Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.

Monetary sanctions in law enforcement, including fines, forfeitures, and related fees, are susceptible to exploitation by agencies for self-serving profit motives. However, a key challenge in addressing this issue is disentangling the agencies’ profit-driven motives from their genuine commitment to upholding law and order. Against this backdrop, this study examines a novel policy design proposal: redirecting revenues from law enforcement to fund local nonprofits. This approach seeks to eliminate conflicts of interest without restricting the use of monetary sanctions as a tool for law enforcement, while simultaneously channeling revenues toward community benefits. Experimental evidence based on a representative sample of US adults (n = 1,030) further highlights this approach’s potential to improve public perceptions of, and attitudes toward, law enforcement agencies. The study concludes by discussing the broader implications of this proposal for the political economy of law enforcement, as well as key considerations and potential challenges for its implementation.

Historians and literary critics often observe that Victorian London had no Baron Haussmann to impose a rational, legible order on its tangle of streets. But the itineraries traced by early forms of public transportation—omnibuses, hackney cabs, and railways—nonetheless invited a reimagining and remapping of the city. Charles Dickens's Sketches by Boz (1836), midcentury encyclopedic cab fare guides, and the debates that preceded the building of the 1863 Metropolitan Underground Railway overwrote the existing geography of the city with a cartographic infrastructure tactically organized into routes, nodes, intervals, and destinations.

This study presents a new density filter for a pipe-shaped structure and its application to fluid topology optimization. A simple and straight pipe-shaped structure for fluid is preferred for many engineering purposes rather than the perplex manifold structure provided by the topology optimization method. To determine an optimal pipe structure for fluid, we develop a new density filter and apply it to fluid topology optimization. Hence, the original spatially varying design variables of the fluid topology optimization are modified based on the pipe density filter. Subsequently, the filter design variables, including a uniform pipe wall thickness and adjusted cross-section, are used for artificial pseudo-rigid bodies in fluid topology optimization. An additional constraint is imposed to maintain a nearly uniform pipe thickness. Several numerical examples are solved to demonstrate the validity of the present pipe density filter for fluid topology optimization problems minimizing the energy dissipation of the fluid and controlling the particles suspended in the fluid.

Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm, Ancylostoma caninum, that is resistant to 3 major classes of anthelmintics is characterized. Various drug assays were used to determine the resistance of BCR to thiabendazole, ivermectin, moxidectin and pyrantel pamoate. When compared to a drug-susceptible isolate of A. caninum, BCR was shown to be significantly resistant to all 4 of the drugs tested. Multiple single nucleotide polymorphisms have been shown to impart benzimidazole resistance, including the F167Y mutation in the β-tubulin isotype 1 gene, which was confirmed to be present in BCR through molecular analysis. The frequency of the resistant allele in BCR was 76.3% following its first passage in the lab, which represented an increase from approximately 50% in the founding hookworm population. A second, recently described mutation in codon 134 (Q134H) was also detected at lower frequency in the BCR population. Additionally, BCR exhibits an altered larval activation phenotype compared to the susceptible isolate, suggesting differences in the signalling pathways involved in the activation process which may be associated with resistance. Further characterization of this isolate will provide insights into the mechanisms of resistance to macrocyclic lactones and tetrahydropyrimidine anthelmintics.

Fe-rich smectite is ubiquitous in soil environments and closely linked to the fate and mobility of hazardous trace metals and particularly to the variations in the biogeochemical redox reactions of structural Fe that determine the sorption and desorption properties of clay minerals. The biotic/abiotic redox reactions of a Fe-rich smectite, nontronite (NAu-1), were performed at various reaction times using the Fe-reducing bacterium Shewanella oneidensis MR-1 at 30°C and Na-dithionite (Na2S2O4), respectively. The extent of biotic Fe-reduction of NAu-1 after 30 days of incubation reached up to 10.7% of total Fe and the range of abiotic Fe-reduction varied from 4.9–46.6% at reaction times of 5 min, 30 min, 1 h, and 4 h. The biotically and abiotically Fe-reduced NAu-1 samples were spiked with Pb concentrations of 0.07, 0.2, 0.5, and 1.0 mg/kg and incubated under aerobic or anaerobic conditions for 24 h.

