A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide. Methods: A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use. Findings: Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%). Interpretation: Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access.

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Protecting the liver with PKD1.

Proliferation of somatic clones deficient in PKD1 prevents fatty liver disease without resulting in tumors.

Size Matters: Influence of Particle Size on Antioxidant, ß-Glucan, and Anti-Inflammatory Potential in Pleurotus floridanus (Agaricomycetes).

Cellular damage resulting from elevated levels of free radicals can lead to persistent health issues. Pleurotus floridanus, an edible white oyster mushroom, is rich in ß-glucans with potent antioxidant and anti-inflammatory properties. In this research, we examined the ß-glucan content, total phenolic content, as well as antioxidant and anti-inflammatory potential of hot water extracts with varying particle sizes (< 75, 75-154, 154-300, and 300-600 µm) of both whole and sliced fruiting bodies of P. floridanus. The findings revealed that the в-glucan content increased as the particle size increased, although no significant differences were observed. Conversely, smaller particle sizes (< 75 µm) of whole and sliced fruiting bodies of P. floridanus exhibited higher phenolic content, 2,2-diphenyl-1-picryl-hy-drazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, and reducing ability compared with larger particle size (> 75 µm). Of the four samples (AW2, AW3, AS1, and AS2) with the highest antioxidant activity selected for anti-inflammatory assays, all demonstrated the ability to reduce nitric oxide and tumor necrosis factor-alpha levels, but did not enhance interleukin-10 expression in lipopolysaccharide-stimulated RAW264.7 cells. Interestingly, particle size < 75 to 300 µm did not appear to influence the anti-inflammatory activity, because no significant differences were observed among the particle sizes. Therefore, a particle size < 300 µm in a P. floridanus hot water extract could serve as a valuable source of antioxidant and anti-inflammatory compounds to counteract the harmful effects of free radicals.

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A high-dimensional, multi-transceiver channel state information dataset for enhanced human activity recognition.

Human Activity Recognition (HAR) has emerged as a critical research area due to its extensive applications in various real-world domains. Numerous CSI-based datasets have been established to support the development and evaluation of advanced HAR algorithms. However, existing CSI-based HAR datasets are frequently limited by a dearth of complexity and diversity in the activities represented, hindering the design of robust HAR models. These limitations typically manifest as a narrow focus on a limited range of activities or the exclusion of factors influencing real-world CSI measurements. Consequently, the scarcity of diverse training data can impede the development of efficient HAR systems. To address the limitations of existing datasets, this paper introduces a novel dataset that captures spatial diversity through multiple transceiver orientations over a high dimensional space encompassing a large number of subcarriers. The dataset incorporates a wider range of real-world factors including extensive activity range, a spectrum of human movements (encompassing both micro-and macro-movements), variations in body composition, and diverse environmental conditions (noise and interference). The experiment is performed in a controlled laboratory environment with dimensions of 5 m (width) × 8 m (length) × 3 m (height) to capture CSI measurements for various human activities. Four ESP32-S3-DevKitC-1 devices, configured as transceiver pairs with unique Media Access Control (MAC) addresses, collect CSI data according to the Wi-Fi IEEE 802.11n standard. Mounted on tripods at a height of 1.5 m, the transmitter devices (powered by external power banks) positioned at north and east send multiple Wi-Fi beacons to their respective receivers (connected to laptops via USB for data collection) located at south and west. To capture multi-perspective CSI data, all six participants sequentially performed designated activities while standing in the centre of the tripod arrangement for 5 s per sample. The system collected approximately 300-450 packets per sample for approximately 1200 samples per activity, capturing CSI information across the 166 subcarriers employed in the Wi-Fi IEEE 802.11n standard. By leveraging the richness of this dataset, HAR researchers can develop more robust and generalizable CSI-based HAR models. Compared to traditional HAR approaches, these CSI-based models hold the promise of significantly enhanced accuracy and robustness when deployed in real-world scenarios. This stems from their ability to capture the nuanced dynamics of human movement through the analysis of wireless channel characteristic from different spatial variations (utilizing two-diagonal ESP32 transceivers configuration) with higher degree of dimensionality (166 subcarriers).

