Search Results (9)

Background/Objectives: CKD-associated pruritus (CKD-aP) is a serious systemic comorbidity occurring in patients with CKD. Despite the burden of CKD-aP, there are limited efficacious treatments available for its management; difelikefalin is the only approved treatment based on its efficacy and safety demonstrated in two clinical studies, namely KALM-1 and KALM-2. This study aimed to evaluate the cost-effectiveness of difelikefalin plus best supportive care (BSC) versus BSC alone when treating moderate-to-severe CKD-aP in patients receiving in-centre haemodialysis, from the perspective of the UK healthcare system. Methods: A de novo lifetime Markov health economic model was built to assess the cost-effectiveness of difelikefalin. The modelled efficacy of difelikefalin was based on data from KALM-1 and KALM-2 pooled at the patient level. The main efficacy driver was the total 5-D Itch scale score. Per-cycle probabilities of changing health states defined by CKD-aP severity were used to derive transition matrices; the model also estimated time-dependent annual probabilities of death and transplant for people on haemodialysis. An increased risk of mortality for modelled patients with very severe, severe, or moderate CKD-aP was applied. Health state utilities and management costs were based on published evidence. Results: Modelled patients treated with difelikefalin were estimated to have a reduced severity of CKD-aP. Consequently, difelikefalin plus BSC was associated with an increased life expectancy of 0.11 years per person and improved HRQoL compared with BSC alone. This translated to higher quality-adjusted life years, at 0.26 per person gained compared to BSC alone. Improved patient outcomes were achieved at an incremental cost of £7814 per person. Conclusions: Overall, at a price of £31.90/vial, difelikefalin was estimated to be a cost-effective treatment for moderate-to-severe CKD-aP at a willingness-to-pay threshold of £30,000/QALY, with conclusions robust to sensitivity analysis. Full article

With the wide application of UAVs in modern intelligent warfare as well as in civil fields, the demand for C-UAS technology is increasingly urgent. Traditional detection methods have many limitations in dealing with “low, slow, and small” targets. This paper presents a pure laser automatic tracking system based on Geiger-mode avalanche photodiode (Gm-APD). Combining the target motion state prediction of the Kalman filter and the adaptive target tracking of Camshift, a Cam–Kalm algorithm is proposed to achieve high-precision and stable tracking of moving targets. The proposed system also introduces two-dimensional Gaussian fitting and edge detection algorithms to automatically determine the target’s center position and the tracking rectangular box, thereby improving the automation of target tracking. Experimental results show that the system designed in this paper can effectively track UAVs in a 70 m laboratory environment and a 3.07 km to 3.32 km long-distance scene while achieving low center positioning error and MSE. This technology provides a new solution for real-time tracking and ranging of long-distance UAVs, shows the potential of pure laser approaches in long-distancelow, slow, and small target tracking, and provides essential technical support for C-UAS technology. Full article

Background: Peri-implantitis (PIT) is highly prevalent in patients with dental implants and is a challenging condition to treat due to the limited outcomes reported for non-surgical and surgical therapies. Therefore, epigenetic therapeutics might be of key importance to treat PIT. However, developing epigenetic therapeutics is based on understanding the relationship between epigenetics and disease. To date, there is still scarce knowledge about the relationship between epigenetic modifications and PIT, which warrants further investigations. Aim: The purpose of this study was to evaluate the level of global DNA methylation associated with implant failure (IF) due to PIT compared to periodontally healthy (PH) patients. Material and Methods: A total of 20 participants were initially enrolled in this pilot, exploratory, single-blinded, cross-sectional clinical human study in two groups: 10 in the PH group and 10 in the IF group. In the participants who have completed the study, gingival tissue and bone samples were harvested from each participant and were used to perform global DNA methylation analysis. The percentage of global DNA methylation (5-mC%) was compared (1) between groups (PH and IF); (2) between the subgroups of gingival tissue and bone separately; (3) in the whole sample, comparing gingival tissue and bone; (4) within groups, comparing gingival tissue and bone. Demographic, periodontal, and peri-implant measurements as well as periodontal staging, were also recorded. All statistical comparisons were made at the 0.05 significance level. Results: Out of the initially enrolled 20 patients, only 19 completed the study and, thus, were included in the final analysis; 10 patients in the PH group and 9 patients in the IF group, contributing to a total of 38 samples. One patient from the IF group was excluded from the study due to systemic disease. The mean implant survival time was 10.8 years (2.17–15.25 years). Intergroup comparison, stratified by group, indicated a similar 5-mC% between the PH and IF groups in both gingival tissue and bone (p = 0.599), only in bone (p = 0.414), and only in gingival tissue (p = 0.744). Intragroup comparison, stratified by the type of sample, indicated a significantly higher 5-mC% in gingival tissue samples compared to bone in both the PH and IF groups (p = 0.001), in the PH group (p = 0.019), and in the IF group (p = 0.009). Conclusions: Within the limitations of this study, higher global DNA methylation levels were found in gingival tissue samples compared to bone, regardless of the study groups. However, similar global DNA methylation levels were observed overall between the IF and PH groups. Yet, differences in the global DNA methylation levels between gingival tissues and bone, regardless of the study group, could reflect a different epigenetic response between various tissues within the same microenvironment. Further studies are necessary to elucidate the present findings and to evaluate the role of epigenetic modifications in IF due to PIT. Full article

