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Diabetic foot ulcers (DFUs) impact a substantial proportion of patients with diabetes, with high recurrence rates, severe complications, and significant financial burden to health care systems. Adherence to treatment advice (e.g., limiting weight-bearing activity) is low with patients reporting dissatisfaction with the way in which advice is communicated. This study aimed to address this problem via the systematic development of a motivation communication training program. The program was designed to support diabetes-specialist podiatrists in empowering patients to actively engage with treatment. The development process followed an intervention mapping approach. Needs assessment involved observations of 24 patient-practitioner consultations within a diabetes-specialist foot clinic. This informed specification of a theory of change (self-determination theory) and relevant evidence-based communication strategies (drawing from motivational interviewing). The training program was developed iteratively with changes made following feedback from five diabetic foot health care professionals. The resulting training program, consisting of six one-hour face-to-face sessions over an 8-week period, was delivered to a further six diabetes specialist podiatrists, with five participating in post-program telephone interviews to assess acceptability. Deductive thematic analysis of interview data revealed positive aspects of the training (e.g., valuable and relevant content), ideas for improvement (e.g., online resources and context-specific video examples), the acceptability of motivation strategies, and challenges putting the strategies into practice (such as time constraints and breaking old communication habits). This study contributes to our understanding of integrating motivation principles into routine consultations and holds potential for enhancing adherence to treatment recommendations in patients living with diabetic foot ulcers.

Purpose This study was performed to assess the risk factors for artificial urinary sphincter (AUS) explantation in a large multicenter cohort. Methods We retrospectively reviewed the medical records for all 1,233 implantations of the AMS-800 AUS device in male nonneurological patients from 2005 to 2020 across 13 French centers. Patients with neurological conditions were excluded from the study. To identify factors associated with explantation-free survival, survival analysis was performed. Explantation was defined as the complete removal of the device, whereas revision referred to the replacement of the device or its components. Results The study included 1,107 patients, of whom 281 underwent AUS explantation. The median survival without explantation was 83 months. The leading causes of explantation were infection and erosion. Univariate analysis revealed several significant risk factors for explantation: age above 75 years (34.6% in the explanted group vs. 25.8% in the nonexplanted group, P=0.007), history of radiotherapy (43.5% vs. 31.3%, P=0.001), and anticoagulant use (15% vs. 8.6%, P

Abstract Rangelands, covering half of the global land area, are critically degraded by unsustainable use and climate change. Despite their extensive presence, global assessments of rangeland condition and sustainability are limited. Here we introduce a novel analytical approach that combines satellite big data and statistical modeling to quantify the likelihood of changes in rangeland conditions. These probabilities are then used to assess the effectiveness of management interventions targeting rangeland sustainability. This approach holds global potential, as demonstrated in Mongolia, where the shift to a capitalist economy has led to increased livestock numbers and grazing intensity. From 1986 to 2020, heavy grazing caused a marked decline in Mongolia’s rangeland condition. Our evaluation of diverse management strategies, corroborated by local ground observations, further substantiates our approach. Leveraging globally available yet locally detailed satellite data, our proposed condition tracking approach provides a rapid, cost-effective tool for sustainable rangeland management.

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992.

Imaging is increasingly used to capture information on the marine environment thanks to the improvements in imaging equipment, devices for carrying cameras and data storage in recent years. In that context, biologists, geologists, computer specialists and end-users must gather to discuss the methods and procedures for optimising the quality and quantity of data collected from images. The 4th Marine Imaging Workshop was organised from 3-6 October 2022 in Brest (France) in a hybrid mode. More than a hundred participants were welcomed in person and about 80 people attended the online sessions. The workshop was organised in a single plenary session of presentations followed by discussion sessions. These were based on dynamic polls and open questions that allowed recording of the imaging community’s current and future ideas. In addition, a whole day was dedicated to practical sessions on image analysis, data standardisation and communication tools. The format of this edition allowed the participation of a wider community, including lower-income countries, early career scientists, all working on laboratory, benthic and pelagic imaging.This article summarises the topics addressed during the workshop, particularly the outcomes of the discussion sessions for future reference and to make the workshop results available to the open public.

