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Process-based forest models combine biological, physical, and chemical process understanding to simulate forest dynamics as an emergent property of the system. As such, they are valuable tools to investigate the effects of climate change on forest ecosystems. Specifically, they allow testing of hypotheses regarding long-term ecosystem dynamics and provide means to assess the impacts of climate scenarios on future forest development. As a consequence, numerous local-scale simulation studies have been conducted over the past decades to assess the impacts of climate change on forests. These studies apply the best available models tailored to local conditions, parameterized and evaluated by local experts. However, this treasure trove of knowledge on climate change responses remains underexplored to date, as a consistent and harmonized dataset of local model simulations is missing.Here, our objectives were (i) to compile existing local simulations on forest development under climate change in Europe in a common database, (ii) to harmonize them to a common suite of output variables, and (iii) to provide a standardized vector of auxiliary environmental variables for each simulated location to aid subsequent investigations. Our dataset of European stand- and landscape-level forest simulations contains over 1.1 million simulation runs representing 135 million simulation years for more than 13,000 unique locations spread across Europe. The data were harmonized to consistently describe forest development in terms of stand structure (dominant height), composition (dominant species, admixed species), and functioning (leaf area index). Auxiliary variables provided include consistent daily climate information (temperature, precipitation, radiation, vapor pressure deficit) as well as information on local site conditions (soil depth, soil physical properties, soil water holding capacity, plant-available nitrogen). The present dataset facilitates analyses across models and locations, with the aim to better harness the valuable information contained in local simulations for large-scale policy support, and for fostering a deeper understanding of the effects of climate change on forest ecosystems in Europe.

Aim:Nymphaea plants were traditionally used to treat diseases associated with endothelial dysfunction. The present study investigated the effects of an ethanolic extract of Nymphaea pubescens Willd. (commonly named water lily, WL) and its main compound 1 (quercetin 3-methyl ether 3′-O-β-xylopyranoside) on vascular function in rats.Materials and methods: The vasorelaxant effects of the WL extract and its main compound 1 and their underlying mechanisms of action were evaluated on isolated mesenteric arteries from Wistar rats. Blood pressure and heart rate were measured in anesthetized rats after infusion (i.v) of vehicle, WL extract, and compound 1 (at 0.01, 0.025, 0.05, 0.1, 0.5, and 1 mg/kg). Nifedipine was used as a positive control.Results: Both WL extract and compound 1 induced vasorelaxant effects (with EC50 of 0.08 ± 0.01 mg/mL and 42.8 ± 6.3 µM, respectively) that were reduced by endothelium removal. A significant decrease in these relaxations was observed with L-NAME but not with apamin–charybdotoxin or indomethacin. In the endothelium-denuded condition, WL extract-induced relaxation was enhanced by 4-aminopyridine and glibenclamide, while iberiotoxin and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one) had no effect. In contrast, compound 1-induced relaxation was not changed by any of these inhibitors. Both WL extract and compound 1 enhanced sodium nitroprusside-induced relaxation and inhibited receptor-operated Ca2+ channels. Only the WL extract was able to reduce PE-induced contraction (p < 0.001). As compared to the vehicle, the infusion of WL extract and compound 1 lowered systolic and diastolic blood pressure. Interestingly, the hypotensive effect of the compound was similar to that of nifedipine. The rebound tachycardia found at the highest dose of nifedipine was not observed with the WL extract or compound 1 (p < 0.05).Conclusion and discussion: Our study demonstrated a vasorelaxant effect of the WL extract and its main compound quercetin 3-methyl ether 3′-O-β-xylopyranoside, relying on the potentiation of the NO-cGMP pathway and calcium inhibitory effects. These vasorelaxant effects were associated with a potent hypotensive effect, providing pharmacological evidence for the traditional use of this plant.

