Molecular mechanism of the metal-independent production of hydroxyl radicals by thiourea dioxide and H2O2.

It is well-known that highly reactive hydroxyl radicals (HO•) can be produced by the classic Fenton system and our recently discovered haloquinone/H2O2 system, but rarely from thiol-derivatives. Here, we found, unexpectedly, that HO• can be generated from H2O2 and thiourea dioxide (TUO2), a widely used and environmentally friendly bleaching agent. A carbon-centered radical and sulfite were detected and identified as the transient intermediates, and urea and sulfate as the final products, with the complementary application of electron spin-trapping, oxygen-18 isotope labeling coupled with HPLC/MS analysis. Density functional theory calculations were conducted to further elucidate the detailed pathways for HO• production. Taken together, we proposed that the molecular mechanism for HO• generation by TUO2/H2O2: TUO2 tautomerizes from sulfinic acid into ketone isomer (TUO2-K) through proton transfer, then a nucleophilic addition of H2O2 on the S atom of TUO2-K, forming a S-hydroperoxide intermediate TUO2-OOH, which dissociates homolytically to produce HO•. Our findings represent the first experimental and computational study on an unprecedented new molecular mechanism of HO• production from simple thiol-derived sulfinic acids, which may have broad chemical, environmental, and biomedical significance for future research on the application of the well-known bleaching agent and its analogs.

TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.

The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining.

The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.

Robust and Multifunctional Ti3 C2 Tx /Modified Sawdust Composite Paper for Electromagnetic Interference Shielding and Wearable Thermal Management.

Robust, ultrathin, and environmental-friendliness papers that synergize high-efficiency electromagnetic interference (EMI) shielding, personal thermal management, and wearable heaters are essential for next-generation smart wearable devices. Herein, MXene nanocomposite paper with a nacre-like structure for EMI shielding and electrothermal/photothermal conversion is fabricated by vacuum filtration of Ti3 C2 Tx MXene and modified sawdust. The hydrogen bonding and highly oriented structure enhance the mechanical properties of the modified sawdust/MXene composite paper (SM paper). The SM paper with 50 wt% MXene content shows a strength of 23 MPa and a toughness of 13 MJ·M-3 . The conductivity of the SM paper is 10 195 S·m-1 , resulting in an EMI shielding effectiveness (SE) of 67.9 dB and a specific SE value (SSE/t) of 8486 dB·cm2 ·g-1 . In addition, the SM paper exhibits excellent thermal management performance including high light/electro-to-thermal conversion, rapid Joule heating and photothermal response, and sufficient heating stability. Notably, the SM paper exhibits low infrared emissivity and distinguished infrared stealth performance, camouflaging a high-temperature heater surface of 147-81 °C. The SM-based e-skin achieves visualization of Joule heating and realizes human motions monitoring. This work presents a new strategy for designing MXene-based wearable devices with great EMI shielding, artificial intelligence, and thermal management applications.

The anti-cancer drug candidate CBL0137 induced necroptosis via forming left-handed Z-DNA and its binding protein ZBP1 in liver cells.

CBL0137, a promising small molecular anti-cancer drug candidate, has been found to effectively induce apoptosis via activating p53 and suppressing nuclear factor-kappa B (NF-κB). However, it is still not clear whether CBL0137 can induce necroptosis in liver cancer; and if so, what is the underlying molecular mechanism. Here we found that CBL0137 could significantly induce left-handed double helix structure Z-DNA formation in HepG2 cells as shown by Z-DNA specific antibody assay, which was further confirmed by observing the expression of Z-DNA binding protein 1 (ZBP1) and adenosine deaminase acting on RNA 1 (ADAR1). Interestingly, we found that caspase inhibition significantly promoted CBL0137-induced necroptosis, which was further supported with the increase of the late apoptosis and necrosis assessed by the flow cytometry. Furthermore, we found that CBL0137 can also induce the expression of the three necroptosis-related proteins: receptor interacting serine/threonine kinase 1 (RIPK1), receptor interacting serine/threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL). Taken together, it was assumed that CBL0137-indued necroptosis in liver cells was due to induction of Z-DNA and ZBP1, which activated RIPK1/RIPK3/MLKL pathway. This represents the first report on the induction of the Z-DNA-mediated necroptosis by CBL0137 in the liver cancer cells, which should provide new perspectives for CBL0137 treatment of liver cancer.

