Search Results (327)

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article

The defects in zinc oxide crystals are of crucial importance for their usability in many applications and are not yet fully understood. Here, we demonstrate that dioxygen species are present as defects in the grown ZnO, resulting in a bending of the atom layers that lie perpendicular to the c-axis. In the Raman spectra, these defects cause the appearance of bands different from the known bands of perfect ZnO crystals allowed by symmetry. These additional Raman bands, which have been frequently reported for ZnO in the past, can thus be fully explained by the presence of dioxygen species, and the widespread assumption of second-order modes for the assignments of these bands is not necessary. Furthermore, the Raman spectrum belonging to perfect zinc oxide in the ideal wurtzite structure is presented, obtained from small domains in ZnO(0001) crystals exposed to pressures up to 2 GPa. The dependence of the O-O stretching modes on the applied pressure proves the presence of dioxygen species in ZnO, which is also confirmed by phonon calculations of structure models with embedded dioxygen species. The surface quality of the ZnO crystals studied is also reflected in the Raman spectra and is included in the analysis. Full article

Recent bioassay studies have unexpectedly supported the high (computationally predicted) binding affinities of angiotensin receptor blockers (ARBs) at α-adrenergic receptors (αARs) in isolated smooth muscle. Computational predictions from ligand docking studies are consistent with very low concentrations of ARBs (e.g., sartans or bisartans) that partially reduce (20–50%) the contractile response to phenylephrine, suggesting that some ARBs may function as partial inverse agonists at αARs. Virtual ligand screening (docking) and molecular dynamics (MD) simulations were carried out to explore the binding affinities and stabilities of selected non-peptide ligands (e.g., ARBs and small-molecule opioids) for several G-protein coupled receptor (GPCR) types, including angiotensin II (AngII) type 1 receptor (AT₁R), α1AR, α2AR, and μ-(µOR) and ժ-opioid receptors (ժOR). Results: All ligands docked preferentially to the binding pocket on the cell surface domain of the GPCR types investigated. Drug binding was characterized by weak interactions (hydrophobic, hydrogen bonding, pi-pi) and stronger ionic and salt-bridge interactions (cation-pi and cation-anion interactions). Ligands specific to each GPCR category showed considerable cross-binding with alternative GPCRs, with small-molecule medications appearing less selective than their peptide or ARB functional equivalents. ARBs that exhibit higher affinities for AT₁R also demonstrate higher affinities for µORs and ժORs than opiate ligands, such as fentanyl and naltrexone. Moreover, ARBs had a higher affinity for αARs than either alpha agonists (epinephrine and phenylephrine) or inhibitors (prazosin and doxazosin). MD simulations of membrane-embedded ARB-GPCR complexes proved stable over nanosecond time scales and suggested that some ARBs may behave as agonists or antagonists depending on the GPCR type. Based on the results presented in this and related investigations, we propose that agonists bind to the resting A-site of GPCRs, while inverse agonists occupy the desensitizing D-site, which partial agonists like morphine and fentanyl share, contributing to addiction. ARBs block both AngII and alpha receptors, suggesting that they are more potent antihypertensive drugs than ACE inhibitors. ARBs have the potential to inhibit morphine tolerance and appear to disrupt receptor desensitization processes, potentially by competing at the D-site. Our results suggest the possible therapeutic potential of ARBs in treating methamphetamine and opiate addictions. Full article

Background/Objectives: Aging is one of the greatest risk factors for neurodegenerative diseases such as Alzheimer’s disease (AD). As the disease progresses, neural loss in brain regions, such as the olfactory cortex (OC), i.e., a set of areas including the mediotemporal and orbitofrontal regions, may lead to dysfunction in the sense of smell and affect other brain regions that relate to the olfactory cortex by either afferent or efferent projections. Methods: The objective of this study was to assess sex-related differences in olfactory cortex volume using magnetic resonance imaging in individuals with mild cognitive impairment, probable dementia of the AD type and in healthy older adults, using the Mini-Mental Statement Examination score, years of education, and total intracranial volume as correction factors. Results: Atrophy of the olfactory cortex was observed in patients of both sexes with probable AD dementia. However, at the MCI stage, significant volumetric loss in the OC was detected in females only but not in males. Conclusions: This finding indicates greater pathological effects in this region in females at an earlier disease stage than in males. This study suggests that OC volume loss occurs differently between the sexes in older adults, with volumetric loss being greater in females. Full article