Ring around the mitochondria.

Hexokinase 1 forms constricting rings around mitochondria that prevent fission induced by energy stress.

The prescription of beta-blockers in older patients with heart failure with reduced ejection fraction: an observational study in Vietnam.

This study in older hospitalized patients with heart failure with reduced ejection fraction (HFrEF) aimed to examine the prevalence of beta-blocker prescription and its associated factors. A total of 190 participants were recruited from July 2019 to July 2020. The inclusion criteria included: (1) aged ≥ 60 years, (2) having a diagnosis of chronic HFrEF in the medical records, (3) hospitalized for at least 48 h. The participants had a mean age of 75.5 ± 9.1, and 46.8% were female. Of these, 55.3% were prescribed beta-blockers during admission. To explore the factors associated with beta-blocker prescription, multivariable logistic regression analysis was applied and the results were presented as odds ratios (OR) and 95% confidence intervals (CI). On multivariate logistic regression models, higher NYHA classes (OR 0.49, 95%CI 0.26-0.94), chronic obstructive pulmonary disease (OR 0.17, 95% CI 0.04-0.85), chronic kidney disease (OR 0.40, 95% CI 0.19-0.83), and heart rate under 65 (OR 0.34, 95% CI 0.12-0.98) were associated with a reduced likelihood of prescription. In this study, we found a low rate of beta-blocker prescriptions, with only around half of the participants being prescribed beta-blockers. Further studies are needed to examine the reasons for the under-prescription of beta-blockers, and to evaluate the long-term benefits of beta-blockers in elderly patients with HFrEF in this population.

Genetic Structure of Ganoderma boninense Populations Associated with Oil Palm at Neighboring Fields with Different Planting Ages in Malaysia.

Ganoderma boninense is a basidiomycete pathogen of African oil palm (Elaeis guineensis) and the causal agent of basal stem rot (BSR) disease, which is the most destructive fungal disease of oil palm in Southeast Asia. The disease is fatal for infected palms and can result in 50 to 80% losses in oil yields because of a reduction in productive life span and a yield decline of infected oil palms. In this study, G. boninense isolates collected from different locations and planting blocks with different palm ages were molecularly characterized using microsatellite genotyping. Results showed high pathogen genetic diversity (He = 0.67 to 0.74) among planting blocks and between oil palm estates. Two nearby planting blocks with similar planting ages (i.e., 1999 and 2001) had a similar percentage of BSR incidence (>20%) but showed distinct Ganoderma genetic structure as detected using STRUCTURE. Similar results were obtained from another trial site where planting blocks differing in planting age but located only less than 1 km apart showed a diverse genetic background. The pathogen genetic admixture of the oldest planting (>30% BSR incidence) differed significantly from the younger planting (1.8 to 2.8% BSR incidence, breeding trial block), suggesting that the host-pathogen genotype interaction may impact the Ganoderma genetic variation over time. The genetic structure of G. boninense, as revealed in this study, implies positive selection resulting from the pathogen genetic variation, host-pathogen interaction, and possible introductions of novel genetic variants (through spores) from adjacent plantings. These findings offer new insights into the genetic changes of G. boninense over time. The information is essential to design disease management strategies and breeding for BSR resistance in oil palm.

Cinnamaldehyde, A Bioactive Compound from the Leaves of Cinnamomum osmophloeum Kaneh, Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the NLRP3 Inflammasome.

Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the quality of life for affected individuals. The effective management of these conditions remains a persistent challenge. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a complex molecular structure, regulates the production of pro-inflammatory cytokines such as interleukin-1ß. Abnormal activation of the NLRP3 inflammasome plays a pivotal role in the development of IBD, making it a compelling target for therapeutic intervention. Our research revealed that cinnamaldehyde (CA), a major bioactive compound found in the leaves of Cinnamomum osmophloeum kaneh, demonstrated a remarkable ability to alleviate colitis induced by dextran sulfate sodium (DSS) in a mouse model. This effect was attributed to CA's ability to downregulate the activation of the NLRP3 inflammasome and reduce the expression of pro-inflammatory mediators in the colon. In the mechanism study, we observed that CA inhibited the NLRP3 inflammasome in macrophages, at least partially, by enhancing the autophagic response, without reducing mitochondrial damage. These findings collectively suggest that CA holds significant potential as a therapeutic agent for enhancing the management of IBD, offering a promising avenue for further research and development.

