共找到 20 条结果
According to Organisation for Economic Co-operation and Development test guideline no. (TG) 487 for the in vitro mammalian cell micronucleus test (MNT), short (pulse) treatment of primary human lymphocytes should be followed immediately by a sampling period of 1.5-2.0 cell cycle lengths in the presence of cytochalasin B. However, TG 487 allows extending the sampling period "if it is known or suspected that the test chemical affects the cell cycling time." It is often unknown in advance whether a test substance induces cell cycle delays, and therefore whether an extension of the sampling period is warranted. Here, we investigate whether extending the sampling time after pulse treatment-by including a recovery period prior to cytochalasin B treatment-affects the sensitivity of the in vitro MNT. Primary human lymphocytes were exposed to 11 mutagens and assessed using two protocols ("recovery" and "no recovery") in parallel from the same treatment culture. Including a recovery period after pulse treatment generally allowed testing of higher concentrations without excessive cytotoxicity. In addition, cultures subjected to a recovery period showed generally higher micronucleus rates at concentrations with acceptable levels of cytotoxicity, compared to cultures not having undergone a recovery period. To compare the sensitivity of both protocols at non-cytotoxic concentrations, benchmark concentration analysis was performed. Here, the "recovery method" proved to be at least as sensitive as the "no recovery method." The reproducibility of these findings was demonstrated in an interlaboratory ring trial using a subset of up to five mutagens. In conclusion, the inclusion of a recovery period after pulse treatment per se covers potential substance-induced cell cycle delays without any loss in sensitivity toward the induced mutagenic effect. The "recovery" protocol can be used for assessing the mutagenic potential of test substances affecting and not affecting the cell cycle.
Pulse oximetry can support better detection of hypoxaemia, an important mortality predictor, and digital clinical decision support algorithms (CDSAs) can strengthen adherence to Integrated Management of Childhood Illness (IMCI) guidelines. This study sought to address evidence gaps on the impact of providing these tools to primary care healthcare providers on under-five hospitalisations and mortality. A pragmatic, parallel group, superiority, cluster randomised controlled trial (RCT) conducted in 172 primary care facilities in India and Tanzania (106 and 66 facilities, respectively). Facilities were randomly allocated (1:1) in India to pulse oximetry (PO) or control and (1:1:1) in Tanzania to PO + CDSA, PO, or control, stratified by facility type and location (India: district; Tanzania: urban/rural). Sick children aged 0-59 months attending study facilities were eligible. Pulse oximeters and CDSAs were given to healthcare providers, along with training and guidance, supportive supervision, monitoring, community engagement, and operational support. Providers were advised to use pulse oximetry for all sick children in India, and in Tanzania for all 1-59 days, and for those 2-59 months with cough, difficulty breathing, or a moderate to severe illness. Urgent referral was recommended for SpO2 <90%. Trained research assistants collected data from caregivers and facility records on Day 0, with a follow-up phone call or visit on Day 7 and 28. Two primary outcomes, based on caregiver report, were assessed centrally: 1) rates of 'severe complication' (death, delayed hospitalisation (≥24 h from the Day 0 consultation) or hospitalisation without Day 0 referral) by Day 7; and 2) rates of hospitalisation within 24 h of the Day 0 consultation, with referral. Intention-to-treat analyses were performed on combined and individual country data, stratified by age (1-59 days, 2-59 months). Primary outcomes were assessed using generalised estimating equations for logistic regression, with facilities as clusters. Results were estimated in terms of odds ratios and risk differences (RDs), adjusted where computable. The trial is registered with clinicaltrials.gov (NCT04910750). A total of 157,677 sick children (1-59 days: 3188 control, 4012 PO, 2386 PO + CDSA; 2-59 months: 54,318 control, 56,968 PO, 36,805 PO + CDSA) were enrolled from 28 March, 2022 to 31 March, 2023 in Tanzania and from 20 June, 2022 to 21 April, 2023 in India. Severe complications were rare in the control arm, with 16 (0·5%) events in 1-59 days, 77 (0·1%) in 2-59 months. No significant difference was observed in 1-59 days in the PO arm, with 27 events (0·7%, RD 0·2% [-0·2%; 0·5%]), but a slight increase was noted in 2-59 months, with 143 events (0·3%, adjusted RD 0·1% [0·0%; 0·2%]). No statistically significant