Low Activity Research Articles

Application of superb microvascular imaging technology in clinical disease activity of rheumatoid arthritis.

Detection of synovitis is essential for assessing the activity and predicting the prognosis of rheumatoid arthritis (RA). The aim of this study was to investigate the diagnostic performance of superb microvascular imaging (SMI) in RA patients with high, moderate, and low activity. One hundred four patients with active RA were selected from the hospital between May 2022 and August 2023. The study observed the correlation between bone erosion of the carpal joint, joint cavity effusion, thickness of synovial hyperplasia of the carpal joint, positivity rate of synovial blood vessels, and their semiquantitative scores with the clinical disease activity of RA using SMI examination. The detection of synovial hyperplasia thickness and joint effusion in the high-activity group was higher than that in the low-activity group, and the difference was statistically significant (P < 0.05). The quantitative SMI test demonstrated that the synovial blood flow grading and semiquantitative grade increased gradually with activity level (P<0.05). During the high, moderate, and low-activity groups, the vascular index (VI) value of the hyperplastic synovial membrane decreased gradually, showing statistical significance both between and within the groups (P<0.05). SMI technology exhibited high sensitivity and accuracy in assessing disease activity in RA. It holds significant clinical application value as a reliable auxiliary tool for assessing disease activity in RA and treatment. Key Points • Super micro-vascular imaging (SMI) demonstrated higher detection rates of microvesselsin RA patients with high disease activity compared to those with low activity, showing statistical significance. • The quantitative SMI test revealed a clear correlation between synovial blood flow grading and disease activity levels in RA patients, highlighting the potential of SMI as a valuable tool for disease activity and treatment of rheumatoid arthritis.

Preparation of magnesium potassium phosphate cement from magnesite tailings under lower calcination temperature

The identification of a more economical source of magnesium, coupled with reduced preparation costs, is essential for enhancing the competitiveness of magnesium potassium phosphate cement (MKPC) production. This study explores the utilization of magnesite tailings, waste materials produced during the mining and ore dressing process of magnesite, as raw materials for the preparation of low-cost dead-burnt magnesium oxide (MgO-T) at comparatively low calcination temperatures. The research demonstrated that impurities, specifically silicon and calcium, formed compounds with MgO during calcination, leading to the encapsulation of certain MgO particles. This encapsulation reduced both the specific surface area and hydration activity of the MgO. Despite the calcination temperature of 1100 °C being significantly lower than that of commercial dead-burnt MgO (MgO-C) at 1700 °C, MgO-T exhibited lower activity compared to MgO-C, which rendered it more suitable for the production of MKPC. Under optimal conditions, characterized by a molar ratio of magnesium to phosphorus (M/P) of 3, a borax retarder content of 15%, and a water-cement ratio of 0.15, the MKPC prepared using MgO-T demonstrated an initial setting time exceeding 60min and achieved a compressive strength of up to 79.6MPa. XRD and microstructural analyses revealed that struvite-K was the primary strength phase; however, the porosity of the specimens had a more pronounced effect on strength. By producing lower activity MgO at reduced calcination temperatures, this method obviates the need for complex purification processes when utilizing magnesite tailings, thereby decreasing the costs associated with MKPC preparation and presenting promising applications for the future.

Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy

USP7 is one of the most studied deubiquitinating enzymes, which is involved in the regulation of multiple cell signaling pathways and has been shown to be associated with the occurrence and progression of a variety of cancers. Inhibitors targeting USP7 have been studied by several teams, but most of them lack selectivity and have low activities. Herein, we reported a serious of pyrrole[2,3-d]pyrimidin-4-one derivatives through scaffold hopping of recently reported 4-hydroxypiperidine compounds. The representative compound Z33 (YCH3124) exhibited highly potent USP7 inhibition activity as well as anti-proliferative activity against four kinds of cancer cell lines. Further study revealed that YCH3124 effectively inhibited the downstream USP7 pathway and resulted in the accumulation of both p53 and p21 in a dose-dependent manner. Notably, YCH3124 disrupted cell cycle progression through restricting G1 phase and induced significant apoptosis in CHP-212 cells. In summary, our efforts provided a series of novel pyrrole[2,3-d]pyrimidin-4-one analogs as potent USP7 inhibitors with excellent anti-cancer activity.