Honokiol Exhibits Anti-NLRP3 Inflammasome and Antimicrobial Properties in Neisseria gonorrhoeae-Infected Macrophages.

Purpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1ß, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages. Methods: Honokiol's impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay. Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1ß, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae. Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.

A gut punch for PCOS.

Suppression of GLP-1 release by a gut microbiota-derived metabolite induces polycystic ovary syndrome.

Limited efficacy of a commercial microbial inoculant for improving growth and physiological performance of native plant species.

Soil microbial inoculants are increasingly being explored as means to improve soil conditions to facilitate ecological restoration. In southwestern Western Australia, highly biodiverse Banksia woodland plant communities are increasingly threatened by various factors including climate change, land development and mining. Banksia woodland restoration is necessary to conserve this plant community. The use of microbial inoculation in Banksia woodland restoration has not yet been investigated. Here, we evaluated the efficacy of a commercial microbial inoculant (GOGO Juice, Neutrog Australia Pty Ltd) for improving the performance of 10 ecologically diverse Banksia woodland plant species in a pot experiment. Plants were subjected to one of two watering regimes (well-watered and drought) in combination with microbial inoculation treatments (non-inoculated and inoculated). Plants were maintained under these two watering treatments for 10 weeks, at which point plants in all treatments were subjected to a final drought period lasting 8 weeks. Plant performance was evaluated by plant biomass and allocation, gas exchange parameters, foliar carbon and nitrogen and stable isotope (δ15N and δ13C) compositions. Plant xylem sap phytohormones were analysed to investigate the effect of microbial inoculation on plant phytohormone profiles and potential relationships with other observed physiological parameters. Across all investigated plant species, inoculation treatments had small effects on plant growth. Further analysis within each species revealed that inoculation treatments did not result in significant biomass gain under well-watered or drought-stressed conditions, and effects on nitrogen nutrition and photosynthesis were variable and minimal. This suggests that the selected commercial microbial inoculant had limited benefits for the tested plant species. Further investigations on the compatibility between the microorganisms (present in the inoculant) and plants, timing of inoculation, viability of the microorganisms and concentration(s) required to achieve effectiveness, under controlled conditions, and field trials are required to test the feasibility and efficacy in actual restoration environments.

The longitudinal dispositions of people diagnosed with adjustment or severe stress disorders.

BACKGROUND: Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that gap, the present article documents the service use and diagnostic outcomes of people with adjustment or stress-related disorders presenting at Singapore's largest psychiatric emergency department. METHODS: Administrative data from 2014 to 2021 was retrieved to follow a group of 683 service users whose first-ever psychiatric presentation in 2014 warranted a diagnosis of adjustment or stress-related disorder. People were grouped a priori depending on whether different diagnoses were recorded within 7 days, 9 months, after 9 months or not at all. Survival curves characterized conversion to other diagnoses and engagement with healthcare services. Service use outcomes include the number of hospitalizations, outpatient appointments, emergency department visits, and prescriptions. RESULTS: Sixty-one percent (n = 417) never received another diagnosis over the 8-year period. This group used emergency services most and received the most pharmacotherapy shortly after their first visit. Of those who received another diagnosis, depression, personality disorders, and psychotic disorders were the most common. Those who received another diagnosis within 7 days (n = 70, 10%) received it on their first day of hospitalization (IQR 1-1), making the most use of inpatient services. The group who received another diagnosis within 9 months (n = 105, 15%) did so after 42 days (IQR 26-84) and had the highest relative number of deaths. Those who received another diagnosis after 9 months (n = 91, 13%) did so after 1,134 days (IQR 613-1,823) and had the longest period of engagement but made the least use of any psychiatric service, potentially suggesting a group whose early index diagnosis heralded vulnerability to future disorders. CONCLUSIONS: A large group of service users with acute stress or adjustment disorders will likely never be given another psychiatric diagnosis and appear to disengage following an initial period of high-intensity service use. The group that received a different diagnosis after the 9-month mark had prolonged contact with services but low intensity of service use and may represent a target for preventative intervention to help them improve their stress-managing skills and avoid developing other disorders.

