Radiation Syndrome Research Articles

Differential One-Carbon Metabolites among Children with Autism Spectrum Disorder: A Case-Control Study

BackgroundDriven by the complex multifactorial etiopathogenesis of autism spectrum disorder (ASD), a growing interest surrounds the disturbance in folate-dependent one-carbon metabolism (OCM) in the pathology of ASD, whereas the evidence remained inconclusive. ObjectivesThe study aims to investigate the association of OCM metabolism and ASD and characterize differential OCM metabolites among children with ASD. MethodsPlasma OCM metabolites were investigated in 59 children with ASD and 40 neurotypical children using ultra-performance liquid chromatography tandem mass spectrometry technology. Differences (significance level < 0.001) were tested in each OCM metabolite between cases and controls. Multivariable models were also performed after adjusting for covariates. ResultsTen out of 22 examined OCM metabolites were significantly different in children with ASD, compared with neurotypical controls. Specifically, S-adenosylmethionine (SAM), oxidized glutathione (GSSG), and glutathione (GSH) levels were increased, whereas S-adenosylhomocysteine (SAH), choline, glycine, L-serine, cystathionine, L-cysteine, and taurine levels were significantly decreased. Children with ASD showed significantly higher SAM/SAH ratio (3.87 ± 0.93 compared with 2.00 ± 0.76, P = 0.0001) and lower GSH/GSSG ratio [0.58 (0.46, 0.81) compared with 1.71 (0.93, 2.99)] compared with the neurotypical controls. Potential interactive effects between SAM/SAH ratio, taurine, L-serine, and gastrointestinal syndromes were further observed. ConclusionsOCM disturbance was observed among children with ASD, particularly in methionine methylation and trans-sulfuration pathways. The findings add valuable insights into the mechanisms underlying ASD and the potential of ameliorating OCM as a promising therapeutic of ASD, which warrant further validation.

Selecting the Most Relevant Mouse Strains for Evaluating Radiation-Induced Multiple Tissue Injury after Leg-Shielded Partial-Body Gamma Irradiation.

Animal studies are needed that best simulate a large-scale, inhomogeneous body exposure after a radiological or nuclear incident and that provides a platform for future development of medical countermeasures. A partial-body irradiation (PBI) model using 137Cs gamma rays with hind limb (tibia) shielding was developed and assessed for the sequalae of radiation injuries to gastrointestinal tract, bone marrow (BM) and lung and among different genetic mouse strains (C57BL/6J, C57L/J, CBA/J and FVB/NJ). In this case, a marginal level of BM shielding (∼2%) provided adequate protection against lethality from infection and hemorrhage and enabled escalation of radiation doses with evaluation of both acute and delayed radiation syndromes. A steep radiation dose-dependent body weight loss was observed over the first 5 days attributed to enteritis with C57BL/6J mice appearing to be the most sensitive strain. Peripheral blood cell analysis revealed significant depression and recovery of leukocytes and platelets over the first month after PBI and were comparable among the four different mouse strains. Latent pulmonary injury was observed on micro-CT imaging at 4 months in C57L/J mice and confirmed histologically as severe pneumonitis that was lethal at 12 Gy. The lethality and radiological densitometry (HUs) dose responses were comparable to previous studies on C57L/J mice after total-body irradiation (TBI) and BM transplant rescue as well as after localized whole-thorax irradiation (WTI). Indeed, the lethal radiation doses and latency appeared similar for pneumonitis appearing in rhesus macaques after WTI or PBI as well as predicted for patients given systemic radiotherapy. In contrast, PBI treatment of C57BL/6 mice at a higher dose of 14 Gy had far longer survival times and developed extreme and debilitating pIeural effusions; an anomaly as similarly reported in previous thorax irradiation studies on this mouse strain. In summary, a radiation exposure model that delivers PBI to unanesthetized mice in a device that provides consistent shielding of the hind limb BM was developed for 137Cs gamma rays with physical characteristics and relevance to relatively high photon energies expected from the detonation of a nuclear device or accidental release of ionizing radiation. Standard strains such as C57BL/6J mice may be used reliably for early GI or hematological radiation syndromes while the C57L/J mouse strain stands out as the most appropriate for evaluating the delayed pulmonary effects of acute radiation exposure and recapitulating this disease in humans.

