Search Results (241)

The Chopart amputation is a controversial amputation level and has been described as a relatively non-functional amputation due to the increased risk for stump deformity and subsequent complications. Recent literature has shown that a tibiotalocalcaneal arthrodesis can subjectively increase function in the Chopart amputation. We describe the use of a tibiotalocalcaneal arthrodesis in a 44-year-old diabetic male with a Chopart amputation for the purpose of limb and gait salvage. After 292 days and an uneventful postoperative course, the patient consented to gait analysis. The case allows us to objectively conclude that the tibiotalocalcaneal arthrodesis can quantitatively increase the functionality of the Chopart amputation and, in turn, expand its indication for use within the more functional populations. Full article

Mobile health units (MHUs) can reach populations facing barriers to traditional primary care, but information about factors associated with their utilization is limited. The objective of this ecological study was to evaluate whether MHU encounter density is increased in census tracts designated as Primary Care Health Professional Shortage Areas (HPSAs) and explore whether associations varied by socioeconomic vulnerability. We analyzed Wayne State University/Wayne Health MHU encounters with adult patients from July 2021 to September 2025. Negative binomial regression models with a log link and log(population) offset tested the a priori hypothesis that encounter density was increased in designated versus undesignated HPSA census tracts. Sensitivity analyses assessed variation by social vulnerability index score quartiles established by the US Centers for Disease Control and Prevention. One quarter of the five-county metropolitan Detroit, Michigan, catchment area census tracts were designated healthcare shortage areas. Overall, 13,852 encounters with 10,924 unique patients occurred across 924 of 1305 census tracts. Encounter rate per adult population was significantly increased by severalfold comparing designated versus undesignated shortage areas, with stronger associations at lower socioeconomic vulnerability index score quartiles (interaction p = 0.0006). These findings support continued efforts to scale and evaluate MHUs to address projected healthcare shortages, particularly in socioeconomically vulnerable areas. Full article

Freezing cold injury (FCI) is a localized injury caused by prolonged exposure to sub-zero temperatures, posing a significant health risk to military personnel operating in extreme climates. This study aimed to explore how FCI affects the health and lives of soldiers in the Norwegian Armed Forces (NAF), addressing the broader context of its impact on military readiness and the personnel’s well-being. Sixteen participants with a history of grade 2 FCI were recruited through the Norwegian Armed Forces Health Registry and interviewed. Systematic content analysis was used to identify key themes related to the causes and consequences of FCI, as well as the influence of military culture. The findings indicate that FCI results from interacting environmental, behavioural, and systemic factors. Environmental contributors included cold exposure and limited opportunities to eat or drink. Behavioural and individual contributors included reduced awareness of bodily cues in cold conditions and the need to remove gloves for weapon handling under time pressure. Systemic contributors, particularly military cultural norms emphasizing strict discipline and toughness, were perceived to discourage early symptom reporting and the use of preventive measures. Most participants (11/16) reported long-term consequences, including chronic physical discomfort, functional limitations, and negative impacts on their careers and daily lives. This study highlights the significant short- and long-term consequences of FCI, which extend beyond physical harm to affect soldiers’ overall health, functioning, and career progression. The findings emphasize the need for targeted preventive measures to mitigate the risks of FCI and protect military personnel in extreme climates. Full article

