Analysis and Discrimination of Canadian Honey Using Quantitative NMR and Multivariate Statistical Methods.

To address the growing concern of honey adulteration in Canada and globally, a quantitative NMR method was developed to analyze 424 honey samples collected across Canada as part of two surveys in 2018 and 2019 led by the Canadian Food Inspection Agency. Based on a robust and reproducible methodology, NMR data were recorded in triplicate on a 700 MHz NMR spectrometer equipped with a cryoprobe, and the data analysis led to the identification and quantification of 33 compounds characteristic of the chemical composition of honey. The high proportion of Canadian honey in the library provided a unique opportunity to apply multivariate statistical methods including PCA, PLS-DA, and SIMCA in order to differentiate Canadian samples from the rest of the world. Through satisfactory model validation, both PLS-DA as a discriminant modeling technique and SIMCA as a class modeling method proved to be reliable at differentiating Canadian honey from a diverse set of honeys with various countries of origins and floral types. The replacement method of optimization was successfully applied for variable selection, and trigonelline, proline, and ethanol at a lower extent were identified as potential chemical markers for the discrimination of Canadian and non-Canadian honeys.

Nutritional Supplements in the Clinical Management of Tendinopathy: A Scoping Review.

INTRODUCTION: Tendinopathy has a high prevalence and incidence in the general population and among athletes, with a lack of consensus among medical practitioners on optimal management strategies. The objective of this scoping review was to evaluate current research on the use of nutritional supplements for treating tendinopathies, including what supplements have been used and what outcomes, outcome measures, and intervention parameters have been reported. METHODS: Databases searched included Embase, SPORTDiscus, the Cochrane Library, MEDLINE, CINAHL, and AMED. This scoping review considered primary studies investigating nutritional supplements for tendinopathies and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. RESULTS: A total of 1527 articles were identified with 16 included in the review. Studies investigated a range of nutritional supplements in the clinical management of various tendinopathies, including several commercially available proprietary blends of several ingredients. TendoActive (mucopolysaccharides, type I collagen, and vitamin C) was used in 2 studies, TENDISULFUR (methylsulfonylmethane, hydrolyzed collagen, L-arginine, L-lysine, vitamin C, bromelain, chondroitin, glucosamine, Boswellia, and myrrh) was used in 3 studies, and Tenosan (arginine-L-alpha ketoglutarate, hydrolyzed collagen type I, methylsulfonylmethane, vitamin C, bromelain, and vinitrox) was used in 2 studies. Collagen peptides were used in 2 studies, with omega-3 fatty acids, combined fatty acids and antioxidants, turmeric rhizome combined with Boswellia, ß-hydroxy ß-methylbutyric, vitamin C in isolation and combined with gelatin, and creatine investigated in one study each. CONCLUSION: Despite a paucity of studies to date, findings from this review suggest that several nutritional compounds may be beneficial in the clinical management of tendinopathies, by exerting anti-inflammatory effects and improving tendon healing. Nutritional supplements may have potential as an adjunctive method to standard treatment methods such as exercise, where their pain-relieving, anti-inflammatory, and structural tendon effects may augment the positive functional outcomes gained from progressive exercise rehabilitation.

Assessment of the reporting quality of resistance training interventions in randomised controlled trials for lower limb tendinopathy: A systematic review.

OBJECTIVES: 1. To describe what exercises and intervention variables are used in resistance training interventions in randomised controlled trials for lower limb tendinopathy 2. To assess completeness of reporting as assessed by the Consensus on Exercise Reporting Template (CERT) and the Toigo and Boutellier framework. 3. To assess the implementation of scientific resistance training principles. 4. To assess therapeutic quality of exercise interventions with the i-CONTENT tool. DATA SOURCES: We searched MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, and the Cochrane library databases. REVIEW METHODS: Systematic review of randomised controlled trials that reported using resistance exercises for lower limb tendinopathies. RESULTS: We included 109 RCTs. Eccentric heel drops were the most common exercise (43 studies), followed by isotonic heel raises (21), and single leg eccentric decline squats (18). Reporting of exercise descriptor items from the Toigo and Boutellier framework ranged from 0-13, with an average score of 9/13, and only 7 studies achieved a full 13/13. Reporting of items from the CERT ranged from 0-18, with an average score of 14/19. No study achieved a full 19/19, however 5 achieved 18/19. Scoring for resistance training principles ranged from 1-10, with only 11 studies achieving 10/10. Reporting across studies for the i-CONTENT tool ranged from 2-7, with an average score of 5 across included studies. A total of 19 studies achieved a full 7/7 score. Less than 50% of studies achieved an overall low risk of bias, highlighting the methodological concerns throughout studies. CONCLUSION: The reporting of exercise descriptors and intervention content was generally high across RCTs for lower limb tendinopathy, with most allowing exercise replication. However, reporting for some tendinopathies and content items such as adherence was poor, limiting optimal translation to clinical practice.