Effects of Connectivity Isomerization on Electron Transport Through Thiophene Heterocyclic Molecular Junction.

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

A Bis-Cyclopentadienyl Ligand-Supported Di-Iron Trihydride Motif as a Synthon for Access to Heterobimetallic Trinuclear Complexes.

Herein, we report the synthesis of a flexible bis-cyclopentadienyl ligand L (the doubly deprotonated form of H2L (1,3-bis(2,4-di-tert-butylcyclopentadienyldimethylsilyl)benzene)), demonstrating its ability to stabilize a series of di-iron hydrido complexes. Notably, this ligand facilitates the isolation of an unprecedented anionic cyclopentadienyl ligand-supported di-iron trihydride complex, LFe2(µ-H)3Li(THF) (2), functioning as a synthon for the [Fe2(µ-H)3]- core and providing access to heterobimetallic complexes 4-6 with coinage metals.

Racial and Ethnic Underserved Populations Prescription Analgesic Use Before and After Lower Extremity Amputation in US Medicare.

BACKGROUND: Racial disparities exist in access to health care and management of multiple health conditions including chronic pain; however, racial disparities in pre- and postoperative pain management in lower extremity amputation are not well-studied. Our objective was to examine the association between different racial and ethnic groups and prescription opioid and other analgesics use before and after lower extremity amputation. We hypothesize prescription opioid and other analgesic use among Black, Hispanic, and Native American US Medicare beneficiaries undergoing lower extremity amputations will be lower compared to White US Medicare beneficiaries. METHODS: This retrospective cohort study included a 5% national sample of all Medicare beneficiaries from 2011 to 2015 and 15% national sample of fee-for-service Medicare beneficiaries from 2016 to 2018 undergoing nontraumatic, lower extremity amputations. The exposure of interest was racial and ethnic group membership (ie, Black, Hispanic, Native American, White, and others-with others being the combination of the categories Asian and other) as provided in Medicare claims data. Using multivariable generalized estimating equations with a logistic link to account for repeated measurements over time, we estimated the odds of prescription opioid use within 6 months before and after lower extremity amputation across different racial and ethnic groups separately, adjusting for sociodemographic and health status factors (eg, Elixhauser index). Adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) were reported. RESULTS: Among 16,068 eligible beneficiaries who underwent major and minor amputations (mean age = 65.1 ± 12.7 years; female = 36.1%), 10,107 (62.9%) were White, 3462 (21.5%) were Black, 1959 (12.2%) were Hispanic, 247 (1.5%) were Native American, and 151 (2.9%) were beneficiaries of other races. During the 6 months before lower extremity amputation, Hispanic beneficiaries (aOR, 0.71, 95% CI, 0.65-0.78) and beneficiaries of other races (aOR, 0.60, 95% CI, 0.47-0.76) had significantly lower odds of using prescription opioids compared to White beneficiaries. Similarly, Hispanic beneficiaries (aOR, 0.78, 95% CI, 0.71-0.84) and beneficiaries of other races (aOR, 0.63, 95% CI, 0.51-0.78) were associated with lower odds of opioid use in the 6 months after amputation compared to White beneficiaries. CONCLUSIONS: Among fee-for-service Medicare beneficiaries, Hispanic and other (eg, Asian) fee-for-service Medicare beneficiaries had lower odds of prescription opioid use than their White counterparts before and after nontraumatic, lower extremity amputations. Efforts to determine the underlying reasons are needed to ensure equitable health care access.

A scoping review and theory-informed conceptual model of professional identity formation in medical education.

INTRODUCTION: Professional identity formation (PIF) is a central tenet of effective medical education. However, efforts to support, assess and study PIF are hindered by unclear definitions and conceptualisations of what it means to 'think, act, and feel like a physician'. Gaps in understanding PIF, and by extension, its support mechanisms, can predispose individuals towards disengaged or unprofessional conduct and institutions towards short-sighted or reactionary responses to systemic issues. METHODS: A Systematic Evidence-Based Approach-guided systematic scoping review of PIF theories was conducted related to medical students, trainees and practising doctors, published between 1 January 2000 and 31 December 2021 in PubMed, Embase, ERIC and Scopus databases. RESULTS: A total of 2441 abstracts were reviewed, 607 full-text articles evaluated and 204 articles included. The domains identified were understanding PIF through the lens of pivotal theories and characterising PIF by delineating the underlying factors that influence it and processes that define it. CONCLUSIONS: Based on regnant theories and frameworks related to self-concepts of identity and personhood, the relationships between key PIF influences, processes and outcomes were examined. A theory-backed integrated conceptual model was proposed to delineate the interconnected relationships among these, aiming to untangle some of the complexities inherent to PIF, to shed light on existing practices and to identify shortcomings in our understanding so as to develop mechanisms in support of its multifaceted, interlinked components.