For the interaction of angiotensin II (AngII) with AngII type 1 receptors (AT₁R), two potential proton hopping pathways have been identified, each associated with distinct physiological outcomes. The octapeptide AngII (Asp¹-Arg²-Val³-Tyr⁴-Ile⁵-His⁶-Pro⁷-Phe⁸) appears to form a charge relay system (CRS) in solution in which the C-terminal carboxylate abstracts a proton from the His⁶ imidazole group, which, in turn, abstracts a proton from the Tyr⁴ hydroxyl (OH) group, creating a tyrosinate anion. When AngII binds to the AT₁R, the CRS can be reconstituted with D281 of the receptor taking up the role of the Phe⁸ carboxylate in the tripartite interaction, whilst the Phe⁸ carboxylate forms a salt bridge with K199 of the receptor. As a consequence, the Tyr⁴ OH of AngII is positioned with accessibility to either the Phe⁸ carboxylate (bound to K199) or the His⁶ imidazole (activated by D281), thereby creating a potential gating mechanism for AT₁R receptor signaling. This study summarizes evidence based on structure activity data for various analogs wherein Tyr⁴ OH interaction with His⁶ imidazole (CRS formation) leads to G protein sequestration and vasoconstriction, whereas Tyr⁴ OH interaction with Phe⁸ carboxylate (bound to K199) engenders arrestin-mediated vasodilation and receptor desensitization. These findings, combined with quantum mechanical (semiempirical) calculations of CRS proton transfer presented herein, provide insights for the therapeutic targeting of angiotensin receptor blockers (sartans) and the development of second-generation drugs (bisartans). Full article

Adults face a higher risk of exposure to COVID-19 than older adults and children due to their labor force participation. This study investigated the uptake of the initial and second doses of the COVID-19 vaccine among adults, stratified by age, race, ethnicity, sex, and their combinations. Data from the Kentucky Immunization Registry were employed to evaluate temporal changes in COVID-19 vaccine uptake among adults in three age groups (college age: 18–24, prime working age: 25–44, and middle age: 45–64) in Jefferson County, Kentucky (2020 population: 782,969). The analysis explored trends by age, race, and ethnicity; intersections of age with race and ethnicity; and interactions of age–race and age–ethnicity with sex. By May 2022, the highest and lowest COVID-19 vaccination rates were observed among White and Black 45–64-year-old adults: 74.8% and 64.0%, respectively, for dose two. The highest and lowest two-dose vaccination rates at ages 25–44 and 18–24 were also among White and Black residents: 67.9% versus 46.0% and 55.2% versus 35.4%, respectively. Disparities in COVID-19 vaccination by race, ethnicity, sex, and their intersections remained evident during the study period. Efforts in vaccine distribution and promotional initiatives should focus on demographically appropriate strategies. Full article

Given the highly variable distribution of seasonal snowpacks in complex mountainous environments, the accurate snow modeling of basin-wide snow water equivalent (SWE) requires a spatially distributed approach at a sufficiently fine grid resolution (<500 m) to account for the important processes in the seasonal evolution of a snowpack (e.g., wind redistribution of snow to resolve patchy snow cover in an alpine zone). However, even well-validated snow evolution models, such as SnowModel, are prone to errors when key model inputs, such as the precipitation and wind speed and direction, are inaccurate or only available at coarse spatial resolutions. Incorporating fine-spatial-resolution remotely sensed snow-covered area (SCA) information into spatially distributed snow modeling has the potential to refine and improve fine-resolution snow water equivalent (SWE) estimates. This study developed 30 m resolution SnowModel simulations across the Big Thompson River, Fraser River, Three Lakes, and Willow Creek Basins, a total area of 4212 km² in Colorado, for the water years 2000–2023, and evaluated the incorporation of a Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat SCA datasets into the model’s development and calibration. The SnowModel was calibrated spatially to the Landsat mean annual snow persistence (SP) and temporally to the MODIS mean basin SCA using a multi-objective calibration procedure executed using Latin hypercube sampling and a stepwise calibration process. The Landsat mean annual SP was also used to further optimize the SnowModel simulations through the development of a spatially variable precipitation correction field. The evaluations of the SnowModel simulations using the Airborne Snow Observatories’ (ASO’s) light detection and ranging (lidar)-derived SWE estimates show that the versions of the SnowModel calibrated to the remotely sensed SCA had an improved performance (mean error ranging from −28 mm to −6 mm) compared with the baseline simulations (mean error ranging from 69 mm to 86 mm), and comparable spatial patterns to those of the ASO, especially at the highest elevations. Furthermore, this study’s results highlight how a regularly updated 30 m resolution SCA could be used to further improve the calibrated SnowModel simulations to near real time (latency of 5 days or less). Full article