Background: Persistent endodontic infections involving Enterococcus faecalis and Candida albicans are a major cause of root canal treatment failure. Although conventional irrigants, such as sodium hypochlorite and chlorhexidine (CHX), exhibit strong immediate antimicrobial activity, microbes may survive and recover from the initial antimicrobial effect, hence limiting their effectiveness, especially in complex root canal anatomies and in the apical terminus of the tooth. Antibacterial dressing techniques were not proven satisfactory due to depletion of the antibacterial component or difficulty in spreading it evenly along the entire root canal. This study aimed to develop and evaluate the antimicrobial efficacy and release characteristics of a novel sustained-release device (SRD), delivering CHX via gutta-percha points coated with a sustained-release formulation used as a temporary intracanal medicament. Methods: Gutta-percha points were coated with two sustained-release CHX varnishes (CHX1 and CHX2) or a placebo and assessed in vitro. Antimicrobial activity against E. faecalis and C. albicans was evaluated using agar diffusion assays over time. Release kinetics were analyzed using Rhodamine-labeled SRD in a 3D-printed acrylic molar tooth model via fluorescence microscopy. Additionally, biofilm-infected acrylic molar teeth were treated with a placebo, a single 2% CHX irrigation, or SRD-coated gutta-percha points placed as an intracanal dressing prior to obturation. Microbial viability was quantified by colony-forming unit (CFU/mL) analysis from root canals and gutta-percha points. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc multiple comparison test (p < 0.05). Results: SRD-coated gutta-percha points demonstrated sustained antimicrobial activity for up to 21 days against E. faecalis and 19 days against C. albicans. Fluorescence analysis, in an acrylic tooth model, confirmed continuous release for up to 15 days, with pronounced diffusion in the isthmus and palatal canals. In biofilm-infected acrylic teeth models, SRD treatment resulted in a significant reduction of 2–3 log₁₀ CFU/mL compared to placebo groups (p < 0.001) and prevented microbial rebound over the 14-day observation period. In contrast, a single application of 2% CHX solution showed only transient reduction followed by regrowth. Conclusions: Sustained-release CHX delivery via polymer-coated gutta-percha points provided prolonged antimicrobial activity against bacterial and fungal biofilms compared to conventional single-dose CHX application in this in vitro model. These findings support the potential use of coated gutta-percha points as a removable intracanal drug delivery platform prior to final obturation, although further studies incorporating direct-release quantification and in vivo validation are required before clinical translation. Full article

Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; however, their effects on S. sanguinis have not been thoroughly studied. Here, we investigated the antimicrobial and antibiofilm efficacy of ZnO NPs against this bacterial species. ZnO NPs exhibited a minimal inhibitory concentration (MIC) of 100 µg/mL and caused rapid, dose-dependent suppression of intracellular ATP levels and overall metabolic activity within 2–4 h of exposure. ZnO NPs induced reactive oxygen species (ROS) production in a dose-dependent manner. The free radical scavenger α-tocopherol partly prevented the antibacterial effect of ZnO NPs, suggesting that lipid peroxidation contributes to ZnO NP-mediated toxicity, although it is not the sole mechanism involved. Short-term exposure (2 h) to ZnO NPs did not significantly affect membrane integrity or cellular morphology, whereas prolonged treatment (24 h) resulted in pronounced membrane permeabilization, membrane hyperpolarization, and cellular swelling. Computational morphometric analyses of high-resolution scanning electron microscopy (HR-SEM) images of planktonic growing bacteria after a 24 h treatment confirmed a significant, dose-dependent increase in cell surface area and surface roughness. Importantly, ZnO NPs also reduced the metabolic activity and compromised the structural integrity of mature, preformed biofilms. Collectively, these findings demonstrate that ZnO NPs exert antimicrobial and antibiofilm effects against S. sanguinis through early metabolic inhibition associated with oxidative stress followed by progressive membrane dysfunction. Full article