Single nickel atoms anchored on porous N-doped nanocarbon with dual reaction sites for highly-efficient transfer hydrogenation of furfural to furfuryl alcohol

The non-precious metal single-atom catalysts (SACs) supported on carbon materials for the catalytic transfer hydrogenation (CTH) of α,β-unsaturated aldehydes (UAL) still suffer from the problems of harsh reaction conditions and low activity. In this work, nickel SACs anchored on porous N-doped nanocarbon (Ni1/NC900) with dual reaction sites were synthesized using the high internal-phase emulsion (HIPE) template method combined with impregnation. The Ni1/NC900 catalyst exhibited remarkable catalytic activity for the CTH of furfural (FF) to furfuryl alcohol (FFA), achieving >99.0 % conversion and selectivity at 100 °C for 60 min, with a turnover frequency (TOF) of 2908.1 h−1, surpassing other reported nickel-based catalysts by 1–3 orders of magnitude. The excellent catalytic performance of Ni1/NC900 was attributed to the high mass transfer efficiency (HMTE) of the support and the dual reaction sites of Ni–N4 and pyridinic N, where Ni–N4 as Lewis acidic site for adsorption of FF and isopropanol (i-PrOH), while the adjacent pyridinic N as Lewis basic site for the deprotonation of i-PrOH. The isotope labeling experiments revealed that the hydrogenation of FF was accomplished by proton transfer with i-PrOH, in agreement with the intermolecular hydride transfer mechanism. Furthermore, Ni1/NC900 demonstrated excellent stability and well general applicability, demonstrating its potential for industrial applications. This work provides a reference for the application of carbon-based non-precious metal SACs in the CTH reaction of UAL.

Natural variation of WBR7 confers rice high yield and quality by modulating sucrose supply in sink organs.

Grain chalkiness is an undesirable trait that negatively regulates grain yield and quality in rice. However, the regulatory mechanism underlying chalkiness is complex and remains unclear. We identified a positive regulator of white-belly rate (WBR). The WBR7 gene encodes sucrose synthase 3 (SUS3). A weak functional allele of WBR7 is beneficial in increasing grain yield and quality. During the domestication of indica rice, a functional G/A variation in the coding region of WBR7 resulted in an E541K amino acid substitution in the GT-4 glycosyltransferase domain, leading to a significant decrease in decomposition activity of WBR7A (allele in cultivar Jin23B) compared with WBR7G (allele in cultivar Beilu130). The NIL(J23B) and knockout line NIL(BL130)KO exhibited lower WBR7 decomposition activity than that of NIL(BL130) and NIL(J23B)COM, resulting in less sucrose decomposition and metabolism in the conducting organs. This caused more sucrose transportation to the endosperm, enhancing the synthesis of storage components in the endosperm and leading to decreased WBR. More sucrose was also transported to the anthers, providing sufficient substrate and energy supply for pollen maturation and germination, ultimately leading to an increase rate of seed setting and increased grain yield. Our findings elucidate a mechanism for enhancing rice yield and quality by modulating sucrose metabolism and allocation, and provides a valuable allele for improved rice quality.

Unhealthy Dietary Pattern Associated with Common Mental Disorders in Adults and Older Adults: A Population-based Study

Background:: Mental and behavioral disorders are influenced by biological, psychological and social factors, especially income, gender, age and family environment, indicating that physical health is directly associated with mental health. In this perspective, food consumption is highlighted as a risk factor for mental health, as healthy behaviors, along with a good quality diet, can reduce symptoms of anxiety and depression. Objective:: The objective of this a study is to investigate the association between CMD and dietary patterns, among other lifestyle and socioeconomic factors. Method:: Cross-sectional population-based and household study conducted with 1574 individuals aged over 20 years, of both sexes, residing in Teresina and Picos, Piaui, Brazil. Sociodemographic, lifestyle and food consumption data were collected. The instrument used to identify the presence of CMDs was the Self Reporting Questionnaire 20 (SRQ-20). Dietary patterns were obtained using the Principal Component Analysis method. Results:: Individuals of female sex, separated, with low education, smokers and lower level of physical activity had a higher prevalence of common mental disorders. As for the eating pattern, after adjustments, individuals who adhered to the unhealthy eating pattern had a 9% higher prevalence of CMD. Furthermore, adherence to the white meat standard represented 12% higher prevalence of CMD. Conclusion:: The results showed that, regardless of other socioeconomic and lifestyle factors, adherence to a more monotonous eating pattern in foods, characterized by the mainly consumption of animal protein and the lack consumption of foods like fruits and vegetables, as well as a less healthy one, characterized by the consumption of ultra-processed foods, increases the risk of developing CMD.

