Search Results (71)

Porosity and roughened surfaces of implant materials have been shown to lead to improved cellular attachment and enhanced osseointegration. These topography changes in the surface also aid in the mechanical interlocking of the material to the bone. Polyetheretherketone (PEEK) has emerged as a popular alternative to titanium-based implants due to its lack of stress-shielding effect, radiolucency, and high chemical resistance. However, PEEK is bioinert, thus requiring surface modifications to elicit appropriate cellular responses that lead to successful osteointegration of the material in vivo. Sulfonation is a process used to modify the surface of PEEK, which can be controlled by varying parameters such as soak time and soak temperature, thereby fabricating a porous surface on the material. This work aimed to ensure the repeatability of a previously optimized sulfonated and hydrothermally treated PEEK surface and subsequently observe the mechanical properties, bacterial attachment, and cellular response of pre-osteoblast MC3T3-E1 cells on the surface. This study found that while all PEEK surfaces had similar cell and Staphylococcus aureus attachment, the sulfonated and hydrothermally treated PEEK (peak mean load of 605 N, p ≤ 0.0001) and the sulfonated only PEEK (peak mean load of 495 N, p = 0.0240) had a higher level of performance in expulsion testing than smooth PEEK due to its mechanical interlocking ability. Imaging and contact angle analysis confirm that a surface with repeatable porosity can be achieved. Full article

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, representing only 5–10% of urothelial carcinoma. The mainstay of treatment for high-risk patients is radical nephroureterectomy. Given the aggressive behavior of this disease, additional treatments could be required perioperatively in terms of chemotherapy (CHT), either in a neoadjuvant or adjuvant setting. On the other hand, low-risk and selected cases can be managed with kidney-sparing surgery (KSS). The ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST) is an ongoing international, multicenter registry of patients undergoing surgery for UTUC. After conducting a literature search in February 2025 using the MEDLINE (via PubMed) and Embase databases, we identified 14 studies based on the ROBUUST data analyses. There are several key topics concerning UTUC that remain under debate and were therefore addressed in these studies, focusing on preoperative evaluation and planning, surgical techniques and intraoperative procedures, additional perioperative treatments, and outcomes. The ROBUUST registry has served as a valuable source for a growing body of investigations focusing on various aspects of UTUC treatment planning, decision-making, and outcomes, providing innovative tools and enabling large-scale, novel analyses. Full article

Evidence appears to be building that direct exposure to natural landscapes characterized by significant green cover, such as forests, can help to reduce chronic health conditions such as obesity, stress, hypertension, chronic cardiovascular conditions, depression, anxiety, cancer, and diabetes. One way to encourage greater exposure to nature may be through the use of nature prescriptions, whereby clinicians formally recommend (or prescribe) time in nature to their patients. Based on self-reported data, we describe the implementation and lessons learned from a pilot field experiment examining the clinical use of nature-based versus conventional exercise recommendations in rural Oregon. We discuss the potential benefits of such recommendations, as well as identify several challenges and opportunities associated with field experiments seeking to evaluate whether nature prescriptions, offered as one part of patients’ overall treatment plans, meaningfully improve human health outcomes in clinical settings. We conclude with several recommendations for practitioners and researchers interested in implementing and evaluating nature-based exercise programs to improve public health. Full article