Analysis of Polar Lipids in Hemp (Cannabis sativa L.) By-Products by Ultra-High Performance Liquid Chromatography and High-Resolution Mass Spectrometry.

Polar lipids were extracted from residual biomass of hemp (Cannabis sativa L.) by-products with EtOH and partitioned into aqueous and chloroform fractions. The chloroform fractions were studied for their lipid composition using solid-phase extraction (SPE) followed by UHPLC/HRMS and NMR analyses. The 1H NMR and gravimetric yield of SPE indicated triacylglycerols covered ≥ 51.3% of the chloroform fraction of hemp seed hulls and hemp cake. UHPLC/HRMS analyses of remaining polar lipids led to the identification of nine diacylglycerols (DAGs), six lysophosphatidylcholines (LPCs), five lysophosphatidylethanolamines (LPEs), eight phosphatidylethanolamines (PEs), and thirteen phosphatidylcholines (PCs) for the first time from hemp seed hulls. The regiospecificity of fatty acyl substitutes in glycerol backbone of individual phospholipids were assigned by analyzing the diagnostic fragment ions and their intensities. The heat-map analysis suggested that DAG 18:2/18:2, 1-LPC 18:2, 1-LPE 18:2, PE 18:2/18:2, and PC 18:2/18:2 were the predominant molecules within their classes, supported by the fact that linoleic acid was the major fatty acid covering > 41.1% of the total fatty acids determined by GC-FID analysis. The 31P NMR analysis confirmed the identification of phospholipids and suggested PC covers ≥ 37.9% of the total phospholipid present in hemp by-products. HPLC purification led to the isolation of 1,2-dilinoleoylphosphatidylcholine and 1-palmitoyl-2-linoleoylphosphatidylcholine. These two major PCs further confirmed the UHPLC/HRMS finding.

Structural Sequencing of Oligopeptides Aided by 1H Iterative Full-Spin Analysis.

This report describes an approach using 1H NMR iterative full-spin analysis (HiFSA) to extract definitive structural information on unknown peptides from 1D 1H NMR data. By comparing the experimental data and HiFSA fingerprint of a known analogue, it is possible to isolate the characteristic 1H subspectrum of the different amino acids and, thus, elucidate the structure of the peptide. To illustrate this methodology, a comprehensive analysis of five new anti-Mycobacterium tuberculosis peptides (2-6), all analogues of ecumicin (1), was carried out. The method was validated by demonstrating congruence of the HiFSA-based structures with all available data, including MS and 2D NMR. The highly reproducible HiFSA fingerprints of the new ∼1600 amu peptides were generated in this process. Besides oligo-peptides, the HiFSA sequencing approach could be extended to all oligomeric compounds consisting of chains of monomers lacking H-H spin-spin coupling across the moieties. HiFSA sequencing is capable of differentiating complex oligomers that exhibit minor structural differences such as shifted hydoxyl or methyl groups. Because it employs the basic and most sensitive 1D 1H NMR experiment, HiFSA sequencing enables the exploration of peptide analogues up to at least 2000 amu, even with basic contemporary spectrometers and when only sub-milligram amounts of isolates are available.

Characterization of Shrimp Oil from Pandalus borealis by High Performance Liquid Chromatography and High Resolution Mass Spectrometry.

Northern shrimp (Pandalus borealis) oil, which is rich in omega-3 fatty acids, was recovered from the cooking water of shrimp processing facilities. The oil contains significant amounts of omega-3 fatty acids in triglyceride form, along with substantial long-chain monounsaturated fatty acids (MUFAs). It also features natural isomeric forms of astaxanthin, a nutritional carotenoid, which gives the oil a brilliant red color. As part of our efforts in developing value added products from waste streams of the seafood processing industry, we present in this paper a comprehensive characterization of the triacylglycerols (TAGs) and astaxanthin esters that predominate in the shrimp oil by using HPLC-HRMS and MS/MS, as well as 13C-NMR. This approach, in combination with FAME analysis, offers direct characterization of fatty acid molecules in their intact forms, including the distribution of regioisomers in TAGs. The information is important for the standardization and quality control, as well as for differentiation of composition features of shrimp oil, which could be sold as an ingredient in health supplements and functional foods.