differences were observed in the CDSA + PO arm, with 21 events (0·9%, RD 0·5% [-0·1%, 1·0%]) in 1-59 days, 128 (0·3%, adjusted RD 0·1% [-0·0%, 0·3%]) in 2-59 months. Day 0 hospitalisations with referral were very rare in the control arm, with 0 events (0·0%) in 1-59 days, 12 (0·0%) in 2-59 months. Arm comparisons were either not computable or not statistically significant, within the PO arm: 9 events (0·2%) in 1-59 days, 22 (0·0%, RD 0·0% [-0·0%, 0·1%]) in 2-59 months; in the CDSA + PO arm: 6 events (0·3%) in 1-59 days, 32 (0·1%, RD 0·0% [-0·0%, 0·1%]) in 2-59 months. When implemented in routine health systems at primary care level in India and Tanzania, contrary to expectations, pulse oximetry and CDSAs were not found to increase rates of hospitalisation within 24 h of primary care referral, nor to decrease deaths, or delayed or un-referred hospitalisations. Wider health system challenges, including referral barriers, inequitable oxygen access and hospital care quality must be addressed if the potential of these tools in delivering child outcome benefits is to be realised. Unitaid grant n°2019-35-TIMCI: Tools for Integrated Management of Childhood Illness.
Aortic wall calcification increases arterial stiffness which is often assessed by carotid-femoral pulse wave velocity (cfPWV). However, the impact of kidney function upon the association between calcification of the aortic wall and cfPWV remains unknown. To examine the association between aortic calcification and cfPWV, we prospectively recruited chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) and patients with normal renal function, planned for invasive coronary angiography. Participants underwent a non-contrast computed tomography scan of the entire aorta with subsequent Agatston scoring of the aortic wall in addition to a standardized cfPWV measurement and biochemical markers. A total of 144 patients (67.1 ± 10.3 years, 24% female), of whom 110 had CKD (26 stage 3a, 33 stage 3b, 24 stage 4, and 27 stage 5), were included. Agatston score was associated with cfPWV in a univariate regression analysis (p < 0.001). So were age (p < 0.001) and diabetes (p = 0.001), but not gender, smoking status, eGFR, office systolic blood pressure, calcium-phosphate product, C-reactive protein nor vasodilator treatment. Multiple regression analysis including all these factors did not significantly change these associations and relative weight analysis revealed Agatston score to account for 30% of the variation in cfPWV in the model (total r 2 = 0.31). In a cohort representing the entire spectrum of kidney function, aortic Agatston score, as well as age and diabetes, were associated with cfPWV after adjustment for other risk factors including eGFR. However, most of the variation in cfPWV remains unexplained by these factors.
Introducing pulse oximeters (PO) at primary care facilities can help health workers identify severely ill children who need referral to hospital thereby allowing for improved child clinical outcomes. Adding clinical decision support algorithms (CDSA) can improve adherence to Integrated Management of Childhood Illness guidelines. The current study analyses the costs of introducing PO either with or without an electronic CDSA using an RCT in India and Tanzania and in a pre-post design with an electronic CDSA in Kenya and Senegal. The impact of the intervention is discussed for the RCT (trial registration NCT04910750) and for the pre-post study (trial registration NCT05065320), following SPIRIT guidelines. Economic data were collected in all four countries using questionnaires administered at primary health facilities and referral hospitals and supplemented by information from administrative sources, following CHEERS guidelines. Trained research assistants at the facilities collected data on children enrolled and health outcomes. Net costs per 100 children managed using PO ranged from $16.62 (Kenya, health center) to $70.51 (Tanzania, dispensary), in both cases using CDSA. Senegal was an outlier at $385.45, using PO and CDSA in the smaller postes de santé. Major causes explaining variation included training modality, numbers of sick children attending the facility, and the effect of PO and CDSA on use of antibiotics, diagnostics, and hospitalizations. Standard care (without PO) was associated with fewer severe complications (primarily untimely hospitalizations), at lower cost, in the two countries where effectiveness data are available, India and Tanzania. Scaling up PO use at primary care level nationally could have an important budgetary impact. Findings suggest ways that costs could potentially be reduced. However, hospitalization costs borne by households may affect both household and provider behavior and limit the potential clinical benefits of pulse oximetry.