Abstract Background Intestinal inflammation, dysbiosis, intestinal permeability (IP), and bacterial translocation (BT) have been identified in patients with spondyloarthritis but the time at which they appear and their contribution to the pathogenesis of the disease is still a matter of debate. Objectives To study the time-course of intestinal inflammation (I-Inf), IP, microbiota modification BT in a rat model of reactive arthritis, the adjuvant-induced arthritis model (AIA). Methods Analysis was performed at 3 phases of arthritis in control and AIA rats: preclinical phase (day 4), onset phase (day 11), and acute phase (day 28). IP was assessed by measuring levels of zonulin and ileal mRNA expression of zonulin. I-inf was assessed by lymphocyte count from rat ileum and by measuring ileal mRNA expression of proinflammatory cytokines. The integrity of the intestinal barrier was evaluated by levels of iFABP. BT and gut microbiota were assessed by LPS, soluble CD14 levels, and 16S RNA sequencing in mesenteric lymph node and by 16S rRNA sequencing in stool, respectively. Results Plasma zonulin levels increased at the preclinical and onset phase in the AIA group. Plasma levels of iFABP were increased in AIA rats at all stages of the arthritis course. The preclinical phase was characterized by a transient dysbiosis and increased mRNA ileal expression of IL-8, IL-33, and IL-17. At the onset phase, TNF-α, IL-23p19, and IL-8 mRNA expression were increased. No changes in cytokines mRNA expression were observed at the acute phase. Increased CD4+ and CD8+ T cell number was measured in the AIA ileum at day 4 and day 11. No increase in BT was observed. Conclusion These data show that intestinal changes precede the development of arthritis but argue against a strict “correlative” model in which arthritis and gut changes are inseparable.

Background: For years, the rupture of the anterior cruciate ligament (ACL) has been a feared injury in young soccer players since it causes physiological and psychological changes while incurring significant economic losses. Methods: Through clinical research, understanding the mechanisms and identifying risk factors has enabled sports and performance professionals to establish robust models to predict and reduce the risk of ACL injury. Developments in medical devices also allow a more precise, more objective assessment and improve the traceability of the various quantitative and qualitative parameters necessary to detect the risk of ACL injury. Results: While general preventive protocols have shown evidence for an overall reduction in injury, there are still limitations regarding ACL injury. Therefore, we can collect personalized data from these models and the variables involved, predict, prevent, and program performance throughout the season. Additionally, the multi-professional team supervising the athlete must establish a close relationship centered on feeling and listening to the player who remains in control of his performance. Conclusion: Let the players decide on their career and not an injury.

Background: The Achilles tendon rupture is a pathology of growing incidence due to the increase in the intensity of amateur sports practices and the continuation of this practice with the rise in age. The rupture follows a degradation of the tendon’s structure, known as degenerative tendinopathy, which is symptomatic only in rare cases. In the absence of prior pain, iterative rupture is the complication to be feared and prevented. Unfortunately, after orthopedic or surgical treatment, there is no consensus concerning criteria for returning to sports. Such criteria would aim to prevent the risk of recurrence and the appearance of other sports injuries. Methods: A current literature review using the PubMed database in June 2021. Results: The literature doesn’t show any validated criteria for returning to sport. Conclusion: Consequently, this work seeks to propose objective criteria for validating the return to sport in connection with the physical and psychological qualities of the subject, abrogating temporal criteria, too formal and remote from the clinical view. Thus, the physiotherapist is advised to take an interest in the ankle's range of motion and the stiffness of the tendon, strength and endurance of the calf muscle, the quality of the proprioceptive and postural functions on a more functional plan, based on the quality of the jumps and then on the subject's running pattern. Finally, a psychological assessment completes the battery of tests that will validate the return to sport.