The moose has good prospects for hunting and game breeding. Peripheral blood indicators can provide information about their health status and adaptive capabilities, as well as non-infectious, infectious, and invasive pathologies. Serum alkaline phosphatase activity is one of the most common clinical biochemical tests in this respect. The study involved blood samples obtained from male moose (n = 75) of four age groups: calves aged 6–7 months, young animals of 18 months old, adults of 2.5–7.5 years old, and adults aged ≥ 8.5 years. The biomaterial sampling was carried out in October – December in the southern taiga subzone, Kirov Region. The blood samples were obtained by cutting the jugular vein (Venae jugularis) immediately after the animal was shot during legal hunting. The blood serum tests involved a semi-automatic biochemical analyzer (Biochem SA High Technology, USA). The alkaline phosphatase activity in male European moose during different periods of ontogenesis demonstrated the following pattern. In the first months of life, the enzyme activity was as high as 222.16 ± 31.14 U/L. This process was typical of intense hydrolysis of organic phosphorus esters, including the exchange of macroergs caused by rapid osteogenesis. At 18 months, the demand for organophosphorus compounds in metabolic processes decreased (46.48 ± 44.09 U/L), as did the role of the enzyme in maintaining homeostasis. In adults of 2.5–7.5 years old, alkaline phosphatase activity dropped to 69.88 ± 11.31 U/L. In 8.5-year-old males, it was as low as 47.34 ± 4.74 U/L. All age groups demonstrated significant differences in alkaline phosphatase activity. Therefore, age had a significant effect on enzyme activity. The study also revealed a certain correlation between alkaline phosphatase activity and body weight. The dynamics of alkaline phosphatase activity in ontogenesis reflected homeostatic changes in the moose body. Indicators of alkaline phosphatase activity can serve as an efficiency marker and an additional criterion in standard selection methods in zootechnical practice.

To achieve an integrated river basin management for the Cagne catchment (France) and better predict floods, various modelling tools are integrated within a unified framework, forming a decision support system (DSS). In the paper, an integrated modeling approach employing deterministic distributed hydrological (MIKE SHE), hydraulic (MIKE 21 FM), and hydrogeological (FEFLOW) models is presented. The hydrological model was validated with recorded data and following a sensitivity analysis for optimizing grid resolution with 20 m. The hydraulic model based on MIKE 21 FM utilizes the results generated by the MIKE SHE model as boundary conditions, producing inundation maps for both normal and extreme periods. The hydrogeological model addresses the various complex relationships taking place within the catchment and was validated with piezometer data. The integration of these three models into a DSS provides a valuable tool for decision-makers to manage the Cagne catchment and the water-related issues more effectively during various hydrological situations. This comprehensive modelling framework underscores the importance of interdisciplinary approaches for addressing complex hydrological processes and contributes to improved flood management strategies in the catchment. HIGHLIGHTS This study combines hydrological, hydraulic, and hydrogeological modeling techniques to do integrated water management and flood forecasting.; This study concentrates on a small-scale catchment, employing high-resolution data to achieve a more detailed and comprehensive analysis.; This study integrates an underground canal into urban flood management, offering a more precise depiction of urban flood dynamics.;