2D NMR barcoding and differential analysis of complex mixtures for chemical identification: the Actaea triterpenes.

The interpretation of NMR spectroscopic information for structure elucidation involves decoding of complex resonance patterns that contain valuable molecular information (δ and J), which is not readily accessible otherwise. We introduce a new concept of 2D-NMR barcoding that uses clusters of fingerprint signals and their spatial relationships in the δ-δ coordinate space to facilitate the chemical identification of complex mixtures. Similar to widely used general barcoding technology, the structural information of individual compounds is encoded as a specifics pattern of their C,H correlation signals. Software-based recognition of these patterns enables the structural identification of the compounds and their discrimination in mixtures. Using the triterpenes from various Actaea (syn. Cimicifuga) species as a test case, heteronuclear multiple-bond correlation (HMBC) barcodes were generated on the basis of their structural subtypes from a statistical investigation of their δH and δC data in the literature. These reference barcodes allowed in silico identification of known triterpenes in enriched fractions obtained from an extract of A. racemosa (black cohosh). After dereplication, a differential analysis of heteronuclear single-quantum correlation (HSQC) spectra even allowed for the discovery of a new triterpene. The 2D barcoding concept has potential application in a natural product discovery project, allowing for the rapid dereplication of known compounds and as a tool in the search for structural novelty within compound classes with established barcodes.

Distinguishing Vaccinium species by chemical fingerprinting based on NMR spectra, validated with spectra collected in different laboratories.

A method was developed to distinguish Vaccinium species based on leaf extracts using nuclear magnetic resonance spectroscopy. Reference spectra were measured on leaf extracts from several species, including lowbush blueberry (Vaccinium angustifolium), oval leaf huckleberry (Vaccinium ovalifolium), and cranberry (Vaccinium macrocarpon). Using principal component analysis, these leaf extracts were resolved in the scores plot. Analysis of variance statistical tests demonstrated that the three groups differ significantly on PC2, establishing that the three species can be distinguished by nuclear magnetic resonance. Soft independent modeling of class analogies models for each species also showed discrimination between species. To demonstrate the robustness of nuclear magnetic resonance spectroscopy for botanical identification, spectra of a sample of lowbush blueberry leaf extract were measured at five different sites, with different field strengths (600 versus 700 MHz), different probe types (cryogenic versus room temperature probes), different sample diameters (1.7 mm versus 5 mm), and different consoles (Avance I versus Avance III). Each laboratory independently demonstrated the linearity of their NMR measurements by acquiring a standard curve for chlorogenic acid (R(2) = 0.9782 to 0.9998). Spectra acquired on different spectrometers at different sites classifed into the expected group for the Vaccinium spp., confirming the utility of the method to distinguish Vaccinium species and demonstrating nuclear magnetic resonance fingerprinting for material validation of a natural health product.

Characterization of a partially saturated and glycosylated apocarotenoid from wheat that is depleted upon leaf rust infection.

Recent semi-targeted metabolomics studies have highlighted a number of metabolites in wheat that associate with leaf rust resistance genes and/or rust infection. Here, we report the structural characterization of a novel glycosylated and partially saturated apocarotenoid, reminiscent of a reduced form of mycorradicin, (6E,8E,10E)-4,9-dimethyl-12-oxo-12-((3,4,5-trihydroxy-6-(2-hydroxyethoxy)tetrahydro-2H-pyran-2-yl)methoxy)-3-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)dodeca-6,8,10-trienoic acid, isolated from Triticum aestivum L. (Poaceae) variety 'Thatcher' (Tc) flag leaves. While its accumulation was not associated with any of Lr34, Lr67 or Lr22a resistance genes, infection of Tc with leaf rust was found to deplete it, consistent with the idea of this metabolite being a glycosylated-storage form of an apocarotenoid of possible relevance to plant defense. A comparative analysis of wheat transcriptomic changes shows modulation of terpenoid, carotenoid, UDP-glycosyltransferase and glycosylase -related gene expression profiles, consistent with anticipated biosynthesis and degradation mechanisms. However, details of the exact nature of the relevant pathways remain to be validated in the future. Together these findings highlight another example of the breadth of unique metabolites underlying plant host-fungal pathogen interactions.

