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Marine Pollution Bulletin Jun 2024An accident at the Barakah Nuclear Power Plant (BNPP) would result in a significant radionuclide release into the semi-closed marine environment. In this research, the...
An accident at the Barakah Nuclear Power Plant (BNPP) would result in a significant radionuclide release into the semi-closed marine environment. In this research, the released radionuclide distribution pattern and dose rate in the Persian/Arabian (Gulf) were calculated using a combined hydrodynamic/radiobiological model. Simulations of the dispersion of artificial radionuclide concentrations were conducted using a HYSPLIT model. To assess prospective hazards in case of an incident, environmental risk from ionizing contaminants: assessment and management (ERICA) tools were used. Using the Fukushima nuclear power accident as a model, the scenario source term profile was developed. The volumetric concentrations levels of pollutants ranged between 1 × 10 mBq m to 1 × 10 mBq m in the radius of 200 km after 48 h. Based on the dose rates of the various marine biotas, Polychaete worms, and Pelagic fish, they had the highest and lowest dose contribution.
PubMed: 38917502
DOI: 10.1016/j.marpolbul.2024.116611 -
PloS One 2024The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.
METHODS
Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.
RESULTS
No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.
CONCLUSION
Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.
Topics: Humans; Female; Anesthesia, Spinal; Cesarean Section; Palonosetron; Adult; Hypotension; Pregnancy; Ondansetron; Antiemetics; Postoperative Nausea and Vomiting; Phenylephrine; Anesthesia, Obstetrical
PubMed: 38917195
DOI: 10.1371/journal.pone.0305913 -
The Pediatric Infectious Disease Journal Jun 2024This study aimed to investigate the efficacy and safety of intravenous colistin in pediatric patients with nosocomial gram-negative bacteria infections and to determine...
Treatment Outcomes and Associated Factors of Intravenous Colistin for Nosocomial Infections in Pediatric Patients: A Retrospective Study in a University Hospital in Thailand.
BACKGROUND
This study aimed to investigate the efficacy and safety of intravenous colistin in pediatric patients with nosocomial gram-negative bacteria infections and to determine factors associated with treatment outcomes.
METHODS
This retrospective study recruited patients aged <18 years receiving intravenous colistin between January 2014 and December 2018. Clinical data and treatment outcomes were reviewed, and factors associated with treatment outcomes were assessed.
RESULTS
This study included 178 patients with a median age of 3.4 years (range, 0.1-17.8). The mean ± SD dose of colistin prescribed to patients without renal impairment was 5.1 ± 0.6 mg/kg/day. The clinical response rate was 70.8% in patients receiving colistin for specific treatment. Infection-related mortality and crude mortality were 17.5% and 19.7%, respectively. The nephrotoxicity rate was 29.8%; approximately 70% of the episodes occurred between the 3rd and 7th day of treatment. The presence of at least 2 organ dysfunctions [adjusted hazard ratio (aHR): 7.17; 95% CI: 1.64-31.40], septic shock (aHR: 2.69; 95% CI: 1.36-5.32) and receiving chemotherapy/immunosuppressants (aHR: 2.68; 95% CI: 1.36-5.25) were observed to be associated with clinical failure. The factors observed to be associated with nephrotoxicity included hypoalbuminemia (aHR: 2.93; 95% CI: 1.26-6.78), receiving amphotericin B (aHR: 2.29; 95% CI: 1.16-4.52), vancomycin (aHR: 3.36; 95% CI: 1.50-7.56) and vasopressors (aHR: 2.57; 95% CI: 1.27-5.21).
CONCLUSION
Colistin is generally effective in the treatment of nosocomial gram-negative bacteria infections in pediatric patients. Close monitoring of renal function should be considered, especially in high-risk patients. Optimal dosage regimens for pediatric populations to promote more favorable clinical outcomes and minimize nephrotoxicity require further investigation.
PubMed: 38916921
DOI: 10.1097/INF.0000000000004450 -
ELife Jun 2024Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2....
Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2. From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform. Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
PubMed: 38916134
DOI: 10.7554/eLife.89961 -
Cureus May 2024Background Vaccines have the most important role in the battle against the COVID-19 pandemic. With the widespread use of vaccines, COVID-19 has remarkably declined....
