treatment for children with overweight or obesity.

ObjectiveEmerging evidence suggests that individual appetitive traits may usefully explain patterns of weight loss in behavioral weight loss treatments for children. The objective of this study was to identify trajectories of child appetitive traits and the impact on child weight changes over time.MethodsSecondary data analyses of a randomized noninferiority trial conducted between 2011 and 2015 evaluated children's appetitive traits and weight loss. Children with overweight and obesity (mean age = 10.4; mean BMI z = 2.0; 67% girls; 32% Hispanic) and their parent (mean age = 42.9; mean BMI = 31.9; 87% women; 31% Hispanic) participated in weight loss programs and completed assessments at baseline, 3, 6,12, and 24 months. Repeated assessments of child appetitive traits, including satiety responsiveness, food responsiveness and emotional eating, were used to identify parsimonious grouping of change trajectories. Linear mixed-effects models were used to identify the impact of group trajectory on child BMIz change over time.ResultsOne hundred fifty children and their parent enrolled in the study. The three-group trajectory model was the most parsimonious and included a high satiety responsive group (HighSR; 47.4%), a high food responsive group (HighFR; 34.6%), and a high emotional eating group (HighEE; 18.0%). Children in all trajectories lost weight at approximately the same rate during treatment, however, only the HighSR group maintained their weight loss during follow-ups, while the HighFR and HighEE groups regained weight (adjusted p-value < 0.05).ConclusionsDistinct trajectories of child appetitive traits were associated with differential weight loss maintenance. Identified high-risk subgroups may suggest opportunities for targeted intervention and maintenance programs

Utility of the SENIORS elderly heart failure risk model applied to the RICA registry of acute heart failure

Background: Heart failure (HF) is predominantly a disease of the elderly. Reliable risk stratification would help in the management of this population, but no model has been well evaluated in elderly HF patients in both acute and chronic settings and not being restricted by ejection fraction. To evaluate the utility of the SENIORS risk model, developed from a clinical trial of elderly patients with chronic HF, in an independent cohort (National Spanish Registry: RICA) of elderly acute HF patients. Methods: We applied the SENIORS risk model to 926 patients in RICA to estimate risk at one year of a) composite outcome of all-cause mortality or cardiovascular hospital admission and b) all-cause mortality. Results: In the RICA registry mean age was 78 years, mean ejection fraction 51% and 87% were in NYHA II and III. At one year death/CV hospitalization occurred in 31.9% and all-cause mortality in 19.5%. The risk model provided good separation of Kaplan Meier curves stratified by tertile for death/CV hospitalization and all-cause mortality. The observed versus expected rates of death/CV hospitalization in the lowest, middle and highest risk tertiles were (%) 34/24, 45/41 and 57/67, and for death 13/16, 32/38 and 44/70 respectively. C-statistic for all-cause mortality or CV hospitalization was 0.60 and for all-cause mortality 0.66. Conclusion: The SENIORS risk model was a reliable tool for relative risk stratification among acute heart failure patients in a “real world” registry, but predicted versus observed risk showed some variability. The model provides a useful basis for clinical risk prediction

Evaluating the Acceptability and Feasibility of Providing Egg or Cereal Breakfast during a Family-Based Treatment for Children with Overweight/Obesity: The Families and Breakfast Pilot Trial.

Background: Family-based behavioral treatment (FBT) is the most successful weight-loss treatment for children with overweight and obesity, however, long-term success is only achieved by a third of children over time. The use of foods that induce satiety, such as eggs, could improve adherence to calorically restricted diets in children and improve outcomes. This study explored the consumption of eggs (FBT+egg) or cereal (FBT+cereal) for breakfast as part of an FBT program, when breakfast foods were provided to families. Methods: Fifty 8-12-year-old children with overweight and obesity and their parents were randomized to a 4-month FBT+egg or FBT+cereal treatment program. Families were provided the ingredients for their assigned breakfast at each treatment session, and instructed to consume the breakfast a minimum of 5 days per week. Families attended assessments at baseline, post-treatment, and 4-months post-treatment. Results: Results showed that both treatments were well liked, FBT attendance was similar, and there was high compliance with consumption of the specified breakfast. Children experienced moderate weight loss at post-treatment [-0.11 standardized BMI (BMIz)] through 4-month follow-up (-0.09 BMIz), with no statistically significant differences (mean difference -0.05 BMIz, 95% confidence interval -0.19 to 0.09) observed between egg and cereal conditions across any anthropometric or appetitive measures. Conclusions: The use of eggs for breakfast in children enrolled in FBT was well tolerated, and future studies should include larger samples and longer follow-up periods to assess the potential differential effects of prescribed breakfasts on children's weight and eating behaviors

Souvenaid in the Management of Mild Cognitive Impairment: An Expert Consensus Opinion

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. Methods An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Summary of opinion Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer’s disease (AD), including those with MCI due to AD (prodromal AD). Conclusion Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a multimodal management approach including lifestyle risk factor modification and consideration of the multinutrient Souvenaid

Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing Competitive Primers.

Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to drug resistance in infectious diseases is crucial for accurate prognostics, therapeutics and disease management at point-of-care. Here, we present a novel amplification method and provide universal guidelines for the detection of SNPs at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based loop-mediated isothermal amplification (sbLAMP) primers and unmodified self-stabilizing (USS) competitive primers that robustly delay or prevent unspecific amplification. Both sets of primers are incorporated into the same reaction mixture, but always targeting different alleles; one set specific to the wild type allele and the other to the mutant allele. The mechanism of action relies on thermodynamically favored hybridization of totally complementary primers, enabling allele-specific amplification. We successfully validate our method by detecting SNPs, C580Y and Y493H, in the Plasmodium falciparum kelch 13 gene that are responsible for resistance to artemisinin-based combination therapies currently used globally in the treatment of malaria. USS-sbLAMP primers can efficiently discriminate between SNPs with high sensitivity (limit of detection of 5 × 101 copies per reaction), efficiency, specificity and rapidness (<35 min) with the capability of quantitative measurements for point-of-care diagnosis, treatment guidance, and epidemiological reporting of drug-resistance

Autofluorescence of stingray skeletal cartilage: hyperspectral imaging as a tool for histological characterization

Tessellated cartilage is a distinctive composite tissue forming the bulk of the skeleton of cartilaginous fishes (e.g. sharks and rays), built from unmineralized cartilage covered at the surface by a thin layer of mineralized tiles called tesserae. The finescale structure and composition of elasmobranch tessellated cartilage has largely been investigated with electron microscopy, micro-computed tomography and histology, but many aspects of tissue structure and composition remain uncharacterized. In our study, we demonstrate that the tessellated cartilage of a stingray exhibits a strong and diverse autofluorescence, a native property of the tissue which can be harnessed as an effective label-free imaging technique. The autofluorescence signal was excited using a broad range of wavelengths in confocal and light sheet microscopy, comparing several sample preparations (fresh; demineralized and paraffin-embedded; non-demineralized and plastic-embedded) and imaging the tissue at different scales. Autofluorescence varied with sample preparation with the signal in both plastic- and paraffin-embedded samples strong enough to allow visualization of finescale (=¿1 µm) cellular and matrix structures, such as cell nuclei and current and former mineralization fronts, identifiable by globular mineralized tissue. A defined pericellular matrix (PCM) surrounding chondrocytes was also discernible, described here for the first time in elasmobranchs. The presence of a PCM suggests similarities with mammalian cartilage regarding how chondrocytes interact with their environment, the PCM in mammals acting as a transducer for biomechanical and biochemical signals. A posterior analysis of hyperspectral images by an MCR-ALS unmixing algorithm allowed identification of several distinct fluorescence signatures associated to specific regions in the tissue. Some fluorescence signatures identified could be correlated with collagen type II, the most abundant structural molecule of cartilage. Other fluorescence signatures, however, remained unidentified, spotlighting tissue regions that deserve deeper characterization and suggesting the presence of molecules still unidentified in elasmobranch skeletal cartilage. Our results show that autofluorescence can be a powerful exploratory imaging tool for characterizing less-studied skeletal tissues, such as tessellated cartilage. The images obtained are largely comparable with more commonly used techniques, but without the need for complicated sample preparations or external staining reagents standard in histology and electron microscopy (TEM, SEM).Postprint (published version

Nerolidol production in agroinfiltrated tobacco: Impact of protein stability and membrane targeting of strawberry (Fragraria ananassa) NEROLIDOL SYNTHASE1

The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP), mediates plant-insect inter- actions across multiple trophic levels with major implications for pest management in agriculture. We compared nerolidol engineering strategies in tobacco using agroinfiltration to transiently express strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS), we have determined that FaNES1 directed to the ER via fusion to the transmembrane domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed significant improvements in terms of transcript levels, protein accumulation, and volatile production when compared to its cytosolic form. However, the highest levels of nerolidol production were observed when FaNES1 was fused to GFP and expressed in the cytosol. This SPME-GCMS method afforded a limit of detection and quantification of 1.54 and 5.13 pg, respectively. Nerolidol production levels, which ranged from 0.5 to 3.0 μg/g F.W., correlated more strongly to the accumulation of recombinant protein than transcript level, the former being highest in FaNES-GFP transfected plants. These results indicate that while the ER may represent an enriched source of FDP that can be exploited in metabolic engineering, protein accumulation is a better predictor of sesquiterpene production

MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia

Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. However, this new armamentarium of therapies faces an old problem: choosing the right treatment for each patient. The lack of predictive biomarkers is particularly worrying for pediatric patients since it impairs the implementation of new treatments in the clinic. In this study, we used the functional assay dynamic BH3 profiling (DBP) to evaluate two new treatments for BCP-ALL that could improve clinical outcome, especially for relapsed patients. We found that the MEK inhibitor trametinib and the multi-target tyrosine kinase inhibitor sunitinib exquisitely increased apoptotic priming in an NRAS-mutant and in a KMT2A-rearranged cell line presenting a high expression of FLT3, respectively. Following these observations, we sought to study potential adaptations to these treatments. Indeed, we identified with DBP anti-apoptotic changes in the BCL-2 family after treatment, particularly involving MCL-1 – a pro-survival strategy previously observed in adult cancers. To overcome this adaptation, we employed the BH3 mimetic S63845, a specific MCL-1 inhibitor, and evaluated its sequential addition to both kinase inhibitors to overcome resistance. We observed that the metronomic combination of both drugs with S63845 was synergistic and showed an increased efficacy compared to single agents. Similar observations were made in BCP-ALL KMT2A-rearranged PDX cells in response to sunitinib, showing an analogous DBP profile to the SEM cell line. These findings demonstrate that rational sequences of targeted agents with BH3 mimetics, now extensively explored in clinical trials, may improve treatment effectiveness by overcoming anti-apoptotic adaptations in BCP-ALL.JM acknowledges the Ramon y Cajal Program, Ministerio de Economia y Competitividad (RYC-2015-18357) and the Spanish National Plan “Retos Investigacion” I + D + i (RTI2018-094533-A-I00) from Ministerio de Ciencia, Innovación y Universidades. This work was supported by the CELLEX foundation and the Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund (ERDF). This work was also partially funded by the CERCA Program and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079). FS: Medical Faculty of Ulm University (Clinician Scientist Programme). K-MD and LM: German Research Foundation (DFG, SFB 1074)