Characterization of an autonomous pathway complex that promotes flowering in Arabidopsis.

Although previous studies have identified several autonomous pathway components that are required for the promotion of flowering, little is known about how these components cooperate. Here, we identified an autonomous pathway complex (AuPC) containing both known components (FLD, LD and SDG26) and previously unknown components (EFL2, EFL4 and APRF1). Loss-of-function mutations of all of these components result in increased FLC expression and delayed flowering. The delayed-flowering phenotype is independent of photoperiod and can be overcome by vernalization, confirming that the complex specifically functions in the autonomous pathway. Chromatin immunoprecipitation combined with sequencing indicated that, in the AuPC mutants, the histone modifications (H3Ac, H3K4me3 and H3K36me3) associated with transcriptional activation are increased, and the histone modification (H3K27me3) associated with transcriptional repression is reduced, suggesting that the AuPC suppresses FLC expression at least partially by regulating these histone modifications. Moreover, we found that the AuPC component SDG26 associates with FLC chromatin via a previously uncharacterized DNA-binding domain and regulates FLC expression and flowering time independently of its histone methyltransferase activity. Together, these results provide a framework for understanding the molecular mechanism by which the autonomous pathway regulates flowering time.

Efficacy of Digital Dance on Brain Imagery, Cognition, and Health: Randomized Controlled Trial.

BACKGROUND: Multidomain interventions have demonstrable benefits for promoting healthy aging, but self-empowerment strategies to sustain long-term gains remain elusive. OBJECTIVE: This study evaluated the effects of digital somatosensory dance game participation on brain imagery changes as primary outcomes and other physical and mental health measures as secondary outcomes related to healthy aging. METHODS: Between August 31, 2020, and June 27, 2021, this randomized controlled trial recruited 60 eligible participants older than 55 years with no recent engagement in digital dance games. A computer-generated randomization sequence was used to allocate participants 1:1, without stratification, to an intervention group (n=30) who underwent digital somatosensory dance game training or a control group (n=30). An anonymized code masked the intervention allocations from the investigators, and individuals who assigned the interventions were not involved in analyzing the study data. The intervention entailed two 30-minute dance game sessions per week for 6 months, and the control group received healthy aging education. Primary outcomes were brain imagery changes. All variables were measured at baseline and the 6-month follow-up, and intervention effects were estimated using t tests with intention-to-treat analyses. RESULTS: Compared with the control group, intervention participants had significantly different brain imagery in the gray matter volume (GMV) of the left putamen (estimate 0.016, 95% CI 0.008 to 0.024; P<.001), GMV of the left pallidum (estimate 0.02, 95% CI 0.006 to 0.034; P=.004), and fractional amplitude of low frequency fluctuations of the left pallidum (estimate 0.262, 95% CI 0.084 to 0.439; P=.004). Additionally, the intervention group had different imagery in the cerebellum VI GMV (estimate 0.011, 95% CI 0.003 to 0.02; P=.01). The intervention group also had improved total Montreal Cognitive Assessment scores (estimate 1.2, 95% CI 0.27 to -2.13; P<.01), quality of life (estimate 7.08, 95% CI 2.35 to 11.82; P=.004), and time spent sitting on weekdays (estimate -1.96, 95% CI -3.33 to -0.60; P=.005). Furthermore, dance performance was significantly associated with cognitive performance (P=.003), health status (P=.14), resilience (P=.007), and demoralization (P<.001). CONCLUSIONS: Digital somatosensory dance game participation for 6 months was associated with brain imagery changes in multiple regions involving somatosensory, motor, visual, and attention functions, which were consistent with phenotypic improvements associated with healthy aging. TRIAL REGISTRATION: ClinicalTrials.gov NCT05411042; https://clinicaltrials.gov/study/NCT05411042.

Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated. METHODS: Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs). RESULTS: A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE-/-) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE-/- mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis. CONCLUSIONS: The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Modeling competitive biosorption for methylene blue removal on rape straw powders using response surface methodology in a ternary dye aqueous solution.

The improvement of biosorption efficiency for selective dye removal in a multi-dye aqueous system has become an increasingly significant research topic. However, the competitive effects of coexisting dyes and the target dye in such systems remain uncertain due to complex interactions between adsorbent and coexisting dyes. Therefore, in this research, response surface methodology (RSM) model was effectively employed to investigate the competitive effects of allura red (AR) and malachite green (MG) on methylene blue (MB) removal in a ternary dye aqueous system using three different parts of rape straw powders. In the current design of RSM, the initial concentrations of AR and MG dyes ranging from 0 mg·L-1 to 500 mg·L-1 were considered as influencing factors, while the removal rates of MB on adsorbents at an initial concentration of 500 mg·L-1 were established as response values. The RSM models exhibited high correlation coefficients with adjusted R2 values of 0.9908 (pith core), 0.9870 (seedpods), and 0.9902 (shells), respectively, indicating a close fitted between predicted and actual values. The proposed models indicated that the perturbation effects of initial AR and MG concentrations were observed on the removal rates of MB by three types of rape straw powders in a ternary dye aqueous system, resulting in a decrease in MB removal rates, particularly at higher initial AR concentration due to stronger competitive effects compared to initial MG concentration. The structures of rape straw powders, including pith core, seedpods and shell, were analyzed using scanning eletron microscoe (SEM), energy dispersive spectroscopy (EDS), N2 physisorption isotherm, frourier transform infared spectroscopy (FTIR), Zeta potential classes and fluorescence spectrum before and after adsorption of MB in various dye aqueous systems. The characteristics of rape straw powders suggested that similar adsorption mechanisms, such as electrostatic attraction, pore diffusion, and group complex formation for MB, AR, and MG, respectively, occurred on the surfaces of adsorbents during their respective adsorption processes. This leads to significant competitive effects on the removal rates of MB in a ternary dye aqueous system, which are particularly influenced by initial AR concentrations as confirmed through fluorescence spectrum analysis.

Impact of AR and MG on MB removal was analyzed using simple methodologies.Competitive behaviors between AR, MG and MB were understood through RSM.Intense restrain effects on MB removal were revealed by AR concentration.

Altered cerebellar and caudate gray-matter volumes and structural covariance networks preceding dual cognitive and mobility impairments in older people.

INTRODUCTION: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS). METHODS: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters. RESULTS: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed. DISCUSSION: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments. HIGHLIGHTS: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome.

Computational fluid dynamics study in children with obstructive sleep apnea.

OBJECTIVES: This study aims to identify characteristics in image-based computational fluid dynamics (CFD) in children with obstructive sleep apnea (OSA). DESIGN: Diagnostic study. SETTING: Hospital-based cohort. PARTICIPANTS: Children with symptoms suggestive of OSA were recruited and underwent polysomnography. MAIN OUTCOME MEASURES: Three-dimensional models of computational fluid dynamics were derived from cone-beam computed tomography. RESULTS: A total of 68 children participated in the study (44 boys; mean age: 7.8 years), including 34 participants having moderate-to-severe OSA (apnea-hypopnea index [AHI] greater than 5 events/h), and 34 age, gender, and body mass index percentile matched participants having primary snoring (AHI less than 1). Children with moderate-to-severe OSA had a significantly higher total airway pressure (166.3 vs. 39.1 Pa, p = .009), total airway resistance (9851 vs. 2060 Newton-metre, p = .004) and velocity at a minimal cross-sectional area (65.7 vs. 8.8 metre per second, p = .017) than those with primary snoring. The optimal cut-off points for moderate-to-severe OSA were 46.2 Pa in the total airway pressure (area under the curve [AUC] = 73.2%), 2373 Newton-metre in the total airway resistance (AUC = 72.5%) and 12.6 metres per second in the velocity at a minimal cross-sectional area (AUC = 70.5%). The conditional logistic regression model revealed that total airway pressure, total airway resistance and velocity at minimal cross-sectional area were significantly associated with an increased risk of moderate-to-severe OSA. CONCLUSIONS: This study demonstrates that CFD could be a useful tool for evaluating upper airway patency in children with OSA.