Background: During the anterior cruciate ligament reconstruction, the graft is taken from the distal hamstring tendon, which causes morphological and neurological changes in these muscles, particularly on the maximum effective angle of the knee flexors. The present study investigates changes in knee flexor following anterior cruciate ligament reconstruction with a hamstring graft. Methods: Two populations participated in this study, a healthy group and a group that underwent anterior cruciate ligament reconstruction with a hamstring graft. First, the test group underwent two postoperative assessments on an isokinetic device at 3 and 6 months. Next, we compared the test group at 3 and 6 months with the control group to highlight the differences between the knee flexors maximum effective angle. And finally, we have compared the knee flexors maximum effective angle with the moment of maximum force to determine whether these two values are related. Results: The maximum effective angle is decreased regardless of the duration of rehabilitation (ρ= 0.0019, ρ = 0.037). It does not change significantly during rehabilitation (ρ = 0.29). It does not depend on the strength gained during rehabilitation but on a neuromotor change due to the morphological changes caused by surgery. Conclusion: The study results show that anterior cruciate ligament reconstruction with hamstring graft causes a decrease in knee flexor maximum effective angle.

Background: The objective of this study is to determine whether the early association of the open kinetic chain (OKC) and the closed kinetic chain (CKC) allows an improvement in the strength and functional qualities of the quadriceps in the context of soccer rehabilitation after anterior cruciate ligament reconstruction. Materials: A collection of prospective data on two groups of 15 subjects who all suffered an after anterior cruciate ligament (ACL). Each subject is assigned to a group according to the type of rehabilitation they have undergone within the center, with only CKC rehabilitation and mixed OKC and CKC rehabilitation. The protocols were introduced four weeks after ACL reconstruction. The measurements were carried out at three months on an isokinetic dynamometer to measure the peak torque (PT) and to be able to determine limb symmetry index (LSI) and the PT concerning the body weight, the relative peak torque (PT/WB). Results: After testing the LSI and the PT/WB between the two groups, there was a significant difference (p

Secondary metabolites have an important impact on the biocontrol potential of soil-derived microbes. In addition, various microbe-produced chemicals have been suggested to impact the development and phenotypic differentiation of bacteria, including biofilms. The non-ribosomal synthesized lipopeptide of Bacillus subtilis, surfactin, has been described to impact the plant promoting capacity of the bacterium. Here, we investigated the impact of surfactin production on biofilm formation of B. subtilis using the laboratory model systems; pellicle formation at the air-medium interface and architecturally complex colony development, in addition to plant root-associated biofilms. We found that the production of surfactin by B. subtilis is not essential for pellicle biofilm formation neither in the well-studied strain, NCIB 3610, nor in the newly isolated environmental strains, but lack of surfactin reduces colony expansion. Further, plant root colonization was comparable both in the presence or absence of surfactin synthesis. Our results suggest that surfactin-related biocontrol and plant promotion in B. subtilis strains are independent of biofilm formation.

Background: Today, anterior cruciate ligament rupture is the most common injury in sportsmen and women, but it can also occur in sedentary subjects. Its treatment, always adapted to the patient's lifestyle, age, and will, often remains surgical. However, despite its frequency and universality, we still find gait disorders after the surgery and can up to several months or even several years after the surgery. Therefore, the present study is interested in determining the risk factors associated with gait disorders after an anterior cruciate ligament reconstruction (ACLR). This study aims to determine the risk factors associated with gait disorders after surgery with hamstring autograft. We are interested in the factors that may exist at 3 and 6 months postoperatively. Methods: Two populations participate in this study, a healthy population and a population with ACLR subjects. The ACLR test group is divided into two subgroups, one with a post-operative delay of 3 months and the second with a delay of 6 months. All subjects are subjected to the same protocol; their gait on the treadmill was analyzed and evaluated by the device OptoGait®. A united and varied analysis was first conducted, and then a multivariate analysis by adjustment method was carried out to eliminate potential confounding factors. Results: Comparison of the results across populations in the unvaried analysis shows an absence of significant results (p>0,05); however, there are trends. The statistical results of the multivariate analysis showed interactions in the two subgroups of the ACLR population. At three months after surgery, there is a tendency for gait disorders to worsen in subjects with a BMI reflecting overweight, when an associated surgical procedure on the meniscus was realized, in subjects over 35 years old and in males subjects. In contrast, at six months after surgery, the worsening trend is only seen in the subgroups represented by subjects with BMI reflecting overweight subjects with meniscal repair associated with ACLR. Conclusion: The present study results show certain factors tend to aggravate these gait disorders after ACLR with hamstring autograft; these factors are different depending on the post-operative delay.