Background Vaccines have the most important role in the battle against the COVID-19 pandemic. With the widespread use of vaccines, COVID-19 has remarkably declined. Adolescents were vaccinated after approvals for this age group, which was later than adults, and a nationwide vaccination program was implemented in August 2021 in Turkey for adolescents ≥12 years of age. Therefore, we aimed to determine the effects of the COVID-19 nationwide adolescent vaccination program on adolescent hospitalizations due to COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by comparing two periods, including the vaccination period (VP) and the pre-VP (PVP). The second aim of this study is to compare the clinical features and disease severity of vaccine-breakthrough COVID-19 hospitalizations with unvaccinated individuals in the VP. Methods A retrospective multicenter study was conducted to determine and compare the number of hospitalizations due to COVID-19 and MIS-C between the VP (September 1, 2021, to August 31, 2022) and PVP (September 1, 2020, to August 31, 2021). We also compared the characteristics, risk factors, and outcomes of breakthrough infections of adolescents aged 12-18, which required hospitalization with the same age group of unvaccinated hospitalized individuals during the VP. Results During the study period, 3967 children (0-18 years) were hospitalized in the PVP and 5143 (0-18 years) in the VP. Of them, 35.4% were adolescents (12-18 years) in the PVP, and this rate was 18.6% in the VP; relative risk was 0.6467 (95% confidence interval [CI]: 0.6058-0.6904; p < 0.001). Patients with breakthrough COVID-19 were older (201 vs. 175 months, p < 0.001) and less commonly hospitalized for COVID-19 (81.5% vs. 60.4%, p < 0.001, odds ratio [OR]: 0.347 [95% CI: 0.184-0.654]). The majority of these infections were asymptomatic and mild (32% vs.72.9%: p < 0.001, OR: 5.718 [95% CI: 2.920-11.200]), and PICU admission was less frequently required (p = 0.011, OR: 0.188 [95% CI: 0.045-0.793]). Most breakthrough COVID-19 infections occurred within three months after the last vaccine dose (54.2%). Conclusions This study demonstrated a significant decrease in adolescent hospitalizations due to COVID-19 and MIS-C after implementing COVID-19 vaccines in Turkey. Breakthrough cases were less severe and mostly occurred three months after the last dose. This study emphasizes the importance of COVID-19 vaccines and that parents' decisions may be changed, particularly those who hesitate to or refuse vaccination.
PubMed: 38915988
DOI: 10.7759/cureus.60940 -
Drug Design, Development and Therapy 2024Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmedetomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial.
OBJECTIVE
Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to compare the safety and efficacy of remimazolam besylate alfentanil versus dexmedetomidine-alfentanil for fiberoptic bronchoscopy (FB).
METHODS
One hundred and twenty patients undergoing FB into this prospective randomized controlled trial were divided into two groups. The anesthesia induction consisted of 6 mg/kg/h of remimazolam besylate in the RA group and 0.5 μg/kg of dexmedetomidine in the DA group. 1-2 mg/kg/h of remimazolam besylate or 0.2-0.7 µg/kg/h of dexmedetomidine were administered to maintain during FB. The lowest oxygen saturation, success rate of FB, hemodynamics, time metrics, bronchoscopy feasibility, drug dose requirements, patient and bronchoscopist satisfaction scores, occurrence of intraoperative awareness, number of patients willing to repeat FB with the same sedation regimen, and occurrence and severity of adverse events.
RESULTS
The lowest oxygen saturation during the FB was significantly higher in the RA group ( = 0.001). Compared with the variables in the DA group, peripheral oxygen saturation, systolic blood pressure, and diastolic blood pressure were significantly lower at T2 and T3 in the RA group ( < 0.05). Heart rates were significantly higher from T2 to T4 in the DA group ( < 0.05). More patients experienced bradycardia in the DA group ( = 0.041). Compared with time metrics in the DA group, the induction time, fully-alert time, and recovery room-leaving time were all significantly shorter in the RA group ( < 0.05). The bronchoscopy feasibility scores in the RA group were significantly lower at T2, whereas they were lower at T3 in the DA group ( < 0.05).
CONCLUSION
Remimazolam besylate is superior to dexmedetomidine when combined with alfentanil during FB, promoting faster patients' recovery, better operative conditions and respiratory stability with similar rates of occurrence and severity of adverse events.
Topics: Humans; Dexmedetomidine; Bronchoscopy; Prospective Studies; Male; Female; Middle Aged; Adult; Benzodiazepines; Hypnotics and Sedatives; Aged
PubMed: 38915861
DOI: 10.2147/DDDT.S460949 -
Frontiers in Neurology 2024To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and...
A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis.
OBJECTIVE
To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS.
METHODS
In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 10 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally.
RESULTS
CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants.
CONCLUSION
The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT06307301.
PubMed: 38915796
DOI: 10.3389/fneur.2024.1415106 -
Oncoimmunology 2024Dendritic cells (DCs) are the main antigen presenting cells of the immune system and are essential for anti-tumor responses. DC-based immunotherapies are used in cancer...