Parkinson's Disease (PD) is a progressive neurodegenerative disorder marked by motor and non-motor symptoms, including cognitive decline, mood disturbances, and sensory deficits. While dopaminergic treatments remain the gold standard, they present long-term side effects and limited impact on non-motor symptoms. Transcranial Pulse Stimulation (TPS) has emerged as a promising adjunct therapy in neurological and psychiatric conditions, but its effects in PD remain underexplored. This open-label, single-arm trial protocol involves 14 PD participants and outlines a personalized 12-session treatment approach combined with a homogeneously distributed TPS intervention among patients with PD. The approach addresses the subject's most prominent symptoms, as identified through validated clinical assessments, encompassing domains related to both motor and non-motor symptoms. Over 2.5 months, besides the intervention sessions, the 14 participants will undergo an MRI brain scan, a baseline assessment, a post-treatment assessment, and a 1-month follow-up assessment. The study aims to determine whether personalized TPS is a feasible and safe intervention and whether it improves PD symptoms across multiple functional domains. This study represents the first structured attempt to evaluate a multimodal, personalized TPS intervention in patients with PD. It addresses gaps in current treatment approaches and may support the development of future strategies for integrated, symptom-targeted neuromodulation.
Recently, multiple pulsed field ablation (PFA)-system were introduced for catheter ablation (CA) of atrial fibrillation (AF). However, data comparing procedural performance, the extent of low-voltage areas (LVA), and myocardial injury between different PFA-systems in a real-world setting remain scarce. Consecutive patients undergoing CA for AF were enrolled. PFA was performed using either a Pentaspline catheter-system (PCS) or a loop catheter-system (LCS). The extent of acute antral LVA was assessed using a 3D-electroanatomical mapping system. High-sensitivity cardiac troponin T (hs-cTnT) was measured the day after the procedure to assess myocardial injury. A total of 120 patients (median age 67 [59-73] years, 29% female) underwent de novo pulmonary vein isolation (PVI). The PCS-group included 90 patients, while the LCS-group included 30 patients. Acute PVI was achieved in all patients (100%). Procedural times were significantly shorter in the PCS compared to the LCS-group, including total procedure duration (57 [48-67] vs 66 [52-83] min, p = 0.016), left atrial dwell time (38 [32-48] vs 54 [38-65] min, p < 0.001), and ablation duration (17 [12-23] vs 24 [20-33] min, p < 0.001). Acute antral LVA and myocardial injury were significantly lower in the PCS compared to the LCS-group (6.6 [5.0-8.9] vs. 19.2 [16.8-25.4] cm², p < 0.001 and hs-cTnT of 1282 [892-1894] vs 1588 [1281-2110] ng/L, p = 0.029. Significant differences were observed between two commercially available PFA-systems. While PCS was associated with significantly shorter procedural time, LCS resulted in a greater extent of acute antral LVA and myocardial injury levels.