Forensic investigations of disasters: Past achievements and new directions.

In the 2020s, understanding disaster risk requires a strong and clear recognition of values and goals that influence the use of political and economic power and social authority to guide growth and development. This configuration of values, goals, power and authority may also lead to concrete drivers of risk at any one time. Building on previous disaster risk frameworks and experiences from practice, since 2010, the 'Forensic Investigations of Disasters (FORIN)' approach has been developed to support transdisciplinary research on the transformational pathways societies may follow to recognise and address root causes and drivers of disaster risk. This article explores and assesses the achievements and failures of the FORIN approach. It also focuses on shedding light upon key requirements for new approaches and understandings of disaster risk research. The new requirements stem not only from the uncompleted ambitions of FORIN and the forensic approach but also from dramatic and ongoing transformational changes characterised by climate change, the coronavirus disease 2019 (COVID-19) pandemic and the threat of global international confrontation, among other potential crises, both those that can be identified and those not yet identified or unknown. Contribution: Disasters associated with extreme natural events cannot be treated in isolation. A comprehensive "all risks" or "all disasters" approach is essential for a global transformation, which could lead to a better world order. To achieve this, an Intergovernmental Panel for Disaster Risk is suggested to assess risk science periodically and work towards sustainability, human rights, and accountability, within a development and human security frame and on a systemic basis and integrated perspective.

Dereplication, residual complexity, and rational naming: the case of the Actaea triterpenes.

The genus Actaea (including Cimicifuga) has been the source of ∼200 cycloartane triterpenes. While they are major bioactive constituents of complementary and alternative medicines, their structural similarity is a major dereplication problem. Moreover, their trivial names seldom indicate the actual structure. This project develops two new tools for Actaea triterpenes that enable rapid dereplication of more than 170 known triterpenes and facilitates elucidation of new compounds. A predictive computational model based on classification binary trees (CBTs) allows in silico determination of the aglycone type. This tool utilizes the Me (1)H NMR chemical shifts and has potential to be applicable to other natural products. Actaea triterpene dereplication is supported by a new systematic naming scheme. A combination of CBTs, (1)H NMR deconvolution, characteristic (1)H NMR signals, and quantitative (1)H NMR (qHNMR) led to the unambiguous identification of minor constituents in residually complex triterpene samples. Utilizing a 1.7 mm cryo-microprobe at 700 MHz, qHNMR enabled characterization of residual complexity at the 10-20 µg level in a 1-5 mg sample. The identification of five co-occurring minor constituents, belonging to four different triterpene skeleton types, in a repeatedly purified natural product emphasizes the critical need for the evaluation of residual complexity of reference materials, especially when used for biological assessment.

Assessing dangerous climate change through an update of the Intergovernmental Panel on Climate Change (IPCC) "reasons for concern".

Article 2 of the United Nations Framework Convention on Climate Change [United Nations (1992) http://unfccc.int/resource/docs/convkp/conveng.pdf. Accessed February 9, 2009] commits signatory nations to stabilizing greenhouse gas concentrations in the atmosphere at a level that "would prevent dangerous anthropogenic interference (DAI) with the climate system." In an effort to provide some insight into impacts of climate change that might be considered DAI, authors of the Third Assessment Report (TAR) of the Intergovernmental Panel on Climate Change (IPCC) identified 5 "reasons for concern" (RFCs). Relationships between various impacts reflected in each RFC and increases in global mean temperature (GMT) were portrayed in what has come to be called the "burning embers diagram." In presenting the "embers" in the TAR, IPCC authors did not assess whether any single RFC was more important than any other; nor did they conclude what level of impacts or what atmospheric concentrations of greenhouse gases would constitute DAI, a value judgment that would be policy prescriptive. Here, we describe revisions of the sensitivities of the RFCs to increases in GMT and a more thorough understanding of the concept of vulnerability that has evolved over the past 8 years. This is based on our expert judgment about new findings in the growing literature since the publication of the TAR in 2001, including literature that was assessed in the IPCC Fourth Assessment Report (AR4), as well as additional research published since AR4. Compared with results reported in the TAR, smaller increases in GMT are now estimated to lead to significant or substantial consequences in the framework of the 5 "reasons for concern."

