Plant Cyanogenic-Derived Metabolites and Herbivore Counter-Defences.

The release of cyanide from cyanogenic precursors is the central core of the plant defences based on the cyanogenesis process. Although cyanide is formed as a coproduct of some metabolic routes, its production is mostly due to the degradation of cyanohydrins originating from cyanogenic glycosides in cyanogenic plants and the 4-OH-ICN route in Brassicaceae. Cyanohydrins are then hydrolysed in a reversible reaction generating cyanide, being both, cyanohydrins and cyanide, toxic compounds with potential defensive properties against pests and pathogens. Based on the production of cyanogenic-derived molecules in response to the damage caused by herbivore infestation, in this review, we compile the actual knowledge of plant cyanogenic events in the plant-pest context. Besides the defensive potential, the mode of action, and the targets of the cyanogenic compounds to combat phytophagous insects and acari, special attention has been paid to arthropod responses and the strategies to overcome the impact of cyanogenesis. Physiological and behavioural adaptations, as well as cyanide detoxification by ß-cyanoalanine synthases, rhodaneses, and cyanases are common ways of phytophagous arthropods defences against the cyanide produced by plants. Much experimental work is needed to further understand the complexities and specificities of the defence-counter-defence system to be applied in breeding programs.

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω1< 165º) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω1> 165º), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly. Moreover, the photostability of the particle depends on the secondary structure of the PPA and its screw sense excess. This fact, in combination with the encapsulation ability of these polymer particles, allows the creation of light stimuli-responsive nanocarriers, whose cargo can be delivered by light irradiation.

Cost-effectiveness analysis of the diagnosis of temporal arteritis.

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, doppler ultrasound) and therapeutic strategies (corticosteroid suspension). MATERIAL AND METHOD: Observational, retrospective study has been carried out on patients with AT (2012-2021). Demographic data, comorbidities, signs and symptoms suggestive of AT were collected. AT was diagnosed with a score ≥ 3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. RESULTS: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not. The cost of the AT diagnosis was 414.7 euros/patient. If we use ACR-SCORE ≥ 3-echodoppler it is 167.2 є/patient (savings 59.6%) and ACR-SCORE ≥ 3-biopsy 339.75 є/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 є/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 є/patient (97.4% savings). CONCLUSIONS: Headache, temporary pain and jaw claudication are predictors of AT. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE ≥ 3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.

Epidemiological Overview of Overweight and Obesity Related to Eating Habits, Physical Activity and the Concurrent Presence of Depression and Anxiety in Adolescents from High Schools in Mexico City: A Cross-Sectional Study.

Overweight and obesity in adolescents has become a serious public health problem worldwide and Mexico City is no exception. Therefore, the objective of this study was to investigate the epidemiological panorama of overweight and obesity related to eating habits, physical activity and the concurrent presence of depression and anxiety in adolescents from high schools in Mexico City. Anthropometric measurements were taken from 2710 adolescents from 33 participating high schools. Likewise, a previously validated eating habit and physical activity questionnaire was administered, which consisted of four different sections, where each of the sections focused on key aspects of the participants' lifestyle: (1) eating habits, (2) intake of non-recommended foods, (3) food and company environment, and (4) physical activity. Moreover, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression was applied. In this study, a high prevalence of overweight and obesity (26.5% overweight and 20.0% obese) was found in adolescents from high schools in Mexico City. Only 13.14% of participants had adequate eating habits and 18.19% physical activity habits. An association was found between having inadequate eating habits and obesity in adolescent women (OR = 1.95; CI 1.009-3.76). Additionally, associations were observed between depression symptoms and obesity (OR = 5.68, CI 1.36-32.81; p = 0.01), while anxiety was associated with underweight and obesity adjusted by other dietary habits and psychological factors. Therefore, it is important to identify adolescents with overweight or obesity and establish prevention strategies for weight control in this age group, promoting healthy eating, physical activity and education in mental health.

Physiotherapy Interventions in Lung Cancer Patients: A Systematic Review.

