Search

Gisèle Pickering,1 Sylvia Engelen,2 Maria Stupar,2 Hervé Ganry,3 Mariëlle Eerdekens2 1Faculty of Medicine Inserm 1107, Clinical Pharmacology Centre, CPC/CIC Inserm 1405 University Hospital, Clermont-Ferrand, France; 2Grünenthal GmbH, Aachen, Germany; 3Hergan Consulting 4U, Amiens, 80000, FranceCorrespondence: Mariëlle Eerdekens, Grünenthal GmbH, Zieglerstrasse 6, Aachen, 52078, Germany, Tel +492415 691090, Email Marielle.Eerdekens@grunenthal.comIntroduction: Capsaicin 179 mg (8% weight per weight) cutaneous patch (“capsaicin patch”) is a recommended topical treatment for peripheral neuropathic pain (PNP). In older patients, topical treatments may be preferred over systemic treatments, but data specific to the older population are scarce.Methods: We conducted pooled analyses of multiple clinical trials to evaluate efficacy and safety of capsaicin patch in older patients. The analysis of efficacy included four randomized, double-blind, 12-week studies with similar trial design comparing a single treatment of capsaicin 179 mg cutaneous patch vs low-dose control patch in post-herpetic neuralgia. For the safety evaluation, data were pooled from 18 interventional studies in which capsaicin patch was used in PNP with varying etiologies.Results: Capsaicin patch had similar analgesic efficacy in elderly (n=582) and non-elderly patients (n=545) in terms of change from baseline to 2– 12 weeks in the 11-point numeric pain rating scale (NPRS) score for average pain over the previous 24 hours. In both age groups, decrease in NPRS score was significantly greater with capsaicin patch vs control. Older patients treated with capsaicin patch were significantly more likely than those in the control group to achieve responder status (ie mean decrease in NPRS score from baseline to week 2– 12 of at least 30% or ≥ 2 points): 36.1% vs 27.1% (odds ratio [OR] [95% CI] 1.52 [1.06, 2.18]; P=0.0231) and 33.1% vs 20.9% (OR [95% CI] 1.90 [1.30, 2.78]; P=0.0009) for active treatment vs control group, respectively. Similar proportions of non-elderly patients (n=2,311) and elderly patients (n=537) treated with capsaicin patch experienced treatment-emergent adverse events (TEAEs) (81.6% and 78.1%, respectively) and serious TEAEs (8.2% and 7.2%), with application-site reactions the most common TEAEs in both groups.Conclusion: The capsaicin patch was equally efficacious and well tolerated in older patients as in younger patients.Plain language summary: Peripheral neuropathic pain is a common challenge among the elderly, yet effective treatments for this age group remain underexplored. This research focuses on the use of a high-concentration capsaicin patch, a specialized treatment for this type of pain. The patch, which is applied directly to the affected skin area, has been shown to reduce pain significantly for up to 12 weeks. This analysis of multiple clinical trials showed that the high-concentration capsaicin patch significantly reduced pain intensity and was well tolerated in older patients with peripheral neuropathic pain.Keywords: capsaicin patch, elderly, peripheral neuropathic pain, pooled analysis, topical treatment

