The following work analyzed the changes in the properties of Fatigue in a 300M aeronautical steel after the application of thermochemical treatments of plasma nitriding and laser carburizing. The ...microstructural characterization of the formed layers and the hardness obtained after the surface treatments were conducted. Thus, a comparison was made between the two treatments to verify which one has better efficacy. It has been observed that the treatment of plasma nitriding improves significantly the fatigue properties of 300 M steel. It was also noted that laser carburizing was not efficient to improve fatigue life.
Aerospace and automotive industries utilize advanced high strength steels due to their exceptional mechanical strength and ductility. Laser beam welding has shown potential in reducing the melted ...zone, heat affected zone, and process time for these steels. This study focused on dissimilar welding between DP 780 and 300M steel sheets, commonly used in the automotive and aerospace industries, respectively. The aim was to expand the range of possibilities and innovations by enabling the use of these steels in both applications. The study investigated the optimal process parameters, microstructure, and mechanical properties for the laser welding process. It also examined the influence of intercritical quenching and tempering on the microstructure and mechanical properties of the laser welded steels. The materials underwent dilution and different phase transformations due to the welding process and heat treatments, as revealed by microstructural characterization. The weld showed a notable increase in hardness, however without compromising toughness. The fractures during tensile testing occurred in the DP 780 steel, far from the MZ and HAZ. Heat treatments increased ultimate tensile strength, but lowered ductility. Welding affected the fatigue life, especially in the intercritically quenched joint, which showed a quasi-cleavage crack growth mechanism and a decrease in fracture toughness.
Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great ...relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation. Female mice received a single 4 Gy whole-brain radiation dose on postnatal day (PND) 21 and were randomized to 0.24% Li2CO
chow or normal chow from PND 49 to 77. Hippocampal neurogenesis was assessed on PND 77, 91, and 105. We found that lithium treatment had a pro-proliferative effect on neural progenitors, but neuronal integration occurred only after it was discontinued. Also, the treatment ameliorated deficits in spatial learning and memory retention observed in irradiated mice. Gene expression profiling and DNA methylation analysis identified two novel factors related to the observed effects, Tppp, associated with microtubule stabilization, and GAD2/65, associated with neuronal signaling. Our results show that lithium treatment reverses irradiation-induced loss of hippocampal neurogenesis and cognitive impairment even when introduced long after the injury. We propose that lithium treatment should be intermittent in order to first make neural progenitors proliferate and then, upon discontinuation, allow them to differentiate. Our findings suggest that pharmacological treatment of cognitive so-called late effects in childhood cancer survivors is possible.
Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in cardiovascular disease (CVD).
This study sought ...to investigate sex differences in circulating biomarkers representative of biological pathways implicated in the development of CVD among Framingham Heart Study participants.
The authors measured 71 circulating CVD protein biomarkers in 7,184 participants (54% women, mean age 49 years). Multivariable models were used to evaluate the associations of sex, menopause, and hormone status with biomarkers. Cox models were used to examine whether sex modified the association of biomarkers with incident CVD.
Of 71 biomarkers examined, 61 (86%) differed significantly between men and women, of which 37 were higher in women (including adipokines and inflammatory markers such as leptin and C-reactive protein), and 24 were higher in men (including fibrosis and platelet markers such as MMP-8 (matrix metalloproteinase-8) and TIMP-1 (tissue inhibitor of metalloproteinases 1); false discovery rate q < 0.05 for all). Sex differences in biomarker profiles were most pronounced between pre-menopausal women versus men, with attenuated sex differences among post-menopausal women not taking hormone replacement therapy. Sex modified the association of specific biomarkers with incident CVD, including CD14 and apolipoprotein B (pinteraction <0.05 for all).
In a predominantly Caucasian population, the authors identified widespread sex differences in circulating biomarkers that reflect distinct pathways implicated in CVD, including inflammation, adiposity, fibrosis, and platelet homeostasis. Menopause and hormone status accounted for some, but not all, of the observed sex differences. Further investigation into factors underlying sex-based differences may provide mechanistic insight into CVD development.
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OBJECTIVES:To evaluate the internal consistency, validity, responsiveness, and minimal important difference of the Functional Status Score for the ICU, a physical function measure designed for the ...ICU.
DESIGN:Clinimetric analysis.
SETTINGS:Five international datasets from the United States, Australia, and Brazil.
PATIENTS:Eight hundred nineteen ICU patients.
INTERVENTION:None.