Abstract Background Nephropathic Cystinosis (NC), a rare disease characterised by intra-lysosomal accumulation of cystine, results in progressive kidney failure (KF). Compliance to lifelong oral cysteamine, the only therapy, is often compromised. The relationship between compliance and costs of NC has not been previously formally assessed. The present study evaluates the impact of compliance on lifetime (direct) costs of treating KF in NC patients in the United Kingdom. Methods A three-state (KF-free, post-KF, death) partitioned survival model was developed for hypothetical ‘Good Compliance’ (GC) and ‘Poor Compliance’ (PC) cohorts. Survival in the KF-free state was determined by a published regression function of composite compliance score (CCS). The CCS is a summation of annual compliance scores (ACS) over treatment duration prior to KF. ACSs are indexed on annual (average) leukocyte cystine levels (LCL). The Poor Compliance cohort was defined to reflect NC patients in a previous study with a mean LCL of 2.35 nmols nmol half-cystine/mg protein over the study period – and an estimated mean ACS of 1.64 over a 13.4 year treatment duration. The Good Compliance cohort was assumed to have an ACS of 2.25 for 21 years. Major KF costs were evaluated – i.e., dialysis, kidney transplants, and subsequent monitoring. Results The mean CCS was 47 for the GC and 22 for the PC cohort respectively, corresponding to estimated lifetime KF costs of £92,370 and £117,830 respectively – i.e., a cost saving of £25,460/patient, or £1,005/patient for every 1-unit improvement in CCS. Conclusion This analysis indicates that lifetime costs of KF in NC can be reduced through improved treatment compliance with oral cysteamine.

Nice Metropolis in Alpes Maritimes, France is prone to flood. The city is crossed by the Lower Paillons River (LPR). Its discharge for a return period of 100 years is estimated at 794 m3/s. Part of the river is covered by 2 km. In addition, there are two retention storages in the river bed and a floodable road tunnel on the left bank. Due to the increase in urban development, flood management is challenging. An existing decision support system, Aquavar, uses DHI Mike tools to reproduce runoff for the Lower Var River in the same region. To extend this system to the LPR and reinforce flood management, a new modelling tool adapted to the characteristics of the LPR is needed. Consequently, this research utilizes the DHI MIKEPLUS tool to develop a 1D -2D coupled model for real-time flood management. The results demonstrate that flood events like those in 2017 and 2019 were correctly reproduced. The linear regression R2 is above 0.8 for all stations. It was also estimated that the covered river should stay clean to avoid widespread flooding in the urban area. Overall, the model is useful for simulating flow in real time and can help sustain urban development. HIGHLIGHTS Coupled 1D–2D hydraulic models are implemented using DHI MIKEPLUS 2023.; Assessments of operational management, data and flood risks of the Lower Paillons River.; Modelling complex river hydraulics for real-time decision support systems.;

Diabetic Foot Ulcers (DFUs) are a major complication of diabetes, with treatment requiring offloading. This study aimed to capture how the accelerometer-assessed physical activity profile differs in those with DFUs compared to those with diabetes but without ulceration (non-DFU). Participants were requested to wear an accelerometer on their non-dominant wrist for up to 8days. Physical activity outcomes included average acceleration (volume), intensity gradient (intensity distribution), the intensity of the most active sustained (continuous) 5–120 min of activity (MXCONT), and accumulated 5–120 min of activity (MXACC). A total of 595 participants (non-DFU = 561, DFU = 34) were included in the analysis. Average acceleration was lower in DFU participants compared to non-DFU participants (21.9 mg [95%CI:21.2, 22.7] vs. 16.9 mg [15.3, 18.8], p < 0.001). DFU participants also had a lower intensity gradient, indicating proportionally less time spent in higher-intensity activities. The relative difference between DFU and non-DFU participants was greater for sustained activity (MXCONT) than for accumulated (MXACC) activity. In conclusion, physical activity, particularly the intensity of sustained activity, is lower in those with DFUs compared to non-DFUs. This highlights the need for safe, offloaded modes of activity that contribute to an active lifestyle for people with DFUs.