Limited research has examined the possible synergistic interrelationships between serious bacterial infections (SBIs) of the heart (i.e., endocarditis), bone, spine, brain, or joints (e.g., osteomylelitis) and hepatitis C virus (HCV) infections. We examined whether syndemic interactions existed between SBI, HCV, and substance-use-related factors in rural communities, hypothesizing that injection-mediated risks elevated the likelihood for both SBIs and HCV infections, which could be exacerbated by synergistic biological–biological or biological and social interactions. We calculated the prevalence ratios (PRs) of past-year SBI associated with each risk factor in separate models. Effect modification among significant risk factors was assessed using multiplicative interaction. Among 1936 participants, 57% were male and 85% White, with a mean age of 36 years. Eighty-nine participants (5%) reported hospitalization for an SBI in the year prior to the survey. More than half tested HCV-antibody-positive (58%); 62 (5.6%) of the participants with a positive HCV antibody result reported past-year hospitalization with an SBI. Injection behaviors were correlated with other SBI risk factors, including multiple injections in the same injection event (MIPIE), injection equipment sharing, and fentanyl use. In adjusted models, MIPIE (PR: 1.79; 95% confidence interval [CI]: 1.03, 3.11) and fentanyl use (PR: 1.68; 95% CI: 1.04, 2.73) were significantly associated with past-year SBI. Our analyses pointed to co-occurring epidemics of SBI and HCV, related to the cumulative health effects of fentanyl use contributing to frequent injections and MIPIE. Both the SBI and HCV epidemics present public health challenges and merit tailored interventions. Full article

A conventional, group-specific PCR method was developed to identify each of the four previously defined major taxa (Myoviridae, Siphoviridae, Podoviridae and Microviridae) of somatic coliphages and used to classify isolates from sewage. Somatic coliphage infectivity detection, occurrence and survival in primary human sewage effluent was observed over time to further understand the presence and behavior of the groups of somatic coliphages at two environmental temperatures (4 and 25 °C). Over time, the taxonomic composition of the somatic coliphage population in sewage changed, with the Microviridae family becoming the most prevalent family in the sewage population after several weeks. Based on their persistence and prevalence in environmental waters, phages belonging to the Microviridae family provide supporting information on sewage contamination and possibly of human enteric viruses in sewage-contaminated water. Full article

Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID). Although HCV has become universally curable since the arrival of direct-acting antivirals, barriers exist to facilitating care and cure in this historically hard-to-reach population, including limited testing and healthcare services and healthcare stigma, issues that are compounded in rural areas. Telehealth is effective in increasing access to HCV care and cure, but innovative approaches of testing and care are required to fully address the need among rural PWID, which led to our study examining a mobile telehealth model for treating HCV. In this commentary, we discuss lessons learned delivering telehealth on a mobile unit, important factors for consideration when designing a mobile intervention, and we suggest an ideal model to increase access to HCV testing and treatment and other services for rural PWID. Full article

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time. Cross- and side-bridged tetraazamacrocylic complexes offer significant advantages over the non-bridged molecular structures in terms of receptor affinity, potential for radiolabelling, and use in therapeutic applications. Our investigation has been extended to the influence of the ring size on bridged tetraazamacrocyclic compounds with the addition of two novel chelators (bis-cross-bridged homocyclen and bis-cross-bridged cyclen) to compare to the bis-bridged cyclam, along with novel metal complexes formed with copper(II) or zinc(II). The in vitro biological assays showed that all of the zinc(II) complexes are high affinity antagonists with a marked increase in CXCR4 selectivity for the bis-cross-bridged cyclen complex, whereas the properties of the copper(II) complexes are highly dependent on metal ion geometry. X-ray crystal structural data and DFT computational studies allow for the rationalisation of the relative affinities and the aspartate residue interactions on the protein surface. Changing the ring size from 14-membered can increase the selectivity for the CXCR4 receptor whilst retaining potent inhibitory activity, improving the key pharmacological characteristics. Full article

Background: Tourette syndrome is a neurodevelopmental movement disorder involving basal ganglia dysfunction. PDE10A inhibitors modulate signaling in the striatal basal ganglia nuclei and are thus of interest as potential therapeutics in treating Tourette syndrome and other movement disorders. Methods: The preclinical pharmacology and toxicology, human safety and tolerability, and human PET striatal enzyme occupancy data for the PDE10A inhibitor EM-221 are presented. Results: EM-221 inhibited PDE10A with an in vitro IC50 of 9 pM and was >100,000 selective vs. other PDEs and other CNS receptors and enzymes. In rats, at doses of 0.05–0.50 mg/kg, EM-221 reduced hyperlocomotion and the disruption of prepulse inhibition induced by MK-801, attenuated conditioned avoidance, and facilitated novel object recognition, consistent with PDE10A’s inhibition. EM-221 displayed no genotoxicity and was well tolerated up to 300 mg/kg in rats and 100 mg/kg in dogs. In single- and multiple-day ascending dose studies in healthy human volunteers, EM-221 was well tolerated up to 10 mg, with a maximum tolerated dose of 15 mg. PET imaging indicated that a PDE10A enzyme occupancy of up to 92.8% was achieved with a ~24 h half-life. Conclusions: The preclinical and clinical data presented here support the study of EM-221 in phase 2 trials of Tourette syndrome and other movement disorders. Full article