Dietary fiber is considered a strong intestinal protector, but we do not know whether dietary fiber protects against the long-lasting mucosal damage caused by ionizing radiation. To evaluate whether a fiber-rich diet can ameliorate the long-lasting pathophysiological hallmarks of the irradiated mucosa, C57BL/6J mice on a fiber-rich bioprocessed oat bran diet or a fiber-free diet received 32 Gray in four fractions to the distal colorectum using a linear accelerator and continued on the diets for one, six or 18 weeks. We quantified degenerating crypts, crypt fission, cell proliferation, crypt survival, macrophage density and bacterial infiltration. Crypt loss through crypt degeneration only occurred in the irradiated mice. Initially, it was most frequent in the fiber-deprived group but declined to levels similar to the fiber-consuming group by 18 weeks. The fiber-consuming group had a fast response to irradiation, with crypt fission for growth or healing peaking already at one week post-irradiation, while crypt fission in the fiber-deprived group peaked at six weeks. A fiber-rich diet allowed for a more intense crypt cell proliferation, but the recovery of crypts was eventually lost by 18 weeks. Bacterial infiltration was a late phenomenon, evident in the fiber-deprived animals and intensified manyfold after irradiation. Bacterial infiltration also coincided with a specific pro-inflammatory serum cytokine profile. In contrast, mice on a fiber-rich diet were completely protected from irradiation-induced bacterial infiltration and exhibited a similar serum cytokine profile as sham-irradiated mice on a fiber-rich diet. Our findings provide ample evidence that dietary fiber consumption modifies the onset, timing and intensity of radiation-induced pathophysiological processes in the intestinal mucosa. However, we need more knowledge, not least from clinical studies, before this finding can be introduced to a new and refined clinical practice. Full article

A wind corridor forest is defined as an urban forest for utilizing the functions of a wind corridor that allow “cool and fresh air (cold air)” generated in forests at night to flow to urban development areas. This study aims to provide planning strategies for implementing a wind corridor forest by analyzing current conditions in Haengbok City (HBC region), Sejong, South Korea. The HBC region had many wind-generating forests (WGF), wind-spreading forests (WSF), and wind-connecting forests (WCF), and secured the connections among the target areas of each wind corridor forest. Despite the favorable conditions for a wind corridor forest, cold air flow showed that there are regions with unfavorable wind conditions in the HBC region. In order to strengthen the functions of a wind corridor forests in the HBC region, four zones were distinguished according to the functional characteristics. Additionally, the planning strategies of a wind corridor forests suitable for each zone were provided, and the strategies for establishing a wind corridor forest were proposed. The results of this study can be used as the fundamental data for establishing guidelines for a wind corridor forest and utilized as resources for selecting regions suitable for a wind corridor forest. Full article