Abstract Understanding development and genetic regulation in the Anopheles gambiae germline is essential to engineer effective genetic control strategies targeting this malaria mosquito vector. These include targeting the germline to induce sterility or using regulatory sequences to drive transgene expression for applications such as gene drive. However, only very few germline-specific regulatory elements have been characterised with the majority showing leaky expression. This has been shown to considerably reduce the efficiency of current genetic control strategies, which rely on regulatory elements with more tightly restricted spatial and/or temporal expression. Meiotic silencing of the sex chromosomes limits the flexibility of transgene expression to develop effective sex-linked genetic control strategies. Here, we build on our previous study, dissecting gametogenesis into four distinct cell populations, using single-cell RNA sequencing to define eight distinct cell clusters and associated germline cell–types using available marker genes. We reveal overexpression of X-linked genes in a distinct cluster of pre-meiotic cells and document the onset of meiotic silencing of the X chromosome in a subcluster of cells in the latter stages of spermatogenesis. This study provides a comprehensive dataset, characterising the expression of distinct cell types through spermatogenesis and widening the toolkit for genetic control of malaria mosquitoes.

Background: Artificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. Objective: To assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design, setting, and participants: We retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients

Conclusions: European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.

Patients with diabetic foot ulcers have poor adherence to treatment recommendations. However, the most effective way to support adherence in this population is unknown. This study aimed to assess the preliminary effectiveness of a motivation communication training programme for healthcare professionals working with these patients, using theory and evidence-based strategies.A proof-of-concept study using a non-randomised, controlled before-and-after design. Six podiatrists took part in the motivation communication training programme. Pre-training, observation was undertaken to examine the communication style currently used by podiatrists in routine consultations. Patients' (n = 25) perceptions of podiatrist autonomy support, self-determination for limiting weight-bearing activity and average daily step count were also assessed. Post training, observations and patient measures were repeated with a different group of patients (n = 24). Observations indicated that podiatrists exhibited a more need-supportive communication style (e.g., taking time to understand patients' perspectives) after undergoing the training programme. Patients in the post-training group reported higher levels of autonomy support, while self-determination to limit weight-bearing activity remained unchanged. Although the post-training group had a lower average daily step count, the difference was not statistically significant. This is the first study to investigate implementation of motivation communication strategies in routine consultations with patients with diabetic foot ulcers. Results suggest that training can enhance healthcare professionals' motivation communication skills with potential for addressing adherence issues, however, a larger cluster randomised controlled trial is necessary to confirm this.

Abstract Background Kidney transplantation is the gold-standard treatment for patients with kidney failure. However, one-third of patients awaiting a kidney transplant are highly sensitized to human leukocyte antigens (HLA), resulting in an increased waiting time for a suitable kidney, more acute and chronic rejection, and a shorter graft survival compared to non-highly sensitised patients. Current standard immunosuppression protocols do not adequately suppress memory responses, and so alternative strategies are needed. Autologous polyclonally expanded regulatory T cells (Tregs) have been demonstrated to be safe in transplant settings and could be a potential alternative to modulate memory immune alloresponses. Methods The aim of this trial is to determine whether adoptive transfer of autologous Tregs into HLA sensitised patients can suppress memory T and B cell responses against specific HLA antigens. This is a two-part, multi-centre, prospective clinical trial, comprising an observational phase (Part 1) aiming to identify patients with unregulated cellular memory responses to HLA (Pure HLA Proteins) followed by an interventional phase (Part 2). The first 9 patients identified as being eligible in Part 1 will undergo baseline immune monitoring for 2 months to inform statistical analysis of the primary endpoint. Part 2 is an adaptive, open labelled trial based on Simon’s two-stage design, with 21 patients receiving Good Manufacturing Practice (GMP)-grade polyclonally expanded Tregs to a dose of 5–10 × 106 cells/kg body weight. The primary EP is suppression of in vitro memory responses for 2 months post-infusion. 12 patients will receive treatment in stage 1 of Part 2, and 9 patients will receive treatment in stage 2 of Part 2 if ≥ 50% patients pass the primary EP in stage 1. Discussion This is a prospective study aiming to identify patients with unregulated cellular memory responses to Pure HLA Proteins and determine baseline variation in these patterns of response. Part 2 will be an adaptive phase IIa clinical trial with 21 patients receiving a single infusion of GMP-grade polyclonally expanded Tregs in two stages. It remains to be demonstrated that modulating memory alloresponses clinically using Treg therapy is achievable. Trial registration EudraCT Number: 2021–001,664-23. REC Number: 21/SC/0253. Trial registration number ISRCTN14582152.

