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The New England Journal of Medicine Mar 2024Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends... (Comparative Study)
Comparative Study Observational Study
BACKGROUND
Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking.
METHODS
We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs.
RESULTS
A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001).
CONCLUSIONS
In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).
Topics: Humans; Carotid Stenosis; Microplastics; Myocardial Infarction; Plaque, Atherosclerotic; Plastics; Prospective Studies; Stroke; Heart Disease Risk Factors; Endarterectomy, Carotid; Carotid Artery Diseases; Follow-Up Studies
PubMed: 38446676
DOI: 10.1056/NEJMoa2309822 -
Sedative Dose for Rapid Sequence Intubation and Postintubation Hypotension: Is There an Association?Annals of Emergency Medicine Oct 2023For patients with hemodynamic instability undergoing rapid sequence intubation, experts recommend reducing the sedative medication dose to minimize the risk of further...
STUDY OBJECTIVE
For patients with hemodynamic instability undergoing rapid sequence intubation, experts recommend reducing the sedative medication dose to minimize the risk of further hemodynamic deterioration. Scant data support this practice for etomidate and ketamine. We sought to determine if the dose of etomidate or ketamine was independently associated with postintubation hypotension.
METHODS
We analyzed data from the National Emergency Airway Registry from January 2016 to December 2018. Patients aged 14 years or older were included if the first intubation attempt was facilitated with etomidate or ketamine. We used multivariable modeling to determine whether drug dose in milligrams per kilogram of patient weight was independently associated with postintubation hypotension (systolic blood pressure < 100 mm Hg).
RESULTS
We analyzed 12,175 intubation encounters facilitated by etomidate and 1,849 facilitated by ketamine. The median drug doses were 0.28 mg/kg (interquartile range [IQR] 0.22 mg/kg to 0.32 mg/kg) for etomidate and 1.33 mg/kg (IQR 1 mg/kg to 1.8 mg/kg) for ketamine. Postintubation hypotension occurred in 1,976 patients (16.2%) who received etomidate and in 537 patients (29.0%) who received ketamine. In multivariable models, neither the etomidate dose (adjusted odds ratio [aOR] 0.95, 95% confidence interval [CI] 0.90 to 1.01) nor ketamine dose (aOR 0.97, 95% CI 0.81 to 1.17) was associated with postintubation hypotension. Results were similar in sensitivity analyses excluding patients with preintubation hypotension and including only patients intubated for shock.
CONCLUSION
In this large registry of patients intubated after receiving either etomidate or ketamine, we observed no association between the weight-based sedative dose and postintubation hypotension.
Topics: Humans; Hypnotics and Sedatives; Etomidate; Rapid Sequence Induction and Intubation; Ketamine; Intubation, Intratracheal; Retrospective Studies; Hypotension
PubMed: 37389494
DOI: 10.1016/j.annemergmed.2023.05.014 -
Science Robotics Sep 2023Using wind to disperse microfliers that fall like seeds and leaves can help automate large-scale sensor deployments. Here, we present battery-free microfliers that can...
Using wind to disperse microfliers that fall like seeds and leaves can help automate large-scale sensor deployments. Here, we present battery-free microfliers that can change shape in mid-air to vary their dispersal distance. We designed origami microfliers using bistable leaf-out structures and uncovered an important property: A simple change in the shape of these origami structures causes two dramatically different falling behaviors. When unfolded and flat, the microfliers exhibit a tumbling behavior that increases lateral displacement in the wind. When folded inward, their orientation is stabilized, resulting in a downward descent that is less influenced by wind. To electronically transition between these two shapes, we designed a low-power electromagnetic actuator that produces peak forces of up to 200 millinewtons within 25 milliseconds while powered by solar cells. We fabricated a circuit directly on the folded origami structure that includes a programmable microcontroller, a Bluetooth radio, a solar power-harvesting circuit, a pressure sensor to estimate altitude, and a temperature sensor. Outdoor evaluations show that our 414-milligram origami microfliers were able to electronically change their shape mid-air, travel up to 98 meters in a light breeze, and wirelessly transmit data via Bluetooth up to 60 meters away, using only power collected from the sun.