Integrated single-cell transcriptomic analyses identify a novel lineage plasticity-related cancer cell type involved in prostate cancer progression

Cancer cell plasticity is the ability of neoplastic cells to alter their identity and acquire new biological properties under microenvironmental pressures. In prostate cancer (PCa), lineage plasticity often results in therapy resistance and trans-differentiation to neuroendocrine (NE) lineage. However, identifying the cancer cells harboring lineage plasticity-related status remains challenging. Based on 13 multi-center human PCa bulk transcriptomic cohorts (samples=3314) and 9 bulk transcriptomic datasets derived from PCa experimental models, we established an integrated lineage plasticity-related gene signature, termed LPSig. Leveraging this gene signature, AUCell enrichment analysis was applied to identify the cell population with high lineage plasticity from a comprehensive single-cell RNA-sequencing (scRNA-seq) meta-atlas assembled by us, which consisted of 10 public human PCa scRNA-seq datasets (samples=93, cells=222,529). Moreover, additional scRNA-seq dataset of human PCa, multiplex immunohistochemistry staining for human PCa tissues, invitro and invivo functional experiments, as well as qPCR and Western blot analyses were employed to validate our findings. We found that LPSig could finely capture the dynamics of tumor lineage plasticity throughout the progression of PCa, accurately estimating the status of lineage plasticity. Based on LPSig, we identified a previously undefined minority population of lineage plasticity-related PCa cells (LPCs) from the human PCa scRNA-seq meta-atlas assembled by this study. Furthermore, in-depth dissection revealed pivotal roles of LPCs in trans-differentiation, tumor recurrence, and poor patient survival during PCa progression. Furthermore, we identified HMMR as a representative cell surface marker for LPCs, which was validated using additional scRNA-seq datasets and multiplexed immunohistochemistry. Moreover, HMMR was transcriptionally inhibited by androgen receptor (AR), and was required for the aggressive adenocarcinoma features and NE phenotype. Our study uncovers a novel population of lineage plasticity-related cells with low AR activity, stemness-like traits, and elevated HMMR expression, that may facilitate poor prognosis in PCa. This work was supported by National Key R&D Program of China (2022YFA0807000), National Natural Science Foundation of China (82160584), Advanced Prostate Cancer Diagnosis and Treatment Technology Innovation Team of Kunming Medical University (CXTD202216), and Reserve Talents of Young and Middle-aged Academic Leaders in Yunnan Province (202105AC160013).

In-situ preparation of BiOBr/Bi-doped CsPbBr3 S-scheme heterojunction for efficient photocatalytic CO2 reduction

Metal halide perovskite nanocrystals have garnered significant attention in the realm of photocatalytic CO2 reduction in recent years owing to their remarkable reducing properties and high selectivity. However, the issue of low photocatalytic activity due to severe carrier recombination phenomena in perovskite has posed a significant challenge. To address this, a one-pot in-situ preparation strategy was employed to create a BiOBr/Bi-doped perovskite nanocrystal S-scheme heterojunction, resulting in a significant improvement in the CO2 photoreduction performance. The heterojunction material exhibited a CO yield of 151.56 μmolg-1h−1, with a selectivity for CO of 93.6 %. The molar ratio of the components was modulated using an in-situ water aging strategy, yielding a photocatalyst performance that exceeded that of pure BiOBr. The synthesis strategy of one-step in-situ preparation of heterojunctions overcomes the problem of insufficient bonding caused by two-step methods. And various characterizations and DFT calculations strongly support the S-scheme mechanism of the photocatalyst. The active site effectively reduces the energy barrier for the transition from *COOH to *CO intermediate, thereby significantly improving photocatalytic activity.