Genetic diversity of species is an important baseline for the domestication process. In Cameroon, Prunus africana, an important and threatened medicinal tree, is among the priority species for domestication. The bark extract has been used to treat various diseases; mainly benign prostatic hyperplasia which affects men above the age of 50. As little is known about the genetic diversity of P. africana in Cameroon, we aimed to determine the genetic diversity and differentiation of several P. africana populations in the western provinces, using sets of chloroplast DNA markers and nuclear microsatellites previously developed for Prunus species. Genetic diversity in the observed populations was considerable and genetic differentiation between populations proved substantial with 21% of the total observed variation detected among populations, revealing a distinct genetic structure among certain populations. However, the lack of correlation between genetic and geographic distances does not support isolation by distance (IBD). The analysis of chloroplast DNA haplotypes revealed no strong phylogeographic component in the genetic structure observed in the western populations of P. africana in Cameroon. The outcome of this study will contribute to improve the genetic characterization of P. africana for its better domestication and conservation in the Cameroon agroforestry system. Full article

The aim of this study is to suggest planning strategies for managing comfortable thermal environments in urban areas by local cold air generated in mountains, which finally contributes to making sustainable and eco-friendly cities. For this purpose, we selected urban areas in the Honam Jeongmaek in Korea and analyzed the nighttime cold airflow and altitude of the cold air layer generated in mountains, by using the KALM (Kaltluftabflussmodell) model which calculates the amount of cold air generated during the nighttime without winds. The results of analysis found that the local airflows generated in Mt. Chuwol, Mt. Mudeung, Mt. Cheonun, Mt. Byeongpung and Mt. Geum influenced the entire study site from across Gwangju Metropolitan City to adjacent areas. Therefore, the mountains generated major cold airflows should be designated as the management area for securing cooling function. As a result of detailed analysis, most developed areas, such as Buk-gu, Seo-gu and Nam-gu, as well as industrial areas, did not have a smooth flow, so management strategies were needed. In particular, Mt. Mudeung and Mt. Cheonun were the source areas of the local cold air generation and the generated flows from the mountains could influence into developed areas of Gwangju Metropolitan City. Thus, thorough preservation policies are required for Mt. Mudeung and Mt. Cheonun from development that causes damages to mountainous terrain and topography. This study could support the establishment of systematic management plans of the Honam Jeongmaek in preparation for climate change. In addition, it is expected to be used to develop policies related to the quantitative expansion of mountain areas with cooling functions and the conservation of sustainable mountain areas. Full article

Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine biosynthesis enzyme ornithine decarboxylase (ODC). However, malignant cells frequently circumvent DFMO therapy by up-regulating polyamine import. Therefore, there is a need to develop compounds that inhibit polyamine transport. Collectively, DFMO and a polyamine transport inhibitor (PTI) provide the basis for a combination therapy leading to effective intracellular polyamine depletion. We have previously shown that the pattern of uptake of a series of polyamine analogues in a Drosophila model epithelium shares many characteristics with mammalian cells, indicating a high degree of similarity between the mammalian and Drosophila polyamine transport systems. In this report, we focused on the utility of the Drosophila epithelial model to identify and characterize polyamine transport inhibitors. We show that a previously identified inhibitor of transport in mammalian cells has a similar activity profile in Drosophila. The Drosophila model was also used to evaluate two additional transport inhibitors. We further demonstrate that a cocktail of polyamine transport inhibitors is more effective than individual inhibitors, suggesting the existence of multiple transport systems in Drosophila. Our findings reinforce the similarity between the Drosophila and mammalian transport systems and the value of the Drosophila model to provide inexpensive early screening of molecules targeting the transport system. Full article

Classification of cattle breeds contributes to our understanding of the history of cattle and is essential for an effective conservation of genetic diversity. Here we review the various classifications over the last two centuries and compare the most recent classifications with genetic data. The classifications devised during the 19th to the late 20th century were in line with the Linnaean taxonomy and emphasized cranial or horn morphology. Subsequent classifications were based on coat color, geographic origin or molecular markers. Several theories were developed that linked breed characteristics either to a supposed ancestral aurochs subspecies or to a presumed ethnic origin. Most of the older classifications have now been discarded, but have introduced several Latin terms that are still in use. The most consistent classification was proposed in 1995 by Felius and emphasizes the geographic origin of breeds. This is largely in agreement with the breed clusters indicated by a biochemical and molecular genetic analysis, which reflect either groups of breeds with a common geographic origin or single breeds that have expanded by export and/or crossbreeding. We propose that this information is also relevant for managing the genetic diversity of cattle. Full article