PubMed: 37703382
DOI: 10.1126/scirobotics.adg4276 -
Trends in Biotechnology Nov 2023If biomanufacturing can become a sustainable route for producing chemicals, it will provide a critical step in reducing greenhouse gas emissions to fight climate change.... (Review)
Review
If biomanufacturing can become a sustainable route for producing chemicals, it will provide a critical step in reducing greenhouse gas emissions to fight climate change. However, efforts to industrialize microbial synthesis of chemicals have met with varied success, due, in part, to challenges in translating laboratory successes to industrial scale. With a particular focus on Escherichia coli, this review examines the lessons learned when studying microbial physiology and metabolism under conditions that simulate large-scale bioreactors and methods to minimize cellular waste through reduction of maintenance energy, optimizing the stress response and minimizing culture heterogeneity. With general strategies to overcome these challenges, biomanufacturing process scale-up could be de-risked and the time and cost of bringing promising syntheses to market could be reduced.
Topics: Bioreactors; Industrial Microbiology
PubMed: 37271589
DOI: 10.1016/j.tibtech.2023.05.002 -
Lupus Aug 2023Studies of real-world effectiveness of belimumab in adults with systemic lupus erythematosus have shown improved disease control and decreased oral glucocorticoid use....
BACKGROUND
Studies of real-world effectiveness of belimumab in adults with systemic lupus erythematosus have shown improved disease control and decreased oral glucocorticoid use. However, belimumab use outside of clinical trial settings has not been well studied in childhood-onset systemic lupus erythematosus (cSLE). We aimed to characterize indications for belimumab use and evaluate oral glucocorticoid doses and disease activity scores in the year following belimumab initiation at a single, large pediatric rheumatology center.
METHODS
We included children and young adults with cSLE who received ≥ 1 dose of belimumab. Repeated measures one-way ANOVA was used to compare SLEDAI-2K scores and prednisone-equivalent daily oral glucocorticoid doses at baseline, 6 months, and 12 months after belimumab initiation for those who continued therapy for a year.
RESULTS
We identified 21 patients with cSLE who received ≥ 1 dose of belimumab. The median disease duration at belimumab initiation was 30.8 months [IQR 21.0-79.1]. At the time of belimumab initiation, 100% of patients were taking an antimalarial, 81% were on oral glucocorticoids, and 91% were on at least one conventional DMARD. Thirteen patients (62%) continued belimumab for ≥6 months and 11 (52%) for ≥12 months. Among those continuing belimumab for ≥12 months, median [IQR] oral prednisone daily doses in milligrams at baseline, 6 months, and 12 months were 12.5 [7.5-17.5], 9 [6.25-10], and 5 [5-9.5], = 0.037, and median [IQR] SLEDAI-2K scores at baseline, 6 months, and 12 months were 8 [5.5-10.5], 6 [3.5-10], and 6 [6-8.5], = 0.548, respectively.
CONCLUSIONS
In our cohort of pediatric patients with lupus and moderate disease activity treated with belimumab for ≥12 months, daily oral glucocorticoid doses were significantly lower 6 and 12 months after belimumab initiation than baseline. Use in patients with active nephritis was uncommon. Further research is needed in a large, multicenter cohort to determine the real-world effectiveness of belimumab in children and develop guidelines for use.
Topics: Young Adult; Humans; Child; Prednisone; Lupus Erythematosus, Systemic; Glucocorticoids; Immunosuppressive Agents; Retrospective Studies; Severity of Illness Index; Treatment Outcome
PubMed: 37410059
DOI: 10.1177/09612033231187752 -
The Journal of Organic Chemistry Apr 2024Polycyclic aromatic hydrocarbons including heteroatoms have found a wide range of applications, for instance, in supramolecular chemistry or material science....