Clinical case of colchicum poisoning

Introduction. Autumn colchicum or crocus is a popular plant among gardeners, characterized by early beautiful flowering, but few people know that it is poisonous. Acute colchicum poisoning is a dangerous urgent clinical situation with high mortality rates. By disrupting cell division, colchicum venom leads to multiple organ failure and death in just a few days. However, colchicum extract in small doses is often used in modern medicine to treat various diseases, due to its high antimitotic and moderate anti-inflammatory activity. The article describes the clinical observation of a patient admitted to the toxicology department after a suicide attempt using a crocus flower, containing the alkaloid colchicine. The results of laboratory and pathological studies are presented. Clinical observation. A clinical case of acute crocus poisoning with the development of hemodynamic disorders, dyspeptic syndrome, respiratory failure, cytolysis syndrome, and oliguria is presented. Treatment was aimed at restoring organ functions and consisted of infusion, detoxification, and hemostatic therapy. Limitations. To carry out this scientific work, a study was conducted within the framework of only one clinical case committed on the territory of the Udmurt Republic. In this case report, there was no comparison group or observation group. The described documents were provided by the Budgetary Health Institution of the Udmurt Republic "City Clinical Hospital no. 6" of the Ministry of Health of the Udmurt Republic and the Budgetary Health Institution of the Udmurt Republic “Bureau of Forensic Medical Examination of the Ministry of Health of the Udmurt Republic” by prior agreement. Conclusion. Colchicum poisoning is a rare and extremely severe pathology, leading to multiple organ failure, agranulocytosis and death. Considering the rapid absorption in the gastrointestinal tract and the initial symptoms in the form of gastrointestinal lesion syndrome, early diagnosis in the absence of anamnesis is difficult, therefore, it is necessary to highlight the issues of diagnosing this poisoning, as well as the study and implementation of modern methods of treating colchicine poisoni

Histone deacetylase inhibitor, Trichostatin A mitigates ionizing radiation induced redox imbalance by regulating NRF2/GPX4/PINK1/PARKIN signaling in mice intestine.

Gastrointestinal-acute radiation syndrome (GI-ARS) caused by moderate to high doses of ionizing radiation exposurecontribute to early death in humans. GI injury is also a common adverse effect seen in cancer patients undergoing abdominal/pelvic radiotherapy. Currently, no countermeasure agents have been approved for medical management of GI-ARS. The present study aims to evaluate the mechanism of action of Trichostatin A(TSA), a pan histone deacetylaseinhibitor, against radiation-induced GI injury. TSA (150ng/kg bw) was administered to mice 1h and 24h after 15Gy abdominal irradiation. Expression of various markers of oxidative stress, mitochondrial dysfunction, and apoptosis were checked in the jejunum, and their possible regulation throughthe Nrf2 signaling pathway was evaluated. TSA administered post-irradiation (15Gy + TSA) elevated intestinal total antioxidant and glutathione levels by regulating the expression of Slc7A11 and antioxidant proteins, GCLC, GPX4, and TXNRD1. Improved mitochondrial membrane potential, ATP levels, downregulation of mitochondrial quality control proteins, (PINK1 and PARKIN), and differential regulation of the apoptotic proteins, (BAX, PUMA and BCL2) with reduced intestinal epithelial cell apoptosis in the TSA-adminstered groupwere observed. TSA also upregulated Nrf2 in the presence of its specific inhibitor, ML385, suggesting its involvement in regulating Nrf2 signaling during oxidative stress induced by radiation in intestine. H & E stained jejunumcross-sections revealed that TSA mitigated radiation-mediated intestinalinjury in mice. Present findingsindicate that TSA is beneficial in mitigating the damaging effects of ionizing radiation in the intestine.

Mitigating the Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Gastrointestinal Acute Radiation Syndrome after Total-Body Irradiation in Mice.

Total-body irradiation (TBI) with gamma rays can damage organisms in various unexpected ways and trigger several organ dysfunction syndromes, such as acute radiation syndrome (ARS). Hematopoietic cells and enterocytes are particularly sensitive to radiation due to their self-renewal ability and rapid division, which leads to hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS). We previously showed that a lipid-based small molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), improved 30-day survival and alleviated H-ARS symptoms in BALB/c mice after a lethal dose (LD70/30) of gamma-ray TBI. In this study, we investigated the mitigating effects of PLAG on radiation-induced GI damage that occurs under the same conditions as H-ARS in BALB/c mice. Our study showed that PLAG facilitated the structural restoration of intestinal tissues by increasing villus height, crypt depth, crypt number, mucin-producing goblet cells, and proliferating cell nuclear antigen (PCNA)-positive crypt cells. PLAG significantly improved intestinal absorptive capacity and reduced intestinal injury-induced bacterial translocation. In addition, PLAG effectively inhibited radiation-induced necroptosis signaling activation in the intestinal crypt cells, which was responsible for sustained tissue damage and the release of high mobility group box 1 (HMGB1), a typical damage-associated molecular pattern. Overall, our findings support the radiation-mitigating potential of PLAG against GI-ARS after accidental radiation exposure.