Background/Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a global health crisis, but current diagnostics are limited. Liver biopsy is invasive, magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is expensive, and quantitative ultrasound methods are low-accuracy, especially in patients with a high body mass index (BMI). This study introduces a novel thermo-acoustic (TA) method that generates ultrasound signals based on tissue electrical conductivity, where lean tissue (high in water and electrolytes) absorbs more radio-frequency (RF) energy than fatty tissue, providing a direct molecular contrast for fat. Methods: A prospective, cross-sectional feasibility study compared a new thermo-acoustic fat fraction (TAFF) score with the reference standard MRI-PDFF in 40 subjects with suspected fatty liver disease. Bland–Altman analysis, Deming regression, and Binary classification performance were tested. To establish system stability, a dedicated Repeatability and Reproducibility (R&R) study (N = 14) evaluated inter-operator and intra-operator consistency using an Intraclass Correlation Coefficient (ICC) derived from a two-way random-effects ANOVA model. Results: TAFF estimates demonstrated a substantial correlation (r = 0.89) with MRI-PDFF and an average absolute error of 3.04% fat fraction. Classification performance was high, with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.92 at the 12% fat fraction threshold and 0.99 at the 20% fat fraction threshold. The R&R study confirmed robust stability (intraclass correlation = 0.89) and a negligible mean inter-operator difference of 0.36%. Estimation errors showed no statistically significant correlation with BMI or other body habitus measurements. Conclusions: These findings support thermoacoustics’ potential as an accurate, non-invasive, point-of-care solution that can serve as a new imaging biomarker. By providing predictive values closely aligned with MRI-PDFF across the full MASLD spectrum, TAFF can complement currently available ultrasound methods to address the cost and access constraints of MRI for the assessment, diagnosis, and monitoring of MASLD. Full article

Precise control of keratinocyte proliferation and differentiation is critical for oral epithelial regeneration, yet the mechanobiological cues guiding these processes remain incompletely defined. Here, we systematically evaluated how electrospun polycaprolactone (PCL) scaffolds with defined fiber orientations (aligned vs. random) and diameters (600–800 nm, 1.2–1.7 µm, 2.0–2.5 µm) direct gingival keratinocyte fate. Using immortalized human gingival keratinocytes, we assessed cell and nuclear morphology, proliferation dynamics, differentiation marker expression, and the effects of basal keratin (KRT5/KRT14) knockdown. Quantitative morphological analysis revealed scaffold-dependent changes in cell shape: aligned medium-diameter fibers (with fiber diameters of 1.2–1.7 µm) induced pronounced cell and nuclear elongation, whereas random fibers (600–800 nm) promoted larger, more rounded cell and nuclear shapes. Time-resolved EdU assays indicated that aligned scaffolds supported sustained proliferation, whereas random scaffolds elicited a transient proliferative burst followed by a decline. Gene expression analysis (ddPCR) demonstrated that random scaffolds (especially 600–800 nm fibers) upregulated basal keratins (KRT5, KRT14) and early differentiation markers (KRT1, KRT10, KRT4, KRT13) relative to aligned scaffolds. At the protein level, differentiation markers involucrin (IVL) and filaggrin (FLG) were likewise elevated on random scaffolds, corroborating the mRNA findings. Functional KRT5/KRT14 knockdown experiments revealed scaffold-specific dependencies: cells on random scaffolds required these keratins for viability, whereas aligned cultures remained viable upon KRT5/14 loss. Furthermore, KRT5/14 depletion differentially altered downstream differentiation markers (IVL, KRT1) and mechanotransduction markers (LMNB1, YAP1) in a scaffold-dependent manner. Collectively, these findings establish fiber orientation and diameter as key design parameters for controlling keratinocyte fate. As a translational concept, layered scaffolds combining aligned and random fibers may enable spatially controlled proliferation and differentiation in engineered oral epithelia. Full article

Novel colourimetric sensors are readily devised by combining multifunctional (nano)materials with miniature optoelectronic components. The demand to detect and monitor metal ions has resulted in the invention of new colourimetric sensing schemes, especially for use at the Point-of-Need (PoN). Nonetheless, the design of fully reversible optical materials for continuous real-time ion monitoring remains a bottleneck in the practical realisation of sensors. Magnesium ion is vital to physiological and environmental processes, but monitoring can be challenging, particularly in the presence of Ca²⁺ as a cross-sensitive interferent in real samples. In this work, a chromophore molecule Hyphan I (1-(2-hydroxy-5-ß-hydroxyethylsulfonyl-phenyl-azo)-2-naphthol) has been grafted onto a cellulose matrix with a simple one-pot vinylsulfonyl process, to form a transparent, biocompatible and highly flexible thin-film colourimetric magnesium ion sensing material (Cellulose Film with Hyphan-CFH). The CFH film has a pH response time of <60 s over the pH range 4 to 9, with a pK_a1 = 5.8. The LOD and LOQ for Mg²⁺ at pH 8 are 0.089 mM and 0.318 mM, respectively, with an RSD = 0.93%. The CFH film exhibits negligible interference from alkaline and alkaline earth metals, but irreversibly binds certain transition metals (Fe³⁺, Cu²⁺ and Zn²⁺). The CFH material has a fast and fully reversible colourimetric response to pH and Mg²⁺ over physiologically relevant ranges without interference by Ca²⁺, demonstrating good potential for integration into microfluidic systems and wearable sensors for biofluid monitoring. Full article