Combined extracorporeal shockwave therapy and exercise for the treatment of tendinopathy: A narrative review.

Tendinopathy is a chronic degenerative musculoskeletal disorder that is common in both athletes and the general population. Exercise and extracorporeal shockwave therapy (ESWT) is among the most common treatments used to mediate tendon healing and regeneration. The review presents the current understanding of mechanisms of action of ESWT and exercise in isolation and briefly synthesises evidence of their effectiveness for various tendinopathies. The central purpose of the review is to synthesize research findings investigating the combination of ESWT and exercise for five common tendinopathies (plantar heel pain, rotator cuff, lateral elbow, Achilles, and patellar tendinopathy) and provide recommendations on clinical applicability. Collectively, the available evidence indicates that ESWT combined with exercise in the form of eccentric training, tissue-specific stretching, or heavy slow resistance training are effective for specific tendinopathies and can therefore be recommended in treatment. Whilst there are at present a limited number of studies investigating combined EWST and exercise approaches, there is evidence to suggest that the combination improves outcomes in the treatment of plantar heel pain, Achilles, lateral elbow, and rotator cuff tendinopathy. However, despite overall positive outcomes in patellar tendinopathy, the combined treatment has not been shown at present to offer additional benefit over eccentric exercise alone.

Interventions for prevention and in-season management of patellar tendinopathy in athletes: A scoping review.

INTRODUCTION: Patellar tendinopathy (PT) has a high prevalence in jumping athletes and presents a significant burden on athletes and clinicians due to its long-lasting duration and persistent symptoms. This scoping review aimed to map existing evidence on prevention and in-season management interventions for PT in athletes, evaluating intervention parameters and outcomes. METHODS: This scoping review was reported in accordance with the PRISMA-ScR. Databases searched included MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, and the Cochrane library (Controlled trials, Systematic reviews). All primary study designs investigating prevention or in-season management interventions for PT, while maintaining athletes in sport were considered for inclusion. RESULTS: 5987 articles were identified with 29 included in the review. Five studies investigated exercise-based prevention interventions on athletes at risk for PT, including two randomized controlled trials (RCTs), two cohort studies and one case-control study. 24 studies investigated in-season management or rehabilitation in athletes with PT, including 18 RCTs, three case reports, one cohort study, one case series, and one retrospective review. Of these 24 studies, 22 used various resistance training interventions, one used ESWT and one used patellar strapping and taping. The types of resistance training included eccentric, heavy-slow, isometric, inertial flywheel, blood-flow restriction, and isotonic training. Eccentric training was used in 9 studies, with single leg decline squats the most common exercise used in 7 studies. Outcome measures and intervention parameters were heterogenous throughout studies. CONCLUSION: Despite a dearth of studies on preventative interventions for athletes with PT, resistance training may be a useful prophylactic method. Eccentric, heavy slow and isometric resistance training have been found to be feasible and clinically beneficial in-season. There are a lack of studies showing that ESWT offers any additional benefit over resistance training in competing athletes. Patellar strapping and taping may offer short-term pain relief during training and competition. Systematic reviews are required to make definitive recommendations for PT.

Blood Flow Restriction Resistance Training in Tendon Rehabilitation: A Scoping Review on Intervention Parameters, Physiological Effects, and Outcomes.

Objective: To identify current evidence on blood flow restriction training (BFRT) in tendon injuries and healthy tendons, evaluating physiological tendon effects, intervention parameters, and outcomes. Methods: This scoping review was reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Databases searched included MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, Cochrane library (Controlled trials, Systematic reviews), and five trial registries. Two independent reviewers screened studies at title/abstract and full text. Following screening, data was extracted and charted, and presented as figures and tables alongside a narrative synthesis. Any study design conducted on adults, investigating the effects of BFRT on healthy tendons or tendon pathology were included. Data were extracted on physiological tendon effects, intervention parameters and outcomes with BFRT. Results: Thirteen studies were included, three on tendinopathy, two on tendon ruptures, and eight on healthy Achilles, patellar, and supraspinatus tendons. A variety of outcomes were assessed, including pain, function, strength, and tendon morphological and mechanical properties, particularly changes in tendon thickness. BFRT intervention parameters were heterogeneously prescribed. Conclusion: Despite a dearth of studies to date on the effects of BFRT on healthy tendons and in tendon pathologies, preliminary evidence for beneficial effects of BFRT on tendons and clinical outcomes is encouraging. As BFRT is a relatively novel method, definitive conclusions, and recommendations on BFRT in tendon rehabilitation cannot be made at present, which should be addressed in future research, due to the potential therapeutic benefits highlighted in this review.

