Search Results (1,837)

Background/Objectives: Oral squamous cell carcinoma (OSCC) exhibits substantial biological heterogeneity, and current clinicopathological risk stratification incompletely reflects tumor metabolic behavior. Stable isotope ratio mass spectrometry enables the quantitative assessment of carbon and nitrogen isotopic composition, potentially capturing cumulative metabolic reprogramming associated with tumor aggressiveness. This study evaluated whether isotopic signatures of tumor tissue and surgical margins are associated with lymph node metastasis and survival outcomes in OSCC. Methods: In this prospective study, 54 consecutive patients undergoing primary surgical treatment for OSCC were enrolled. Paired samples derived from tumor tissue and surgical margins were analyzed using isotope ratio mass spectrometry to determine the relative abundance of nitrogen-15 and carbon-13 isotopes. The primary endpoint was pathological lymph node metastasis. Secondary endpoints included disease-free survival and overall survival. Paired comparisons were performed using Wilcoxon signed-rank tests with false discovery rate correction. Logistic regression models for nodal metastasis were constructed using Firth penalization with bootstrap internal validation, while survival outcomes were evaluated using Cox proportional hazards models with model complexity restricted according to the number of events. Results: Tumor tissues demonstrated significantly lower δ¹³C and δ¹⁵N values and higher nitrogen-to-carbon ratios compared with surgical margins (all adjusted p < 0.05). In multivariable analysis, tumor δ¹⁵N was independently associated with lymph node metastasis and modestly improved model discrimination. However, it was not independently associated with disease-free or overall survival. Exploratory analyses indicated that higher δ¹³C values in surgical margins were independently associated with shorter disease-free survival. Conclusions: These findings suggest that isotope ratio mass spectrometry-based isotopic profiling identifies reproducible metabolic differences between tumor and margin tissues in OSCC. Tumor δ¹⁵N is associated with lymph node metastasis, whereas margin δ¹³C may reflect recurrence risk and potentially capture metabolic field effects. These findings are hypothesis-generating and warrant validation in larger, independent cohorts. Full article

Purpose: Natural polysaccharides have shown considerable potential in the management of type 2 diabetes mellitus (T2DM) due to their multi-target metabolic regulatory effects. However, their clinical translation is limited by poor oral stability and low intestinal permeability. Snow lotus polysaccharide (SIP), a representative plant-derived polysaccharide, exhibits promising metabolic benefits but suffers from these delivery barriers. This study aimed to develop an oral nanodelivery system to enhance the gastrointestinal stability and intestinal transport of SIP, thereby improving its in vivo efficacy. Methods: SIP-loaded chitosan–tripolyphosphate nanoparticles (SIP@CS-TPP) were prepared via ionic crosslinking and characterized in terms of particle size, surface charge, morphology, and structural features. In vitro release behavior under simulated gastrointestinal conditions was evaluated. Ex vivo intestinal permeation was assessed using an isolated intestinal sac model. The metabolic regulatory effects were further investigated in a high-fat diet/streptozotocin-induced T2DM rat model. Results: SIP@CS-TPP nanoparticles exhibited a uniform particle size of 188.9 ± 12.8 nm, a surface charge of 28.3 ± 5.1 mV, and good stability after freeze-drying. A pH-responsive and diffusion-controlled release profile was observed. Ex vivo studies demonstrated significantly enhanced intestinal transport, with an approximately 3.7-fold increase in apparent permeability compared with free SIP. In vivo, SIP@CS-TPP improved glycemic control, glucose tolerance, insulin resistance, lipid metabolism, oxidative stress, and inflammatory responses more effectively than free SIP at the same dose. Conclusions: The CS-TPP nanodelivery system effectively enhances the oral delivery and metabolic regulatory effects of SIP. This study highlights the potential of a delivery-oriented strategy to improve the in vivo performance of natural polysaccharides and provides a promising approach for their application in metabolic disease management. Full article