Automated and seamless integration of reinforcement is one of the main unresolved challenges in large-scale additive construction. This study leverages a dual-reinforcement solution consisting of high-dosage steel fiber (up to 2.5% by volume) and short vertical reinforcements as a complementary reinforcement technique for 3D-printed elements. The mechanical performance of the printing material was characterized by measuring the compressive, flexural, and uniaxial tensile strengths of mold-cast specimens. Furthermore, the flexural performance of the plain and fiber-reinforced 3D-printed beams was evaluated in the three main loading directions (X, Y, and Z-directions in-plane). In addition, short vertical threaded reinforcements were inserted into the fiber-reinforced 3D-printed beams tested in the Z-direction. The experimental results revealed the superior flexural performance of the fiber-reinforced beams loaded in the longitudinal directions (X and Y). Moreover, the threaded reinforcement significantly increases the flexural strength and ductility of beams loaded along the interface, compared to the control. Overall, the proposed dual-reinforcement approach, which exhibited notably less porosity compared to the mold-cast counterpart, holds great potential as a reinforcement solution for 3D-printed structures without the need for manual operations.

Abstract In the past two decades, drifting fish aggregation devices (FADs) have revolutionized pelagic fisheries, and are now responsible for the majority of tuna purse seine catches. Here, we argue that by taking advantage of the same proven aggregative properties, FADs could be used to enhance the benefits provided by blue water marine protected areas (MPAs). Using models of commercially targeted fish populations, we explore the potential benefits that could be achieved if unfished conservation FADs—designed as self‐powered devices capable of remaining semi‐stationary—were deployed within blue water MPAs. By increasing the residence time of exploited species in MPAs, conservation FADs will reduce average mortality rates. By increasing the local density of exploited species, they may also improve the function of ecosystems in blue water MPAs. Conservation FADs could, therefore, amplify the benefits of blue water MPAs. We find this amplification is largest in those contexts where blue water MPAs have attracted the most criticism—when their area is small compared to both the open ocean and the distribution of fish stocks that move through them.

BackgroundUse of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment.MethodsThe ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232.FindingsThe seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT.InterpretationRegulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression.FundingThe 7th EU Framework Programme.

El presente estudio abarca las metodologías activas que incorporan el uso de las Tic’s para desarrollar habilidades lectoras dando énfasis al WhatsApp como una herramienta de comunicación para el desarrollo de las actividades educativas. Es importante utilizar Whatsapp como metodología activa, ya que hace al estudiante más participativo y comunicativo con su docente. Los sistemas educativos enfrentan una nueva realidad por la crisis sanitaria. Tiene como objetivo detallar los usos que los docentes dan a las herramientas Tic´s cuando aplican las metodologías activas de aprendizaje para desarrollar habilidades lectoras en estudiantes. Se aplicó un diseño metodológico de tipo exploratorio-descriptivo con enfoque mixto; las herramientas empleadas para la recolección de datos fueron la encuesta y la entrevista; obteniendo como resultado que existen diferentes aplicaciones para poder evaluar las habilidades lectoras. Se concluyó que la estrategia metodológica aplicada por los docentes es el aprendizaje basado en proyecto y la herramienta Tic´s más usada es el WhatsApp para difundir videos o para el envío de diferentes recursos Tic´s como los Blogs, Wikis, Podcast, infografías fomentando las habilidades lectoras mediante la reflexión, el análisis y el debate con la participación activa de los estudiantes y la posibilidad de aprender en cualquier momento y lugar.