Inertial Flywheel Resistance Training in Tendinopathy Rehabilitation: A Scoping Review.

Background: Inertial Flywheel Resistance Training (IFRT) has recently emerged as a beneficial rehabilitation option for some musculoskeletal disorders. Although the use of resistance training as treatment for tendinopathy has become widespread, it is unclear if IFRT has efficacy as a treatment option for tendinopathies. Objective: To identify current evidence on IFRT in the treatment of tendinopathy, evaluating intervention parameters and outcomes. Methods: This scoping review was reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Databases searched included MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, Cochrane library (Controlled trials, Systematic reviews), and five trial registries. Two independent reviewers screened studies at title, abstract and full text. Following screening, data were extracted and charted, and presented as figures and tables alongside a narrative synthesis. Any study design conducted on adults, investigating the effects of IFRT for tendinopathy were included. Data were extracted on intervention parameters and outcomes of IFRT interventions. Results: Four studies on patellar tendinopathy were included. A variety of outcomes were assessed, including pain, function, strength, power, and tendon morphological and mechanical properties, particularly changes in tendon thickness. IFRT intervention parameters were largely homogenously prescribed, with slight variances. Conclusion: Despite a paucity of studies to date on the effects of IFRT for treating tendinopathy, preliminary evidence for beneficial effects of IFRT on clinical outcomes in patellar tendinopathy is encouraging. As IFRT is a relatively new and unexplored method in tendinopathy rehabilitation, definitive conclusions, and recommendations cannot be made at present, which should be addressed in future research, due to the potential therapeutic benefits highlighted in this review.

Resistance Training Interventions for Lower Limb Tendinopathies: A Scoping Review of Resistance Training Reporting Content, Quality, and Scientific Implementation.

The objectives of this scoping review were as follows: (1) to describe what exercises and intervention variables are used in resistance training interventions for lower limb tendinopathy, (2) to assess the completeness of reporting as assessed by the Consensus on Exercise Reporting Template (CERT) and the Toigo and Boutellier framework, and (3) to assess the implementation of scientific resistance training principles. We searched MEDLINE, CINAHL, AMED, Embase, SPORTDiscus, and Cochrane Library databases. Randomized controlled trials, cohort studies, case series, case reports, and observational studies that reported using resistance exercises for lower limb tendinopathies were considered for inclusion, with 194 studies meeting the inclusion criteria. Completeness of the reporting of exercise descriptors and programme variables was assessed by the CERT and the Toigo and Boutellier framework. Reporting of exercise descriptor items from the Toigo and Boutellier framework ranged from 0 to 13, with an average score of 9/13, with only 9 studies achieving a full 13/13. Reporting of items from the CERT ranged from 0 to 18, with an average score of 13/19. No study achieved a full 19/19; however, 8 achieved 18/19. Scoring for resistance training principles ranged from 1 to 10, with only 14 studies achieving 10/10. Eccentric heel-drops were the most common exercise (75 studies), followed by isotonic heel raises (38), and single-leg eccentric decline squats (27). The reporting of exercise descriptors and intervention content was high across studies, with most allowing exercise replication, particularly for Achilles and patellar tendinopathy. However, reporting for some tendinopathies and content items such as adherence was poor, limiting optimal translation to clinical practice.

Molecular characterization of zebrafish embryogenesis via DNA microarrays and multiplatform time course metabolomics studies.