Hyaluronic acid (HA) is a glycosaminoglycan commonly administered orally, and its molecular weight (MW) influences its physicochemical behavior and potential interactions with the gut microbiota. However, MW-dependent effects on community assembly and fermentation-derived metabolites within the low-molecular-weight (LMW) range remain insufficiently resolved. In this study, five HA samples (6.9–35 kDa) were evaluated using an in vitro human fecal fermentation model. Microbial composition was profiled by 16S rRNA gene sequencing, and SCFAs were quantified by UPLC. Compared with the control under the same basal medium, HA supplementation was associated with shifts in community structure and higher alpha diversity. The 6.9 and 9.5 kDa groups were associated with significantly higher total SCFA concentrations, particularly butyrate, than the 13, 17, and 35 kDa groups under the same basal medium. Because soluble starch was present in the fermentation medium, these differences should be interpreted as modulation effects rather than direct evidence of HA-specific fermentation. 16S-based functional prediction suggested MW-dependent differences in predicted central carbohydrate metabolism potential, which were consistent with the observed SCFA patterns but should be interpreted as inferred functional potential rather than direct evidence of pathway activity. These findings indicate that HA molecular weight is associated with differential microbial and SCFA response patterns under the present in vitro conditions. Lower-MW HA within the tested range was associated with higher SCFA output, particularly butyrate, under a shared starch-containing basal medium, highlighting molecular weight as a potential formulation parameter in HA microbiota-centered applications. Full article

Background/Objectives: The rapid expansion of New Approach Methodologies (NAMs) is transforming oral biopharmaceutics by offering mechanistically rich, human-relevant tools that can reduce reliance on animal testing while improving translational confidence. Regulatory agencies, including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), are increasingly open to NAM-generated evidence, provided that methods are fit-for-purpose and scientifically justified. This review synthesizes current advances and evaluates how NAMs can be integrated across drug-development stages to enhance the prediction of oral absorption, formulation performance, and regulatory decision-making. Methods: A comprehensive literature review was conducted across classical and emerging methodologies, including in vitro permeability and solubility models, organoids, organ-on-a-chip (OoC) systems, machine learning frameworks, and mechanistic approaches such as the physiologically based pharmacokinetic (PBPK) and biopharmaceutics (PBBM) models. Emphasis was placed on physiological relevance, predictive performance, validation status, and regulatory applicability. Results: Classical tools remain essential for the Biopharmaceutics Classification System (BCS)-based biowaivers and risk-based assessments, yet they often lack physiological fidelity. NAMs provide enhanced representation of intestinal architecture, hydrodynamics, transporter activity, and metabolism. Organoids and microphysiological systems generate high-quality permeability and metabolic data, while computational NAMs enable scalable prediction of ADME properties and formulation behavior. When integrated into PBPK/PBBM models, these methods have great potential in predicting in vivo performance in humans. Evidence demonstrates that NAMs can refine, reduce, and, in specific contexts, replace animal studies without compromising scientific rigor. Conclusions: NAMs complement, rather than displace, classical biopharmaceutic tools, enabling a more mechanistic, human-centered, and ethically responsible framework for drug development. Their effective implementation will depend on continued validation, standardization, and regulatory harmonization as the field transitions toward fully NAM-supported biopharmaceutical assessment. Full article

Background: Obesity is a heterogeneous chronic disease in which eating behavior phenotypes may influence treatment response. Yet, anti-obesity medication (AOM) selection is still largely guided by anthropometric and metabolic parameters, with limited use of behavioral phenotyping in routine practice. We evaluated whether multidimensional eating behavior changes, measured by the Brazilian Eating Behavior Phenotype Scale (Escala de Fenótipos do Comportamento Alimentar, EFCA), differ across commonly used AOMs in a real-world cohort. Methods: We conducted a retrospective, observational, real-world study in obesity outpatient care settings in São Paulo, Brazil. Adults with obesity (18–65 years) treated with a single principal AOM for 6 months and paired baseline/6-month follow-up EFCA and anthropometric data were included. Analyses focused on early responders (≥5% total body weight loss at 3 months). Five AOM groups available in Brazil were analyzed: semaglutide (oral or subcutaneous), naltrexone/bupropion, sibutramine, topiramate, and tirzepatide. Outcomes included percent weight loss, EFCA total score, and five EFCA subscales (hedonic, emotional, compulsive, hyperphagic, disorganized). Within-medication behavioral changes were assessed using paired tests and standardized effect sizes (Cohen’s dz, 95% CI), summarized in heatmap form. Results: The analytical cohort comprised 66 early responders with paired EFCA assessments at baseline and 6 months. EFCA profiling revealed distinct behavioral response fingerprints across AOMs. Effect size mapping showed predominantly large behavioral effects (many dz ≥ 0.8) in hedonic, emotional, hyperphagic, and compulsive domains. Strongest signals included emotional eating reductions with naltrexone/bupropion (dz 2.04), tirzepatide (dz 1.77), semaglutide (dz 1.52), and topiramate (dz 1.54); hedonic reductions with tirzepatide (dz 2.06), semaglutide (dz 1.55), and naltrexone/bupropion (dz 1.52); hyperphagic reductions with tirzepatide (dz 1.50) and semaglutide (dz 1.34); and compulsive reductions with topiramate (dz 1.41) and consistent effects across tirzepatide, semaglutide, and sibutramine (≈dz 0.95–0.96). Disorganized eating showed heterogeneous/attenuated responsiveness, from near-null with tirzepatide (dz 0.03) to large but imprecise effects in smaller groups (e.g., topiramate dz 1.24, wide CI). Conclusions: In this responder-enriched real-world cohort, AOMs showed distinct and reproducible EFCA behavioral signatures, supporting a clinically actionable phenotype-informed framework to prioritize, sequence, and monitor obesity pharmacotherapy beyond nonspecific weight reduction, while highlighting disorganization as a potential target for adjunctive behavioral strategies. Full article