Study of Effect of Radiation Hazards in Human Life

In this paper, we have investigated the effect of radiations on human life by expressing the exponential decay law curve, dose curve, shielding effectiveness curve and radiation exposure simulation curve. Also this research investigates the impact of radiation hazards on human health, focusing on both quantitative data and qualitative case studies. Utilizing a comprehensive analysis of radiation exposure levels and their associated health outcomes, we plotted various graphs to illustrate the correlation between radiation dose and adverse health effects. Our research combines empirical data with in-depth case studies to assess how different levels and types of radiation influence human life. The findings reveal a significant relationship between radiation exposure and increased risks of several health conditions, including cancer and radiation sickness. By analyzing the plotted data and case studies, this paper provides a detailed understanding of the short-term and long-term effects of radiation hazards. The results underscore the importance of effective radiation safety measures and informed public health policies to mitigate these risks.

Anti-Ceramide ScFv Prophylaxis for First Responders to a Limited Nuclear Attack.

After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.

Preliminary Promising Findings for Manganese Chloride as a Novel Radiation Countermeasure Against Acute Radiation Syndrome.

Military members and first responders may, at moment's notice, be asked to assist in incidents that may result in radiation exposure such as Operation Tomadachi in which the U.S. Navy provided significant relief for the Fukushima Daiichi Nuclear Reactor accident in Japan after an earthquake and tsunami in 2011. We are also currently facing potential threats from nuclear power plants in the Ukraine should a power disruption to a nuclear plant interfere with cooling or other safety measures. Exposure to high doses of radiation results in acute radiation syndrome (ARS) characterized by symptoms arising from hematopoietic, gastrointestinal, and neurovascular injuries. Although there are mitigators FDA approved to treat ARS, there are currently no FDA-approved prophylactic medical interventions to help protect persons who may need to respond to radiation emergencies. There is strong evidence that manganese (Mn) has radiation protective efficacy as a promising prophylactic countermeasure. All animal procedures were approved by the Institutional Animal Care and Use Committee. Male and female B6D2F1J mice, 10 to 11 weeks old, were used for neurotoxicity studies and temporal effects of Mn. Four groups were evaluated: (1) vehicle injection, (2) dose of 4.5 mg/kg for 3 days, (3) dose of 13.5 mg/kg, and (4) sham. Irradiated mice were exposed to 9.5 Gy whole body Co60 γ-radiation. MRI was performed with a high dose of manganese chloride (MnCl2) (150 mg/kg) to assess the distribution of the MnCl2. The mice have promising survival curves (highest survival-13.5 mg/kg dose over 3 days of MnCl2 at 80% [87% female, 73% male] P = 0.0004). The complete blood count (CBC) results demonstrated a typical hematopoietic response in all of the irradiated groups, followed by mildly accelerated recovery by day 28 in the treated groups. No difference between groups was measured by Rota Rod, DigiGait, and Y-maze. Histologic evaluation of the bone marrow sections in the group given 13.5 mg/kg dose over 3 days had the best return to cellularity at 80%. MRI showed a systemic distribution of MnCl2. The preliminary data suggest that a dose of 13.5 mg/kg of MnCl2 given over 3 days prior to exposure of radiation may have a protective benefit while not exhibiting the neurobehavioral problems. A countermeasure that can prophylactically protect emergency personnel entering an area contaminated with high levels of radiation is needed, especially in light that nuclear accidents are a continued global threat. There is a need for a protective agent with easy long-term storage, easy to transport, easy to administer, and low cost. Histologic evaluation supports the promising effect of MnCl2 in protecting tissue, especially the bone marrow using the dose given over 3 days (4.5 mg/kg per day) of MnCl2. Initial experiments show that MnCl2 is a promising safe and effective prophylactic countermeasure against ARS. MRI data support the systemic distribution of MnCl2 which is needed in order to protect multiple tissues in the body. The pathology data in bone marrow and the brain support faster recovery from radiation exposure in the treated animals and decreased organ damage.

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

Long-term exposure to air pollution and the risks of venous thromboembolism: a nationwide population-based retrospective cohort study.

To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1month, one quarter, and 1year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. Exposures to particulate matter (PM) smaller than 2.5µm (PM2.5) and those smaller than 10µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1month was linearly associated with a greater risk of VTE up to 28.0µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.

Significant Reduction of Radiation-Induced Death in Mice Treated with PrC-210 and G-CSF after Irradiation.