The aim of this study was to assess the association of office arterial stiffness and 24 h arterial stiffness as measured by pulse wave velocity (PWV) with subclinical target organ damage (TOD) in a hypertensive cohort. We evaluated associations of TOD with office carotid-femoral PWV (cf-PWV) by radial tonometry (SphygmoCor) and 24-h ambulatory PWV measurements by brachial oscillometry (Mobil-O-Graph 24-h PWA Monitor) in 636 hospital inpatients (age 54 ± 13 years, 465 males) with primary hypertension. Subclinical TOD was assessed as left ventricular hypertrophy (LVH) obtained by echocardiography quantified by LV mass index (LVMI), carotid intima-media thickness (CIMT) >0.9 mm and chronic kidney disease including urine albumin-creatinine ratio (ACR) >3.5 mg/mmol in females and >2.5 mg/mmol in males or estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2. After adjusting for confounding factors, both cf-PWV and 24-h PWV or night-PWV showed significant association with LVMI (p < 0.05). Only day-PWV was associated with eGFR (p = 0.037). When cf-PWV, 24-h PWV, day- and night-PWV including confounding factors were forced into the same logistic regression model, only cf-PWV (OR = 1.109 [1.001-1.228], p = 0.033) remained a significant determinant of increased LVH. Day-PWV (OR = 0.538 [0.415-0.696], p < 0.001) was significantly correlated with eGFR. For ACR, each 1 m/s increase in day-PWV was associated with risk of increased ACR (OR = 1.685 [1.178-2.410], p = 0.004). For CIMT >0.9 mm, neither ambulatory PWV nor cf-PWV was significant. Compared with 24-h ambulatory PWV, cf-PWV has a better correlation with LVH, while ambulatory PWV has a greater correlation with the decline in renal function.
暂无摘要（点击查看详情）
To compare the capsulotomy rim morphology of anterior lens capsules obtained by 5 femtosecond laser-assisted cataract surgery (FLACS) platforms: Catalys, FEMTO LDV Z8, LensAR, LenSx, and Victus. University of Basel, Basel, Switzerland. Experimental study. Anterior lens capsules from 6 interventions per laser platform were collected (N = 30). 4 of each were assessed under light microscopy (LM; n = 20), and 2 were assessed under scanning electron microscopy (n = 10). A qualitative evaluation of all samples was conducted, as well as a semiquantitative analysis of the extent of irregularities present in LM samples. The Dunn multiple comparisons test was conducted to determine which lasers produced significantly smoother capsulotomies. Irregularities along the lens capsule rim were observed in all samples. Distinct irregularities were observed for Catalys (unconnected laser pulses bordering the capsulotomy), FEMTO LDV Z8 (numerous additional rows of laser pulses), and LensAR (at least one section with multiple rows of laser pulses). Victus demonstrated a significantly higher degree of smoothness of capsulotomy (median = 306 degrees) compared with Catalys (median = 171 degrees) ( P = .02). The medians for other laser platforms fell between these values. Different laser platforms produce morphologically and quantitatively distinct irregularities, which may influence capsulotomy strength differently. FEMTO LDV Z8, a low-energy laser, did not produce a smoother capsulotomy than the high-energy lasers. Our results suggest that, with current technologies, the precision of the laser is more important than the pulse energy in determining the regularity of the capsulotomy surface.
Arterial hypertension (AH) impairs vascular function which, in turn, may reduce cardiopulmonary function. However, the impact of AH on cardiorespiratory fitness (CRF) and its potential mechanisms remains insufficiently investigated. We compared cardiopulmonary function during exercise testing (CPET) between adults with and without AH (part 1) and evaluated the effects of high-intensity interval training (HIIT) in adults with AH on submaximal cardiopulmonary CPET parameters (part 2). Thirty-eight adults with AH and 19 controls without AH partook in the study. Adults with AH were randomized into either HIIT or a control group. CPET assessed CRF and submaximal exercise parameters, including the oxygen uptake efficiency slope (OUES), V̇E/V̇CO 2 slope, PETCO 2 , V̇O 2 /work rate (WR) slope, and O 2 pulse. The HIIT intervention consisted of triweekly sessions over 8 weeks. Adults with AH had a 6.5 ml kg -1  min -1 (95% confidence interval: 1.7-11.3) lower CRF, a steeper V̇E/V̇CO 2 slope (moderate-large effect size), lower PETCO 2 (large effect size), flatter V̇O 2 /WR slope (moderate effect size), and lower O 2 pulse (small-moderate effect size) than adults without AH. HIIT improved CRF and altered certain cardio-circulatory parameters in AH, including OUES (small-large effect size), V̇O 2 /WR slope (small-moderate effect size, low precision) and O 2 pulse (small-moderate effect size). However, effects of HIIT on pulmonary-vascular parameters were inconclusive, with large variability observed in the V̇E/V̇CO 2 slope and PETCO 2 . Adults with controlled AH might have lower CRF, indicating limitations in pulmonary-vascular and cardio-circulatory organ systems. A short-term 8-week HIIT enhances CRF and cardio-circulatory function, however, evidence is limited for improvements in pulmonary-vascular function.