Dendritic cells (DCs) are the main antigen presenting cells of the immune system and are essential for anti-tumor responses. DC-based immunotherapies are used in cancer treatment, but their functionality is not optimized and their clinical efficacy is currently limited. Approaches to improve DC functionality in anti-tumor immunity are therefore required. We have previously shown that the loss of β2-integrin-mediated adhesion leads to epigenetic reprogramming of bone marrow-derived DCs (BM-DCs), resulting in an increased expression of costimulatory markers (CD86, CD80, and CD40), cytokines (IL-12) and the chemokine receptor CCR7. We now show that the loss of β2-integrin-mediated adhesion of BM-DCs also leads to a generally suppressed metabolic profile, with reduced metabolic rate, decreased ROS production, and lowered glucose uptake in cells. The mRNA levels of glycolytic enzymes and glucose transporters were reduced, indicating transcriptional regulation of the metabolic phenotype. Surprisingly, although signaling through a central regulator of immune cell metabolisms, the mechanistic target of rapamycin (mTOR), was increased in BM-DCs with dysfunctional integrins, rapamycin treatment revealed that mTOR signaling was not involved in suppressing DC metabolism. Instead, bioinformatics and functional analyses showed that the Ikaros transcription factor may be involved in regulating the metabolic profile of non-adhesive DCs. Inversely, we found that induction of metabolic stress through treatment of cells with low levels of an inhibitor of glycolysis, 2-deoxyglucose (2DG), led to increased BM-DC activation. Specifically, 2DG treatment led to increased levels of and mRNA, increased production of IL-12, increased levels of cell surface CCR7 and increased migration and T cell activation potential. Furthermore, 2DG treatment led to increased histone methylation in cells (H3K4me3, H3K27me3), indicating metabolic reprogramming. Finally, metabolic stress induced by 2DG treatment led to improved BM-DC-mediated anti-tumor responses in a melanoma cancer model, B16-OVA. In conclusion, our results indicate a role for β2-integrin-mediated adhesion in regulating a novel type of metabolic reprogramming of DCs and DC-mediated anti-tumor responses, which may be targeted to enhance DC-mediated anti-tumor responses in cancer immunotherapy.
Topics: Dendritic Cells; Animals; Mice; CD18 Antigens; Mice, Inbred C57BL; Cell Adhesion; Receptors, CCR7; Melanoma, Experimental; Signal Transduction; TOR Serine-Threonine Kinases; Humans; Metabolic Reprogramming
PubMed: 38915784
DOI: 10.1080/2162402X.2024.2369373 -
BioRxiv : the Preprint Server For... Jun 2024To investigate ultra-high-dose rate helium ion irradiation and its potential FLASH sparing effect with the endpoint acute brain injury in preclinical in vivo settings.
PURPOSE
To investigate ultra-high-dose rate helium ion irradiation and its potential FLASH sparing effect with the endpoint acute brain injury in preclinical in vivo settings.
MATERIAL AND METHODS
Raster-scanned helium ion beams were administered to explore and compare the impact of dose rate variations between standard dose rate (SDR at 0.2 Gy/s) and FLASH (at 141 Gy/s) radiotherapy (RT). Irradiation-induced brain injury was investigated in healthy C57BL/6 mice via DNA damage response kinetic studies using nuclear γH2AX as a surrogate for double-strand breaks (DSB). The integrity of the neurovascular and immune compartments was assessed via CD31+ microvascular density and microglia/macrophages activation. Iba1+ ramified and CD68+ phagocytic microglia/macrophages were quantified, together with the expression of inducible nitric oxide synthetase (iNOS).
RESULTS
Helium FLASH RT significantly prevented acute brain tissue injury compared with SDR. This was demonstrated by reduced levels of DSB and structural preservation of the neurovascular endothelium after FLASH RT. Moreover, FLASH RT exhibited reduced activation of neuroinflammatory signals compared with SDR, as detected by quantification of CD68+ iNOS+ microglia/macrophages.
CONCLUSION
To our knowledge, this is the first report on the FLASH-sparing neuroprotective effect of raster scanning helium ion radiotherapy in vivo.
PubMed: 38915610
DOI: 10.1101/2024.06.13.598785 -
Journal of Korean Medical Science Jun 2024Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the...
BACKGROUND
Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea.
METHODS
We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI).
RESULTS
Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis.
CONCLUSION
For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.
Topics: Humans; Male; Female; Neoplasms; Republic of Korea; COVID-19 Vaccines; COVID-19; Middle Aged; Aged; SARS-CoV-2; Adult; Myocardial Infarction; Cardiovascular Diseases; Vaccination; Myocarditis; ChAdOx1 nCoV-19; Venous Thromboembolism; Stroke; Young Adult; Adolescent; Pericarditis
PubMed: 38915282
DOI: 10.3346/jkms.2024.39.e190