Spherical sponge-inspired design of chitosan/silver cluster-loaded cellulose nanofibrils/Cu-ZIF-8 gel beads for efficient removal of Cr(VI)

Traditional photocatalysts for Cr(VI) often suffer from low catalytic activity, difficult separation and recovery, and weak stability. To address these limitations, we proposed a spherical sponge-inspired design to construct chitosan/silver cluster-loaded cellulose nanofibrils/Cu-ZIF-8 gel beads (CSCZ). This design featured a chitosan-based gel bead (the shell of the spherical sponge), silver cluster-loaded cellulose nanofibrils (the flagella of the spherical sponge), and Cu-ZIF-8 (the collar cell of the spherical sponge), which collectively endowed the CSCZ with remarkable properties. These included a high adsorption capacity (171.2 mg/g), a notable rate constant (0.2812 min−1), and enhanced stability (retaining 84.9 % of its initial removal rate after 10 cycles). In addition to the structural design, the “adsorption–reduction” synergy significantly enhanced Cr(VI) removal efficiency, as confirmed by both experimental characterizations and theoretical calculations. Furthermore, the CSCZ was utilized to treat industrial wastewater, and a custom-built flow-through reactor packed with CSCZ demonstrated the efficiency and practicability of CSCZ. This study demonstrates CSCZ’s potential to efficiently remove Cr(VI) and advances the development of photocatalytic adsorbents inspired by spherical sponge concepts.

Prevalence and Related Factors of Dizziness Among Older Adults: A Cross-Sectional Study in Ardakan City, Iran.

Dizziness and balance disorders are directly related to aging in humans- Dizziness is one of the most important factors causing the burden of disability after the age of 65. Bearing in mind the increase in the elderly population in Iran and the world and the prevalence of dizziness in old age, early diagnosis of dizziness and determination of the factors affecting its severity facilitate its treatment and are effective in preventing its adverse consequences. To determine the prevalence of dizziness and its related factors among older adults in Ardakan city, Yazd province, Iran, in 2022. This cross-sectional study was conducted in four comprehensive health centers of Ardakan city with the participation of 260 elderly people aged ≥60 years, who were randomly included in the study. Data were collected using a series of questionnaires which were completed by interviewing the participants. The variables of this study included demographic information, information related to the dizziness status, diseases, medications, use of mobility aids, physical activity level, fear of falling, quality of life and depression. The prevalence of dizziness among older adults of Ardakan city was 48.5%. In terms of the severity of dizziness, 38.8% had substantial dizziness, and 9.6% had mild dizziness. Dizziness was significantly related to physical activity (p<0.05), fear of falling (p <0.01), depression (p <0.05), history of falling (p <0.01), use of mobility aids (p <0.01), age (p<0.01), education level (p<0.01), gender (p <0.05) and diseases such as high blood pressure (p<0.05), hypothyroidism (p <0.01) and ear diseases(p <0.01). Also, elderly people with dizziness used significantly more medications such as sedatives (p<0.01), antihypertensive drugs (p <0.05) and cytotoxic drugs (p <0.01). About half of the older adults experience dizziness, and this problem is associated with depression, fear of falling, history of falling, low physical activity, age, female gender, ear diseases, high blood pressure, and hypothyroidism. In addition, the use of medications such as anti- hypertensives, sedatives and cytotoxic drugs is related to dizziness. Families with elderly people, doctors and healthcare workers need to be educated and pay more attention to the above.

Prefrontal cortex engagement during an fMRI task of emotion regulation as a potential predictor of treatment response in borderline personality disorder.

Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed. BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group. All female samples. Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection.