Titanium alloys are commonly used for implants, but the naturally forming oxides are bioinert and not ideal for bacterial resistance or osseointegration. Anodization processes are a modification technique that can crystallize the oxides, alter oxide surface topography, and introduce beneficial chemistries. Crystalline titanium oxides are known to exhibit photocatalytic activity (PCA) under UVA light. Anodization was used to create mixed-phase oxides on six titanium alloys including commercially pure titanium (CPTi), Ti-6Al-4V (TAV), Ti-6Al-7Nb (TAN), two forms of Ti-15Mo (TiMo-β and TiMo-αβ), and Ti-35Nb-7Zr-5Ta (TNZT). Combined EDS and XPS analyses showed uptake of the electrolyte and substrate alloying elements into the oxides. The relative oxide PCA was measured using methylene blue degradation assays. CPTi and TAN oxides exhibited increased PCA compared to other alloys. Combined XRD and EBSD oxide phase analyses revealed an unfavorable arrangement of anatase and rutile phases near the outermost surfaces, which may have reduced PCA for other oxides. The relative Staphylococcus aureus attachment to each oxide was also assessed. The CPTi and TiMo-αβ oxides showed significantly reduced S. aureus attachment after 1 h of UVA compared to un-anodized CPTi. Cell culture results verified that the UVA irradiation did not negatively influence the MC3T3-E1 attachment or proliferation on the mixed-phase oxides. Full article

Bottlenose dolphins (Tursiops spp.) inhabit bays, sounds, and estuaries (BSEs) throughout the southeast region of the U.S.A. and are sentinel species for human and ecosystem-level health. Dolphins are vulnerable to the bioaccumulation of contaminants through the coastal food chain because they are high-level predators. Currently, there is limited information on the spatial dynamics of mercury accumulation in these dolphins. Total mercury (THg) was measured in dolphin skin from multiple populations across the U.S. Southeast Atlantic and Gulf of Mexico coasts, and the influence of geographic origin, sex, and age class was investigated. Mercury varied significantly among sampling sites and was greatest in dolphins in St. Joseph Bay, Florida Everglades, and Choctawhatchee Bay (14,193 ng/g ± 2196 ng/g, 10,916 ng/g ± 1532 ng/g, and 7333 ng/g ± 1405 ng/g wet mass (wm), respectively) and lowest in dolphins in Charleston and Skidaway River Estuary (509 ng/g ± 32.1 ng/g and 530 ng/g ± 58.4 ng/g wm, respectively). Spatial mercury patterns were consistent regardless of sex or age class. Bottlenose dolphin mercury exposure can effectively represent regional trends and reflect large-scale atmospheric mercury input and local biogeochemical processes. As a sentinel species, the bottlenose dolphin data presented here can direct future studies to evaluate mercury exposure to human residents in St. Joseph Bay, Choctawhatchee Bay, and Florida Coastal Everglades, as well as additional sites with similar geographical, oceanographic, or anthropogenic parameters. These data may also inform state and federal authorities that establish fish consumption advisories to determine if residents in these locales are at heightened risk for mercury toxicity. Full article