Background: Rehabilitation following an anterior cruciate ligament reconstruction (ACLR) will allow the patient to regain his functional capacities and support him in the resumption of sports activity. Rehabilitation also aims to minimize the recurrence risk, ensuring the good development of the patient’s muscular capacities until returning to sport. Isokinetism allows the strengthening and evaluation of this muscular strength of the thigh muscle groups. Still, controversy exists about its use by resistance to knee extension in the open kinetic chain, which would cause the graft's distension. This study aims to determine the influence of muscle strengthening of the quadriceps in the open kinetic chain by using isokinetism on the possible laxity of the anterior cruciate ligament and being able to develop risk factors for it. Methods: The study is based on a population having benefited from an ACLR with a hamstring graft six months postoperatively. Two groups are differentiated; one group exposed to isokinetic during their rehabilitation, the other group, undergoing rehabilitation without the use of isokinetism is the unexposed group. An anterior knee laxity test is performed six months postoperatively using the unexposed group. According to the same protocol, the anterior knee laxity test is performed 6 months post-operatively using all subjects' GNRB® machine. The test results underwent statistical analysis to determine the relative risk of plastic surgery for each study group. Results: Comparing each group's results by a univariate analysis did not reveal any significant results. Multivariate analysis to show interactions between the study groups. It was found that the use of isokinetism would seem not to affect the risk of developing distension for the majority of subjects in the exposed group. A tendency towards protection was found for exposed subjects aged between 25 and 35 regarding the graft's distension. Also, a tendency to protection was found in the exposed subjects regarding an alteration of the graft leading to an anatomically comparable difference. Conclusion: The use of isokinetism does not seem to cause distension of the graft in patients operated on ACLR when this method is introduced three months postoperatively.

Background: The optimization of this return to athletic activity passes by a better understanding of the muscle's behavior involved in knee function. In this study, we focused on the muscle's muscular activity involved in the flexion of the knee. Precisely on the relation between the gastrocnemius's muscular activity and the hamstring among the patient that underwent an anterior cruciate ligament reconstruction with a hamstring graft. The study's objective is to compare the muscular activity of the flexor knee muscle in patients who underwent an anterior cruciate ligament reconstruction with hamstring autograft and the individuals who have not undergone surgery. Methods: The participants have been divided into two groups: a healthy group and an experimental group that underwent an anterior cruciate ligament reconstruction with a hamstring graft. The participants had to perform a strength test on an isokinetic dynamometer. The medial gastrocnemius activity, lateral gastrocnemius, femoral biceps, and the semitendinosus were measured during this test. The first group individuals mentioned the muscle's muscular activity compared to those in the second group via statistical analysis. Then, a ratio of the gastrocnemius muscle activity on the activity of the hamstring has calculated. The results of the experimental group were then compared to the results of the control group. Results: The results showed a significant difference in activity of the medial gastrocnemius (p = 0,004901), the biceps femoris (p = 5,394.10-6), and the semitendinosus muscles (p = 1,822.10-6 ): the experimental group results were superior to the control group results. However, the evaluation of the activity reporting has shown significant differences in the two groups. Conclusion: This study has shown a difference in the gastrocnemius and hamstring muscle activity between patients who underwent an anterior cruciate ligament reconstruction surgery and healthy participants. However, our approach has not allowed us to identify the relationship between a heightened gastrocnemius activity and a diminished hamstring activity following an anterior cruciate ligament reconstruction with a hamstring graft. Quite on the contrary, we observed higher activity of the two muscle groups. Nevertheless, it seems necessary to have a variation in situations during the gastrocnemius muscle analysis to fully understand its purpose in the functional activity of the knee of patients who have undergone an anterior cruciate ligament reconstruction.