Abstract Background In soybeans, faster canopy coverage (CC) is a highly desirable trait but a fully covered canopy is unfavorable to light interception at lower levels in the canopy with most of the incident radiation intercepted at the top of the canopy. Shoot architecture that influences CC is well studied in crops such as maize and wheat, and altering architectural traits has resulted in enhanced yield. However, in soybeans the study of shoot architecture has not been as extensive. Results This study revealed significant differences in CC among the selected soybean accessions. The rate of CC was found to decrease at the beginning of the reproductive stage (R1) followed by an increase during the R2-R3 stages. Most of the accessions in the study achieved maximum rate of CC between R2-R3 stages. We measured Light interception (LI), defined here as the ratio of Photosynthetically Active Radiation (PAR) transmitted through the canopy to the incoming PAR or the radiation above the canopy. LI was found to be significantly correlated with CC parameters, highlighting the relationship between canopy structure and light interception. The study also explored the impact of plant shape on LI and CO2 assimilation. Plant shape was characterized into distinct quantifiable parameters and by modeling the impact of plant shape on LI and CO2 assimilation, we found that plants with broad and flat shapes at the top maybe more photosynthetically efficient at low light levels, while conical shapes were likely more advantageous when light was abundant. Shoot architecture of plants in this study was described in terms of whole plant, branching and leaf-related traits. There was significant variation for the shoot architecture traits between different accessions, displaying high reliability. We found that that several shoot architecture traits such as plant height, and leaf and internode-related traits strongly influenced CC and LI. Conclusion In conclusion, this study provides insight into the relationship between soybean shoot architecture, canopy coverage, and light interception. It demonstrates that novel shoot architecture traits we have defined here are genetically variable, impact CC and LI and contribute to our understanding of soybean morphology. Correlations between different architecture traits, CC and LI suggest that it is possible to optimize soybean growth without compromising on light transmission within the soybean canopy. In addition, the study underscores the utility of integrating low-cost 2D phenotyping as a practical and cost-effective alternative to more time-intensive 3D or high-tech low-throughput methods. This approach offers a feasible means of studying basic shoot architecture traits at the field level, facilitating a broader and efficient assessment of plant morphology.

In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and-wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures. This study aimed to investigate responsiveness to visual and somatosensory stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established rat model for absence epilepsy. Animals were imaged under non-curarized awake state using a quiet, zero echo time, functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole-brain hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to explain the changes of neural responsiveness to visual stimulation between states. During a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In the cortex, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The mean-field simulation revealed restricted propagation of activity due to stimulation and agreed well with fMRI findings. Results suggest that sensory processing is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.

The research focused on optimizing the accelerated solvent extraction (ASE) of carotenoids and polyphenols from pumpkin powder. The study optimized accelerated solvent extraction (ASE) of carotenoids and polyphenols from pumpkin powder. Using a mix of standard score (SS) and artificial neural network (ANN) methods, the extraction process was fine-tuned. The ANN model assessed extraction parameters' significance, achieving high predictability for total carotenoid content (TCC), total phenolic content (TPC), and free radical scavenging capacity (DPPH and ABTS methods). The analysis highlighted the most effective extraction at 50 % concentration, 120 °C temperature, 5 min duration, and 2 cycles, yielding high carotenoid and phenolic content (TCC 571.49 µg/g, TPC 7.85 mg GAE/g). HPLC-DAD profiles of the optimized ASE extract confirmed major carotenoids and phenolic compounds. Strong correlations were found between bioactive compounds and antioxidant activity, emphasizing potential health benefits.

Abstract The ability of Mycobacterium tuberculosis (Mtb) to persist in the host complicates and prolongs tuberculosis (TB) patient chemotherapy. Here we demonstrate that a neglected two-component system (TCS) of Mtb, TcrXY, is an autoregulated acid-sensing TCS that controls a functionally diverse 70-gene regulon required for bacterial persistence. Characterisation of two representatives of this regulon, Rv3706c and Rv3705A, implicate these genes as key determinants for the survival of Mtb in vivo by serving as important effectors to mitigate redox stress at acidic pH. We show that genetic silencing of the response regulator tcrX using CRISPR interference attenuates the persistence of Mtb during chronic mouse infection and improves treatment with the two front-line anti-TB drugs, rifampicin and isoniazid. We propose that targeting TcrXY signal transduction blocks the ability of Mtb to sense and respond to acid stress, resulting in a disordered program of persistence to render the organism vulnerable to existing TB chemotherapy.