Abstract Introduction Despite increased focus on development of mental health services worldwide, many adolescents still hesitate to reach out to the services when they need them. This might be linked to the lack of adolescent involvement in the development of services. This study aimed to explore adolescents' perspectives on the ideal healthcare services to meet their mental health needs. Methods A two‐stage qualitative study was carried out to explore the perspectives of adolescents on the healthcare services to support their mental health. In the first stage, data from 295 adolescents attending a mental health seminar were analysed using qualitative content analysis. In the second stage, in‐depth perspectives of 10 adolescent coresearchers were gathered through self‐reflection and group discussions to further explore the categories developed in the first stage. Thematic analysis was used to develop the themes answering the research question. Ten adolescent coresearchers planned the study, collected and analysed data and authored the manuscript, with the support of a senior researcher. Results Five themes describe adolescents' perspectives on the ideal healthcare services to meet their mental health needs: (1) Culturally Sensitive and Responsive; (2) Communication of Information; (3) Easy Access; (4) Variety of Support; and (5) Consistency. Culturally Sensitive and Responsive services influenced all other themes. The themes describe suggestions for mental health service improvement, including how to manage the barriers that adolescents face to receive help from the mental health services. Discussion This study highlights the importance of culturally sensitive and responsive services. It raises the need for an expanded definition of culture going beyond nationality and ethnic background. Adolescents need flexible services that meet their individual mental health needs. This has implications for practitioners, educators, system organizers and researchers, who should also involve adolescents in planning, implementing and assessing the services. There is a need for a self‐learning system to continuously adapt to user feedback. Conclusion This study provides insight into adolescents' perspectives on the ideal mental health services. It offers suggestions for ways to improve services to better meet the individual mental health needs of adolescents. Additional research is needed to further develop and implement service changes, as well as to assess their acceptability, effectiveness, cost‐effectiveness and safety. Patient or Public Contribution This is a study lead by adolescents. Adolescent coresearchers have, with the support of a senior researcher, planned and carried out the study, collected and analysed data and authored the manuscript.

Abstract Myopia is the leading cause of low vision worldwide and can lead to significant pathological complications. Therefore, to improve patient outcomes, the field continues to develop novel interventions for this visual disorder. Accordingly, this first‐in‐human study reports on the safety profile of a novel dopamine‐based ophthalmic treatment for myopia, levodopa/carbidopa eye drops. This phase I, first‐in‐human, monocenter, placebo‐controlled, double‐blind, paired‐eye, multidose, randomized clinical trial was undertaken in healthy adult males aged 18–30 years (mean age 24.9 ± 2.7) at the University of Canberra Eye Clinic, Australia. Participants were randomly assigned to receive either a low (1.4 levodopa:0.34 carbidopa [μmoles/day], n = 14) or standard dose (2.7 levodopa:0.68 carbidopa [μmoles/day], n = 15) of levodopa/carbidopa eye drops in one eye and placebo in the fellow eye once daily for 4 weeks (28 days). Over this 4‐week trial, and after a 4‐month follow‐up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non‐ocular adverse events. These results indicate that topical levodopa/carbidopa is safe and tolerable to the eye, paving the way for future studies on the efficacy of this novel ophthalmic formulation in the treatment of human myopia. The findings of this study have implications not only for the treatment of myopia, but in a number of other visual disorders (i.e., amblyopia, diabetic retinopathy, and age‐related macular degeneration) in which levodopa has been identified as a potential clinical intervention.