Introduction: Hallux valgus is the most common condition found in the foot, caused by a progressive failure of the first ray stabilization means. The hallux is deviated into valgus, the first metatarsal into varus, and their association leads to a subluxation of the metatarsophalangeal joint of the first ray. Surgery is a treatment frequently used to correct this condition. So, is the static postural balance altered after corrective surgery? Materials and Method: 23 subjects participated in the study, all women, divided into two groups: control and hallux valgus. The hallux valgus group was evaluated three months post-operatively. Bipodal tests were carried out on a stabilometry platform, one with eyes open and one with eyes closed. The pressure center parameters were recorded and analyzed, such as the length or the area of the pressure center. Results: The results obtained showed significant differences between the two groups and were statistically significant, with a p-value of 0,05. The pressure center values are higher in the hallux valgus group. Conclusion: Some results found in the literature agree with the results of the present study. There are significant deficits in the static postural balance three months after corrective surgery. Other studies with a larger sample may be performed to confirm or not the results of this study.

Background: the deformation of the hallux into a valgus constitutes the most frequent deformation of the forefoot and one of the most performed corrective surgeries in the region. This deformation is the cause of many biomechanical disorders and causes gait disturbances. This review aims to analyze the restoration of space-time and kinematic parameters of walking in the aftermath of corrective surgery for hallux valgus. Methods: four studies were analyzed according to the main criteria of walking speed, support time, step length and kinematics of the ankle and foot before and after the intervention. Results: If some of the results obtained in the analyzed works show an improvement of these criteria in post-operative, the subjects having benefited from hallux valgus surgery seem to present some persistent issues in the spatiotemporal and kinematic parameters. Conclusion: This work does not demonstrate the superiority of one surgical technique over another in the recovery of gait. This recovery does not seem absolute, but this review highlights above all the lack of literature on this subject.

Background: The anterior cruciate ligament (ACL) tear is the most common sports injury. Surgery is often proposed, but single-leg and double-leg static postural disorders have been discovered several months after surgery. Our aims are to compare postural disorders after ligament reconstruction by hamstring tendon graft in the three months after surgery to those caused by aging. Methods: 2 groups of subjects underwent bilateral and unilateral postural tests. An analysis of the center of pressure’s displacement is carried out for each test. Results: Comparison of the two groups shows no significant difference for the injured leg on the unilateral and bilateral tests only (p-value>0,05). Conclusion: Postural alteration after an ACL reconstruction on the injured leg and bilateral posture can be compared to postural disorders caused by age.

Abstract Background Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice. Methods Mice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes. Results Immunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment. Conclusions Overall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure.

The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal cap structure with the addition of a methyl group on the ribose 2'-O position of the first transcribed nucleotide (m7GpppNmpRNA) and sometimes on the adjoining nucleotide (m7GpppNmpNmpRNA). In higher eukaryotes, the DXO protein was previously shown to be responsible for both decapping and degradation of RNA transcripts harboring aberrant 5' ends such as pRNA, pppRNA, GpppRNA, and surprisingly, m7GpppRNA. It was proposed that the interaction of the cap binding complex with the methylated cap would prevent degradation of m7GpppRNAs by DXO. However, the critical role of the 2'-O-methylation found in higher eukaryotic cap structures was not previously addressed. In the present study, we demonstrate that DXO possesses both decapping and exoribonuclease activities toward incompletely capped RNAs, only sparing RNAs with a 2'-O-methylated cap structure. Fluorescence spectroscopy assays also revealed that the presence of the 2'-O-methylation on the cap structure drastically reduces the affinity of DXO for RNA. Moreover, immunofluorescence and structure-function assays also revealed that a nuclear localisation signal is located in the amino-terminus region of DXO. Overall, these results are consistent with a quality control mechanism in which DXO degrades incompletely capped RNAs.

[This corrects the article DOI: 10.1371/journal.pone.0193804.].

Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein-Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.

Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify 240 modified alternative splicing events upon infection which belong to transcripts frequently involved in the regulation of gene expression and RNA metabolism. Using mass spectrometry, we also confirm modifications to transcript-specific peptides resulting from AS in virus-infected cells. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection.

Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism.Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals.Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians.The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.

Twenty-four-hour dietary recalls can provide high-quality dietary intake data, but are considered expensive, as they rely on trained professionals for both their administration and coding. The objective of this study was to develop an automated, self-administered web-based 24-h recall (R24W) for a French-Canadian population. The development of R24W was inspired by the United States Department of Agriculture (USDA) Automated Multiple-Pass Method. Questions about the context of meals/snacks were included. Toppings, sauces and spices frequently added to each food/dish were suggested systematically. A list of frequently forgotten food was also suggested. An interactive summary allows the respondent to track the progress of the questionnaire and to modify or remove food as needed. The R24W prototype was pre-tested for usability and functionality in a convenience sample of 29 subjects between the ages of 23 and 65 years, who had to complete one recall, as well as a satisfaction questionnaire. R24W includes a list of 2865 food items, distributed into 16 categories and 98 subcategories. A total of 687 recipes were created for mixed dishes, including 336 ethnic recipes. Pictures of food items illustrate up to eight servings per food item. The pre-test demonstrated that R24W is easy to complete and to understand. This new dietary assessment tool is a simple and inexpensive tool that will facilitate diet assessment of individuals in large-scale studies, but validation studies are needed prior to the utilization of the R24W.

The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5' end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed.

Objectives: To develop a physiotherapist-led consensus statement on the definition and provision of high-value care for people with musculoskeletal conditions., Design: We performed a three-stage study using Research And Development/University of California Los Angeles Appropriateness Method methodology. We reviewed evidence about current definitions through a rapid literature review and then performed a survey and interviews with network members to gather consensus. Consensus was finalised in a face-to-face meeting., Setting: Australian primary care., Participants: Registered physiotherapists who are members of a practice-based research network (n=31)., Results: The rapid review revealed two definitions, four domains of high value care and seven themes of high-quality care. Online survey responses (n=26) and interviews (n=9) generated two additional high-quality care themes, a definition of low-value care, and 21 statements on the application of high value care. Consensus was reached for three working definitions (high value, high-quality and low value care), a final model of four high value care domains (high-quality care, patient values, cost-effectiveness, reducing waste), nine high-quality care themes and 15 statements on application., Conclusion: High value care for musculoskeletal conditions delivers most value for the patient, and the clinical benefits outweigh the costs to the individual or system providing the care. High-quality care is evidence based, effective and safe care that is patient-centred, consistent, accountable, timely, equitable and allows easy interaction with healthcare providers and healthcare systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The disconnect between research and clinical practice leads to research evidence that is often not useful for clinical practice. Practice-based research networks are collaborations between researchers and clinicians aimed at coproducing more useful research. Such networks are rare in the physiotherapy field. We aimed to describe (i) clinicians' motivations behind, and enablers to, participating in a network, (ii) the process of network establishment and (iii) research priorities for a practice-based network of physiotherapists in the Hunter Region of New South Wales (NSW), Australia that supports research coproduction., Methods: We describe the methods and outcomes of the three steps we used to establish the network. Step 1 involved consultation with local opinion leaders and a formative evaluation to understand clinicians' motivations behind, and enablers to, participating in a network. Step 2 involved establishment activities to generate a founding membership group and codesign a governance model. Step 3 involved mapping clinical problems through a workshop guided by systems thinking theory with local stakeholders and prioritizing research areas., Results: Through formative evaluation focus groups, we generated five key motivating themes and three key enablers for physiotherapists' involvement in the network. Establishment activities led to a founding membership group (n = 29, 67% from private practice clinics), a network vision and mission statement, and a joint governance group (9/13 [70%] are private practice clinicians). Our problem-mapping and prioritization process led to three clinically relevant priority research areas with the potential for significant change in practice and patient outcomes., Conclusions: Clinicians are motivated to break down traditional siloed research generation and collaborate with researchers to solve a wide array of issues with the delivery of care. Practice-based research networks have promise for both researchers and clinicians in the common goal of improving patient outcomes., (© 2023. The Author(s).)