Polycyclic aromatic hydrocarbons including heteroatoms have found a wide range of applications, for instance, in supramolecular chemistry or material science. Phosphangulene derivatives are P-containing polycyclic aromatic hydrocarbons presenting a concave aromatic surface suitable for building supramolecular receptors. However, the applications of this convenient building block have been strongly hampered by a difficult and multistep preparation requiring several protection-deprotection sequences along with the use of harmful reagents. Here, we report a straightforward, protecting-group-free, three-step, and hundred-milligram-scale synthesis of a chiral phosphangulene oxide derivative via a triple phospho-Fries rearrangement. This compound was easily resolved by chiral HPLC and further functionalized, giving rise to versatile chiral phosphangulene derivatives. Following this strategy, chiral phosphangulene oxides with low symmetry were synthesized. Molecular crystal structures revealed a variety of molecular organization in the solid. This opens the way to wider use of this compound as a building block for cages or new materials.
PubMed: 38568746
DOI: 10.1021/acs.joc.3c02674 -
Prostate International Dec 2023To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted... (Review)
Review
OBJECTIVE
To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted radical prostatectomy (MP-RARP) via a meta-analysis.
METHODS
For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 15, 2022. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI).
RESULTS
Of the 368 retrieved abstracts, 41 underwent full-text review, and seven studies were included in the final analysis, comprising a total cohort of 1,934 cases of RARP (355 SP-RARP cases and 1,579 MP-RARP cases). Compared to MP-RARP, the SP-RARP group had less postoperative pain score (MD = -0.7, 95% CI -1 to -0.4, <0.001), morphine milligram equivalents usage (MD = -3.8, 95% CI -7.5 to -0.1, =0.04), hospital stay (MD = -1, 95% CI -1.8 to -0.1, =0.019), and urinary catheterization time (MD = -1.1, 95% CI -1.9 to -0.3, =0.008). However, the SP-RARP group had a longer console time than the MP-RARP group (MD = 5.3, 95% CI 2.6 to 7.9, <0.001).
CONCLUSIONS
Our study demonstrated that early results were mostly equivalent with the single-port approach. This technology may help to reduce the hospital stay and postoperative pain for patients undergoing radical prostatectomy compared to MP-RARP, without compromising the functional and early oncological outcomes.
PubMed: 38196552
DOI: 10.1016/j.prnil.2023.04.002 -
Cureus Oct 2023Introduction Caffeine is a psychoactive stimulant frequently found in coffee, tea, energy drinks, and some medications. Various mental health challenges, including...
Introduction Caffeine is a psychoactive stimulant frequently found in coffee, tea, energy drinks, and some medications. Various mental health challenges, including stress, anxiety, and depression, commonly affect college students. Moreover, an individual's mental and physical health can be significantly impacted by stress, anxiety, and depression. However, the impact of caffeine on mental health, particularly its association with depressive and anxiety symptoms, remains inconclusive. Thus, this study aimed to evaluate the amount of caffeine consumed by university students and its association with depression, anxiety, and stress levels. Material and method This cross-sectional study was performed on Taibah University students in Medina from both health-related and non-health-related colleges. We used a self-administrated questionnaire composed of four sections: the informed consent section; sociodemographic information; the Depression, Anxiety, and Stress Scale (DASS-21), which assessed the depression, anxiety, and stress levels; and a caffeine-measuring questionnaire, which reported daily caffeine intake in milligrams per day. Result This cross-sectional study examined a 520 convenience sample of Taibah University students with an age range from 17 to 29 years. The majority of the participants were single (95.2%), most of them were female (73.8%), and slightly more than half (51.5%) were recruited from health-related colleges. According to the study's DASS-21 score results, 45.8% of the students had extremely severe stress, 61% had extremely severe anxiety, and 51% had extremely severe depression. The most frequently reported sources of daily caffeine among the participants were Arabic coffee (69.6%), specialty coffee (57.5%), black tea (56.3%), cola (48.7%), and regular coffee (48.5%). The overall daily amount of consumed caffeine ranged from zero to 4276.7 mg/oz. However, no significant association was found between the severity of the DASS-21 score and the daily consumption of caffeine among Taibah University students. Conclusion Our study shows no significant association between the severity of depression, anxiety, and stress and daily caffeine consumption among university students. This proves the opposite of the theory that high levels of caffeine consumption can be correlated to high levels of depression, stress, and anxiety.