The determination of ultra-trace 239Pu and 240Pu isotopes such as those in the Southern Hemisphere remains a challenge in soils. Most techniques have been developed for relatively higher Pu activity concentrations, which are not suitable for soils with low Pu content. This study aimed to develop an optimized leaching and separation procedure for soils collected from a subtropical catchment in Brazil, and to evaluate its performance against a fusion digestion procedure with ICP-MS. We carried out multiple adjustments to an established procedure such as increasing the acid volume in the TEVA (TEtraValent Actinides and technetium) resin separation steps, using Fe(II) for redox stabilization, reducing sample mass, and increasing the flow rate through a vacuum box. While Pu activities and ratios were generally consistent across methods, our results revealed that using Fe(II) and increasing the acid volume in the separation step with an increased flow rate led to better method performance. The optimal procedure, named the "PULSE method" (Plutonium extraction from Soils at Low concentrations with high prEcision), achieved a high Pu recovery rate of 69 ± 8% and a mean 238U separation factor of 1.29 × 104. Measurement uncertainties were kept below 10% and the detection limits for 239Pu and 240Pu amounted to 0.0027 Bq/kg and 0.0008 Bq/kg, respectively. Thus, the PULSE method is a practicable and scalable method that allows for a reliable determination of Pu isotopes, which are considered long-term alternative tracers to shorter-lived radionuclides like 137Cs for soil and sediment redistribution processes.
Cardiovascular disease remains the leading cause of mortality worldwide, yet its origins lie in early life. Cardiovascular risk factors track from childhood into adulthood, and vascular abnormalities detected in youth predict future cardiovascular outcomes. Despite compelling evidence, vascular assessment in youth has been impeded by a lack of reference values, standardised measurement protocols, and consensus on distinguishing physiological from pathological vascular ageing. The Youth Vascular Consortium (YVC) was established in 2020 to address these gaps through international collaboration between leading experts in the field. The YVC comprises 33 research centers from 27 countries across five continents, including 29,704 participants aged 2 to 40 years. All centers assessed at least one validated vascular measure including pulse wave velocity, central blood pressure, augmentation index, intima-media thickness, carotid distensibility, or flow-mediated dilatation. The YVC has generated major outputs advancing vascular health assessment in youth, including international expert consensus on standardised definitions of early vascular ageing from birth through young adulthood and evidence-based recommendations for vascular assessment protocols. In addition, device-specific reference values for pulse wave velocity were established with age and sex specific percentile curves, enabling identification of youth with elevated arterial stiffness. The YVC provides an international platform for investigating vascular health from early life. Harmonising diverse datasets and establishing evidence-based standards, the Consortium aims to improve the vascular health of children and young people, thereby enabling early identification and targeted prevention strategies when vascular trajectories remain modifiable, ultimately reducing the global cardiovascular disease burden across the lifespan.