Spotted wing drosophila (SWD), Drosophila suzukii (Diptera: Drosophilidae), are invasive vinegar flies of East Asian origin that are an increasingly global threat to the small fruit industry. It is essential that new classes of eco-friendly insecticides and cost-effective strategies for SWD control are developed. Here, we describe the preparation of a strain of RNA interference (RNAi) Saccharomyces cerevisiae expressing shRNA that specifically targets the SWD RNA-binding Fox protein 1 (Rbfox1) gene. The yeast effectively silences the SWD Rbfox1 gene, resulting in significant loss of fly neural activity. Laboratory trials demonstrated that the RNAi yeast can be mixed with soda, which functions as SWD attractive targeted sugar bait (ATSB) that can be delivered in a soda bottle feeder. The ATSB, mixed with yeast that was heat-killed prior to suspension in the ATSB, resulted in 92 ± 1% mortality of SWD flies that consumed it, yet had no impact on non-target dipterans. Rbfox.687 yeast delivered in ATSB feeders may one day be a useful component of integrated SWD control programs. Full article

Background: The processing of harvested fat for transplantation is critical to fat graft performance. In breast reconstruction, larger volumes of fat are being grafted and, in some clinical cases, are being implanted within radiated tissue. This preclinical animal study evaluated the effects of radiation on retention volume and fat graft quality after processing by decantation or REVOLVE™ technology (Allergan Aesthetics, an AbbVie Company), a filtration-based device that can process lipoaspirates and remove unwanted contaminants prior to grafting. Methods: Lipoaspirate was collected from human donors (n = 6), processed using either REVOLVE™ technology or decantation, and implanted (0.5 cc) into 60 athymic mice for 4 weeks with or without a single 35-Gy radiation dose 12 weeks prior. Volume composition, MRI, and weight-based volumetric assessment of grafted fat were performed and compared between radiated and non-radiated mice. Results: Volume composition analysis demonstrated significantly higher fat content and lower aqueous fluid with REVOLVE™ technology than with decantation, with minimal cellular debris and free oil. MRI-based and weight-based volume analysis demonstrated a significantly higher percent retention with REVOLVE™ technology than decantation in nonirradiated and irradiated sites, respectively. Pathology scoring showed a significant decrease in fibrosis within grafts processed with REVOLVE™ technology in nonirradiated sites. Conclusions: Results suggest that fat processed using REVOLVE™ technology provides better early volume retention and quality of fat grafts compared to decantation, both in healthy and radiation-treated surgical sites. Full article