The search for single or combined radiation countermeasures that mitigate the development of Acute Radiation Syndrome (ARS) after radiation exposure remains a prominent goal of the U.S. government. This study was undertaken to determine whether PrC-210 and G-CSF, when administered 24-48 h postirradiation, would confer an additive or synergistic survival benefit and mitigate ARS in mice that had received an otherwise 96% lethal radiation dose. Our results show that optimum systemic doses of PrC-210 and G-CSF, when administered 24 h or later after a 96% lethal dose of whole-body irradiation, conferred: 1. strong individual survival benefits (PrC-210 44%, P = 0.003), (G-CSF 48%, P = 0.0002), 2. a profound combined 85% survival benefit (P < 0.0001) when administered together, and on day 14 postirradiation, 3. peripheral white blood cell/lymphocyte counts equal to unirradiated controls, 4. dense bone marrow cell density (>65% of unirradiated controls), 5. jejunal villi density that equaled 90% of unirradiated controls, and 6. spleen weights that equaled 93% of unirradiated controls. Our results show that PrC-210 and G-CSF given together 24 h after irradiation confer strong additive efficacy by protecting the immune system, and enabling recovery of the bone marrow, and they work synergistically to enable recovery of peripheral white blood cells in circulating blood.

Biomarker dosimetry of acute low level of thermal neutrons and radiation adaptive response effect on rats

In this paper, we demonstrated the biological effects of acute low-dose neutrons on the whole body of rats and investigated the impact of that level of neutron dose to induce an in vivo radio-adaptive response. To understand the radio-adaptive response, the examined animals were exposed to acute neutron radiation doses of 5 and 10 mSv, followed by a 50 mSv challenge dose after 14 days. After irradiation, all groups receiving single and double doses were kept in cages for one day before sampling. The electron paramagnetic resonance (EPR) method was used to estimate the radiation-induced radicals in the blood, and some hematological parameters and lipid peroxidation (MDA) were determined. A comet assay was performed beside some of the antioxidant enzymes [catalase enzyme (CAT), superoxide dismutase (SOD), and glutathione (GSH)]. Seven groups of adult male rats were classified according to their dose of neutron exposure. Measurements of all studied markers are taken one week after harvesting, except for hematological markers, within 2 h. The results indicated lower production of antioxidant enzymes (CAT by 1.18–5.83%, SOD by 1.47–17.8%, and GSH by 11.3–82.1%). Additionally, there was an increase in red cell distribution width (RDW) (from 4.61 to 25.19%) and in comet assay parameters such as Tail Length, (from 6.16 to 10.81 µm), Tail Moment, (from 1.17 to 2.46 µm), and percentage of DNA in tail length (DNA%) (from 9.58 to 17.32%) in all groups exposed to acute doses of radiation ranging from 5 to 50 mSv, respectively. This emphasizes the ascending harmful effect with the increased acute thermal neutron doses. The values of the introduced factor of radio adaptive response for all markers under study reveal that the lower priming dose promotes a higher adaptation response and vice versa. Ultimately, the results indicate significant variations in DNA%, SOD enzyme levels, EPR intensity, total Hb concentration, and RDWs, suggesting their potential use as biomarkers for acute thermal neutron dosimetry. Further research is necessary to validate these measurements as biodosimetry for radiation exposure, including investigations involving the response impact of RAR with varied challenge doses and post-irradiation behavior.

Molecular prevalence and subtype characteristics of Blastocystis among school children in Hainan, the tropical island province of China

Blastocystis is one of the most common zoonotic intestinal protozoa with global distribution and can cause gastrointestinal syndrome mainly characterized by diarrhea. School children are the main susceptible population. No epidemiological data on Blastocystis among school children in Hainan, the only tropical island province in China. Between March 2021 and June 2023, 1973 fecal samples were collected from school children across three regions in Hainan province. Blastocystis was examined by amplifying the small subunit ribosomal RNA (SSU rRNA) gene via polymerase chain reaction (PCR), and subtypes were identified through DNA sequencing and phylogenetic analysis. The overall prevalence of Blastocystis was 7.3 % (144/1973). The differences in infection rates across different regions, nationalities, and educational stages are statistically significant (P < 0.001). Five subtypes were identified, of which ST3 was the dominant subtype (60.4 %; 87/144), followed by ST1 (27.8 %; 40/144), ST7 (10.4 %; 15/144), ST6 (0.7 %; 1/144), and ST2 (0.7 %; 1/144). 42 known sequences and 15 novel sequences were identified including eight new variations of the ST1 (ST1–16∼ST1–23) with similarities ranging from 98.3 % to 99.78 % and seven new variations of the ST7 (ST7–7∼ST7–13) with similarities ranging from 97.7 % to 99.79 % by intra-subtype genetic polymorphisms analysis. The results evaluate the public health risks of Blastocystis among school children in Hainan and the sources of infection were discussed, providing important basic data for the effective prevention and control of intestinal parasitic diseases in Hainan.