АДГЕЗИВНАЯ АКТИВНОСТЬ МИКРООРГАНИЗМОВ К СТОМАТОЛОГИЧЕСКИМ МАТЕРИАЛАМ ДЛЯ 3D ПЕЧАТИ И ВАКУУМНОЙ ФОРМОВКИ

Relevance: The adhesive activity of the oral microbiome to new generation materials is the subject of study by the global medical community, and the issue of choosing structural materials is still being discussed in the scientific community and is of a controversial nature. Objective: To study the adhesion of representatives of the oral microbiome to samples of modern dental materials under experimental conditions (in vitro). Materials and methods: Samples of photopolymer resins for 3D printing: Dental Crown LCD, Dental Sand A1-A2, Dental Clear Pro, (n=30), (1-3 groups), thermoforming plates for vacuum forming: EV Gasket Bleaching 080, Bioplast multicolor 3.0*123 mm, Bioplast color 3.0*125 mm (n=30), (groups 4-6); clinical isolates of the microbiome as test strains: Staphylococcus aureus, Streptococcus oralis, Neisseria subflava, Actinomyces oris, Candida albicans (n=5). Research methods: experimental, microbiological, cultural, analytical and statistical. Results: The degree of adhesion of representatives of the oral microbiome to the studied structural materials is in the range from 0 to 4.91 (Ia) and depends on both the species composition of the microbiome and the physico-chemical properties of the materials. The high adhesion index for all microbiota groups was noted for vacuum forming materials (4.91), and the lowest was Dental Crown LCD (0), which makes it possible to recommend it for practical use. Conclusions: The choice of structural material should be made, including taking into account the adhesive activity of the oral microbiome in order to reduce the risk of complications. It is recommended to give preference to materials with a low adhesive activity index.

Biofilm-mediated antibiotic tolerance in Staphylococcus aureus from spinal cord stimulation device-related infections.

Staphylococcus aureus is a predominant cause of infections in individuals with spinal cord stimulation (SCS) devices. Biofilm formation complicates these infections, commonly requiring both surgical and antibiotic treatments. This study explored the biofilm matrix composition and antimicrobial susceptibility of planktonic and biofilm-growing S. aureus isolates from individuals with SCS-related infections. Whole-genome sequencing (WGS) examined genotypes, virulome, resistome, and the pan-genome structure. The study also analyzed biofilm matrix composition, early surface adhesion, hemolytic activity, and antibiotic-susceptibility testing. WGS revealed genetic diversity among isolates. One isolate, though oxacillin susceptible, contained the mecA gene. The median number of virulence factor genes per isolate was 58. All isolates harbored the biofilm-related icaA/D genes. When assessing phenotypic characteristics, all strains demonstrated the ability to form biofilms in vitro. The antimicrobial susceptibility profile indicated that oxacillin, rifampin, and teicoplanin showed the highest efficacy against S. aureus biofilm. Conversely, high biofilm tolerance was observed for vancomycin, trimethoprim/sulfamethoxazole, and levofloxacin. These findings suggest that S. aureus isolates are highly virulent and produce robust biofilms. In cases of suspected biofilm infections caused by S. aureus, vancomycin should not be the primary choice due to its low activity against biofilm. Instead, oxacillin, rifampin, and teicoplanin appear to be more effective options to manage SCS infections.IMPORTANCESCS devices are increasingly used to manage chronic pain, but infections associated with these devices, particularly those caused by Staphylococcus aureus, present significant clinical challenges. These infections are often complicated by biofilm formation, which protects bacteria from immune responses and antibiotic treatments, making them difficult to eradicate. Understanding the genetic diversity, virulence, and biofilm characteristics of S. aureus isolates from SCS infections is critical to improving treatment strategies. Our study highlights the need to reconsider commonly used antibiotics like vancomycin, which shows reduced activity against biofilm-growing cells. Identifying more effective alternatives, such as oxacillin, rifampin, and teicoplanin, provides valuable insight for clinicians when managing biofilm-related S. aureus infections in patients with SCS implants. This research contributes to the growing evidence that biofilm formation is crucial in treating device-related infections, emphasizing the importance of tailoring antimicrobial strategies to the biofilm phenotype.

Advancements in cobalt‐based oxide catalysts for soot oxidation: Enhancing catalytic performance through modification and morphology control

AbstractThe widespread use of diesel engines results in significant environmental contamination due to emitted pollutants, particularly soot particles. These pollutants are detrimental to public health. At present, one of the most effective ways to remove soot particles is the catalytic diesel particulate filter after‐treatment technology, which requires the catalyst to have superior low temperature activity. Compared with cerium oxide which is widely used, cobalt oxide in transition metal oxides has been widely studied in recent years because of its high redox ability and easy to control morphology. This paper elaborates on the influence of modification techniques such as doping, loading, and solid solution on the catalytic performance of cobalt‐based catalysts in soot oxidation. Along the same lines, it further reviews the research progress on cobalt‐based oxide catalysts with specific dimensional structures and morphologies in soot oxidation. Finally, it provides an outlook on the challenges faced by the theoretical basis and applied research of cobalt‐based catalysts in soot oxidation.