The amounts of Pb in the supernatants were analyzed using an Inductively Coupled Plasma Mass Spectrometer (ICP-MS) and Multi-collector (MC)-ICP-MS. The amounts of Pb removed from the supernatants were negatively related to the extent of Fe(III) reduction in the abiotically Fe-reduced NAu-1 samples. In contrast, less Pb (~15%) was removed from the biotically Fe-reduced NAu-1 samples with a similar extent of Fe(III) reduction. Changes in the isotopic 208/204Pb ratio indicated that the lighter 204Pb isotope was preferentially adsorbed to the NAu-1 samples with less Fe reduction and indicated that variations in the net layer charge affected isotopic fractionation. Significant differences in the 208/204Pb ratios for NAu-1 samples that were biotically Fe-reduced under anaerobic conditions were measured and indicate that the reversibility of the structural/chemical modifications that occur under redox conditions can affect Pb removal and, thus, isotope fractionation. These results collectively infer that the biogeochemical properties of clay minerals should be considered in order to understand the fate of trace metals in natural environments.

Dioctahedral smectite was prepared hydrothermally from dickite [Al2Si2O5(OH)4] as a starting material by autoclaving in a closed stainless steel vessel with variable temperature, pressure, time and pH conditions. Highly crystalline smectite can be obtained at 290°C under a pressure of 69 bar for 48 h. The pH of the solution was an important factor and should be maintained at 10 to 11 for the successful formation of smectite. Characterization by X-ray powder diffraction, scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential thermal analysis and the Greene-Kelly test showed that the smectite synthesized was Na-beidellite, mostly because of the heat treatment of the starting material and the stoichiometric batch composition.

Focus here is placed on the pharmaceutical and biomedical applications of novel clay-drug hybrid materials categorized by methods of administration. Clay minerals have been used for many years as pharmaceutical and medicinal ingredients for therapeutic purposes. A number of studies have attempted to explore clay-drug hybrid materials for biomedical applications with desired functions, such as sustained release, increased solubility, enhanced adsorption, mucoadhesion, biocompatibility, targeting, etc. The present review attempts not only to summarize the state-of-the-art of clay-drug hybrid materials and their advantages, depending on the methods of administration, but also to deal with challenges and future perspectives of clay mineral-based hybrids for biomedical applications.

Blood carotenoid concentration measurement is considered the gold standard for fruit and vegetable (F&V) intake estimation; however, this method is invasive and expensive. Recently, skin carotenoid status (SCS) measured by optical sensors has been evaluated as a promising parameter for F&V intake estimation. In this cross-sectional study, we aimed to validate the utility of resonance Raman spectroscopy (RRS)-assessed SCS as a biomarker of F&V intake in Korean adults. We used data from 108 participants aged 20–69 years who completed SCS measurements, blood collection and 3-d dietary recordings. Serum carotenoid concentrations were quantified using HPLC, and dietary carotenoid and F&V intakes were estimated via 3-d dietary records using a carotenoid database for common Korean foods. The correlations of the SCS with serum carotenoid concentrations, dietary carotenoid intake and F&V intake were examined to assess SCS validity. SCS was positively correlated with total serum carotenoid concentration (r = 0·52, 95 % CI = 0·36, 0·64, P < 0·001), serum β-carotene concentration (r = 0·60, 95 % CI = 0·47, 0·71, P < 0·001), total carotenoid intake (r = 0·20, 95 % CI = 0·01, 0·37, P = 0·04), β-carotene intake (r = 0·30, 95 % CI = 0·11, 0·46, P = 0·002) and F&V intake (r = 0·40, 95 % CI = 0·23, 0·55, P < 0·001). These results suggest that SCS can be a valid biomarker of F&V intake in Korean adults.