The research covers the creative strategies for the development of reading, with the objective of analyzing the didactic strategies used by teachers for the teaching-learning of reading comprehension in the middle basic sublevel of the C03_04 circuit of the Buena Fe Canton. The applied methodology had a qualitative approach of an exploratory type, taking the position of several authors and the opinion of two experts on the subject that allowed affirming the criteria proposed in the investigation. A survey was applied to teachers to identify the teaching strategies they use to develop reading comprehension in students and an interview with experts to determine the characteristics of the creative teaching resources that teachers should use. The results reflect the limited application of creative strategies to encourage reading comprehension in students. It was concluded that the results of the research determine different innovative strategies through ICTs that teachers can use and in turn allow the student to build their own knowledge, considering their particularity or style at the time of learning.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), has re-emerged as one of the major concerns for global wheat production since the evolution of Ug99 and other virulent pathotypes of Pgt from East Africa, Europe, Central Asia, and other regions. Host resistance is the most effective, economic, and eco-friendly approach for managing stem rust. Understanding the virulence nature, genetic diversity, origin, distribution, and evolutionary pattern of Pgt pathotypes over time and space is a prerequisite for effectively managing newly emerging Pgt isolates through host resistance. In the present study, we monitored the occurrence of stem rust of wheat in India and neighboring countries from 2016 to 2022, collected 620 single-pustule isolates of Pgt from six states of India and Nepal, analyzed them on Indian stem rust differentials, and determined their virulence phenotypes and molecular genotypes. The Ug99 type of pathotypes did not occur in India. Pathotypes 11 and 40A were most predominant during these years. Virulence phenotyping of these isolates identified 14 Pgt pathotypes, which were genotyped using 37 Puccinia spp.-specific polymorphic microsatellites, followed by additional phylogenetic analyses using DARwin. These analyses identified three major molecular groups, demonstrating fewer lineages, clonality, and long-distance migration of Pgt isolates in India. Fourteen of the 40 recently released Indian wheat varieties exhibited complete resistance to all 23 Pgt pathotypes at the seedling stage. Twelve Sr genes were postulated in 39 varieties based on their seedling response to Pgt pathotypes. The values of slow rusting parameters i.e. coefficient of infection, area under disease progress curve, and infection rates, assessed at adult plant stage at five geographically different locations during two crop seasons, indicated the slow rusting behavior of several varieties. Six Sr genes (Sr2, Sr57, Sr58, Sr24, Sr31, and Sr38) were identified in 24 wheat varieties using molecular markers closely linked to these genes. These findings will guide future breeding programs toward more effective management of wheat stem rust.

IntroductionWomen are vulnerable during pregnancy as they experience multiple physical and psychological problems which can lead to stress and poor quality of life ultimately affecting the development of the fetus and their health during and after pregnancy. Prior evidence suggests that prenatal yoga can improve maternal health and well-being and can have a beneficial effect on immune system functioning. To date, no study has been conducted in a rural, low-resource setting in India to assess the feasibility, acceptability, and preliminary efficacy of a yoga-based intervention on perceived stress, quality of life, pro-inflammatory biomarkers, and symptoms of upper respiratory tract infections.MethodsTo address this gap and assess whether a yoga-based intervention could improve maternal mental health and immunity during the COVID-19 crisis (Yoga-M2 trial), a single-blind individual randomized parallel group-controlled pilot trial with a 1:1 allocation ratio was implemented. We randomly allocated 51 adult pregnant women, with gestational age between 12-24 weeks in the Yoga-M2 arm (n = 25) or the enhanced usual care arm (EUC) (n = 26). Feasibility and acceptability were assessed using the process data and In-Depth Interviews (IDIs) with the trial participants and yoga instructors. Multiple linear regression was used to compare follow-up scores for quantitative outcomes.ResultsA three-month follow-up assessment was completed for 48 out of 51 participants (94.12%). We did not find any statistically significant difference between both arms in total Perceived Stress Scale scores, quality of life (Eq-5D-5L index), and serum C Reactive Protein levels at the three-month follow-up assessment. The critical barriers to practicing yoga were lack of knowledge about the benefits of yoga, lack of ‘felt need' to practice yoga, lack of time to practice, lack of space, lack of transport, and lack of peer group to practice yoga. Despite this, women who regularly practiced yoga described the benefits and factors which motivated them to practice regularly.DiscussionThe learnings from this trial will help design the explanatory trial in the future and the study findings can also be used by the primary health care system to deliver yoga-based interventions in the newly created health and wellness centers.Trial registrationThis trial was prospectively registered with the Clinical Trials Registry of India on 25 January 2022. https://www.ctri.nic.in/Clinicaltrials/showallp.php?mid1=65173&EncHid=&userName=CTRI/2022/01/039701. Trial registration number: CTRI/2022/01/039701.