Background/Objectives: Unhealthy dietary behaviors and suboptimal oral hygiene practices remain common among Italian children, potentially affecting both nutritional and oral health. Dental caries, a preventable yet highly prevalent condition in pediatric populations, has a multifactorial etiology in which lifestyle factors play a key role. This study aimed to assess the prevalence of dental caries, dietary habits, and oral hygiene behaviors in school-aged children in Lombardy, and to identify factors associated with prevalent caries status. Methods: A cross-sectional study was conducted on 307 schoolchildren aged 9–10 years from ten schools in Northern Italy. Oral health status was evaluated through the plaque index and the DMFT/dmft index during school-based dental examinations. Dietary habits, lifestyle, and oral hygiene practices were collected through structured questionnaires. A mixed-effects logistic regression model was developed to explore potential associations between variables and prevalent caries status. Results: The dietary patterns, weight status, oral hygiene behaviors, and oral health conditions were generally consistent with the national data. Higher plaque index, skipping breakfast, consuming mid-morning snacks, and parental reports of previous caries experiences were retained in the final model. Internal validation suggested reasonable discriminatory ability overall, whereas calibration shows heterogeneity across schools. Conclusions: The findings highlight suboptimal dietary and oral hygiene behaviors among Lombardy schoolchildren and confirm their association with dental caries. Lifestyle-related factors, particularly oral hygiene practices and eating patterns, showed a relevant association with prevalent caries status in the analyzed sample. These results underscore the need for targeted preventive strategies integrating nutritional education and oral health promotion in pediatric populations. Full article

Chlorogenic acid (CGA) is a natural polyphenol with various biological activities, but its poor stability and premature release in the gastrointestinal tract limit oral application. Herein, a pH-responsive bilayer hydrogel based on sodium alginate (SA) and carboxymethyl cellulose (CMC) was developed to enhance the gastrointestinal stability and controlled release of CGA. CGA-loaded SA hydrogels were prepared via Ca²⁺-induced ionotropic gelation, followed by CMC coating to form a bilayer structure. The SA/CMC hydrogels showed a drug loading capacity of 15.2–16.7% and pH-dependent swelling behavior. In vitro release studies revealed that the bilayer hydrogel suppressed CGA release in simulated gastric fluid (pH 1.2), with a cumulative release of approximately 30%, while enabling sustained release in simulated intestinal fluid (pH 6.8), reaching about 70% within 10 h. Release kinetics indicated that CGA release was controlled by Fickian diffusion under acidic conditions and by a diffusion-polymer relaxation mechanism under intestinal conditions. Moreover, encapsulation in the SA/CMC hydrogel improved the thermal, light, and pH stability of CGA while maintaining its antioxidant activity and biocompatibility. These results indicate that SA/CMC bilayer hydrogels provide a promising strategy for stabilized gastrointestinal delivery of chlorogenic acid. Full article