MEASUREMENTS AND MAIN RESULTS:Clinimetric analyses were initially conducted separately for each data source and time point to examine generalizability of findings, with pooled analyses performed thereafter to increase power of analyses. The Functional Status Score for the ICU demonstrated good to excellent internal consistency. There was good convergent and discriminant validity, with significant and positive correlations (r = 0.30–0.95) between Functional Status Score for the ICU and other physical function measures, and generally weaker correlations with nonphysical measures (|r| = 0.01–0.70). Known group validity was demonstrated by significantly higher Functional Status Score for the ICU scores among patients without ICU-acquired weakness (Medical Research Council sum score, ≥ 48 vs < 48) and with hospital discharge to home (vs healthcare facility). Functional Status Score for the ICU at ICU discharge predicted post-ICU hospital length of stay and discharge location. Responsiveness was supported via increased Functional Status Score for the ICU scores with improvements in muscle strength. Distribution-based methods indicated a minimal important difference of 2.0–5.0.
CONCLUSIONS:The Functional Status Score for the ICU has good internal consistency and is a valid and responsive measure of physical function for ICU patients. The estimated minimal important difference can be used in sample size calculations and in interpreting studies comparing the physical function of groups of ICU patients.
Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially ...in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.
Abstract
Background
We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort.
Methods
REPRIEVE is a prospective, ...double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40–75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored.
Results
Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range IQR 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk.
Conclusions
Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up.
In a multinational cohort of human immunodeficiency virus (HIV), more than one-third of participants reported differences in self-reported functional status. Differences in risk factors were associated with functional status across global disease burden regions, and associated with cardiometabolic risk.
Among antiretroviral therapy (ART)-treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease ...(CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH.
Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL).
The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels.
Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects.
NCT0234429.
Abstract
Background
Reproductive aging may contribute to cardiometabolic comorbid conditions. We integrated data on gynecologic history with levels of an ovarian reserve marker (anti-müllerian ...hormone AMH) to interrogate reproductive aging patterns and associated factors among a subset of cisgender women with human immunodeficiency virus (WWH) enrolled in the REPRIEVE trial.
Methods
A total of 1449 WWH were classified as premenopausal (n = 482) (menses within 12 months; AMH level ≥20 pg/mL; group 1), premenopausal with reduced ovarian reserve (n = 224) (menses within 12 months; AMH <20 pg/mL; group 2), or postmenopausal (n = 743) (no menses within12 months; AMH <20 pg/mL; group 3). Proportional odds models, adjusted for chronologic age, were used to investigate associations of cardiometabolic and demographic parameters with reproductive aging milestones (AMH <20 pg/mL or >12 months of amenorrhea). Excluding WWH with surgical menopause, age at final menstrual period was summarized for postmenopausal WWH (group 3) and estimated among all WWH (groups 1–3) using an accelerated failure-time model.
Results
Cardiometabolic and demographic parameters associated with advanced reproductive age (controlling for chronologic age) included waist circumference (>88 vs ≤88 cm) (odds ratio OR, 1.38; 95% confidence interval, 1.06–1.80; P = .02), hemoglobin (≥12 vs <12 g/dL) (2.32; 1.71–3.14; P < .01), and region of residence (sub-Saharan Africa 1.50; 1.07–2.11; P = .02 and Latin America and the Caribbean 1.59; 1.08–2.33; P = .02, as compared with World Health Organization Global Burden of Disease high-income regions). The median age (Q1, Q3) at the final menstrual period was 48 (45, 51) years when described among postmenopausal WWH, and either 49 (46, 52) or 50 (47, 53) years when estimated among all WWH, depending on censoring strategy.
Conclusions
Among WWH in the REPRIEVE trial, more advanced reproductive age is associated with metabolic dysregulation and region of residence. Additional research on age at menopause among WWH is needed.
Clinical Trials Registration
NCT0234429.
Abstract Purpose The purpose of the study is to compare neuromuscular electrical stimulation (NMES) vs sham on leg strength at hospital discharge in mechanically ventilated patients. Materials and ...methods We conducted a randomized pilot study of NMES vs sham applied to 3 bilateral lower extremity muscle groups for 60 minutes daily in the intensive care unit (ICU). Between June 2008 and March 2013, we enrolled adults who were receiving mechanical ventilation within the first week of ICU stay and who could transfer independently from bed to chair before hospital admission. The primary outcome was lower extremity muscle strength at hospital discharge using Medical Research Council score (maximum, 30). Secondary outcomes at hospital discharge included walking distance and change in lower extremity strength from ICU awakening. Clinicaltrials.gov: NCT00709124. Results We stopped enrollment early after 36 patients due to slow patient accrual and the end of research funding. For NMES vs sham, mean (SD) lower extremity strength was 28 (2) vs 27 (3), P = .072. Among secondary outcomes, NMES vs sham patients had a greater mean (SD) walking distance (514 389 vs 251 210 ft, P = .050) and increase in muscle strength (5.7 5.1 vs 1.8 2.7, P = .019). Conclusions In this pilot randomized trial, NMES did not significantly improve leg strength at hospital discharge. Significant improvements in secondary outcomes require investigation in future research.
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