Search Results (4,215)

Stroke is one of the leading causes of disability worldwide. Its sequelae require early, intensive, and repetitive rehabilitation, but is often ineffective due to a lack of patient motivation. Gamification has been incorporated in recent years as a response to this issue. The aim of incorporating games is to motivate patients to perform therapeutic exercises. This study presents PACTUS, a new version of a gamified device for stroke neurorehabilitation. Using a series of colored cards, a touchscreen station, and a sensorized handle with an RGB sensor, patients can interact with three games specifically programmed to work on different areas of neurorehabilitation. In addition to presenting the technical design (including energy consumption and sensor signal processing), the results of an observational study conducted with neurological patients, healthy older adults, and caregivers (who also completed the System Usability Scale) are also presented. This usability, safety, and satisfaction study provided an assessment of the device for future iterations. The inclusion of the experiences of the three groups (patients, caregivers, and older adults) provided a more comprehensive and integrated view of the device, enriching our understanding of its strengths and limitations. Although the results were preliminarily positive, areas for improvement were identified. Full article

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions. Full article

Background: Instrument separation is a frequent issue in root canals, often complicated by intriguing anatomical variations that make treatment more challenging. These variations in canal structure can lead to various iatrogenic complications, such as missed canals, instrument separation, gouging, perforation, and overextension of obturation materials. One such complication is instrument breakage, which can disrupt the cleaning and shaping processes and potentially cause pain or discomfort. Materials and Methods: The present systematic review was conducted following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The present systematic review aimed to identify all clinical trials focused on the removal of separated instruments from endodontic canals using an endodontic surgical approach. Results: A total of 21 studies were included, reporting 22 cases involving surgical approaches for separated instrument removal. Conclusions: The analysis of available evidence, although prim Information added.arily based on clinical cases and case series, emphasizes that surgical approaches for removing separated endodontic instruments are a viable therapeutic option when non-surgical treatments are ineffective or not feasible. Techniques such as apicoectomy, intentional replantation, surgical removal, and the technique provide innovative, customized solutions for addressing complications related to separated instruments, showing favorable clinical and radiographic success rates in follow-up assessments. Full article

The growing ineffectiveness of common antibiotics against multidrug-resistant pathogens has made antimicrobial resistance (AMR) a serious global health concern. This review emphasizes that natural antibiotics from animals, bacteria, fungi, and plants are worthy alternatives for combating this crisis. Evolutionary pressure has shaped these molecules, leading to antibiotic-resistant bacteria that can withstand single-target synthetic drugs but are vulnerable to multiple attack pathways (e.g., cell wall disruption, protein synthesis inhibition, biofilm interference) from natural compounds. Natural antibiotics are frequently incorporated into treatment strategies or drug-delivery systems for minimizing side effects, reducing doses, and improving their effectiveness. The review discusses recent progress in this field, describing the mechanisms of action of natural antibiotics, their incorporation into several drug-delivery systems, and their ‘omics’-driven discovery to improve production, while expressing the challenges that remain. Extracellular application of these compounds, however, is compromised by their low stability in the extracellular environment; furthermore, formulation advancements, such as nanoparticle encapsulation, have been shown to enhance the bioavailability and activity of these substances. Combining indigenous knowledge and modern scientific advances, natural antibiotics may be developed to fight AMR both as monotherapy and adjuvants in a sustainable way. Leveraging these synergies, alongside the latest advances in research, is key to bridging the antibiotic discovery–resistance gap and may provide a route to clinical translation and global AMR control. The promise of natural antibiotics is clear, but their path to mainstream medicine is fraught with obstacles like reproducibility, standardization, and scalability. It is more realistic to see these substances as powerful complements to existing therapies, not outright replacements. Their true strength is in their ability to interfere with resistance mechanisms and create new possibilities for drug development, positioning them as a vital, though complicated, part of the global effort to combat AMR. Full article

Rhizobia have been used for decades as biopreparations, successfully replacing synthetic nitrogen fertilizers in legume cultivation. They have a beneficial effect on the growth and yield of these plants when cultivated in soils that are deficient in both nitrogen and indigenous rhizobia. However, such preparations, containing strains that are characterized by high effectiveness in reducing atmospheric dinitrogen, are not universal. Their use is ineffective when plants are grown in soils that are already rich in strains with low effectiveness, because such inoculant strains are unable to effectively compete with native soil populations. This review discusses issues related to the rhizobia–legume symbiosis, with particular emphasis on inter-strain competition occurring in the soil and in the colonized plant tissues. The importance of Nod factors (NFs) in symbiosis and their broad impact on plant physiological and developmental processes are also discussed. Research results on the effects of NF-containing biopreparations on legume growth and yield are summarized. Moreover, this review explains how such preparations can support the growth and yield of legumes growing in soils containing numerous populations of low-effectiveness rhizobia. Finally, the potential for the application of this technology to non-legume plants is presented. Full article