Confession and repentance, being the sacrament of the Church, constitute a place of meeting between God’s grace and human freedom, which is thus transformed into the true freedom of God’s sons and daughters. A man who loves the beauty and purity of graceful, sacramental, and virtuous life cannot live without confession. Just like any Christian who does not participate in the communion of Christ, in the liturgical gifts of Christ’s Body and Blood, cannot call himself by this holy name, the neglect of the grace by which those who confess educate themselves represents spiritual death. The correct and salvific life in freedom, as given in the Church, cannot actualize if one neglects repentance and confession. Modern man, sick from the consequences of sin, cannot get better without the salvific confession. Many psychological and somatic disorders stem from reducing the confession to mere “custom” and obligation. Rediscovering the pure spring of the graceful life in Christ and renovating graceful freedom through the tears of repentance and honest confession represent a way threaded by the Church’s Fathers. If we want to show the graceful perspective of freedom and God’s love to modern humanity, we are obliged to personally and communally approach Christ through confession and repentance, so we might be transformed into gods by grace. A cleansed and Christ-bearing man is truly free and capable of living as God has intended – in eternal joy and grace of God’s Kingdom. This cleansing and transfiguration begin in time and continue in eternity. The education for eternal life is based on confession and our decision to follow Christ and fulfill his commandments. We rise if we fall and stumble, all thanks to Christ, who brings us into eternal life.

Patients with Kennedy Class I are usually treated with clasp-retained removable partial dentures (RPDs) as the prosthetic gold standard. For additional stabilization of the RPD, clinicians are often confronted with the question of secondary implant placement, which requires the fabrication of new prostheses. This case report is part of an ongoing multi-center randomized controlled study (RCT) investigating conventional RPDs without and with supplementary implants. A design of the RPD framework, including matrix housings, is crucial to enable subsequent implant retention or support. Ultra-short implants (Straumann TL 4.1 × 4 mm) offer the opportunity for additional support and retention in the edentulous posterior region, where bone availability is often reduced. This future-oriented and minimally invasive approach with virtual treatment planning and guided implant surgery offers the possibility of simplified functional and cost-effective aftercare.

This study aimed to determine the influence of body composition on the muscle fitness of selected judokas. This study was conducted on a sample of 23 judokas (cadets n = 12, juniors n = 11), members of the male national team of Serbia. The assessment of body composition was performed using the InBody 720 (Biospace Co., Ltd., Seoul, Republic of Korea) and calipers. Muscle fitness was assessed using “Optojump” (Microgate, Bolzano, Italy), Fitrodine Premium (Fitronic, Bratislava, Slovakia), and a digital force instrument IMADA Z2H-1100 (Imada Inc., Northbrook, IL, USA). Regression analysis revealed a notable association between muscle mass and measures of explosive strength (countermovement jump (CMJ) p = 0.023; drop jump (DJ) p = 0.026). Moreover, this study’s results showed that back extension (p = 0.006; R2 = 0.61) and hand grip (p = 0.009; R2 = 0.52) provide a strong positive association with muscle mass. The findings suggest that tailored training and nutritional strategies that improve muscle mass might significantly enhance muscle fitness in young judokas, optimizing their performance.

Since the dawn of agriculture, crops have been genetically altered for desirable characteristics. This has included the selection of natural and induced mutants. Increasing the production of plant oils such as soybean (Glycine max) oil as a renewable resource for food and fuel is valuable. Successful breeding for higher oil levels in soybeans, however, usually results in reduced seed protein. A soybean fast neutron population was screened for oil content, and three high oil mutants with minimal reductions in protein levels were found. Three backcross F2 populations derived from these mutants exhibited segregation for seed oil content. DNA was pooled from the high-oil and normal-oil plants within each population and assessed by comparative genomic hybridization. A deletion encompassing 20 gene models on chromosome 14 was found to co-segregate with the high-oil trait in two of the three populations. Eighteen genes in the deleted region have known functions that appear unrelated to oil biosynthesis and accumulation pathways, while one of the unknown genes (Glyma.14G101900) may contribute to the regulation of lipid droplet formation. This high-oil trait can facilitate the breeding of high-oil soybeans without protein reduction, resulting in higher meal protein levels.