The Relationship Between Voluntary Participation Status and Health Promotion Lifestyle Among Middle-Aged and Older Adults in the Community.

The purpose of this study was to understand the relationship between the characteristics, health status, and health-promoting lifestyles of volunteer workers who participate in the community among middle-aged and older adults. A cross-sectional study was conducted to collect data from 173 middle-aged and older adults volunteers from 2 communities in North Taiwan. Data were collected using a structured questionnaire that included Demographic Characteristics Form, Self-Rated Health Status Scale, and Health Promotion Lifestyle Scale. Most of the volunteers were female, with an average age of 60.41 (±9.30) years. The average item score for the health promotion lifestyle was 74.07 (SD = 19.27). Participants scored highest on the social support subscales and lowest on the exercise subscales, followed by health responsibility subscales. Multiple regression analysis revealed that an average of 6 to 8 hours of volunteer services per week, diversity of volunteer services, and self-rated health status were each significantly associated with a greater health promotion lifestyle. Community health care workers should strengthen community volunteer support networks and motivate volunteers to attend health-related classes. Various community activities can remind each volunteer of their health responsibilities and awareness of a healthy promotion lifestyle.

The impact of psychological interventions on surgical site wound healing post-surgery in psoriasis patients: A meta-analysis.

This meta-analysis investigates the impact of psychological interventions on the wound healing process at surgical sites in patients with psoriasis who have undergone various surgical procedures. Following the PRISMA guidelines, an extensive database search was conducted, initially identifying 679 articles, with 6 studies ultimately meeting our rigorous selection criteria. These studies, which included both Randomized Controlled Trials and observational designs, utilized a range of scales, such as the REEDA and Manchester Scar Scale (MSS), to measure the healing of surgical wounds. Statistical analyses were performed using Review Manager and SPSS, revealing that psychological interventions significantly expedited wound healing as early as 1 week post-surgery (I2 = 93%; Random: SMD = -3.01, 95% CI: [-4.35, -1.66], p < 0.01), according to the REEDA scale. At the one-month follow-up, a continued positive effect was observed on the MSS (I2 = 69%; Random: SMD = 2.31, 95% CI: [1.54, 3.08], p < 0.01). The studies demonstrated a low risk of bias, and funnel plot analysis suggested no significant publication bias. These results highlight the beneficial role of psychological support in the postoperative recovery of psoriasis patients, suggesting a need for a more integrated approach to patient care that includes psychological well-being as a component of comprehensive treatment strategies.

Evaluating the carbon footprint of sedation practices in intensive care.

BACKGROUND: Healthcare's carbon footprint contributes to 4.4% of global net emissions and intensive care units (ICUs) are very resource intensive. Existing studies on environmental sustainability in ICUs focused on carbon footprint generated from energy and electricity consumption, use of medical consumables and equipment, but few studies quantified carbon footprint generated from pharmaceuticals used in ICUs. AIM: To evaluate carbon footprint arising from sedation practices in the ICUs. STUDY DESIGN: A pilot, prospective observational study was conducted in two ICUs from 1 August to 22 September 2022 in Singapore General Hospital. Adult patients who were consecutively sedated, intubated and expected to be mechanically ventilated for at least 24 h were included. Total amount of analgesia and sedatives used and wasted in eligible patients were collected. Carbon emission from ICU sedation practices were then quantified using available life cycle assessment data. RESULTS: A total of 31 patients were recruited. Top analgesia and sedative used in both ICUs were fentanyl and propofol, respectively. Carbon footprint from sedative usage and wastage across 7 weeks in both ICUs were 2.206 kg CO2-e and 0.286 g CO2-e, respectively. In total, this equates to driving 15.8 km by car. Proportion of drug wasted ranged from 5.1% to 25.0%, with the top reason for wastage being the drug was no longer clinically indicated. Recommendations to reduce carbon footprint include choosing sedatives with lower carbon emissions where possible and having effective communication among doctors and nurses regarding management plans to minimize unnecessary wastage. CONCLUSION: Our study quantified carbon footprint arising from sedation practices, mainly drug usage and wastage in two ICUs in Singpore General Hospital. RELEVANCE TO CLINICAL PRACTICE: Adopting a holistic approach to environmental sustainability in the ICU, sedation practices also contribute to generating greenhouse gases, albeit small, and can be targeted to reduce unnecessary carbon footprint.