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41 pages, 2949 KiB  
Review
Nanocarriers Containing Curcumin and Derivatives for Arthritis Treatment: Mapping the Evidence in a Scoping Review
by Beatriz Yurie Sugisawa Sato, Susan Iida Chong, Nathalia Marçallo Peixoto Souza, Raul Edison Luna Lazo, Roberto Pontarolo, Fabiane Gomes de Moraes Rego, Luana Mota Ferreira and Marcel Henrique Marcondes Sari
Pharmaceutics 2025, 17(8), 1022; https://doi.org/10.3390/pharmaceutics17081022 - 6 Aug 2025
Abstract
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water [...] Read more.
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article
(This article belongs to the Special Issue Advances in Polymer-Based Devices and Platforms for Pain Management)
18 pages, 2476 KiB  
Article
Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway
by Tsung-Hsun Hsieh, Jar-Yi Ho, Chih-Chien Wang, Feng-Cheng Liu, Chian-Her Lee, Herng-Sheng Lee and Yi-Jen Peng
Cells 2025, 14(15), 1208; https://doi.org/10.3390/cells14151208 - 6 Aug 2025
Abstract
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. [...] Read more.
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article
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21 pages, 3832 KiB  
Article
Effects of Water Use Efficiency Combined with Advancements in Nitrogen and Soil Water Management for Sustainable Agriculture in the Loess Plateau, China
by Hafeez Noor, Fida Noor, Zhiqiang Gao, Majed Alotaibi and Mahmoud F. Seleiman
Water 2025, 17(15), 2329; https://doi.org/10.3390/w17152329 - 5 Aug 2025
Abstract
In China’s Loess Plateau, sustainable agricultural end products are affected by an insufficiency of water resources. Rising crop water use efficiency (WUE) through field management pattern improvement is a crucial plan of action to address this issue. However, there is no agreement among [...] Read more.
In China’s Loess Plateau, sustainable agricultural end products are affected by an insufficiency of water resources. Rising crop water use efficiency (WUE) through field management pattern improvement is a crucial plan of action to address this issue. However, there is no agreement among researchers on the most appropriate field management practices regarding WUE, which requires further integrated quantitative analysis. We conducted a meta-analysis by quantifying the effect of agricultural practices surrounding nitrogen (N) fertilizer management. The two experimental cultivars were Yunhan–20410 and Yunhan–618. The subplots included nitrogen 0 kg·ha−1 (N0), 90 kg·ha−1 (N90), 180 kg·ha−1 (N180), 210 kg·ha−1 (N210), and 240 kg·ha−1 (N240). Our results show that higher N rates (up to N210) enhanced water consumption during the node-flowering and flowering-maturity time periods. YH–618 showed higher water use during the sowing–greening and node-flowering periods but decreased use during the greening-node and flowering-maturity periods compared to YH–20410. The N210 treatment under YH–618 maximized water use efficiency (WUE). Increased N rates (N180–N210) decreased covering temperatures (Tmax, Tmin, Taver) during flowering, increasing the level of grain filling. Spike numbers rose with N application, with an off-peak at N210 for strong-gluten wheat. The 1000-grain weight was at first enhanced but decreased at the far end of N180–N210. YH–618 with N210 achieved a harvest index (HI) similar to that of YH–20410 with N180, while excessive N (N240) or water reduced the HI. Dry matter accumulation increased up to N210, resulting in earlier stabilization. Soil water consumption from wintering to jointing was strongly correlated with pre-flowering dry matter biological process and yield, while jointing–flowering water use was linked to post-flowering dry matter and spike numbers. Post-flowering dry matter accumulation was critical for yield, whereas spike numbers positively impacted yield but negatively affected 1000-grain weight. In conclusion, our results provide evidence for determining suitable integrated agricultural establishment strategies to ensure efficient water use and sustainable production in the Loess Plateau region. Full article
(This article belongs to the Special Issue Soil–Water Interaction and Management)
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14 pages, 1579 KiB  
Article
Predisposing Anatomical Patellofemoral Factors for Subsequent Patellar Dislocation
by Anna Kupczak, Bartłomiej Wilk, Ewa Tramś, Maciej Liszka, Bartosz Machnio, Aleksandra Jasiniewska, Jerzy Białecki and Rafał Kamiński
Life 2025, 15(8), 1239; https://doi.org/10.3390/life15081239 - 4 Aug 2025
Abstract
Background: Primary patellar dislocation is a relatively uncommon knee injury but carries a high risk of recurrence, particularly in young and physically active adolescent individuals. Anatomical features of the patellofemoral joint have been implicated as key contributors to instability. The purpose of this [...] Read more.
Background: Primary patellar dislocation is a relatively uncommon knee injury but carries a high risk of recurrence, particularly in young and physically active adolescent individuals. Anatomical features of the patellofemoral joint have been implicated as key contributors to instability. The purpose of this study was to evaluate anatomical risk factors associated with recurrent patellar dislocation following a primary traumatic event, using MRI-based parameters. Methods: Fifty-four patients who sustained a first-time lateral patellar dislocation were included. MRI was used to measure tibial tuberosity–trochlear groove (TT–TG) distance, tibial tuberosity–posterior cruciate ligament (TT–PCL) distance, Insall–Salvati ratio (IS), sulcus angle (SA), patellar tilt angle (PTA), patella length, and patellar tendon length. Trochlear dysplasia was assessed according to the Dejour classification. Recurrence was defined as a subsequent dislocation occurring within three years of the primary injury. Results: Significant differences were observed in TT–TG distance and patellar tendon length (p < 0.05). Patients with recurrent dislocation had lower TT–TG values and shorter patellar tendon lengths. Other parameters, including PTA, IS, and patella height, did not show statistically significant differences. Conclusion: Anatomical factors may contribute to the risk of recurrent patellar dislocation. Identifying these variables using imaging may support clinical decision making and guide individualized treatment plans following primary injury. Full article
(This article belongs to the Section Medical Research)
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56 pages, 1035 KiB  
Review
Trace Elements—Role in Joint Function and Impact on Joint Diseases
by Łukasz Bryliński, Katarzyna Brylińska, Filip Woliński, Jolanta Sado, Miłosz Smyk, Olga Komar, Robert Karpiński, Marcin Prządka and Jacek Baj
Int. J. Mol. Sci. 2025, 26(15), 7493; https://doi.org/10.3390/ijms26157493 - 2 Aug 2025
Viewed by 423
Abstract
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a [...] Read more.
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article
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31 pages, 2032 KiB  
Review
Leflunomide Applicability in Rheumatoid Arthritis: Drug Delivery Challenges and Emerging Formulation Strategies
by Ashish Dhiman and Kalpna Garkhal
Drugs Drug Candidates 2025, 4(3), 36; https://doi.org/10.3390/ddc4030036 - 1 Aug 2025
Viewed by 207
Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) [...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article
(This article belongs to the Section Marketed Drugs)
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13 pages, 1454 KiB  
Article
Lower Limb Inter-Joint Coordination and End-Point Control During Gait in Adolescents with Early Treated Unilateral Developmental Dysplasia of the Hip
by Chu-Fen Chang, Tung-Wu Lu, Chia-Han Hu, Kuan-Wen Wu, Chien-Chung Kuo and Ting-Ming Wang
Bioengineering 2025, 12(8), 836; https://doi.org/10.3390/bioengineering12080836 (registering DOI) - 31 Jul 2025
Viewed by 247
Abstract
Background: Residual deficits after early treatment of developmental dysplasia of the hip (DDH) using osteotomy often led to asymmetrical gait deviations with increased repetitive rates of ground reaction force (GRF) in both hips, resulting in a higher risk of early osteoarthritis. This [...] Read more.
Background: Residual deficits after early treatment of developmental dysplasia of the hip (DDH) using osteotomy often led to asymmetrical gait deviations with increased repetitive rates of ground reaction force (GRF) in both hips, resulting in a higher risk of early osteoarthritis. This study investigated lower limb inter-joint coordination and swing foot control during level walking in adolescents with early-treated unilateral DDH. Methods: Eleven female adolescents treated early for DDH using Pemberton osteotomy were compared with 11 age-matched healthy controls. The joint angles and angular velocities of the hip, knee, and ankle were measured, and the corresponding phase angles and continuous relative phase (CRP) for hip–knee and knee–ankle coordination were obtained. The variability of inter-joint coordination was quantified using the deviation phase values obtained as the time-averaged standard deviations of the CRP curves over multiple trials. Results: The DDH group exhibited a flexed posture with increased variability in knee–ankle coordination of the affected limb throughout the gait cycle compared to the control group. In contrast, the unaffected limb compensated for the kinematic alterations of the affected limb with reduced peak angular velocities but increased knee–ankle CRP over double-limb support and trajectory variability over the swing phase. Conclusions: The identified changes in inter-joint coordination in adolescents with early treated DDH provide a plausible explanation for the previously reported increased GRF loading rates in the unaffected limb, a risk factor of premature OA. Full article
(This article belongs to the Special Issue Biomechanics and Motion Analysis)
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16 pages, 261 KiB  
Review
Sport-Specific Risks of Osteochondritis Dissecans Across Athletic Disciplines: A Narrative Review
by Tomasz Poboży, Michał Derczyński and Wojciech Konarski
Healthcare 2025, 13(15), 1857; https://doi.org/10.3390/healthcare13151857 - 30 Jul 2025
Viewed by 255
Abstract
Osteochondritis Dissecans (OCD) is a joint condition characterized by damage to the surface of the joint and the underlying subchondral bone, leading to early-onset osteoarthritis. It predominantly affects the knee, elbow, and ankle, with higher prevalence in juveniles actively participating in sports, which [...] Read more.
Osteochondritis Dissecans (OCD) is a joint condition characterized by damage to the surface of the joint and the underlying subchondral bone, leading to early-onset osteoarthritis. It predominantly affects the knee, elbow, and ankle, with higher prevalence in juveniles actively participating in sports, which complicates the condition due to slow healing processes and prolonged restrictions on physical activities. This review aims to summarize current knowledge on OCD in athletes, with emphasis on sport-specific risk factors, diagnosis, and treatment, to support clinical decision-making and future research. We conducted searches in the PubMed and Embase databases, covering the period from 2014 to 2024. The keywords used in the search covered most common sports in combination with term osteochondritis dissecans. This review examines the impacts of various sports on the development of OCD, analyzing prevalence and risk factors, with a focus on sports-specific risks across athletic disciplines like football, basketball, baseball, and gymnastics. The significance of early detection, intervention, and sport-specific conditioning is underscored to prevent the condition and manage it effectively. Moreover, the review highlights the positive prognosis for athletes, particularly adolescents, recovering from OCD, with a high rate of return to sport. Understanding the sports-specific risks, ensuring early intervention, and adopting a cautious, stepwise return to sport are critical for managing OCD effectively, thereby safeguarding the health and careers of athletes. Full article
(This article belongs to the Special Issue Dysfunctions or Approaches of the Musculoskeletal System)
11 pages, 737 KiB  
Article
Generation of an In Vitro Cartilage Aging Model Using Human Sera from Old Donors
by Sophie Hines, Meagan J. Makarczyk, Joseph Garzia and Hang Lin
Bioengineering 2025, 12(8), 823; https://doi.org/10.3390/bioengineering12080823 - 30 Jul 2025
Viewed by 351
Abstract
Cartilage degradation is a key feature of osteoarthritis (OA), a joint disease that significantly impacts the quality of life of the elderly population. While advanced age is recognized as one of the major risk factors for OA, the underlying mechanisms are not fully [...] Read more.
Cartilage degradation is a key feature of osteoarthritis (OA), a joint disease that significantly impacts the quality of life of the elderly population. While advanced age is recognized as one of the major risk factors for OA, the underlying mechanisms are not fully understood. Research involving cartilage from aged animals has improved our understanding of the changes associated with aging. However, studies with aged animals can be time-consuming and costly. In this study, we investigate the use of human sera from older donors as a stressor to induce aging-like changes in cultured human chondrocytes. First, we assess the expression levels of markers related to chondrogenesis, hypertrophy, fibrosis, and inflammation in human chondrocytes treated with sera from younger or older human donors. Next, we evaluate the regenerative potential of these sera-treated chondrocytes by stimulating them with the anabolic factor transforming growth factor (TGF)-β3. The results show that treatment with sera from older donors induced an aging-like phenotype in chondrocytes and impaired their ability to generate new cartilage. These findings provide insight into the role of systemic factors (serum) in cartilage aging and offer a novel in vitro model for studying age-related changes in chondrocytes. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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16 pages, 317 KiB  
Review
Combination Antibiotic Therapy for Orthopedic Infections
by Eric Bonnet and Julie Lourtet-Hascoët
Antibiotics 2025, 14(8), 761; https://doi.org/10.3390/antibiotics14080761 - 29 Jul 2025
Viewed by 288
Abstract
Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may [...] Read more.
Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
8 pages, 1696 KiB  
Case Report
Topical Chlormethine Gel in the Treatment of Lymphomatoid Papulosis: A Case Report and Literature Review
by Miriam Teoli, Martina Caviglia, Federica Rega, Luca Barbieri, Marco Ardigò and Victor Desmond Mandel
J. Clin. Med. 2025, 14(15), 5338; https://doi.org/10.3390/jcm14155338 - 29 Jul 2025
Viewed by 332
Abstract
Background: Lymphomatoid papulosis (LyP) is a primary cutaneous CD30-positive T-cell lymphoproliferative disorder presenting with self-healing erythematous papulonodular lesions that may ulcerate and scar. Treatment varies by lesion extent, location, and severity. Case Report: We describe a 57-year-old man with acral LyP [...] Read more.
Background: Lymphomatoid papulosis (LyP) is a primary cutaneous CD30-positive T-cell lymphoproliferative disorder presenting with self-healing erythematous papulonodular lesions that may ulcerate and scar. Treatment varies by lesion extent, location, and severity. Case Report: We describe a 57-year-old man with acral LyP successfully treated with chlormethine gel (CG). The patient experienced impaired second finger mobility for over 3 months due to an ulcerated nodular mass. After 3 months of CG treatment, complete remission, symptom resolution, and full joint recovery were achieved. Six months post-treatment, the patient remained in remission. Conclusions: This case underscores the effectiveness of CG in achieving sustained remission in acral LyP, suggesting its potential as a treatment option for this rare condition. Full article
(This article belongs to the Section Dermatology)
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22 pages, 1317 KiB  
Review
Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies
by Mohammad Iftekhar Ullah and Sadeka Tamanna
Medicines 2025, 12(3), 19; https://doi.org/10.3390/medicines12030019 - 28 Jul 2025
Viewed by 700
Abstract
Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years [...] Read more.
Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article
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20 pages, 300 KiB  
Review
Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review
by Beatrice Baldo, Ilaria Bonemazzi, Antonella Morea, Roberta Rossi, Alessandro Ferretti, Vittorio Sciruicchio, Alessia Raffagnato, Vincenzo Raieli, Antonia Versace and Irene Toldo
Life 2025, 15(8), 1198; https://doi.org/10.3390/life15081198 - 28 Jul 2025
Viewed by 382
Abstract
Many headaches at night arise due to primary headache disorders, which occur independently of other symptoms and are not caused by another medical condition. Primary headache disorders with nighttime attacks can include tension-type headaches, migraines, hypnic headaches, and cluster headaches. A hypnic headache [...] Read more.
Many headaches at night arise due to primary headache disorders, which occur independently of other symptoms and are not caused by another medical condition. Primary headache disorders with nighttime attacks can include tension-type headaches, migraines, hypnic headaches, and cluster headaches. A hypnic headache is sometimes called an “alarm clock headache” because symptoms tend to arise at the same time of night. Apart from considering primary headaches, secondary causes of nighttime headaches should be considered and ruled out, in particular headaches secondary to intracranial hypertension, temporomandibular joint issues (like bruxism) and sleep apnea. Treatments vary based on headache type but often include a combination of medications and prevention strategies. This review article covers the basics of nighttime primary headaches in children, including pathophysiology, etiology, clinical features of the different forms and their treatment. It will also discuss the differences in headache features between children and adults. Full article
(This article belongs to the Section Medical Research)
8 pages, 232 KiB  
Article
Clinical Analysis of TMJ Replacement Using a Customized Prosthesis
by Sergio Olate, Víctor Ravelo, Gonzalo Muñoz, Carlos Gaete, Rodrigo Goya and Rômulo Valente
J. Clin. Med. 2025, 14(15), 5314; https://doi.org/10.3390/jcm14155314 - 28 Jul 2025
Viewed by 207
Abstract
Background/Objectives: This study aims to uncover the variables related to the success of the intervention. Methods: A retrospective study was conducted on patients who underwent joint replacement surgery utilizing a customized alloplastic system between 2018 and 2023, comprising subjects with complete records for [...] Read more.
Background/Objectives: This study aims to uncover the variables related to the success of the intervention. Methods: A retrospective study was conducted on patients who underwent joint replacement surgery utilizing a customized alloplastic system between 2018 and 2023, comprising subjects with complete records for both the planning and follow-up phases. The Student’s t-test was applied with a significance threshold of p < 0.05. Results: Forty-eight subjects were admitted for initial analysis, and 31 subjects were evaluated with a minimum follow-up of 1 year and a maximum of 7 years, with a mean age of 36.37 ± 15.53. The TMJ diagnosis was mainly with degenerative TMJ disease, followed by ankylosis and craniofacial syndromes, and an average of 2.1 ± 1.2 previous surgeries were noted. Degenerative joint disease correlated with increased pain (p < 0.0001) and a higher prevalence of prior joint surgery (p < 0.0001). Thirty-one subjects were followed up with 47 prostheses installed; 74.4% underwent complementary surgery with other facial osteotomies. Significant improvements (p < 0.0001) were observed when comparing pain levels pre- and postoperatively, with a decrease from 5.5 (±2.3) to 2.2 (±0.4). Concerning the interincisal opening, there was a significant increase (p < 0001) from 25.85 (±10.2) mm to 35.93 (±4.2) mm in mouth opening. TMJ replacement treatment is efficient and effective, demonstrating stability in follow-up assessments for up to 7 years. Conclusions: The indications for replacement are diverse and may benefit patients who have not yet progressed to end-stage TMJ disease. Full article
(This article belongs to the Special Issue Innovations in Plastic and Reconstructive Research)
23 pages, 5594 KiB  
Article
Dynamic Properties of Steel-Wrapped RC Column–Beam Joints Connected by Embedded Horizontal Steel Plate: Experimental Study
by Jian Wu, Mingwei Ma, Changhao Wei, Jian Zhou, Yuxi Wang, Jianhui Wang and Weigao Ding
Buildings 2025, 15(15), 2657; https://doi.org/10.3390/buildings15152657 - 28 Jul 2025
Viewed by 331
Abstract
The performance of reinforced concrete (RC) frame structures will gradually decrease over time, posing a threat to the safety of buildings. Although the performance of some buildings may still meet the safety requirements, they cannot meet new usage requirements. Therefore, this paper proposes [...] Read more.
The performance of reinforced concrete (RC) frame structures will gradually decrease over time, posing a threat to the safety of buildings. Although the performance of some buildings may still meet the safety requirements, they cannot meet new usage requirements. Therefore, this paper proposes a new-type joint to promote the development of research on the reinforcement and renovation of RC frame structures in response to this situation. The RC beams and columns of the joints are connected by embedded horizontal steel plate (a single plate with dimension of 150 mm × 200 mm × 5 mm), and the beams and columns are individually wrapped in steel. Through conducting low cyclic loading tests, this paper analyzes the influence of carrying out wrapped steel treatment and the thickness of wrapped steel of the beam and connector on mechanical performance indicators such as hysteresis curve, skeleton curve, stiffness, ductility, and energy dissipation. The experimental results indicate that the reinforcement using steel plate can significantly improve the dynamic performance of the joint. The effect of changing the thickness of the connector on the dynamic performance of the specimen is not significant, while increasing the thickness of wrapped steel of beam can effectively improve the overall strength of joint. The research results of this paper will help promote the application of reinforcement and renovation technology for existing buildings, and improve the quality of human living. Full article
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