Background/Objectives: Sleep-disordered breathing (SDB), including obstructive sleep apnea, is common in children and is associated with mouth breathing, snoring, and neurobehavioral disturbances. In pediatric orthodontic patients, oral habits and craniofacial imbalances may contribute to airway dysfunction, making orthodontic evaluation a potential setting for early identification of SDB. This study aimed to estimate the prevalence of SDB and to evaluate its associations with parent-reported behavioral symptom profiles in a cohort of pediatric orthodontic patients. Methods: A multicenter cross-sectional study was conducted in 186 children aged 7–13 years attending orthodontic clinics in Oradea and Târgu Mureș, Romania. Parents completed a structured questionnaire on oral habits, the 22-item Pediatric Sleep Questionnaire (PSQ), with SDB defined as 8 or more positive responses, and a parent-reported behavioral screening form assessing ADHD symptom subtypes, oppositional-defiant disorder (ODD), conduct disorder, and anxiety/depression. These behavioral outcomes were based on screening measures and were not intended as clinical psychiatric diagnoses. Associations were analyzed using chi-square or Fisher’s exact tests, and multivariable logistic regression analyses were performed adjusting for age, sex, and weight status. Results: Mouth breathing was reported in 61.8% of participants, snoring in 26.9%, and SDB in 13.4%. Positive screens for ADHD-inattentive (p < 0.001), ADHD-hyperactive/impulsive (p < 0.001), ADHD-combined (p < 0.001), ODD (p < 0.001), and anxiety/depression (p < 0.001) were significantly more frequent among children with SDB. In multivariable analysis, SDB remained independently associated with ADHD-combined subtype (OR = 6.22), ADHD-hyperactive/impulsive symptoms (OR = 5.84), oppositional-defiant disorder (OR = 4.91), and anxiety/depression (OR = 4.38). Conclusions: SDB was identified in a meaningful proportion of pediatric orthodontic patients and was significantly associated with multiple screening-defined behavioral symptom domains. These findings support consideration of brief airway- and sleep-oriented screening during orthodontic assessment, particularly in school-aged children presenting with mouth breathing, snoring, or behavioral concerns. Given the cross-sectional and questionnaire-based design, the findings should be interpreted as associative and warrant confirmation in prospective studies using objective sleep measures. Full article

Aluminum chloride (AlCl₃)-induced rat models are widely used to investigate Alzheimer-like neurodegeneration, yet substantial methodological variability limits cross-study comparability. A structured synthesis focused specifically on the methodological architecture of these models, including dose, exposure duration, route of administration, and behavioral assessment, remains lacking. This review aimed to synthesize the behavioral paradigms used to assess learning and memory in rat models of aluminum chloride-induced Alzheimer’s disease, with particular emphasis on dose, duration, and route of administration. A structured narrative review incorporating systematic elements was conducted following PRISMA-informed procedures using PubMed, Web of Science, and Scopus. The reviewed literature showed a predominance of oral administration, low-to-moderate AlCl₃ doses and subchronic exposure durations, most commonly 31–60 days. Behavioral assessment was dominated by hippocampal-dependent paradigms, particularly the Morris water maze and Y-maze. Across studies, AlCl₃ exposure was associated with multidomain behavioral impairment accompanied by consistent hippocampal and cortical histopathological abnormalities and convergent biochemical and molecular changes, including cholinergic dysfunction, oxidative stress, neuroinflammation, and amyloid- and tau-related alterations. Overall, the available literature does not support a standardized experimental protocol or a clear overall dose–effect or duration–effect relationship. Greater harmonization of study design is needed to improve reproducibility and translational relevance. Full article

Background/Objectives: Poor aqueous solubility limits the oral absorption and bioavailability of many active pharmaceutical ingredients. Simple formulation approaches suitable for hospital and community pharmacy compounding are therefore needed. This study aimed to develop and evaluate melt-filled hard capsules containing nifedipine, a model of poorly water-soluble BCS class II drug, using polyethylene glycol (PEG) carriers to improve dissolution performance. Methods: PEG blends of different molecular weights (PEG 400, PEG 1500, and PEG 4000) were prepared by melt mixing, followed by incorporation of nifedipine and manual filling into hard gelatin capsules. The formulations were characterized regarding mass variation, drug content, in vitro dissolution, rheological behavior, and solid-state properties using Fourier transform infrared (FTIR) spectroscopy. Dissolution profiles were kinetically modeled and compared with pure nifedipine. Results: All capsules met pharmacopoeial requirements for mass uniformity and showed acceptable drug content. PEG-based melt-filled formulations exhibited markedly enhanced dissolution compared with crystalline nifedipine. Faster drug release was associated with lower-molecular-weight PEGs and reduced viscosity, with the PEG 400/PEG 1500 blend demonstrating the most rapid dissolution. Rheological analysis confirmed shear-thinning behavior, while FTIR findings suggested intermolecular interactions and partial amorphization of nifedipine within the PEG matrices. Conclusions: This study provides a translational adaptation of solid dispersion principles into a compounding-compatible melt-filling approach. Full article