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Implementation of the Lupus Low Disease Activity State in Pediatric Rheumatology Care: The Role of the Visual Analog Scale.

We compared the measurement properties of a traditional physician global assessment of disease activity (PhGA) 10-cm visual analog scale (PhGA0-10) with that of the three-point numeric scale (PhGA0-3) in childhood-onset systemic lupus erythematosus (cSLE) as part of the childhood Lupus Low Disease Activity State (cLLDAS). We used a secondary data analysis from a convenience sample of 100 patients with cSLE followed every three months for up to seven visits. Ratings of PhGA0-10, PhGA0-3, parent assessment of patient well-being (ParGA) (range: 0= very poorly, 10 = very well), disease activity as measured by the SLE disease activity index 2000 (SLEDAI-2k), Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI, and the British Isles International Lupus Activity Group index (BILAG; A = 9, B = 3, C = 1, D/E = 0) were compared. After linear transformation of PhGA0-10 to a 0 to 3 range (tPhGA0-10), the frequency of PhGA0-3 ≤1 was assessed to estimate the impact of scale type on the scoring of the cLLDAS. In 600 visits, the median (range) scores of PhGA0-10, PhGA0-3, SLEDAI-2k, SELENA-SLEDAI, and BILAG were 2 (0-10), 1(0-3), 4 (0-28), 4 (0-32), and 2 (0-28), respectively. PhGA0-10 and PhGA0-3 ratings were strong to moderately correlated with (r = 0.73; P < 0.0001) and with more variability for PhGA0-3 ≥2. SELENA-SLEDAI and SLEDAI-2k scores were moderately correlated with PhGA0-10 (r = 0.56/0.54; P < 0.0001). ParGA values were weakly correlated with all other measures considered (all r = -0.19 to -0.34). There were 490 of 600 visits with PhGA0-3 ≤1 and 497 of 600 visits with tPhGA0-10 ≤1 (κ (SE) =0.59 (0.04), McNemar P = 0.4). PhGA0-3 and PhGA0-10 have comparable measurement properties and yield almost identical cLLDAS rates when used in cSLE.

Common neural correlates of disgust processing in childhood maltreatment and peer victimisation.

Childhood maltreatment and peer victimisation are common sources of early-life interpersonal stress. Childhood maltreatment is associated with atypical frontolimbic emotion processing and regulation, and increased vulnerability for self-harm/suicide. However, few studies have compared the neurofunctional correlates between caregiver- versus peer-inflicted mistreatment. We compared the alterations of neurofunctional correlates of facial emotion processing in youths exposed to childhood maltreatment or peer victimisation, and explored their associations with self-harm. Functional magnetic resonance imaging data were collected from 114 age- and gender-matched youths (39 childhood maltreatment, 37 peer victimisation and 38 controls) during an emotion discrimination task. Region-of-interest (amygdala, insula) and whole-brain analyses were conducted. Groups differed significantly during disgust processing only. Both groups had lower activation in the right amygdala and bilateral posterior insula than controls; left insular underactivation was furthermore related to increased self-harm in maltreated youths. Compared with controls, at the whole-brain level, both groups also had underactivation in a cluster of bilateral limbic-thalamic-striatal, precuneus/posterior cingulate, temporal, fusiform/lingual and cerebellar regions, which was negatively associated with emotional problems in controls, as well as a cluster of somatosensory regions associated with increased self-harm in maltreated youths. Early-life interpersonal stress from caregivers or peers is associated with common underactivation of limbic-thalamic-striatal, precuneus/posterior cingulate and somatosensory regions during disgust processing. The hypoactivation of key emotion and sensory processing and self-referential brain regions could be a potential suppressive mechanism to cope with the aversive emotion; however, it may also entail increased risk of affective psychopathology in seemingly healthy youths.