One of the greatest strengths of "-omics" technologies is their ability to capture a molecular snapshot of multiple cellular processes simultaneously. Transcriptomics, proteomics, and metabolomics have, individually, been used in wide-ranging studies involving cell lines, tissues, model organisms, and human subjects. Nonetheless, despite the fact that their power lies in the global acquisition of parallel data streams, these methods continue to be employed separately. We highlight work done to merge transcriptomics and metabolomics technologies to study zebrafish (Danio rerio) embryogenesis. We combine information from three bioanalytical platforms, that is, DNA microarrays, (1)H nuclear magnetic resonance ((1)H NMR), and mass spectrometry (MS)-based metabolomics, to identify and provide insights into the organism's developmental regulators. We apply a customized approach to the analysis of such time-ordered measurements to provide temporal profiles that depict the modulation of metabolites and gene transcription. Initially, the three data sets were analyzed individually but later they were fused to highlight the advantages gained through such an integrated approach. Unique challenges posed by fusion of such data are discussed given differences in the measurement error structures, the wide dynamic range for the molecular species, and the analytical platforms used to measure them (i.e., fluorescence ratios, NMR, and MS intensities). Our data analysis reveals that changes in transcript levels at specific developmental stages correlate with previously published data with over 90% accuracy. In addition, transcript profiles exhibited trends that were similar to the accumulation of metabolites over time. Profiles for metabolites such as choline-like compounds (Trimethylamine-N-oxide, phosphocholine, betaine), creatinine/creatine, and other metabolites involved in energy metabolism exhibited a steady increase from 15 hours post fertilization (hpf) to 48 hpf. Other metabolite and transcript profiles were transiently rising and then falling back to baseline. The "house keeping" metabolites such as branched chain amino acids exhibited a steady presence throughout embryogenesis. Although the transcript profiling corresponds to only 16 384 genes, a subset of the total number of genes in the zebrafish genome, we identified examples where gene transcript and metabolite profiles correlate with one another, reflective of a relationship between gene and metabolite regulation over the course of embryogenesis.

Autoregulation in Resistance Training for Lower Limb Tendinopathy: A Potential Method for Addressing Individual Factors, Intervention Issues, and Inadequate Outcomes.

Musculoskeletal disorders, such as tendinopathy, are placing an increasing burden on society and health systems. Tendinopathy accounts for up to 30% of musculoskeletal disorders, with a high incidence in athletes and the general population. Although resistance training has shown short-term effectiveness in the treatment of lower limb tendinopathy, more comprehensive exercise protocols and progression methods are required due to poor long-term outcomes. The most common resistance training protocols are predetermined and standardized, which presents significant limitations. Current standardized protocols do not adhere to scientific resistance training principles, consider individual factors, or take the importance of individualized training into account. Resistance training programs in case of tendinopathy are currently not achieving the required intensity and dosage, leading to high recurrence rates. Therefore, better methods for individualizing and progressing resistance training are required to improve outcomes. One potential method is autoregulation, which allows individuals to progress training at their own rate, taking individual factors into account. Despite the finding of their effectiveness in increasing the strength of healthy athletes, autoregulation methods have not been investigated in case of tendinopathy. The purpose of this narrative review was 3-fold: firstly, to give an overview and a critical analysis of the individual factors involved in tendinopathy and current resistance training protocols and their limitations. Secondly, to give an overview of the history, methods, and application of autoregulation strategies both in sports performance and physiotherapy. Finally, a theoretical adaptation of a current tendinopathy resistance training protocol using autoregulation methods is presented, providing an example of how the method could be implemented in clinical practice or future research.

Autoregulated heavy slow resistance training combined with radial shockwave therapy for plantar heel pain: Protocol for a mixed-methods pilot randomised controlled trial.

BACKGROUND: Plantar heel pain (PHP) is considered a tendinopathy and it affects up to 10% of the population. Both heavy slow resistance training (HSRT) and extracorporeal shockwave therapy (ESWT) have shown effectiveness for treating PHP in isolation. However, more comprehensive exercise protocols and progression methods are needed due to poor long-term outcomes, and better standardisation of ESWT protocols are required. Autoregulation of resistance training involves self-selecting exercise dosage based on individual factors. Although autoregulation has proven effective for strength gains in athletes, it has not been investigated in tendinopathy. Recent studies recommend that PHP should not be treated by one treatment intervention in isolation. However, there is a dearth of research investigating the feasibility and effectiveness of combined treatment interventions for PHP. Currently, no studies have investigated autoregulated HSRT combined with ESWT, despite their individual efficacy. The optimal treatment protocol for PHP is unknown, and there is a need to ascertain whether the addition of ESWT to autoregulated HSRT leads to better outcomes compared to either alone. METHODS: A three-arm randomised controlled trial (RCT) comparing these groups would be the ideal way to investigate this question, with a pilot RCT testing trial procedures and process evaluation required prior to a definitive RCT. Patients expectations, feasibility and acceptability of combined ESWT and exercise for PHP also remain unknown. Therefore, the addition of qualitative interviews in a mixed-methods pilot RCT would help ascertain acceptability and help explain the intervention outcomes.