BACKGROUND: Lung cancer is a very common disease and leads to a series of sequelae such as reduced lung capacity or reduced functional capacity in patients, which are associated not only with the disease itself, but also with medical treatment. Thus, physiotherapeutic interventions are needed to improve quality of life and reduce these symptoms. OBJECTIVES: To find out the effects of physiotherapy on functional capacity, lung capacity, dyspnea, pain, and quality of life in lung cancer patients. METHODS: A systematic review was carried out in five databases. Randomized clinical trials published between 2019-2023 were selected, in which the physiotherapeutic treatment was physical exercise and/or respiratory physiotherapy. RESULTS: Nine articles were included, in which the total sample consisted of 635 lung cancer patients. When combined, respiratory physiotherapy and physical exercise improved functional capacity and lung capacity (p < 0.05). Dyspnea also improved, but less significance was shown in the included studies. CONCLUSIONS: Multimodal physiotherapy interventions may offer benefits for some lung cancer patients, but the extent and nature of these benefits may vary depending on the intervention applied. Therefore, it would be of great interest to carry out further scientific research to support this conclusion.

Fully automated contrast selection of joint bright- and black-blood late gadolinium enhancement imaging for robust myocardial scar assessment.

PURPOSE: Joint bright- and black-blood MRI techniques provide improved scar localization and contrast. Black-blood contrast is obtained after the visual selection of an optimal inversion time (TI) which often results in uncertainties, inter- and intra-observer variability and increased workload. In this work, we propose an artificial intelligence-based algorithm to enable fully automated TI selection and simplify myocardial scar imaging. METHODS: The proposed algorithm first localizes the left ventricle using a U-Net architecture. The localized left cavity centroid is extracted and a squared region of interest ("focus box") is created around the resulting pixel. The focus box is then propagated on each image and the sum of the pixel intensity inside is computed. The smallest sum corresponds to the image with the lowest intensity signal within the blood pool and healthy myocardium, which will provide an ideal scar-to-blood contrast. The image's corresponding TI is considered optimal. The U-Net was trained to segment the epicardium in 177 patients with binary cross-entropy loss. The algorithm was validated retrospectively in 152 patients, and the agreement between the algorithm and two magnetic resonance (MR) operators' prediction of TI values was calculated using the Fleiss' kappa coefficient. Thirty focus box sizes, ranging from 2.3mm2 to 20.3cm2, were tested. Processing times were measured. RESULTS: The U-Net's Dice score was 93.0 ± 0.1%. The proposed algorithm extracted TI values in 2.7 ± 0.1 s per patient (vs. 16.0 ± 8.5 s for the operator). An agreement between the algorithm's prediction and the MR operators' prediction was found in 137/152 patients (κ= 0.89), for an optimal focus box of size 2.3cm2. CONCLUSION: The proposed fully-automated algorithm has potential of reducing uncertainties, variability, and workload inherent to manual approaches with promise for future clinical implementation for joint bright- and black-blood MRI.

The RIN4-like/NOI proteins NOI10 and NOI11 modulate the response to biotic stresses mediated by RIN4 in Arabidopsis.

KEY MESSAGE: NOI10 and NOI11 are two RIN4-like/NOI proteins that participate in the immune response of the Arabidopsis plant and affect the RIN4-regulated mechanisms involving the R-proteins RPM1 and RPS2. The immune response in plants depends on the regulation of signaling pathways triggered by pathogens and herbivores. RIN4, a protein of the RIN4-like/NOI family, is considered to be a central immune signal in the interactions of plants and pathogens. In Arabidopsis thaliana, four of the 15 members of the RIN4-like/NOI family (NOI3, NOI5, NOI10, and NOI11) were induced in response to the plant herbivore Tetranychus urticae. While overexpressing NOI10 and NOI11 plants did not affect mite performance, opposite callose accumulation patterns were observed when compared to RIN4 overexpressing plants. In vitro and in vivo analyses demonstrated the interaction of NOI10 and NOI11 with the RIN4 interactors RPM1, RPS2, and RIPK, suggesting a role in the context of the RIN4-regulated immune response. Transient expression experiments in Nicotiana benthamiana evidenced that NOI10 and NOI11 differed from RIN4 in their functionality. Furthermore, overexpressing NOI10 and NOI11 plants had significant differences in susceptibility with WT and overexpressing RIN4 plants when challenged with Pseudomonas syringae bacteria expressing the AvrRpt2 or the AvrRpm1 effectors. These results demonstrate the participation of NOI10 and NOI11 in the RIN4-mediated pathway. Whereas RIN4 is considered a guardee protein, NOI10 and NOI11 could act as decoys to modulate the concerted activity of effectors and R-proteins.