Background/Objectives: Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases; however, evidence in the literature indicates anti-inflammatory, analgesic, and immunomodulatory properties, suggesting potential for therapeutic repositioning. This study aimed to evaluate the analgesic and anti-inflammatory effects of ambroxol in an experimental model of osteoarthritis (OA). Methods: Adult male Wistar rats underwent OA induction on day zero (D0) by sodium monoiodoacetate (MIA) injection and were allocated into the following groups: Healthy, negative control (CTRL−), and groups treated with meloxicam (2 mg/kg) or ambroxol (10, 50, and 100 mg/kg). Treatments were administered orally (gavage) once daily for 28 days. Behavioral tests were performed, including rotarod, walkway gait analysis, weight-bearing, Von Frey, and Rat Grimace Scale assessments, along with radiographic and histopathological analyses and quantification of pro- and anti-inflammatory cytokines (IL-1β, IL-6, and IL-10). Results: Ambroxol treatment improved nociceptive parameters and motor function, reduced radiographic and histopathological scores, and showed performance comparable to meloxicam in several tests. There was a marked reduction in IL-1β and IL-6 levels, while IL-10 levels were lower in ambroxol-treated groups, suggesting early control of the inflammatory response. Conclusions: The results indicate that ambroxol exhibits antinociceptive and anti-inflammatory actions and suggest a potential chondroprotective effect, reinforcing its viability as a candidate for therapeutic repositioning in osteoarthritis. Further studies are required to more precisely elucidate its mechanisms of action, define optimal dosing and treatment duration, and support translation to clinical models. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is a tumor characterized by heterogeneous clinical behavior and prognosis. The tumor immune microenvironment plays a significant role in tumor progression and patient prognosis. p16 expression has been investigated as a surrogate biomarker in certain subtypes of head and neck squamous cell carcinomas, but its prognostic significance in oral squamous cell carcinoma remains incompletely elucidated. Methods: A retrospective cohort of 59 patients diagnosed with primary oral squamous cell carcinoma was analyzed. Tumor samples were evaluated for p16 expression and immunohistochemical markers associated with immune cell populations. Associations between immune microenvironment features, p16 status, and clinical outcomes such as recurrence and survival rate were analyzed. Results: p16-positive tumors were predominantly associated with immunotype A and exhibited higher densities of CD8+ cytotoxic T lymphocytes and natural killer (NK) cells. In contrast, immunotype B tumors showed similar characteristics regardless of p16 status, with no significant differences between p16-positive and p16-negative cases. Distinct immune profiles were variably associated with clinicopathological features and patient outcomes. Conclusions: These findings suggest that the immunological phenotype of oral squamous cell carcinoma may represent a potential prognostic factor. Full article