Background: Although children can contract COVID-19, their typically lower immune reactivity appears to shield them from the intense hyperinflammatory response observed in other age groups, leading to milder disease symptoms. Nonetheless, children’s infection raises the possibility of unwanted transmission of the coronavirus to others, especially because most infected children are asymptomatic. Objectives: This study examines the uptake of the first and second doses of the COVID-19 vaccine among children by combinations of age, race, ethnicity, and sex. Methods: Data from the immunization registry were utilized to assess changes over time in COVID-19 vaccine uptake among children in Jefferson County, Kentucky’s most populous county. The analysis examined trends by age, race, ethnicity, and combinations of age-race, age-ethnicity, age-race-sex, and age-ethnicity-sex during the first six quarters of the COVID-19 vaccination rollout. Results: By May 2022, in 16–17-year-olds, the highest and lowest COVID-19 vaccination rates were observed among White and Black children (64.8% versus 41.2%, respectively, for dose two). The highest two-dose vaccination rate at ages 12–15 years was among Multiracial and White children (63.3% and 62.9%, respectively), the lowest among Black children (38.8%). The highest two-dose vaccination rate at ages 5–11 years was among children of Some Other Races, Asian, and White children (37.0%, 36.7%, and 35.5%, respectively), and the lowest among Black children (17.2%). Conclusions: Inequalities in COVID-19 vaccination based on race, ethnicity, and sex persisted throughout the study period. Efforts in vaccine distribution and promotional initiatives should focus on increasing vaccination rates among children from racial and ethnic minority groups and males. Full article

Background: Continuous vital sign monitoring using wearable sensors has gained traction for the early detection of patient deterioration, particularly with the advent of virtual wards. Objective: The objective was to evaluate the reliability of a wearable sensor for monitoring heart rate (HR), respiratory rate (RR), and temperature in acutely unwell hospital patients and to identify the optimal time window for alert generation. Methods: A prospective cohort study recruited 500 patients in a single hospital. Sensor readings were compared to standard intermittent nurse observations using Bland–Altman plots to assess the limits of agreement. Results: HR demonstrated good agreement with nurse observations (intraclass correlation coefficient [ICC] = 0.66, r = 0.86, p < 0.001), with a mean difference of 3.63 bpm (95% LoA: −10.87 to 18.14 bpm). RR exhibited weaker agreement (ICC = 0.20, r = 0.18, p < 0.001), with a mean difference of −2.72 breaths per minute (95% LoA: −10.91 to 5.47 bpm). Temperature showed poor to fair agreement (ICC = 0.30, r = 0.39, p < 0.001), with a mean difference of −0.57 °C (95% LoA: −1.72 to 0.58 °C). A 10 min averaging window was identified as optimal, balancing data retention and real-time alerting. Conclusions: Wearable sensors demonstrate potential for reliable continuous monitoring of vital signs, supporting their future integration into real-world clinical practice for improved patient safety. Full article

Background/Objectives: Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. Methods: This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. Results: Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher postvaccination hemagglutination inhibition assay geometric mean titers and fold rises and seroconversion rates observed with qIRV versus QIV for A strains, with no consistent pattern for B strains. Cell-mediated immune responses to qIRV by Day 7 showed overall higher T-cell responses against all strains versus QIV. Antibody and cell-mediated immune responses showed comparable trends across qIRV doses in 18- through 85-year-olds; a dose-related pattern was observed in 65- through 85-year-olds (60 μg > 30 μg). Conclusions: Phase 3 investigations of qIRV 60 µg in older adults and qIRV 30 µg in younger adults are warranted (ClinicalTrials.gov Identifier: NCT05052697). Full article

Probiotics have been used to promote pioneer colonization by beneficial bacteria in poultry. The purpose of the present study (four trials) was to determine if an in ovo injection with Bifidobacterium saeculare (B2-2, B3-4) and/or lactic acid bacteria (LAB18, LAB46) at d18 of embryogenesis reduced Enterococcus and Gram-negative bacterial colonization in the gut at hatch. An environmental challenge model was used to simulate microbial contamination in large-scale hatch cabinets in a laboratory setting. In all trials, gut homogenates obtained from chicks at hatch were plated to enumerate relevant bacterial populations. Performance was evaluated in trials two and four. The top treatments in trial one were selected for further testing in trials 2–4. The significance level for all analyses was set at p < 0.05. A meta-analysis of gut bacterial recovery for trials 2–4 revealed that the administration of probiotic treatments increased LAB and/or bifidobacteria at hatch compared to non-treated groups. LAB46 + B2-2 was more effective at reducing Gram-negative bacteria and Enterococcus in the gut compared to other probiotic treatments. All treatments improved d14 BW and d0–14 BWG compared to non-treated groups. These results indicate that exposure to beneficial bacteria during late embryogenesis can prevent colonization by opportunistic pathogens associated with contamination in commercial hatch cabinets and may also improve early performance in broiler chickens. Full article