Cinnamaldehyde inhibits the NLRP3 inflammasome by preserving mitochondrial integrity and augmenting autophagy in Shigella sonnei-infected macrophages.

BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1ß and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. METHODS: Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. RESULTS: CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1ß and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. CONCLUSION: CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.

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The lactate wasteland.

Activation of GPR81 in white adipose tissue by lactate results in cancer-associated cachexia.

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Green and Heavy-Duty Anticorrosion Coatings: Waterborne Epoxy Thermoset Composites Modified through Variation of Zinc Dust Loading and Incorporation of Amine-Capped Aniline Trimer and Graphene Oxide.

In this study, an array of environmentally friendly and heavy-duty anticorrosion composite coatings were prepared. The synthesis involved amine-capped aniline trimer (ACAT) produced by an oxidative coupling reaction and graphene oxide (GO) prepared based on Hummer's method, and later, the waterborne epoxy thermoset composite (WETC) coatings were prepared by thermal ring-opening polymerization of EP 147w, a commercial waterborne epoxy resin, in the presence of ACAT and/or GO with zinc dust (ZD). A synergistic effect was observed by replacing a significant amount of the ZD loading in the WETC by simultaneously incorporating a small amount of ACAT and GO. The electrochemical corrosion measurements of the as-prepared WETC coatings indicated that incorporating 5% w/w ACAT or 0.5% w/w GO separately replaced approximately 30% w/w or 15% w/w of the ZD, respectively. Moreover, the WETC coatings containing 5% w/w ACAT and 0.5% w/w GO simultaneously were found to replace 45% w/w of the ZD. A salt spray test based on ASTM B-117 also showed a consistent trend with the electrochemical results. Incorporating small amounts of ACAT and GO in WETC coatings instead of ZD not only maintains the anticorrosion performance but also enhances adhesion and abrasion resistance, as demonstrated by the adhesion and abrasion tests.

Simplifying medication regimens for residents of aged care facilities: Pharmacist and physician use of a structured five-step medication simplification tool.

BACKGROUND: Pharmacist-led medication regimen simplification using a structured approach can reduce unnecessary medication regimen complexity in residential aged care facilities (RACFs), but no studies have investigated simplification by different health professionals, nor the extent to which simplification is recommended during comprehensive medication reviews. OBJECTIVES: To compare medication regimen simplification opportunities identified by pharmacists, general medical practitioners (GPs), and geriatricians and to determine if pharmacists identified simplification opportunities during routinely conducted comprehensive medication reviews in RACFs for these same residents. METHODS: Three pharmacists, three GPs and three geriatricians independently applied the Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) to medication data for 83 residents taking medications at least twice daily. Interrater agreement was calculated using Fleiss's kappa. Pharmacist medication review reports for the same 83 residents were then examined to identify if the pharmacists conducting these reviews had recommended any of the simplification strategies. RESULTS: Overall, 77 residents (92.8 %) taking medications at least twice daily could have their medication regimen simplified by at least one health professional. Pharmacists independently simplified 53.0-77.1 % of medication regimens (Κ = 0.60, 95%CI 0.46-0.75, indicating substantial agreement), while GPs simplified 74.7-89.2 % (Κ = 0.44, 95%CI 0.24-0.64, moderate agreement) and geriatricians simplified 41.0-66.3 % (Κ = 0.30, 95%CI 0.16-0.44, fair agreement). No simplification recommendations were included in the reports previously prepared by pharmacists as part of the comprehensive medication reviews undertaken for these residents. CONCLUSION: Pharmacists, GPs, and geriatricians can all identify medication regimen simplification opportunities, although these opportunities differ within and between professional groups. Although opportunities to simplify medication regimens during comprehensive medication reviews exist, simplification is not currently routinely recommended by pharmacists performing these reviews in Australian RACFs.