The pulse wave analysis technology in the specialist SphygmoCor XCEL device has now been implemented in the CONNEQT Pulse device, which is a conventional sphygmomanometer suitable for home blood pressure (BP) monitoring. The aim of this study was to compare the correlation and consistency of measurements between the two devices. The study was conducted in participants admitted to the Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. Brachial BP (bBP), central BP (cBP), augmentation pressure (AP), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured with the CONNEQT Pulse and the SphygmoCor XCEL devices, both using a calibrated cuff-based brachial waveform. A total of 367 eligible subjects, aged 23-92 (57.6 ± 13.0) years, of whom 254 (69.2%) were male, was enrolled in this study. Paired t tests showed relatively low bias and elevated standard deviation: cSBP mm Hg ([121.7 ± 17.2] vs. [117.5 ± 14.5], p < 0.001), cDBP ([80.6 ± 11.0] vs. [78.3 ± 11.4], p < 0.001), cPP ([41.0 ± 12.7] vs. [39.2 ± 9.5], p < 0.001), AP mm Hg ([11.5 ± 6.2] vs. [12.8 ± 6.6], p < 0.001), AI ([26.4 ± 9.0]% vs. [31.9 ± 14.0]%, p < 0.01), and SEVR ([135.6 ± 25.5]% vs. [137.8 ± 26.4]%, p = 0.02). cDBP (r = 0.812) measured by both devices was strongly correlated, cSBP (r = 0.762), cPP (r = 0.702) and SEVR (r = 0.778) were strongly correlated, whereas AP (r = 0.587) and AIx (r = 0.522) were moderately correlated (all p < 0.001). For intraclass correlation coefficient (ICC) for both devices, cDBP (ICC = 0.794) and SEVR (ICC = 0.776) showed good reproducibility, while cSBP (ICC = 0.727), cPP (ICC = 0.666), AIx (ICC = 0.428), and AP (ICC = 0.575) showed good to modest reproducibility. The differences between cSBP, cDBP, cPP, AP, AIx, and SEVR measured by the two devices were 4.2 ± 11.2 mm Hg, 2.3 ± 6.9 mm Hg, -1.8 ± 9.0 mm Hg, -1.3 ± 5.8 mm Hg, -5.6 ± 12.0%, and 2.1 ± 17.3%, respectively. Both devices show strong cBP-bBP correlations and low bias, suggesting that the new CONNEQT Pulse provides similar measurements of cBP to the original SphygmoCor XCEL. Although there is greater variability in waveform parameters, the magnitude of differences is within acceptable limits for meaningful use in conventional home BP monitoring. The relatively elevated variability in measurement precision (standard deviation), most likely due to sequential measurements with both devices in the same arm, needs to be further evaluated using simultaneous measurements in both arms.
To develop a clinically applicable method for magnetization transfer (MT) imaging of the lung at 0.55 T. MT imaging of the chest was explored in healthy volunteers at 0.55 T using a self-gated 3D half-radial dual-echo balanced steady-state free precession sequence (bSTAR), a 2D multi-slice gradient echo method (GRE) acquired in end-expiratory breath-hold, and a self-gated 3D half-radial single-echo ultra-short TE (UTE) approach. MT contrast relied on RF pulse prolongation for bSTAR and on pulsed off-resonance irradiation for UTE and GRE. Data reconstruction from the self-gated scans was performed offline and for the end-expiratory tidal phase using a compressed sensing algorithm. MT ratio (MTR) maps were derived from an MT-weighted and a non-MT-weighted scan and took 8:32 min for bSTAR, 17:16 min for UTE, and 0:48 min for GRE. In addition, patients with pulmonary diseases underwent bSTAR MTR imaging. MT imaging was successfully performed in all volunteers with highly similar average MTR values for the lung of 28.8 pu (UTE), 29.4 pu (GRE), and 30.7 pu (bSTAR). In terms of resolution, however, bSTAR clearly outperformed both UTE and GRE variants. Finally, MTR imaging with bSTAR demonstrated high reproducibility in volunteers and showed substantially different MTR values for patients with various pulmonary diseases. At 0.55 T, MT-sensitized bSTAR offers in vivo high-resolution free-breathing MTR imaging of the entire lung in clinically acceptable scan times and shows high reproducibility. Initial results suggest that MTR imaging at 0.55 T may potentially serve as a noninvasive biomarker for investigating and differentiating pulmonary diseases.