Background: The global SARS-CoV-2 pandemic revealed stark variability in clinical outcomes across populations, underscoring the need for region-tailored vaccination strategies. To inform standardised global immunisation efforts, this study compared longitudinal binding antibody responses and neutralisation capacities in mild COVID-19 cases from Uganda and the United Kingdom (UK). Methods: IgG responses to spike (S) and nucleocapsid (N) proteins, along with IgM responses to S and receptor-binding domain (RBD) proteins, were assessed in 29 Ugandan and 14 UK participants over 84 and 82 days, respectively. Antibody levels were quantified using a validated enzyme-linked immunosorbent assay (ELISA), alongside pseudovirus neutralisation assays targeting the D614G variant. Results: Ugandan participants exhibited higher early IgG and IgM levels, particularly against spike and RBD, with a rapid onset of responses that waned quickly. UK participants showed a slower but sustained increase in IgG and IgM levels. Neutralisation titres revealed elevated responses in 16.4% of Ugandan participants (>2000) compared to 4.5% of UK participants, suggesting a greater sensitivity to viral neutralisation. Conversely, 31.8% of UK participants exhibited low titres (<25) compared to 14.8% of Ugandan participants, indicating differences in resistance mechanisms. Neutralisation correlated strongly with spike and receptor-binding domain IgG in the UK cohort but showed weaker correlations in Ugandan participants. Conclusions: These findings highlight distinct population-level immune responses, suggesting that geographic factors shaped the quality and durability of SARS-CoV-2 immunity. Tailored vaccination strategies are essential to optimise immunity across diverse populations and improve global epidemic preparedness. Full article

Microalgae, a marine-derived natural ingredient, has emerged as a rich source of bioactive compounds with the potential to modulate gut–brain axis activities. The objective of this study was to investigate whether supplementation with a microalgae extract from Tetradesmus obliquus strain Mi175.B1.a (TOME) influences gut health and reduces stress and anxiety in healthy adults experiencing mild to moderate gastrointestinal (GI) distress. Methods: Fifty-six healthy adults (age: 31.9 ± 7.7 years; body weight: 71.8 ± 12.6 kg; BMI: 24.6 ± 2.8 kg/m²) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arm clinical trial. Participants were randomly allocated to receive capsules containing either 250 mg/day of TOME or a placebo for four weeks. Primary outcomes included the assessment of GI symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) and Bristol Stool Scale (BSS). Secondary outcomes focused on subjective evaluation of mood, stress, and anxiety, as well as blood pressure responses to sympathetic nervous system activation induced by the cold pressor test (CPT). In addition, stool, plasma, and saliva samples were collected to assess biomarkers associated with stress, sympathetic activation, intestinal permeability, and GI health. 16S rRNA sequencing was performed to analyze changes in gut microbial populations. Results: Daily supplementation for four weeks with TOME was safe and well tolerated in the study population. In addition, TOME significantly reduced GSRS global scores (p = 0.02), as well as constipation (p = 0.05) and indigestion (p = 0.03) subcomponent scores compared to Placebo. There was also a significant increase in Shannon’s index before FDR correction (p = 0.05; FDR = 0.12) and stool butyrate level was significantly lower in the TOME group than in Placebo after 4 weeks of supplementation (p = 0.039). Both groups showed a significant reduction in perceived stress scores, but the TOME intervention group also had reduced Negative Affect scores (p < 0.001). In addition, plasma chromogranin A, a stress biomarker, was significantly reduced after TOME intervention (p = 0.03). There were no negative effects on blood lipids or other parameters related to sympathetic activation or cardiovascular health. Conclusions: Overall, these results suggest that 4-week supplementation with T. obliquus strain Mi175.B1.a improves GI symptoms, potentially through effects on the gut microbiota, and may promote positive effects on mental health. Additional research should follow up on mental health outcomes in populations with increased stress and anxiety and investigate mechanisms underlying improvements in GI health. This trial was registered at clinicaltrials.gov as NCT06425094. Full article