How to remove a well-fixed metaphyseal sleeve in revision knee arthroplasty: A step-by-step surgical procedure.

BACKGROUND: The rising incidence and complexity of revision knee arthroplasty has led to an increase in the use of metaphyseal reconstruction systems. One of the most widely used systems are metaphyseal sleeves as they have demonstrated excellent long-term survival. However, there is concern about the possible difficulty of extracting a sleeve if it were necessary, as no known procedures have yet been validated. METHODS: We examined the outcomes of removing 23 well-integrated metaphyseal sleeves using the same systematized technique. RESULTS: All sleeves were extracted without any intraoperative complications. Four subjects required an osteotomy to complete the extraction, while 62% of the sample were found to have an AORI IIB defect. All cases were successfully reconstructed with a new metaphyseal fixation, implanting a new sleeve in 38% of subjects compared with cones in the remaining 62%. CONCLUSIONS: The technique described here produced successful, reproducible outcomes for the removal of integrated metaphyseal sleeves with minimal bone loss and no intraoperative complications.

Prehospital Lessons From the War in Ukraine: Damage Control Resuscitation and Surgery Experiences From Point of Injury to Role 2.

The ongoing war in Ukraine presents unique challenges to prehospital medical care for wounded combatants and civilians. The purpose of this article is to identify, describe, and address gaps in prehospital care, casualty evacuation, and medical evacuation throughout Ukraine to share lessons for other providers. Observations and experiences of medical personnel were collected and analyzed, focusing on pain management, antibiotic use, patient assessment, mass casualty triage, blood loss, hypothermia, transport immobilization, and clinical governance. Gaps identified include limited access to pain management, lack of antibiotic guidance, inadequate patient assessment and triage, access to damage control resuscitation and blood, challenged transport immobilization practices, and challenges with clinical governance for both local and foreign providers. Improved prehospital care and casualty and medical evacuation in Ukraine are required, through increased use of empiric pain management, focused antibiotic guidance, enhanced patient assessment and triage in the form of training, access to prehospital blood, and better transport immobilization practices. A robust and active lessons learned program, trauma data capture, and quality improvement process is needed to reduce preventable morbidity and mortality in the war zone. The recommendations presented in this article serve as a starting point for improvements in prehospital care in Ukraine with potential to change prehospital training for the NATO alliance and other organizations operating in similar areas of conflict. Graphical Abstract.

Tailored electrocardiographic-based criteria for different pacing locations within the left bundle branch.

BACKGROUND: Electrocardiographic (ECG)-based criteria are used to confirm left bundle branch (LBB) pacing (LBBP), but current cutoff values have never been validated for different pacing locations. OBJECTIVE: The purpose of this study was to describe diagnostic performance of V6-R wave peak time (RWPT), V6-V1 interpeak interval, and aVL-RWPT for different pacing sites within the LBB and to determine 100% specific values for each criterion at each pacing location. METHODS: Consecutive patients with confirmed LBBP were selected. Population was divided into subgroups based on the site of pacing: left bundle trunk pacing (LBTP), left septal fascicular pacing (LSFP), left posterior fascicular pacing (LPFP), and left anterior fascicular pacing (LAFP). RESULTS: A total of 147 patients with unequivocal LBB capture were analyzed. Left fascicular pacing was more frequently achieved (82.8%) than LBTP (17.2%). Diagnostic performance of V6-RWPT, V6-V1 interpeak interval, and aVL-RWPT for discrimination of LBBP was good in all subgroups. V6-RWPT cutoff values with 100% specificity (SP) for LBBP discrimination were 75 ms in LBTP, 68 ms in LPFP, 81 ms in LAFP, and 79.5 ms in LSFP. V6-V1 interpeak interval cutoff values with 100% SP for LBBP discrimination were 35.5 ms in LBTP, 53.5 ms in LPFP, 41 ms in LAFP, and 46 ms in LSFP. In LAFP, aVL-RWPT cutoff value with 100% SP for LBBP discrimination was 68 ms, but was 74 ms in LBTP, 74.5 ms in LSFP, and 73.5 ms in LPFP. CONCLUSIONS: Tailored ECG-based criteria might be useful to confirm LBBP at different pacing locations within the LBB.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Ensembl 2024.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.