Background: In older people, syphilis diagnosis might be undervalued due to both clinical conditions and age-related changes that obscure symptom presentation and physician discomfort with sexual history-taking, creating a dual barrier to timely recognition. Methods: Case presentation with literature review. Results: An 80-year-old woman was referred to the Dermatology Department of Cagliari University by her oncologist, with a 2-month history of intermittent episodes of pruritus associated with papular–nodular skin lesion eruptions, accompanied with asthenia, night sweats, and unintentional weight loss, indicative of a paraneoplastic syndrome or an adverse drug reaction. Careful evaluation indicated the need to perform serological testing, which confirmed secondary syphilis (RPR 1:64 and TPHA 1:5120). Specific questioning regarding sexual behaviors pointed out oral and anal intercourse. The 83-year-old husband did not have active lesions at visit but reported a self-healing generalized skin rash, episodes of asthenia, arthralgia, and headache he had never suffered before. Blood tests showed positive RPR 1:64 and TPHA 1:5120. Targeted sexual history assessment disclosed patient’s engaging with commercial sex workers, clarifying the chain of transmission in this conjugal STI case. Treatment with Benzathine penicillin G 2.4 million units IM in a single dose resulted in complete recovery in both patients. Conclusions: The observation highlights the importance of maintaining a high index of suspicion for syphilis even at advanced age. Persistent stigma regarding elderly sexuality should be faced, and targeted interventions are necessary to improve the clinician’s ability to identify STIs in older adults, but also to reduce sexual stigma and taboo persistence in the general population. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease linked to epidermal barrier dysfunction, Th2-skewed immune polarization, and disrupted gut microbiota homeostasis. While probiotic interventions show promise in managing AD, the mechanisms governing strain-specific efficacy—particularly systemic modulation via the “gut–skin axis”—remaining to be fully elucidated. Methods: This study systematically compared the oral therapeutic effects of three Lacticaseibacillus rhamnosus strains (MG-A047, MG-A054, and LGG) in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Results: By integrating behavioral, histopathological, and serological assessments with 16S rRNA-based gut microbiota profiling and in vitro functional assays, this study offers a multidimensional evaluation of the strain-specific advantages and potential therapeutic mechanisms of three L. rhamnosus strains. The results demonstrate that MG-A054 most effectively alleviated cutaneous inflammation and pruritus, significantly reduced serum IgE and IL-4 levels, and attenuated epidermal hyperplasia and inflammatory cell infiltration (including mast cells and eosinophils). Mechanistically, this strain may directly inhibit hyaluronidase activity and mast cell degranulation, and specifically remodel the gut microbiota structure, thereby promoting a shift toward a healthier functional profile. Conclusions: These findings suggest that the superior efficacy of MG-A054 may be achieved through coordinated modulation of the gut–skin axis and related pathways. This study offers new mechanistic clues for understanding the strain-specific actions of probiotics and lays a preclinical foundation for the further development of MG-A054 as a potential targeted microecological therapy for AD. Full article

Background: Facial asymmetry in patients with dentofacial deformity is often associated with occlusal asymmetry, functional differences in mastication, and temporomandibular joint (TMJ) conditions. However, side-to-side differences in the stability of masticatory movement and their relationship with oral function have not been fully clarified. Therefore, this study aimed to investigate differences in masticatory movement, oral function, and the prevalence of MRI-based structural features of the temporomandibular joint between the deviated and non-deviated sides in patients with facial asymmetry. Methods: Twenty-one patients with dentofacial deformity and facial asymmetry were included in this study. Oral function was evaluated by measuring occlusal contact area, occlusal force, and masticatory performance. Masticatory movement was recorded using a mandibular movement recording system, and parameters related to the masticatory path and chewing speed were calculated. The stability of masticatory movement was evaluated using the variance of these parameters across chewing cycles. Temporomandibular joint structural features were assessed using CT and MRI. Comparisons between the deviated and non-deviated sides were performed using paired statistical tests. Results: Occlusal contact area and occlusal force were significantly greater on the deviated side than on the non-deviated side (p = 0.001 and p = 0.006, respectively), whereas no significant difference was observed in masticatory performance (p = 0.211). The deviated side showed a smaller closing angle (p = 0.005) and maximum lateral amplitude (p = 0.019), indicating a more vertical chewing pattern. The stability of masticatory movement, evaluated using the variance of masticatory path and velocity parameters, was significantly greater on the deviated side (e.g., variance of cycle axis angle, p = 0.002; variance of maximum closing velocity, p = 0.006). In addition, the prevalence of imaging-based structural features of the temporomandibular joint was significantly higher on the deviated side (p = 0.016). Conclusions: Patients with dentofacial deformity and facial asymmetry were associated with functional asymmetry between the deviated and non-deviated sides. The deviated side showed greater occlusal contact area, occlusal force, and stability of masticatory movement. These findings suggest that the deviated side may be functionally favorable for mastication and may be related to a tendency toward preferential chewing behavior. However, because the habitual chewing side was not directly evaluated in the present study, this interpretation should be considered cautiously and viewed as hypothesis-generating. Full article