In the present study, the nutritional and sensory properties of spelt cookies without wild garlic, cookies with fresh wild garlic, cookies with osmodehydrated wild garlic in sugar beet molasses, and cookies with osmodehydrated wild garlic in an aqueous solution of sucrose and salt were evaluated and compared. The tested cookie samples were characterized in terms of total antioxidative activity, the total content of phenols, flavonoids, and thiosulfates, the presence of dominant phenols, the content of betaine and dietary fiber, antioxidant activity after in vitro digestion, and sensory attributes for appearance, taste, smell, and texture. The results proved that the addition of wild garlic leaves osmodehydrated in molasses provided the cookies with the best nutritional and bioactive properties: 1.75 times higher total phenols content, 2.4 times higher total flavonoids content, 1.52 times higher total thiosulfates content, and 1.56 times higher betaine content, and a total quality increase of 54% compared to the control cookies. The cookies enriched with osmodehydrated wild garlic in molasses were rated as pleasant and acceptable, but also more complex compared to other cookies. The production of this nutritionally and sensory-improved cookie would contribute to expanding the assortment of flour confectionery products, especially for consumers who care about health and nutrition.

The objective of this research was to optimize the natural deep eutectic solvent (NADES) extraction process from sour cherry kernels (Prunus cerasus L.). For polyphenol isolation, conventional solid–liquid extraction was employed using different concentrations of ethanol (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 96%), as well as the innovative NADES extraction technique. In the initial phase of the research, a screening of 10 different NADESs was conducted, while extraction was carried out under constant parameters (50 °C, 1:20 w/w, 60 min). NADES 4, composed of lactic acid and glucose in a molar ratio of 5:1, exhibited the highest efficiency in the polyphenol isolation. In the subsequent phase of the research, response surface methodology (RSM) was utilized to optimize the extraction process. Three independent variables, namely temperature, extraction time, and solid–liquid (S/L) ratio, were examined at three different levels. The extracted samples were analyzed for total phenol (TP) and antioxidant activity using the DPPH, ABTS, and FRAP assays. ANOVA and descriptive statistics (R2 and CV) were performed to fit the applied model. According to RSM, the optimal extraction conditions were determined as follows: temperature of 70 °C, extraction time of 161 min, and S/L ratio of 1:25 w/w.

For agricultural production is used almost 40% of the global land from where it dominates conventional agriculture which uses large amounts of inputs in the form of fertilizers and pesticides leading to the contamination of soil, water resources, air pollution and land erosion, affects biodiversity and extinction of many plants and animals. On the other hand, the world's population is constantly growing and currently numbers more than 8 billion people and it is estimated that food production will have to double by 2050. In order to meet the future needs of the population for food raw materials, food production must significantly increase, and at the same time, the impact of agriculture on the environment and natural resources must be drastically reduced. Sustainable agriculture is emerging as one of the solutions. This way of agricultural practice refers to the management and preservation of natural resources through organizational and technological changes in modern agricultural production in order to satisfy human needs and preserve the environment. One of the most important natural resources on which the entire agricultural production relies is land. In intensively cultivated lands, there is a noticeable trend of intense degradation, which represents a major problem facing humanity. The paper reviews the decrease in soil fertility based on the samples collected during the five-year monitoring, as well as a proposal for measures to increase fertility and future preservation of this environmental resource.

Abstract Objective Few clinical prediction models are available to clinicians to predict the recovery of patients with post-collision neck pain and associated disorders. We aimed to develop evidence-based clinical prediction models to predict (1) self-reported recovery and (2) insurance claim closure from neck pain and associated disorders (NAD) caused or aggravated by a traffic collision. Methods The selection of potential predictors was informed by a systematic review of the literature. We used Cox regression to build models in an incident cohort of Saskatchewan adults (n = 4923). The models were internally validated using bootstrapping and replicated in participants from a randomized controlled trial conducted in Ontario (n = 340). We used C-statistics to describe predictive ability. Results Participants from both cohorts (Saskatchewan and Ontario) were similar at baseline. Our prediction model for self-reported recovery included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity and headache intensity (C = 0.643; 95% CI 0.634–0.653). The prediction model for claim closure included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity, headache intensity and depressive symptoms (C = 0.637; 95% CI 0.629–0.648). Conclusions We developed prediction models for the recovery and claim closure of NAD caused or aggravated by a traffic collision. Future research needs to focus on improving the predictive ability of the models.