Grasslands cover more than 25% of the Earth’s surface and play essential ecological roles, such as forage production, supporting pollinators, and carbon sequestration. This study aimed to evaluate the recovery of a degraded pasture of Urochloa decumbens cv. Basilisk through aerial dry mass production, plant height, and foliar macronutrients concentration and uptake after fertilization with polyhalite. The experiment was carried out at the Teaching, Research, and Extension Farm of the School of Agrarian and Technological Sciences, UNESP—Dracena Campus, in a dystrophic red–yellow latosol soil. A randomized block design with four replications was used. The treatments included the following: (T1) control, (T2) N + P + liming, (T3) T2 + 30 kg ha⁻¹ K₂O (polyhalite), (T4) T2 + 60 kg ha⁻¹ K₂O (polyhalite), (T5) T2 + 60 (30 + 30) kg ha⁻¹ K₂O (polyhalite), and (T6) 60 kg ha⁻¹ K₂O (polyhalite). The treatment with N + P + liming + 60 kg ha⁻¹ K₂O (polyhalite) resulted in 93% more dry mass production when compared with the control treatment. This treatment was most effective for grassland recovery, whereas polyhalite alone was ineffective. Tissue N and S concentrations increased as a result of the addition of N + P + liming + 60 kg ha⁻¹ K₂O (polyhalite). Full article

Background: Obesity remains a major global health challenge, and a significant proportion of bariatric surgery patients continue to experience dysfunctional emotional eating and body image concerns after surgery. Neurofeedback training (NFT) has been investigated as a potential intervention for maladaptive eating behaviours, but evidence in post-bariatric populations is still limited. Methods: Thirty-six patients who underwent sleeve gastrectomy were included, divided into an NFT group (N = 18) and a control group (N = 18). Assessments were performed at baseline and after 10 NFT sessions, using the Eating Disorder Inventory (EDI) and the Body Uneasiness Test (BUT). The intervention aimed to enhance alpha and theta waves with real-time feedback. Results: Compared with the control group, the NFT group showed significant improvements; specifically, reductions were observed in EDI subscales such as Drive for Thinness (p = 0.023, d = 0.51), Bulimia (p = 0.008, d = 0.92), Body Dissatisfaction (p = 0.015, d = 0.52), Ineffectiveness (p = 0.002, d = 0.89), Perfectionism (p = 0.006, d = 0.70), Interpersonal Distrust (p = 0.008, d = 0.82), and Interoceptive Awareness (p = 0.001, d = 0.91). Significant reductions were also found in BUT subscales including Weight Phobia (p = 0.041, d = 0.84), Body Image Concern (p = 0.039, d = 0.90), Avoidance (p = 0.027, d = 0.83), Compulsive Self-Monitoring (p = 0.013, d = 0.83), and Depersonalisation (p = 0.033, d = 0.85). Conclusions: The data indicate that NFT may help reduce emotional eating and related psychological factors in post-bariatric patients in the short term. However, studies with larger samples and longer follow-ups are needed to confirm its effectiveness and assess its clinical applicability. Full article

The micro-interface slip damping mechanism is insensitive to temperature, making it suitable for applications where the operating environment makes viscoelastic polymers ineffective. Damping material systems that rely on micro-interface slip typically embody randomly disposed interlocking units leading to complex material behaviors. This work studies a compressed coir vibration isolator that provides a lightweight, low cost and environmentally friendly alternative to common polymer devices. Under cyclic loading, it displays highly nonlinear hysteresis and a gradual change in properties based on the load history. The nonlinear hysteresis is captured with a Masing model, which has been shown to provide an adequate phenomenological representation of systems with large numbers of miniature stick-slip contacts. This study further explores a new way to enrich the Masing model by encoding time evolution using restoring force or displacement time integral, directly adopted from mem-models, a new family of models transferred from electrical engineering. In addition to using the data from the coir isolator, two additional datasets from clayey soil, another application of micro-interface slip damping, are used to validate the modeling approach. Full article

Essential oils (EOs) from the leaves of Origanum vulgare subsp. virens (Hoffmanns. & Link) Bonnier & Layens, representing three chemotypes—thymol-rich, carvacrol-rich, and a mixed thymol–carvacrol type—were chemically characterized and comparatively assessed for their antifungal, insecticidal, and enzyme-inhibitory activities. This integrated approach provides a comparative assessment of all three chemotypes across multiple biological models, including phytopathogenic fungi, insect bioassays, and key enzyme targets. All EOs displayed antifungal activity for the tested phytopathogenic fungi (Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum) at concentrations above 0.5 mg/mL, with the thymol-rich chemotype showing the highest activity. The minimum inhibition concentration for Oidium farinosum conidial growth was determined and found to be similar for thymol and carvacrol chemotypes and lower for the terpene mixture. Insect control activity was evaluated by an antifeeding assay, where carvacrol and especially thymol chemotypes can be classified as feeding deterrents. EOs and standards revealed a weak toxicity against Ceratitis capitata, with less than 20% mortality at a concentration of 50 mg/mL, and both chemotypes were found to be ineffective in preventing egg deposition. The acetylcholinesterase (AChE) inhibition assay revealed that carvacrol had the greatest inhibitory effect on AChE, followed by EOs, and, finally, thymol. Regarding the α- and β-glucosidase (α- and β-GLU) inhibitory assays, thymol had the strongest inhibitory effect on α-GLU, while plant β-GLU was not inhibited by the standards or OEs. Full article