Background: Non-absorbable polyvinyl alcohol sponges (Merocel) are widely used in otolaryngology for nasal and ear packing but are prone to bacterial colonization and biofilm formation, which may increase infection risk and drive frequent use of systemic antibiotics. Sustained-release drug delivery systems enable prolonged local antiseptic activity at the site of packing while minimizing systemic exposure. Methods: We developed a sustained-release varnish containing chlorhexidine (SRV-CHX) and coated sterile Merocel sponges. Antibacterial, in vitro, activity against Staphylococcus aureus and Pseudomonas aeruginosa was evaluated using kinetic diffusion assays on agar, optical density (OD₆₀₀) measurements of planktonic cultures, drop plate, ATP-based viability assays, biofilm analysis by MTT metabolic assay, crystal violet bio-mass staining, high-resolution scanning electron microscopy (HR-SEM), and spinning disk confocal microscopy. Results: SRV-CHX-coated sponges produced sustained zones of inhibition on agar plates for up to 37 days against S. aureus and 39 days against P. aeruginosa, far exceeding the usual 3–5 days of clinical sponge use. Planktonic growth was significantly reduced compared with SRV-placebo, and a bactericidal effect persisted for up to 16 days for S. aureus and 5 days for P. aeruginosa before becoming predominantly bacteriostatic. Biofilm formation was markedly inhibited, with suppression of metabolic activity and biomass for at least 33 days for S. aureus and up to 16 days for P. aeruginosa. HR-SEM and confocal imaging confirmed sparse, discontinuous biofilms and predominance of non-viable bacteria on SRV-CHX-coated sponges compared with dense, viable biofilms on the placebo controls. Conclusions: Coating Merocel sponges with SRV-CHX provides prolonged antibacterial and anti-biofilm activity against clinically relevant pathogens. This strategy may reduce dependence on systemic antibiotics and improve infection control in nasal and ear packing applications in otolaryngology. Full article

Justice-involved boys are more likely to become teenage fathers than their community peers. This is linked to numerous negative outcomes, including increased delinquent behavior. To help legal practitioners better identify which boys are at risk of becoming a teen parent, this study identifies factors at the time of boys’ very first arrest that prospectively predict their odds of becoming a teen father. Data were drawn from a longitudinal study of 1216 adolescent boys at the time of their first arrest. Binary logistic regression models were used to predict the odds of becoming a teen father across three domains: individual factors, social and contextual factors, and risky behaviors. Approximately 15% of the total sample (n = 171) reported becoming a teen father after their first arrest. At the time of first arrest, poorer neighborhood conditions, increased peer delinquency, substance use, and self-reported offending history increased the odds that boys would become a teen father. Additional models indicated that substance use was the strongest driver of teen fatherhood. However, all factors failed to reached significance once condom use was included in this model. Practical implications for policymakers are discussed, along with suggestions for interventions to reduce teen pregnancy. Full article