The VICTORION-1 PREVENT (V-1P) trial is evaluating the efficacy of inclisiran versus placebo on cardiovascular events in primary prevention patients at high-risk for ASCVD. We assessed whether V-1P eligibility, based on Pooled Cohort Equations (PCE) and Predicting Risk of Cardiovascular Disease Events (PREVENT) equations, was associated with subclinical cardiovascular and inflammatory abnormalities in a healthy European population. We included individuals from the STANISLAS cohort in France aged 40-79 years, LDL-C 70-189 mg/dL and without ASCVD or liver disease. Participants were categorized as V-1P eligible using 10-year ASCVD risk using PCE and PREVENT. Associations with vascular, echocardiographic, and biomarkers were assessed using age- and sex-adjusted linear regression. Among 848 participants (mean age 60 years, 51% female), 16% were eligible per PCE, of which 7% were also eligible with PREVENT. Only one participant was eligible by PREVENT alone. Compared with non-eligible participants, V-1P-eligible individuals, whether by PCE alone or PCE and PREVENT, displayed significant subclinical abnormalities. Compared with V-1P ineligible participants, V-1P eligible participants had increased intima media thickness (+51 µm, p < 0.009 for PCE+PREVENT) and increased mean pulse wave velocity (+0.89 m/s, p < 0.001 for both PCE and PCE+PREVENT) on vascular ultrasound. V-1P eligible participants by PCE+PREVENT also showed signs of subclinical myocardial injury and inflammation, with a 1.3 fold higher troponin (p = 0.015), 1.6-fold higher interleukin-6 (p < 0.001) and a 2-fold higher high sensitivity C-reactive protein (p < 0.001). A large proportion of asymptomatic individuals without known cardiovascular disease would be eligible for the V-1P trial based on both PCE and PREVENT equations. V-1P eligible participants had evidence of subclinical cardiovascular and inflammatory abnormalities.
Semiconductor materials are the foundation of modern electronics, and their functionality is dictated by the interactions between fundamental excitations occurring on (sub-)picosecond timescales. Using time-resolved Raman spectroscopy and transient reflectivity measurements, the ultrafast dynamics in germanium are elucidated. An increase in the optical phonon temperature is observed in the first few picoseconds, driven by the energy transfer from photoexcited holes, and the subsequent decay into acoustic phonons through anharmonic coupling. Moreover, the temperature, Raman frequency, and linewidth of this phonon mode show strikingly different decay dynamics. This difference is ascribed to the local thermal strain generated by the ultrafast excitation. Brillouin oscillations are also observed, given by a strain pulse traveling through germanium, whose damping is correlated to the optical phonon mode. These findings, supported by density functional theory and molecular dynamics simulations, provide a better understanding of the energy dissipation mechanisms in semiconductors.
Cuffless blood pressure (BP) monitoring devices represent a promising innovation in hypertension management. This scientific statement provides a comprehensive update on these emerging technologies, their specific validation requirements, their potential clinical applications, and their present and future challenges. These devices generate considerable interest by enabling non-invasive BP measurement without arterial occlusion, thereby eliminating the discomfort associated with traditional cuff-based monitoring, particularly during sleep. The technologies on which these devices are based comprise a heterogeneous group, primarily utilizing pulse wave propagation time or waveform analysis through contact or non-contact sensors. They can be categorized as continuous or intermittent, automated or manual, calibration-free or requiring cuff/demographic calibration, and wearable or stationary. This technological diversity necessitates validation protocols distinct from those used for conventional cuff-based monitors, with specific requirements for each device category. Potential clinical applications include widespread out-of-office BP monitoring, unbiased assessment of circadian BP patterns and BP variability, improved detection of nocturnal hypertension, enhanced treatment adherence and long-term BP control, and continuous monitoring in hospital settings. Additionally, their lower cost compared with conventional technologies could enhance the early detection of hypertension in resource-limited settings. However, due to insufficient accuracy validation, this scientific statement does not recommend their use in clinical decisions in spite of their potential interest, in line with international guidelines not recommending their use in hypertension management. Key challenges ahead include developing standardized validation protocols, establishing normative BP data, managing the resulting burden on clinicians in handling huge volumes of data, exploring additional haemodynamic parameters, and advancing sensor technology, mathematical models, and algorithms.