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included in animal feed mixtures due to the presence of Kunitz (KTi) and Bowman–Birk protease inhibitors (BBis), which reduces animal productivity. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBis), but such treatment is energy-intensive, adds expense, and negatively impacts the quality of seed proteins. As an alternative approach, we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild-type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays, and qRT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss-of-function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed-specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

Medicinal and aromatic plants, such as wild garlic (Allium ursinum), are valuable sources of bioactive compounds in traditional and modern medicine. However, the challenges in cultivating wild garlic and its seasonality limit its availability primarily to early spring. To maintain the quality of wild garlic, effective postharvest practices are essential, considering the delicate nature of its leaves and their susceptibility to rapid decay. This study focuses on implementing eco-friendly postharvest practices to address the seasonality and perishability of wild garlic. Optimizing storage conditions and drying processes is essential for extending its shelf life and preserving bioactive components. Two postharvest approaches were evaluated, with vacuum packaging at 4 °C demonstrating the most effective preservation of sensory attributes and bioactive composition over a 9-day period. Additionally, different drying methods, including convective and vacuum drying at various temperatures, were investigated. When the best drying temperature was selected, the results revealed that convective drying is more efficient at preserving phenolic compounds in wild garlic leaves at 60 °C. Conversely, vacuum drying shows superior preservation of alliinase activity and total thiosulfinate content at 70 °C. Furthermore, this study explores the utilization of unused wild garlic, which is typically discarded as waste during storage. By employing suitable drying methods, this material can be preserved and provide a valuable source of phenolic compounds (7.17–10.12 g GAE/100 g) and thiosulfinate (9.35–12.72 mg AC/110 g) compounds for various extraction processes. Accordingly, this research presents significant implications for the integration of wild garlic into diverse industries, particularly in the fields of food and pharmaceutical sectors. The findings offer opportunities for sustainable utilization, economic benefits, and a more environmentally friendly and economically viable approach to wild garlic production and processing.

β-cyclodextrin (β-CD) is a good host for the encapsulation of fennel and basil essential oils (FEO and BEO, respectively) and the formation of inclusion complexes (ICs) using the co-precipitation method. According to the results of the GC/MS analysis conducted in this study, monoterpenes and monoterpenoids were the dominant chemical groups in total FEO, while in BEO, these two groups occurred along with sesquiterpenes and sesquiterpenoids. The presence of dominant compounds from both EOs was validated using the FT-IR spectra of ICs, which indicated successful complexation. Analyses conducted using SPME/GC-MS showed the continuous emission of volatiles over 24 h from both ICs. Under SEM, particles of both ICs appeared to have a rectangular or rhomboid morphology and few aggregates. The insecticidal properties of EOs and ICs with β-CD were tested on the Colorado potato beetle (CPB) as a model pest. The inclusion complex of β-CD with FEO altered the developmental dynamic and body mass of the CPB. The initial increase in the proteolytic activity of CPB larvae fed with potato plants sprayed with ICs was not maintained for long, and the proteolytic efficacy of treated larvae remained in line with that of the control larvae. Future investigations will focus on manipulating the volume of EOs used and the treatment duration for optimal efficacy and potential application.

Utilizing natural plant extracts as food additives represents a promising strategy for enhancing the quality, nutritional value, and safety of food products, benefiting both consumers and the environment. Therefore, the primary objective of this study was to develop an environmentally sustainable process for the production of solid powder derived from Allium ursinum liquid extract, with the intent of utilizing it as a natural food additive. To address the challenge of instability and enhance the solubility of bioactive compounds in A. ursinum extracts obtained through subcritical water extraction, this study employed the spray drying process. Notably, the results demonstrated the remarkable efficiency of the spray drying process, with maltodextrin as a carrier, yielding uniformly encapsulated particles with an average size of approximately 4 µm, spherical shape with smooth, intact surfaces. The most optimal conditions for achieving the highest content of total phenolics (23.10 mg GAE/g) and total flavonoids (4.92 mg CE/g) in the A. ursinum extract were identified, involving an inlet temperature of 120 °C and an 80% maltodextrin concentration. The encapsulated powders showed excellent stability, with minimal loss of total phenolics (12.64%) and total flavonoids (10.52%) after three months of storage. Physicochemical analysis confirmed the successful preservation of bioactive compounds through microencapsulation using maltodextrin, suggesting its potential for application in innovative food or pharmaceutical products.