The materials traditionally used for implant applications, such as titanium alloys, cobalt chromium, and zirconium, often require surface modifications to achieve the desired osseointegration. These materials still have the problematic stress-shielding effect. To limit stress shielding, PEEK is the superior alternative to fulfill implant needs. However, the traditional methods of modifying and functionalizing the surface of PEEK are often expensive, time consuming, and are not easily translated into commercialization. Sulfonation is a process, which is dependent on controllable factors. Thus far, no research has been performed to optimize the sulfonation process. Our data suggest that the process factors can be controlled and optimized. Cellular activity was examined on the optimized PEEK surfaces through testing with pre-osteoblast MC3T3-E1 cells through cell viability (MTT assay), cell proliferation (DNA assay), cell differentiation (ALP assay), and cell mineralization (Alizarin red assay). Overall, sulfonated and heat-treated PEEK exhibited a statistically significant increase in DNA content over the course of 21 days, indicating more cell proliferation and viability for that surface. In vitro testing results showed that the optimized sulfonated and heat-treated PEEK exhibited superior cell proliferation and mineralization performance over smooth PEEK and sulfonated-only PEEK. Full article

Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFG’s physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk. Full article

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS. Full article

The fast-growing tree, eastern cottonwood (Populus deltoides), currently is being planted to catalyze native forest restoration on degraded agricultural sites in the southeastern United States. Many of these restoration sites are appropriate for short rotation woody crop (SRWC) culture that addresses climate mitigation objectives, but information needed to optimize climate mitigation objectives through such plantings is limited. Therefore, we established a 10-year experiment on degraded agricultural land located in the Mississippi Alluvial Valley, USA, aiming to quantify the dynamics of aboveground carbon (AGC) accumulation in a cottonwood planting of four replicated spacing levels (3.7 × 3.7 m, 2.7 × 1.8 m, 2.1 × 0.8 m, and (0.8 + 1.8) × 0.8 m) aligned with SRWC systems targeting various ecosystem services. Annual sampling revealed a substantial range in increments of AGC and year 10 carbon stocks among stands of different densities. Mean annual increments for AGC (MAI_AGC) were similar for the two tightest spacing levels, peaking higher than for the other two spacings at about 7.5 Mg ha⁻¹ y⁻¹ in year 7. Year 10 AGC ranged between 22.3 Mg ha⁻¹ for stands spaced 3.7 × 3.7 m and 70.1 Mg ha⁻¹ for stands of the two tightest spacings, leading us to conclude that a spacing between 2.1 × 0.8 m and 2.7 × 1.8 m would maximize aboveground carbon stocks through year 10 on sites of similar agricultural degradation. Increments and accumulation of AGC on the degraded site trended lower than values reported from more productive sites but illustrate that quick and substantial transformation of the carbon stock status of degraded agricultural sites can be achieved with the application of SRWCs to restore forests for climate mitigation and other compatible ecosystem services. Full article

Grazing and hay forage crops reduce erosion compared to annual crops, but few studies have compared soil and nutrient loss among grazing systems compared to a control. We evaluated runoff water quality and nutrient loss among three grazing systems and a hay crop production field with manure application (control) using a paired watershed design. Four edge-of-field sites at a research farm in central Wisconsin were managed as hay during calibration (2013–2018) followed by a grazing treatment phase (2018–2020). Grazing treatments of different stocking methods included continuous stocking (CS), primary paddock stocking (PPS), and adaptive multi-paddock stocking (AMPS). Runoff, sediment, nitrogen (N), and phosphorus (P) loads were monitored year-round. Grazing increased average runoff volume by as much as 1.7-fold depending on stocking method and tended to decrease event mean N and P concentrations. CS had larger mean sediment (2.0-fold), total N (1.9-fold), and total P loads (1.2-fold) compared to the control and had the lowest average pasture forage mass. AMPS had lower N and P loss as a percentage of that applied from manure application/livestock excretion (1.3 and 1.6%, respectively) compared to the control (2.5 and 2.1%), PPS (2.5 and 2.6%), and CS (3.2 and 3.0%). Stocking method had a marked impact on nutrient loss in runoff from these systems, suggesting water quality models should account for pasture management, but nutrient losses from all perennial forage systems were small relative to previous data from annual cropping systems. Full article