Abstract Introduction In spite of adolescents' rights to be involved in decisions that concern their health and life, limited research has been published reporting on their involvement in mental health research. Therefore, we aim to present experiences and reflections based on the involvement of adolescents in mental health research, to describe the collaborative relationship between researchers and coresearchers, including the values that underpin their collaboration. Methods An autoethnographic approach was used, combined with group reflections. The process was jointly developed, carried out and analysed by adolescent coresearchers and the project's lead researcher over a period of 2 years. The article is jointly authored by the researcher and the ten coresearchers. Results Six themes were developed to describe our collaborative relationship, resulting in the involvement of adolescents in decisions about research priorities; in planning and carrying out the research; through to analysis, dissemination and communication of results. The themes include: (1) Commitment motivated by altruism, personal interests and a common purpose; (2) Inclusiveness and support to reduce social uncertainty and strengthen collaboration; (3) Reduced power differentials while ensuring clarity of roles and tasks; (4) Diversity in representation to expand the perspectives of ‘the adolescent voice’; (5) Self‐determination—supporting adolescents' involvement in decision‐making processes; and (6) Flexible and systematic project management. The themes describe the collaboration, the underlying values and motives, the challenges faced and how they were overcome. Conclusion This self‐reflective process describing a 4‐year collaborative research project resulted in the development of recommendations for involving adolescents in mental health research. The recommendations could potentially contribute to a change of ‘research culture’ to expand the currently limited involvement of adolescents in research. Patient or Public Contribution Adolescents have contributed as coresearchers through all phases of the research project and as coauthors of this article, including planning, participation in the self‐ and group‐reflective processes, analysis and authoring the article.

Abstract Aim This study aims to explore the feasibility of using serial MRI without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot, in order to decide whether a large‐scale trial is warranted. Methods A multicentre, randomised, prospective, two arm, open, feasibility study (CADOM) of people with diabetes with a suspected or confirmed diagnosis of Charcot neuroarthropathy. Participants were randomised (1:1) to ‘standard care plus', including repeated foot temperature measurements and X‐rays, or the intervention arm, with additional three‐monthly MRI, until remission of Charcot neuroarthropathy or a maximum 12 months (active phase). Participants were then followed‐up for a further 6 months, post remission to monitor for relapse of the Charcot neuroarthropathy (follow‐up phase). Feasibility outcomes were recruitment, retention, data completeness, adherence to study procedures and safety of the intervention MRI. We also collected clinical efficacy outcomes, this included time in cast/off‐loading device which will be the primary outcome of a future definitive trial. Finally, we collected patient reported outcomes, and data on health and social care usage. Results One‐hundred and five people were assessed for eligibility at five sites. 64/105 potential participants meet the eligibility criteria to participate in the study. Forty‐three participants were randomised: 20 to standard care plus and 23 to MRI intervention. The main reason for ineligibility was a previous episode of Charcot neuroarthropathy. Thirteen participants were withdrawn post‐randomisation due to an alternative diagnosis being made. Of the remaining 30 participants, 19 achieved remission, 6 had not gone into remission at the end of the 12 month active phase so exited the study. Five participants were lost to follow‐up. Of the MRIs that were not disrupted by COVID‐19 pandemic 26/31 (84%) were completed. For the visits that were conducted face‐to‐face, completion rates of patient‐reported outcome measures were between 71 and 100%. There were no safety incidents associated with the intervention MRI. As this was a feasibility study it was not designed to test the effectiveness of serial MRI in diagnosing remission. The time in cast/off‐loading device was 235 (±108.3) days for the standard care plus arm compared to 292 (±177.4) days for the intervention arm. There was no statistical difference in the time in cast/off‐loading device between the two arms of the study: Hazard Ratio (HR) 0.405 (95% CI 0.140–1.172), p = 0.096. Discussion The findings support a definitive randomised controlled trial to evaluate the effectiveness of MRI in diagnosing remission in Charcot neuroarthropathy. The rates of recruitment, retention, data, and MRI completeness show that a definitive study is feasible. Study registration ISRCTN, 74101606. Registered on 6 November 2017.