Early molecular events underlying ethanol-induced oral squamous cell carcinoma development remain insufficiently understood, primarily due to a lack of suitable in vitro systems that recapitulate the initial stages of premalignant transformation. Therefore, a cell culture model of human gingival keratinocytes representing progressive stages of early ethanol-induced cell transformation was established and comprehensively characterized. The three cell lines, named “gingival keratinocytes” (GK), “epithelioid” (EPI) and “fibroblastoid” (FIB), and their derivatives were analyzed by morphological, cell biological and biochemical methods, with an emphasis on epithelial-to-mesenchymal transition (EMT)-related signaling pathways. All cell lines were non-tumorigenic in vitro. Chronic ethanol exposure induced distinct morphological and molecular alterations that capture early premalignant changes in vitro. This includes reduced E-Cadherin and enhanced Vimentin expression, accompanied by an increased production of reactive oxygen species. Notably, even morphologically stable cell lines displayed metabolic susceptibility to EMT induction, indicating the early activation of transformation-associated signaling cascades even in a premalignant state. These alterations, however, closely mirrored pathohistological features of oral squamous cell carcinomas such as loss of epithelial integrity and acquisition of mesenchymal characteristics. Collectively, the presented model provides a robust and accessible in vitro platform for investigating very early ethanol-induced oral carcinogenesis mechanisms that are relevant in a premalignant state and may facilitate the identification of diagnostic and preventive biomarkers to improve patient outcomes in alcohol-associated oral cancer and precursor lesions. Full article

Oral microbial biofilms play a critical role in the development of various oral infectious diseases, including periodontitis and tooth caries, with Streptococcus mutans recognized as a key biofilm-forming bacterium due to its strong adhesion and acidogenic capacity. Zinc oxide nanoparticles (ZnO NPs) have demonstrated antibacterial properties against various bacteria. This study investigated the antibacterial and antibiofilm properties of ZnO NPs on S. mutans and elucidated their mode of action. Bacterial cultures were exposed to increasing concentrations of ZnO NPs, and planktonic growth, biofilm biomass and biofilm metabolic activity were measured. Complementary assays assessed bacterial ATP content, pH shift in the media, reactive oxygen species (ROS) production, membrane integrity (SYTO 9/PI live/dead staining) and membrane potential. Morphological changes were examined by high-resolution scanning electron microscopy (HR-SEM), while gene expression was analyzed by real-time qPCR. We observed that ZnO NPs inhibited S. mutans growth and biofilm formation in a dose-dependent manner, with both the minimum inhibitory and biofilm inhibitory concentration of 0.5 mg/mL. ZnO NP treatment disrupted bacterial membranes, caused cytoplasmic leakage, and induced ROS production. EPS production determined by Congo Red staining was significantly reduced. Gene expression analysis revealed significant upregulation of vicR, luxS, wapA, gtpB, nox and ftsZ, and downregulation of spaP, gtpC and atpB. In conclusion, ZnO NPs compromise S. mutans viability and biofilm development through oxidative stress and membrane disruption, highlighting their potential use as bioactive materials in oral healthcare. Full article

Background/Objectives: Doyle nasal silicone splints are commonly used in nasal surgeries to maintain the shape of the nasal passage and prevent scar tissue formation. However, these implants are prone to bacterial colonization, particularly by Staphylococcus aureus, which is associated with severely recurrent and recalcitrant cases of infected sinonasal cavities. The aim of this study was to develop a sustained-release varnish (SRV) with antibacterial properties that can be applied to Doyle splints to provide an antibacterial environment for an extended period. Methods: Doyle nasal splints (1 cm × 1 cm segments) were coated with SRV containing one of the three antibiotics: augmentin, ciprofloxacin, or chloramphenicol. A placebo varnish without antibiotics served as a control. The coated splints were exposed daily to a fresh culture of S. aureus, and antibacterial activity was assessed by monitoring bacterial growth. Antibiofilm activity was determined using an MTT metabolic assay. Antibacterial activity was further studied by the kinetic disk diffusion assay, where the stents were transferred daily to new, freshly coated S. aureus plates. Biofilm formation on the coated splints was visualized by high-resolution scanning electron microscopy (HR-SEM). Results: Doyle segments coated with augmentin, ciprofloxacin, or chloramphenicol effectively inhibited S. aureus planktonic growth for 9 ± 1, 18 ± 1, and 21 ± 1 days, respectively. Biofilm formation was prevented for 10 ± 1, 18 ± 1, and 21 ± 1 days, and bacterial clearance occurred for 14 ± 1, 52 ± 1, and >65 days, respectively. HR-SEM images showed the prevention of biofilm formation on the coated segments. Conclusions: Our findings demonstrate that coating Doyle nasal silicon splints with SRV containing augmentin, ciprofloxacin, or chloramphenicol provides long-term antibacterial and antibiofilm activity, with SRV–chloramphenicol being superior. Further studies are needed to confirm the in vivo efficacy of this approach. Full article