Background/Objectives: This case represents the successful treatment of cervical spine injury from high-speed rear-impact motor vehicle collision and abnormal cervical kyphosis with left arm radiculopathy, utilizing conservative spine care rehabilitation methods. This patient was treated with a multimodal treatment approach integrating a cervical spine extension traction protocol. Subject and Methods: A 50-year-old male with a history of motor vehicle collision presented with left arm radiculopathy, as well as cervical and upper thoracic spine pain. Notably the cervical spine presented with kyphotic deformity. The patient presented, after a being struck during a rear-end motor vehicle collision, with neck, upper back, and left arm radiculopathy. Prescription medication and traditional chiropractic care proved ineffective for substantive symptom and quality-of-life improvement. Treatment frequency was three times per week for eight weeks using the Chiropractic Biophysics^® protocol of mirror image (MI^®) postural exercise, spinal adjustment, and cervical spinal traction. On completion of in-office care, the patient was treated monthly, performed home care at least three times per week, and was re-examined at one year. Results: Final examination after eight weeks of care showed significant improvement in cervical lordosis (21.8 degrees), resulting in reduced cervical kyphosis. The patient completed outcome indices before, during, and 12 months after cessation of active care, all indicating improvement. Conclusions: This case report demonstrates both subjective and objective improvement in cervical spine kyphosis and attendant symptoms. The successful treatment of chronic pain, peripheral weakness, and radiculopathy with long-term follow-up using CBP care is documented as well. The treatment was designed to improve sagittal balance and reduce radiographic abnormalities evincing spinal misalignment. Administration of subjective, objective, and health-related quality-of-life outcome indices during, following, and 12 months post-treatment are suggestive of long-term efficacy of Chiropractic BioPhysics^® (CBP) treatment methods. Larger studies are needed to substantiate this given the limitations of a case report. Full article

The high prevalence and diversity of liver diseases present a significant problem for modern healthcare. Despite FDA approval of gene therapy drugs to treat hemophilia A and B, available treatment methods for other hereditary liver diseases are mainly limited to the frequently ineffective traditional therapies and surgical intervention. In recent years, significant progress has been made in the treatment of hepatitis C, but hepatitis B is still considered an incurable disease. In this regard, the treatment of hereditary and viral liver diseases using gene or cell therapy remains relevant. This review is focused on the current state of the induced pluripotent stem cells (iPSCs) field in the context of modeling and treatment of hereditary, viral, and some other liver diseases, both ex vivo and in vivo. Here we present a detailed discussion of the possible ways of modeling liver diseases ex vivo using iPSCs (reprogramming of patient somatic cells and genetic engineering (GE) of healthy iPSCs), summarize gene editing (GE) and non-GE approaches for the treatment of liver diseases, and demonstrate that iPSCs and their derivatives are widely used to treat liver diseases in vivo. Taken together, we are presenting a comprehensive analysis of 2D and 3D iPSC-based products in the context of liver diseases, discussing the advantages and disadvantages of this platform, including the comparison with other types of stem cells and animal models. This analysis may help understand not only the potential but also the limitations associated with the use of iPSCs in the context of various types of liver diseases. Full article

The global unregulated drug supply faces a critical challenge with the emergence of nitazenes, a class of novel synthetic opioids (NSOs) structurally distinct from fentanyl and associated with extreme potency and high risk of fatal overdose. First synthesised in the late 1950s, etonitazene was a target of preclinical research in rats and rhesus monkeys, but it never reached clinical trials due to an unfavourable balance between therapeutic and toxic effects. Nitazenes’ consistent reappearance began in 2019 with isotonitazene, followed by a rapid proliferation of analogues worldwide, many reported to be hundreds to thousands of times more potent than morphine and, in some cases, stronger than fentanyl. This rise is fuelled by their ease of synthesis, low production costs, and evasion of regulatory controls. Nitazenes are frequently mis-sold as counterfeit medications or adulterated into other drugs, resulting in unintentional exposure and overdose, particularly among opioid-naïve users. The primary cause of death is severe and prolonged respiratory depression. Analytical challenges are significant, as traditional screening methods are ineffective, and the low concentration in biological samples requires expensive and highly sensitive liquid chromatography mass spectrometry techniques. This perspective paper highlights critical gaps in detection, clinical management, and regulatory readiness for nitazenes. Urgent efforts are needed to improve surveillance, develop robust analytical methodologies, provide clinical guidance to nitazene intoxications, and strengthen international policy to curb their proliferation. Full article

Background: FLT3 mutations, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) point mutations, represent common genetic alterations in acute myeloid leukemia (AML), with FLT3-ITD associated with poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs), such as quizartinib (Quiz) and gilteritinib, have improved clinical outcomes, secondary TKD mutations, particularly the gatekeeper mutation F691L, confer significant resistance. We previously demonstrated that chlorpromazine (CPZ), an antipsychotic drug, inhibits clathrin-mediated endocytosis and selectively suppresses the growth of cancer cells harboring mutant receptor tyrosine kinases. Methods: In this study, we examined the efficacy of CPZ in overcoming TKI resistance using Ba/F3 cells expressing FLT3-ITD or FLT3-ITD/F692L, the murine analog of F691L. Results: Quiz inhibited proliferation of FLT3-ITD cells but was ineffective against FLT3-ITD/F692L cells. CPZ suppressed growth in both cell types. Co-treatment with CPZ and Quiz exhibited synergistic effects in FLT3-ITD cells, but not in FLT3-ITD/F692L cells. CPZ reduced STAT5 phosphorylation and modulated downstream signaling in FLT3-ITD cells, while only partially affecting STAT5 in FLT3-ITD/F692L cells. Expression of constitutively active STAT5 partially rescued CPZ-induced growth inhibition. Conclusions: These findings suggest that STAT5 suppression is a key mechanism of CPZ’s antileukemic activity and support its potential as a therapeutic strategy for FLT3-ITD-positive AML. Full article

Background/Objectives: Some marine plants and algae are known to exert health benefits. However, the long-term effects and underlying mechanisms of these health benefits are still poorly understood. For this reason, we have investigated an extract from the marsh samphire Salicornia europaea for its life-prolonging potential. Methods: We investigated the effect of an aqueous extract of Salicornia europaea (SEE) on the lifespan of several wild-type strains of Drosophila. In addition, we used deficient flies to elucidate the mechanism of the life-prolonging effects. Finally, we comprehensively phenotyped the treated animals. Results: Supplementing a standard diet with SEE extended the lifespan of different Drosophila laboratory strains by up to a third (37% in w¹¹¹⁸ and 19% in yw). A total of 0.05% of SEE were ineffective, whereas 0.2% induced robust lifespan prolongation. This effect was strictly sex-specific, as the SEE application was completely ineffective in males, while prolonging life in females. We found that the body fat content of SEE-treated female flies was lower compared to controls. The extract also positively impacted the lifespan of flies fed a high-fat diet but not a high-sugar diet. SEE exhibited a lipase-inhibitory activity in vitro. Moreover, SEE counteracted aging-associated loss of intestinal barrier integrity. The sex-specific lifespan extensions induced by the SEE entirely depended on functional Tor signaling in the flies. Tissue-specific silencing of the Tor signaling pathway in different cellular compartments of the intestine reduced, but did not altogether abolish, the lifespan-prolonging effect in females. Conclusions: SEE is a promising candidate for a health-promoting intervention, as it induces lifespan-prolonging and anti-obesogenic effects in a sex-specific manner. These effects depend on functional Tor and partially on FoxO signaling. Future studies should identify the active compounds in the extract. Full article

Gray mold (Botrytis cinerea) and brown rot (Monilinia fructicola) are devastating diseases in stone fruit production. In this work, a series of 3-acyl-6-bromoindoles, including six new compounds, were synthesized via green and efficient microwave-assisted methodology to evaluate their antifungal potential. Bioassays revealed a remarkable duality in the compounds’ mechanism of action. The starting material, 6-bromoindole (I), proved to be a highly potent inhibitor of mycelial growth, with a remarkable EC₅₀ of 11.62 µg/mL against B. cinerea and 18.84 µg/mL against M. fructicola, surpassing BC-1000^® and Captan^® and comparable to Mystic^®. Conversely, compound I was ineffective at inhibiting conidial germination. In stark contrast, the simple acetylated derivative 3-acetyl-6-bromoindole (II) emerged as a formidable inhibitor of spore germination, achieving 100% inhibition for B. cinerea and 96% for M. fructicola, outperforming several controls. This suggests that, while compound I is effective against established infections, compound II acts as a powerful preventative agent against initial spore-based propagation. The antifungal activity of the compounds directly correlates with their ability to bind to the enzymes SDH and MfCat2, the latter being the main mechanism of action. These findings highlight the potential of developing specialized fungicides from the 6-bromoindole scaffold, targeting different stages of fungal development. Full article