Clinicopathologic findings and causes of mortality in 100 pet rabbits from the Canary Islands, Spain, 2011-2022.

The European domestic rabbit (Oryctolagus cuniculus domesticus) is commonly kept as a pet, with increasing popularity among pet owners. Despite the increasing body of information on lagomorph medicine and pathology, comprehensive published compilations of causes of mortality in pet rabbits are limited. We analyzed health disorders, pathology findings, and most probable causes of death in 100 pet rabbits submitted to the Anatomopathological Diagnostic Service of the Veterinary School of the University of Las Palmas de Gran Canaria, Canary Islands, Spain, from 2011 to 2022. We reviewed clinical data and gross and histopathologic findings to classify the various disorders into infectious (n = 39), noninfectious (n = 45), and idiopathic conditions (n = 16). Within infectious disease processes, Encephalitozoon cuniculi infection (n = 14) and rabbit hemorrhagic viral disease (n = 14) had the highest prevalence. Regarding the noninfectious conditions, perioperative mortality (n = 10), gastrointestinal syndrome (n = 7), and trauma (n = 6) were the most common clinicopathologic entities observed.

Effect of Age at Time of Irradiation, Sex, Genetic Diversity, and Granulopoietic Cytokine Radiomitigation on Lifespan and Lymphoma Development in Murine H-ARS Survivors.

Acute, high-dose radiation exposure results in life-threatening acute radiation syndrome (ARS) and debilitating delayed effects of acute radiation exposure (DEARE). The DEARE are a set of chronic multi-organ illnesses that can result in early death due to malignancy and other diseases. Animal models have proven essential in understanding the natural history of ARS and DEARE and licensure of medical countermeasures (MCM) according to the FDA Animal Rule. Our lab has developed models of hematopoietic (H)-ARS and DEARE in inbred C57BL/6J and Jackson Diversity Outbred (JDO) mice of both sexes and various ages and have used these models to identify mechanisms of radiation damage and effective MCMs. Herein, aggregate data from studies conducted over decades in our lab, consisting of 3,250 total-body lethally irradiated C57BL/6J young adult mice and 1,188 H-ARS survivors from these studies, along with smaller datasets in C57BL/6J pediatric and geriatric mice and JDO mice, were examined for lifespan and development of thymic lymphoma in survivors up to 3 years of age. Lifespan was found to be significantly shortened in H-ARS survivors compared to age-matched nonirradiated controls in all four models. Males and females exhibited similar lifespans except in the young adult C57BL/6J model where males survived longer than females after 16 months of age. The incidence of thymic lymphoma was increased in H-ARS survivors from the young adult and pediatric C57BL/6J models. Consistent with our findings in H-ARS, geriatric mice appeared more radioresistant than other models, with a lifespan and thymic lymphoma incidence more similar to nonirradiated controls than other models. Increased levels of multiple pro-inflammatory cytokines in DEARE bone marrow and serum correlated with shortened lifespan and malignancy, consistent with other animal models and human data. Of interest, G-CSF levels in bone marrow and serum 8-11 months after irradiation were significantly increased in females. Importantly, treatment with granulopoietic cytokine MCM for radiomitigation of H-ARS did not influence the long-term survival rate or incidence of thymic lymphoma in any model. Taken together, these findings indicate that the lifespan of H-ARS survivors was significantly decreased regardless of age at time of exposure or genetic diversity, and was unaffected by earlier treatment with granulopoietic cytokines for radiomitigation of H-ARS.

Comparison of early characteristics of multisystemic inflammatory syndrome and Kawasaki disease in children and the course of Kawasaki disease in the pandemic

IntroductionMultisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings. In this study, the clinical findings, organ involvements, similarities, and differences in laboratory and imaging of the children with MIS-C and KD at the time of admission will be revealed in detail, and the treatment methods and follow-up results will be revealed.Material and methodOur study was a single-center study and included pediatric patients who were treated with a diagnosis of MIS-C between March 2020 and July 2023 in the pediatric cardiology, pediatric emergency, pediatric infection, and pediatric intensive care clinics at Celal Bayar University and who were treated with a diagnosis of KD (complete/incomplete) between January 2015 and July 2023. MIS-C diagnosis was made according to the Turkish Ministry of Health COVID-19 guidelines. