Search Results (1,830)

Background/Objectives: Occlusal disturbances occurring during central occlusion, mandibular movements and mastication may contribute to the development of temporomandibular disorders (TMDs). To reduce the disclusion time (DT) in all mandibular contacts, a procedure known as enameloplasty can be applied. The aim of this study was to evaluate the effect of occlusion-correcting treatments on disclusion time reduction, determination of the center of force, and the distribution of masticatory forces on the right and left side, through digital occlusal analysis in patients with TMD. Methods: The single-centered, prospective study including 106 patients with TMD after 6 months of prosthetic treatment. Digital occlusal analysis was performed before and after the enameloplasty to assess occlusion time, disclusion time and symmetry of occlusal contacts. Results: Selective enameloplasty significantly reduced disclusion time in the whole study population (0.8 vs. 0.4 s; p < 0.001), with greater improvement observed in patients with inappropriate Center of Force (COF) and premature occlusal contacts. Conclusions: Digital occlusal analysis-guided selective enameloplasty effectively reduces disclusion time and can improve occlusal parameters in TMD patients. Full article

Therapy with chimeric antigen receptor (CAR)-T cells has revolutionized the treatment of hematological malignancies. However, their application in solid tumors remains a formidable challenge due to obstacles such as the immunosuppressive tumor microenvironment, tumor heterogeneity, and limited T cell persistence. Although second- and third-generation CAR-T cells have shown restricted efficacy in clinical trials, next-generation strategies—including cytokine-armored CAR-T cells (e.g., IL-15, IL-7/CCL19), logic-gated systems, and localized delivery approaches—demonstrate promising potential to overcome these limitations. This review examines the major barriers impeding CAR-T cell efficacy in solid tumors, evaluates clinical outcomes from conventional CAR constructs, and highlights innovative strategies being tested in recent clinical trials. Key advances discussed include the use of dominant-negative receptors (e.g., TGFβRII) to combat immunosuppression and the co-expression of bispecific T cell engagers (BiTEs) to address antigen escape. Full article

Stomoxys calcitrans (Linnaeus, 1758) is a hematophagous fly species of veterinary importance, known for its negative effects on animal health and productivity. The stress caused by their painful bites results in losses in milk and meat production. Despite its impact, data on its ecology and activity in Algeria are lacking. Such knowledge is needed to evaluate its potential effects on livestock production and rural health, and to support surveillance, outbreak prediction, and control strategies. This study aimed to investigate the monthly and daily dynamics of S. calcitrans in livestock farms in the Batna region and evaluate the influence of climatic factors on its abundance. From July 2022 to July 2023, Vavoua traps were placed monthly from 7 a.m. to 6 p.m. on four farms in the Batna region, representing different livestock types. Captured flies were identified, sexed, and counted every two hours. Climatic data were collected both in situ and from NASA POWER datasets. Fly abundance was analyzed using non-parametric statistics, Spearman’s correlation, and multiple regression analysis. A total of 1244 S. calcitrans were captured, mainly from cattle farms. Activity occurred from August to December, with a peak in September. Males were more abundant and exhibited a bimodal activity in September. Fly abundance was positively correlated with temperature and precipitation and negatively correlated with wind speed and humidity. This study presents the first ecological data on S. calcitrans in northeastern Algeria, highlighting its seasonal dynamics and the climatic drivers that influence it. The results highlight the species’ preference for cattle and indicate that temperature and rainfall are key factors influencing its abundance. These findings lay the groundwork for targeted control strategies against this neglected pest in Algeria. Full article

Human subcutaneous dirofilariasis caused by Dirofilaria repens is an emerging zoonotic parasitic infection increasingly observed in southern Europe. We report a case of a woman from western Sicily, who likely acquired the infection locally through a mosquito bite. The high prevalence of D. repens in the local canine population (up to 20.4%) suggests a role of dogs as a probable reservoir for transmission to humans in the local population. With ultrasound analysis being inconclusive, only after surgical removal was the presence of an adult worm evident, and only after molecular analysis through DNA sequencing of the cytochrome oxidase subunit I gene (COI) could a definitive D. repens infection diagnosis be obtained. This case highlights the need for enhanced vector control, animal health surveillance and public awareness to limit the transmission to humans of D. repens. A correct parasitological diagnosis would be imperative for the recognition of human cases. Full article

Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4⁺ Th1 and CD8⁺ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8⁺ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article

Introduction: Pediatric lower-lip dog bite injuries are challenging due to contamination, tissue loss, and the need to maintain function, appearance, and psychological well-being. This single case describes immediate definitive closure using sharp debridement with adjunct polyhexanide (PHMB), a full-thickness skin graft (FTSG), and a polyurethane (PU) compression foam bolster. Methods: A 10-year-old boy with a severe contaminated lower-lip defect underwent debridement and 0.04% PHMB irrigation. An upper-arm FTSG was inset and compressed with a suture-anchored PU dressing. Topical PHMB gel was used perioperatively and for seven days after bolster removal. Oral antibiotics were given for five days. The patient was discharged eight days after the injury with detailed wound care instructions. Results: Immediate definitive closure was achieved with complete graft survival and no infection, necrosis, unplanned early dressing changes, or reoperations. At 12 months, oral competence, speech, lip mobility, and contour were preserved. However, mild residual esthetic differences remained (dyschromia, shallow border indentation, vellus hairs on the graft). Conclusion: In this single descriptive case, primary closure of a lower-lip injury with the combined intervention was associated with an uncomplicated functional course and manageable esthetic trade-offs at 12 months. These observations are descriptive; comparative studies with standardized functional, esthetic, and psychosocial measures are needed. Full article

Background/Objectives: Anterior open bite is a multifact orial malocclusion influenced by genetic and environmental factors. Variants in the Collagen type I, alpha 1 (COL1A1) gene, particularly rs1800012, have been implicated in bone quality, but their role in craniofacial anomalies remains unclear. Methods: A case–control study was conducted with 60 participants (30 anterior open bite cases; 30 matched controls). DNA was extracted from buccal swabs, and rs1800012 genotyping was performed using TaqMan assays. Genotype and allele distributions were compared with chi-square and Fisher’s exact tests; Hardy–Weinberg equilibrium was assessed in controls. Results: Genotype (GG/GT/TT: 53.3/40.0/6.7% vs. 60.0/33.3/6.7%) and allele (T allele: 26.7% vs. 23.3%) frequencies did not differ significantly between cases and controls. No association was detected under additive, dominant, or recessive models (all p > 0.05). Wide confidence intervals indicated limited precision of effect estimates. Conclusions: This study provides no evidence of association between COL1A1 rs1800012 and anterior open bite in this Turkish cohort. The relatively small sample size, the rarity of the TT genotype, and the multifactorial nature of craniofacial development represent important limitations. Larger, multi-gene, and functionally integrated studies are required to clarify the genetic architecture of open bite malocclusion. Full article

Insect bite hypersensitivity (IBH) is a seasonally recurrent allergic dermatitis representing one of the most prevalent dermatological conditions in horses worldwide. This condition, driven by hypersensitivity to salivary allergens of Culicoides spp., causes substantial discomfort, welfare impairment, and potentially economic loss in equine populations. The pathogenesis of IBH is complex, involving genetic predisposition, epithelial barrier dysfunction, and a skewed T-helper 2 (Th2)-mediated immune response with elevated IgE production and eosinophilic inflammation. Advances in immunogenetics and molecular immunology have improved the understanding of the disease’s multifactorial nature. Research on immunotherapy and cytokine-targeted treatments is contributing to the development of more effective therapeutic options. This review synthesizes current knowledge on the immunopathogenesis and genetic determinants of IBH and discusses both conventional and emerging strategies for its clinical management. Full article

The increasing prevalence of Lyme disease, tick-borne encephalitis (TBE), and other tick-borne infections such as Babesia, Ehrlichia, Rickettsia, and Anaplasma is a growing public health concern. Existing tick bite prevention strategies are insufficient; therefore, vaccines represent a promising preventive measure. At the moment, only a vaccine for tick-borne encephalitis is available on the market. A vaccine for Lyme disease, however, is at an advanced stage of clinical trials. In this article, we focus on describing the progress in the invention of vaccines for tick-borne diseases. This article analyzes their development and effectiveness. Full article

The reconstruction of segmental bone defects requires patient-specific scaffolds that combine mechanical safety, biological functionality, and rapid manufacturing. We converted CT-derived mandibular geometry into a functionally graded Ti-6Al-4V lattice and optimised porosity, screw layout, and strut thickness through a cyber-physical loop that joins high-fidelity FEM, millisecond ANN, and a BN for uncertainty quantification. Fifteen candidate scaffolds were fabricated by direct metal laser sintering and hot isostatic pressing and were mechanically tested. FEM predicted stress and stiffness with 98% accuracy; the ANN reproduced these outputs with 94% fidelity while evaluating 10,000 designs in real time, and the BN limited failure probability to <3% under worst-case loads. The selected 55–65% porosity design reduced titanium use by 15%, shortened development time by 25% and raised multi-objective optimisation efficiency by 20% relative to a solid-plate baseline, while resisting a 600 N bite with a peak von Mises stress of 225 MPa and micromotion < 150 µm. Integrating physics-based simulation, AI speed, and probabilistic rigour yields a validated, additively manufactured scaffold that meets surgical timelines and biomechanical requirements, offering a transferable blueprint for functional scaffolds in bone and joint surgery. Full article

One of the most common malocclusions encountered in everyday practice by orthodontists is skeletal Class II malocclusion, namely a protrusion of the maxilla, a retrusion of the mandible or a combination of both. To correct it, many clinicians use functional devices that guide the mandible into a more forward position. This stimulates bone growth, correcting the skeletal discrepancy. Controversy exists as to whether these appliances accelerate the growth rate, helping the mandible reach its final size earlier, or whether the growth of the mandible is observed as a positive response to the stimuli. This study examined whether the protrusion of the mandible in rats accelerates the growth rate or increases the overall growth of the mandible in the long run. Relapse was also assessed by removing the appliance prior to the end of the experiment. Seventy-two four-week-old Wistar rats were used. The treatment group, which consisted of 36 rats, had a device fitted on their upper incisors that led to a protrusion of their mandible. The device, a bite-jumping appliance, consisted of an iron-cast inclined plane and was fitted for 24 h a day, inducing a 3.5 mm anterior protrusion and 3 mm inferior displacement of the mandible. The control group consisted of 36 rats that were fed the same soft diet as the treatment group. Both groups were divided into three subgroups. The first was sacrificed 30 days after the onset of the experiment, the second at 60 days, and the last subgroup had the appliance removed for 30 days and was sacrificed 90 days after the onset of the experiment. At the beginning of the experiment, as well as at each time interval prior to the sacrifice of the animals, the appliances were removed, and cone beam-computed tomography was performed on every animal. Linear measurements were made on each 3D scan, measuring the growth of the mandible. Measurements of mandibular growth were higher compared to the control group. For instance, Gonion-Menton was 1.18 mm higher on month 2 compared to month 1 in the control group, whereas the same measurement marked a 1.82 mm difference in the experimental group. Condylion–Menton on the same intervals marked a 0.84 mm difference in the control, whereas a 1.35 mm difference was noted in the experimental group. Given the results, true mandibular growth is achieved using functional appliances for Class II malocclusion correction in rats. Full article

Rodents are recognized as significant reservoirs for a broad range of zoonotic pathogens, including bacteria, viruses, and parasites, many of which have substantial implications for human and animal health. The intensifying interaction between humans and rodent populations, fuelled by urbanization, climate change, and global trade, has amplified the risk of zoonotic disease transmission. This review compiles and examines current knowledge on key rodent-borne bacterial diseases, including leptospirosis, rat-bite fever, plague, salmonellosis, tularemia, Lyme disease, rickettsioses, Babesiosis, and associated parasitic infections such as toxoplasmosis and Chagas disease. Each disease is analyzed in terms of its etiology, transmission, clinical manifestations, diagnostic tools, and treatment options, with a particular focus on the impact of environmental changes. Emphasizing a One Health perspective, this work highlights the importance of interdisciplinary approaches to the surveillance, prevention, and control of rodent-borne zoonoses, particularly in the context of increasing climate variability and anthropogenic pressures. Full article

Rickettsia parkeri strain Atlantic rainforest is an emerging pathogen in Brazil, but human infections remain rarely reported. We report the first confirmed case in the municipality of Caraguatatuba on the northern coast of São Paulo State, Brazil. A 37-year-old man was bitten by an Amblyomma ovale tick while visiting a forested area. Six days later, he developed a papular skin lesion with a necrotic center at the tick bite site, accompanied by regional lymphadenopathy, myalgia, and flu-like symptoms. Ticks parasitizing both the patient and his dog were collected, along with the eschar. Two ticks were analyzed for Rickettsia isolation, and R. parkeri was successfully isolated from one infected specimen. The patient’s infection was confirmed by molecular testing through the PCR amplification of the gltA and ompA genes from an eschar inoculation sample. This represents the sixth confirmed case of rickettsiosis caused by R. parkeri in Brazil, and it reinforces the need for increased epidemiological surveillance in endemic regions for spotted fever caused by this pathogen. With the increasing recognition of R. parkeri in South America, further research is needed to better understand its transmission dynamics, clinical manifestations, and potential public health impact. Full article

Tissue factor (TF), also known as CD142, is a 47 kDa transmembrane glycoprotein belonging to the class II cytokine receptors superfamily. High expression of TF has been reported to be correlated with poor prognosis in various cancers. In this study, we aimed to clarify the cytotoxicity of bi-specific T-cell engagers (BiTE) targeting TF on cervical cancer cell lines. We designed and characterized the novel humanized BiTE targeting TF using an anti-human CD3 single-chain variable fragment (scFv) linked to human TF scFv. TF-Bite replication and potency were assessed in cervical cancer cell lines. The expression of the TF-BiTE and the activation and proliferation of T cells induced along with the T-cell-mediated cytotoxicity were evaluated by flow cytometry in vitro. TF expression was confirmed in SiHa, ME-180, and HeLa cell lines. The TF-BiTE showed potent TF-specific cytotoxicity and induced T-cell activation, proliferation, degranulation, and cytokine release. These effects were not observed in TF-negative control cells. Our findings support TF-BiTE as a promising therapeutic candidate for cervical cancer immunotherapy. Full article

The aims of the study were to evaluate the effectiveness of audio detection for identifying feeding sounds in free grazing sheep and to assess whether the recognition of these sounds could be influenced by pasture characteristics. Twelve Valle del Belice dry ewes were grazed on two mixed swards: on 10 May, grass-rich sward (G); on 13 May, legume-rich sward (L). Each ewe was fitted with a collar equipped with a point of view (POV) camera. All audio files (without viewing the videos) were listened to and sounds recognized as herbage prehension and rumination activity were highlighted. Time spent eating and ruminating was then calculated. To validate the audio file analysis, all video files were subjected to observation of the same behavioral aspects detected with audio. The regression between the prehensions number estimated using sound alone and the actual values recorded through video was significant (r² 0.743; p < 0.001). No differences were found in recognizing grazing behavior between data obtained by listening or watching the videos and between the two swards. The acoustic analysis of the single bites on grass and legume forages reveals significant differences between the two forage classes (p ≤ 0.001) particularly in terms of energy, temporal structure, and spectral features. Since sheep showed a strong selective activity towards legumes even in the grass-rich sward (selectivity index 3.1), this may have reduced acoustic differences between swards. Full article