Dark-field and directional dark-field on low-coherence x ray sources with random mask modulations: validation with SAXS anisotropy measurements.

Phase-contrast imaging, dark-field, and directional dark-field imaging are recent x ray imaging modalities that have been demonstrated to reveal different information and contrast from those provided by conventional x ray imaging. Access to these new types of images is currently limited because the acquisitions require coherent sources such as synchrotron radiation or complicated optical setups. This Letter demonstrates the possibility of efficiently performing phase-contrast, dark-field, and directional dark-field imaging on a low-coherence laboratory system equipped with a conventional x ray tube, using a simple, fast, and robust single-mask technique.

Core outcomes and factors influencing the experience of care for children with severe acute exacerbations of asthma: a qualitative study.

OBJECTIVE: To identify the outcomes considered important, and factors influencing the patient experience, for parents and caregivers of children presenting to hospital with a severe acute exacerbation of asthma. This work contributes to the outcome-identification process in developing a core outcome set (COS) for future clinical trials in children with severe acute asthma. DESIGN: A qualitative study involving semistructured interviews with parents and caregivers of children who presented to hospital with a severe acute exacerbation of asthma. SETTING: Hospitals in 12 countries associated with the global Pediatric Emergency Research Networks, including high-income and middle-income countries. Interviews were conducted face-to-face, by teleconference/video-call, or by phone. FINDINGS: Overall, there were 54 interviews with parents and caregivers; 2 interviews also involved the child. Hospital length of stay, intensive care unit or high-dependency unit (HDU) admission, and treatment costs were highlighted as important outcomes influencing the patient and family experience. Other potential clinical trial outcomes included work of breathing, speed of recovery and side effects. In addition, the patient and family experience was impacted by decision-making leading up to seeking hospital care, transit to hospital, waiting times and the use of intravenous treatment. Satisfaction of care was related to communication with clinicians and frequent reassessment. CONCLUSIONS: This study provides insight into the outcomes that parents and caregivers believe to be the most important to be considered in the process of developing a COS for the treatment of acute severe exacerbations of asthma.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study.

PURPOSE/BACKGROUND: Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. METHODS: A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. RESULTS: Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a significant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+68.9 m vs. -27.2 m, p = 0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. -0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). CONCLUSION: Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specific and expensive tests are not available. TRIAL REGISTRATION: Registered in ClinicalTrials.gov in August 2018 with registration number https://clinicaltrials.gov/study/NCT03618329?cond=Prehabilitation%20cancer&term=arroyo&distance=50&rank=1  (NCT03618329). Initial results published in Supportive Care in Cancer: Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. DOI: https://doi.org/10.1007/s00520-021-06343-1 .

Pork organs as a potential source of flavour-related substances.

The increase in world population has generated a higher demand for quality proteins, increasing the production in meat industry but also the generation of thousands of tons of by-products, with a negative economic and environmental impact. The valorisation of slaughterhouse by-products by giving by-products a new use as food ingredient is one of the best strategies to add value while reducing environmental damage. Flavour is one of the most influential parameters in the purchasing decision of consumers, and in meat products it is mostly influenced by the content in free amino acids and nucleotides. In this study, the potential of 4 pork organs (liver, kidney, lung, and brain) as a source of flavour-related substances was investigated. Liver proved to be the organ showing the highest content of free and total amino acids related to taste, while kidney was the organ with the highest content of umami nucleotides. The results of the Taste Activity Value indicated that umami, sweet, and bittersweet amino acids are main responsible for the taste of the organs. On the other hand, the synergy between amino acids and nucleotides in relation with umami taste was determined, showing liver and kidney the best values in Equivalent Umami Content. In addition, the antioxidant activity of the organs was determined, and liver and kidney showed the highest antioxidant activity in all assays (p < 0.05). In conclusion, pork organs, especially liver and kidney, may be good candidates to be used as raw materials to produce functional flavouring ingredients.