Background/objectives: Geographic and ethnic differences influence the genetic landscape of hemophagocytic lymphohistiocytosis (HLH) and the frequency of familial HLH (FHL); this in turn can affect outcomes. Methods: We collected data on 98 patients treated for HLH between 1 January 2001 and 31 July 2024 at four tertiary centers, characterizing the genotype/phenotype correlations. Results: Half of the patients, 51 (52%), were symptomatic by age 1 year and 43 (44%) were diagnosed by that age. Our varied population included 43% Sephardic/Ashkenazi/Ethiopian Jews, 50% Muslim Arabs, and 7% Druze. Molecular analysis was performed on 90.5% of patients and revealed an FHL-related variant in 72%. The genetic variation included biallelic variants in PRF1 (21), UNC13D (12), STXBP2 (15), and STX (1). Eight hemizygous variants were found in X-linked lymphoproliferative disorder-related genes. A RAB27A monoallelic variant in an infant with a severe phenotype was considered pathogenic. The recently described HLH-related gene, ZNFX1, was mutated with varying penetrance in three symptomatic siblings. Overall, of the 94/98 with follow-up, 77% are alive. Strikingly, 5/12 (41.6%) patients with UNC13D variants died while 14/15 (93.3%) patients with STXBP2 variants survived. Logistic regression found poor prognosis associated with young age at diagnosis (p < 0.001), any variant (p = 0.016), UNC13D variant (p < 0.001), poor initial treatment response (p = 0.009), and no BMT (p = 0.005). Conclusions: Our cohort included an extremely high rate of genetic testing and detection of FHL-related variants. UNC13D variations are associated with exceedingly poor outcomes. Response to initial treatment seems crucial for positive outcomes, as does access to hematopoietic stem cell transplantation. Overall, we report a high survival rate, possibly due to a high index of suspicion and prompt diagnosis. Full article

Background: It is well documented that limb salvage interventions may induce or exacerbate biomechanical dysfunction in the residual limb. As a result, patients with Charcot’s neuroarthropathy (CN) are at theoretical risk for progression of or novel neuroarthropathic breakdown, which has been observed in the midfoot after amputation; however, this has not been investigated in rearfoot interventions such as partial calcanectomy. Methods: We retrospectively identified eight patients during a 7.25-year period who had a history of CN and partial calcanectomy in the ipsilateral limb. Patients with contralateral involvement were excluded, and included medical records were analyzed and radiographically characterized. Results: The mean patient age was 73.9 years (range, 59–86 years), and the mean body mass index was 31.4 (range, 22–50). Two patients (25.0%) demonstrated multijoint breakdown. Two feet (25.0%) were characterized as Sanders-Frykberg (SF) II, one (12.5%) as SF III, and three (37.5%) as SF IV/V breakdown. Three patients developed CN a mean of 350.3 days after partial calcanectomy was performed. The mean age and body mass index of patients who experienced post–vertical contour calcanectomy CN was 70.7 years (range, 59-83 years) and 29.0 years (range, 22-35 years), respectively. All instances of postcalcanectomy CN resulted in rearfoot breakdown, with one (33.3%) isolated to the tibiotalar joint and two (66.7%) at the tibiotalar and subtalar joints. A 66.7% limb salvage rate was found in patients who developed postcalcanectomy CN. Conclusions: We conclude that partial calcanectomy in patients with antecedent CN does not result in clinically significant changes that further threaten the limb but identified three instances where partial calcanectomy destabilized the rearfoot and resulted in rearfoot CN breakdown. Although this knowledge should not discourage the use of calcanectomies, clinicians should be cognitive of complications such as CN breakdown that can further threaten the limb. Full article