This article provides a practice-oriented overview of current concepts in rapid musculoskeletal MRI of central and peripheral joints, focusing on echo train optimization and the application of modern acceleration techniques. Parallel imaging, simultaneous multislice acquisition, and compressed sensing-based undersampling can be applied independently or in combination to expedite MRI of the joints. Clinically available three- to eightfold acceleration of two-dimensional (2D) and three-dimensional turbo spin-echo (TSE) pulse sequences enables comprehensive 5-10-minute MRI protocols of joints. This acceleration allows for the efficient integration of advanced metal artifact reduction techniques into clinical MRI protocols. When conventional image reconstruction techniques fail, clinically available deep learning-based image reconstruction and superresolution augmentation methods effectively reconstruct images from highly accelerated acquisitions. Together, moderate acceleration and advanced image reconstruction techniques provide high diagnostic image quality of heavily undersampled MRI data, enabling three- to sixfold accelerated 2D TSE MRI of multiple joints in 4-6 minutes. Recent studies indicate that specially designed and trained deep learning methods may achieve 10-fold accelerated musculoskeletal MRI, with acquisition times under 3 minutes. Although further research and data are necessary, these promising developments are poised to enhance the value of musculoskeletal MRI.
Maintaining the pro- and antioxidative balance during pregnancy is crucial. Oxidative stress (OS) can complicate pregnancy and disrupt maternal-foetal communication, which is partly mediated by extracellular vesicles (EVs). This study investigated how OS affects EV secretion by bovine caruncular epithelial cells isolated from the established bovine placenta (4th month of gestation). To induce OS, cells were treated for 48 h with 1% cigarette smoke extract (CSE), known to increase reactive oxygen species (ROS) levels, while controls remained untreated. EVs were isolated via ultracentrifugation (UC) and size-exclusion chromatography (SEC) and characterized using Tunable Resistive Pulse Sensing (TRPS) technology, transmission electron microscopy (TEM), and Western blotting (WB). WB confirmed small-EV enrichment in fractions 5-8 of SEC by detecting CD9 and flotillin-1 markers. TRPS analysis demonstrated that OS increased EV concentration. In fractions 5-6, CSE treatment increased EV concentration from 1.79 × 109 (mode diameter 127 nm) to 3.12 × 109 particles/mL (122 nm). In fractions 7-8 of SEC, concentration rose from 4.48 × 1010 (84 nm) to 7.53 × 1010 particles/mL (80 nm). These data indicate that OS increases EV secretion by bovine maternal epithelial cells, providing a basis for future studies on the potential role of stress-induced EVs in foetal-maternal communication.
To explore associations of clinic and 24-hour ambulatory blood pressure (BP) monitoring (ABPM) with cardiovascular death (CVD), parameters were modeled for age and sex in this large cohort in primary care. In the Spanish ABPM Registry, 59.124 patients had complete data on mortality, age, sex, and all ABPM. Office, mean, 24-hour, daytime, and nighttime systolic BP (SBP), diastolic BP, and pulse pressure (PP) were related to CVD according to age and sex and were modelled with restricted cubic splines to get trajectories. During a median of 9.7 years, 2361 patients had CVD (1229 males, 1132 females). Nonlinear relationships for office, 24-hour mean, daytime, and nighttime SBP, diastolic BP, and PP (P<0.0001 for all) for both sexes were observed. Until 75 years, SBP was higher in males than females, but differences were minimized after ≈60 to 70 years (P for interaction <0.0001). High SBP and PP are associated with CVD without heterogeneity between sexes and across aging. The increase of SBP and PP was higher at a higher age for females than males (P for interaction <0.0001). CVD was age-dependent, and ABPM, in particular nighttime BP did more closely associated with risk than office BP in younger than in older individuals. Twenty-four-hour mean, nighttime BP, and PP were closely associated with risk being higher in elderly females than males after 75 years, corresponding to a rise in BP in older females. Guidelines should continue to mandate the evaluation of 24-hour ABPM data for risk prediction.