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p&amp;lt;0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p&amp;lt;0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

Association between clinical ischemic risk and thrombogenicity phenotype and their prognostic prediction in patients undergoing percutaneous coronary intervention

Abstract Introduction The CHADS-P2A2RC score has been developed to provide better prognostic precision and improved selection of at-risk patients with coronary artery disease (CAD). The linkage of this clinical ischemic risk with thrombogenicity and their prognostic implication remain still unknown. Purpose We investigated the values of thrombogenicity indices according to the CHADS-P2A2RC score and their combined prognostic prediction in CAD patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (PCI) (n=2,705), clinical ischemic risk was classified with CHADS-P2A2RC score ("high risk": ≥ 4) and thrombogenicity indices were assessed using thromboelastography (TEG). Major adverse cardiovascular events (MACEs: a composite of all-cause death, myocardial infarction, or stroke) and major bleeding were evaluated were monitored for up to 3 years. Results Compared with "low/moderate-risk group" (67.7%), "high-risk group" (32.3%) had higher platelet-fibrin clot strength (PFCS: 67.3±7.9 vs. 65.2±7.2 mm; P &amp;lt; 0.001) and lower fibrinolytic activity (clot lysis at 30 min [LY30]: 0.9±2.1% vs. 1.1±2.4%, P &amp;lt; 0.001]. The "high-risk group" showed higher rates of "high PFCS phenotype (≥ 68 mm)" (35.3% vs. 49.7%; P &amp;lt;0.001), MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; P = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; P = 0.013) than the "low/moderate-risk group", respectively. Among the "low/moderate-risk group", "high MA phenotype" independently predicted MACE (HRadjusted: 1.51; 95% CI: 1.00-2.27; P = 0.048) and all-cause mortality (HRadjusted: 1.90; 95% CI: 1.06-3.4; P = 0.031). Likewise, this phenotype increased the risks of MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; p = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; p = 0.013) in the "high-risk group" (Table 1 and Figure 1). Prognostic impact of "high MA phenotype" on major bleeding was not significantly different across the risk-group (HRadjusted: 1.02; 95% CI: 0.39-2.72; P = 0.963 in the "low/moderate-risk group" and HRadjusted: 1.08; 95% CI: 0.50-2.34; P = 0.884 in the "high-risk group", respectively). Conclusion In PCI-treated patients, CHADS-P2A2RC score was significantly associated with a worse clinical outcome and more thrombogenic profile. Regardless of the ischemic-risk group, the level of clot-strength had an addictive effect on predicting the risk of ischemic event, indicating assessment of thrombogenicity indices using TEG may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Assessment of controlled assistance from e-bikes as a mitigation strategy for individual PM exposure

Abstract Background While promoting active mobility and outdoor activities can benefit health (HLT), it also increases Exposure (EXP) to air pollutants, such as particulate matter (PM), due to the increased ventilation rate (VR) under physical activity. Traditional assessments of individual (IND) PM EXP involve costly equipment inaccessible to the public, but real-time low-cost sensors (LCS) are now emerging. This study presents a proof of concept to demonstrate the use of LCS for examining the real-time IND respiratory dose deposited (RDD) to PM cycling across the Brescia province. Methods An e-bike was ridden 33 times between 2022 and 2023 wearing a LCS for PM concentration [PM] linked to a GPS. Respiratory dose deposited(RDD) was calculated for six different locations within each route based on experimental PM and various VR. Results The LCS allows for the study of the spatial and temporal variability of [PM], revealing a significant difference (p &amp;lt; 0.01) according to the heating system operation and no significant difference (p &amp;gt; 0.05) depending on the location. RDD increases with [PM] and VR. Real-time and integrated RDD is calculated for routes with high (&amp;gt; 50 µg/m3), medium (25 µg/m3), and low (&amp;lt;10 µg/m3) [PM2.5]. The e-bike assistance is activated when the WHO interim target 4 of [PM] is reached to reduce VR, which corresponds to a shift to a lower physical activity intensity. The RDD calculated using the e-bike assistance over the path reduces RDD by about 23% and 11% over the high and medium [PM], while it never activates for the low [PM]. Conclusions This study demonstrates that the use of LCS allows the estimation of IND RDD, and the implementation of mitigation strategies based on controlled assistance from e-bikes would enable the reduction of PM individual EXP. Key messages • The integration of HLT data from wearable and air quality LCS enables the promotion of active mobility and outdoor activities controlling the EXP to air pollutants. • Establishing generalized guidelines based on this mitigation strategies for individual exposure reduction may also inform policy recommendations for promoting active and green mobility.