PubMed: 37916247
DOI: 10.7759/cureus.48018 -
Current Oncology (Toronto, Ont.) Sep 2023The aims of the study were to (1) describe types of pain in cancer patients, (2) examine the predictors and consequences of pain, (3) investigate the association between...
OBJECTIVES
The aims of the study were to (1) describe types of pain in cancer patients, (2) examine the predictors and consequences of pain, (3) investigate the association between type of pain and survival, and (4) examine potential biological mediators of pain and survival.
METHODS
This was a secondary analysis of baseline data from patients diagnosed with cancer. Patients answered questionnaires that assessed sociodemographic characteristics, pain, depression, sleep, and fatigue. Blood was collected and cytokine assays were performed. Analysis of variance, Kaplan-Meier, and Cox regression survival analyses were used to test the aims.
RESULTS
Of the 779 patients diagnosed with cancer, the mean age was 63.5 years, 57.8% male, and 90.6% White. Of those who reported pain (total 70.3%), 46.5% stated their pain was cancer-related while 53.5% stated their pain was non-cancer-related. While both cancer and non-cancer-related pain was associated with depressive symptoms, fatigue, and sleep duration, those with cancer-related pain had significantly higher rates of depressive symptoms (F(1,516) = 21.217, < 0.001) and fatigue (F(1,516) = 30.973, < 0.001) but not poorer sleep (F(1,497) = 0.597, = 0.440). After adjusting for sociodemographic, disease-related characteristics, depression, sleep duration, and morphine milligram equivalent, patient reports of cancer-related pain were significantly associated with poorer survival (HR = 0.646, 95% CI = 0.459-0.910, = 0.012) compared to those with non-cancer-related pain, which was not associated with survival (HR = 1.022, 95% CI = 0.737-1.418, = 0.896). Cytokines did not significantly mediate the link between pain and survival.
CONCLUSION
While nearly half of the pain reported was cancer-related, both types of pain resulted in greater symptom burden, but only cancer-related pain was associated with survival.
Topics: Humans; Male; Middle Aged; Female; Cancer Pain; Depression; Neoplasms; Pain; Neoplasms, Second Primary; Fatigue
PubMed: 37887537
DOI: 10.3390/curroncol30100637 -
ACS Bio & Med Chem Au Aug 20233'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin during the early stages of the innate immune...
3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin during the early stages of the innate immune response. ddhCTP has been shown to act as a chain terminator of flavivirus RNA-dependent RNA polymerases. To date, synthesis of ddhCTP requires complicated synthetic protocols or isolation of the enzyme viperin to catalyze the production of ddhCTP from CTP. Recombinant viperin approaches preclude the production of highly pure ddhCTP (free of contaminants such as CTP), whereas the chemical synthesis involves techniques or equipment not readily available to most laboratories. Herein, we describe the chemoenzymatic synthesis of ddhCTP, starting from commercially available ddhC. We utilize these methods to produce milligram quantities of ddhCTP, ddhCDP, and ddhCMP. Using purified semisynthetic ddhCTP and fully synthetic ddhCTP, we also show ddhCTP does not inhibit NAD-dependent enzymes such as glyceraldehyde 3-phosphate dehydrogenase, malate dehydrogenase, or lactate dehydrogenase, contrary to a recent report.
PubMed: 37599790
DOI: 10.1021/acsbiomedchemau.3c00014