Birds in flight are prone to collide with various transparent or reflective structures. While bird–window collision has been recognised as a critical conservation issue, collision with other transparent structures has been less understood. Noise barriers made of transparent materials are considered critical hazards for birds; however, little is known about the bird mortality they cause. We conducted the first nationwide-scale estimates of bird-collision mortality caused by transparent noise barriers (TNBs) along roads in the Republic of Korea. The total length of existing roadside transparent noise barriers was estimated at 1,416 km nationwide (as of 2018), and it had been increasing exponentially. Based on carcass surveys at 25 sites, daily mortality at the observed barriers was 0.335 ± 1.132 birds/km on average, and no difference in observed mortality was detected between both sides of a single barrier and between road types (i.e. local roads and motorways). Finally, we estimated that approximately 186,000 birds (95% confidence interval: 162,465–204,812 birds) are killed annually by collisions with roadside TNBs. As privately installed barriers were not considered in this study, the actual mortality is likely be higher than our estimates. Thus, collision with TNBs could become an emerging threat to avian conservation, especially in developing and urbanising regions around the world. As such structures are not formally recognised as conservation issues of importance, more systematic surveys aided by citizen science, both for the status of TNBs and bird-collision mortality, are needed in addition to management and mitigation policies.

Mineral consumption has been suggested to have an impact on gastric cancer (GC) prevention. However, the protective effect of potassium against gastric carcinogenesis remains inconclusive. The causal link between inflammation and cancer is well established. Notably, potassium intake and potassium channels may play certain roles in regulating the production of TNF-α (TNF-α). We aimed to determine whether dietary potassium intake is related to the risk of GC. We further observed whether this association was modified by TNF-α rs1800629. We designed a case–control study comprising 377 GC cases and 756 controls. Information on dietary potassium intake was collected using a semiquantitative food frequency questionnaire. Genotyping was performed by the Affymetrix Axiom Exom 319 Array platform. Unconditional logistic regression models were used to assess associations. A significantly reduced GC risk was found for those who consumed higher dietary potassium levels (OR = 0·63, 95 % CI = 0·45, 0·89, P for trend = 0·009). In the dominant model, we observed a non-significant association between TNF-α rs1800629 and GC risk (OR = 1·01, 95 % CI = 0·68, 1·49). In females, those who were homozygous for the major allele (G) of rs1800629 with a higher intake of dietary potassium exhibited a decreased risk of GC (OR = 0·40, 95 % CI = 0·20, 0·78, P interaction = 0·041). This finding emphasises the beneficial effect of potassium intake on GC prevention. However, this association could be modified by TNF-α rs1800629 genotypes. A greater protective effect was exhibited for females with GG homozygotes and high potassium intake.

Identification of geographical areas with high burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in schools using spatial analyses has become an important tool to guide targeted interventions in educational setting. In this study, we aimed to explore the spatial distribution and determinants of coronavirus disease 2019 (COVID-19) among students aged 3–18 years in South Korea. We analysed the nationwide epidemiological data on laboratory-confirmed COVID-19 cases in schools and in the communities between January 2020 and October 2021 in South Korea. To explore the spatial distribution, the global Moran's I and Getis-Ord's G using incidence rates among the districts of aged 3–18 years and 30–59 years. Spatial regression analysis was performed to find sociodemographic predictors of the COVID-19 attack rate in schools and in the communities. The global spatial correlation estimated by Moran's I was 0.647 for the community population and 0.350 for the student population, suggesting that the students were spatially less correlated than the community-level outbreak of SARS-CoV-2. In schools, attack rate of adults aged 30–59 years in the community was associated with increased risk of transmission (P < 0.0001). Number of students per class (in kindergartens, primary schools, middle schools and high schools) did not show significant association with the school transmission of SARS-CoV-2. In South Korea, COVID-19 in students had spatial variations across the country. Statistically significant high hotspots of SARS-CoV-2 transmission among students were found in the capital area, with dense population level and high COVID-19 burden among adults aged 30–59 years. Our finding suggests that controlling community-level burden of COVID-19 can help in preventing SARS-CoV-2 infection in school-aged children.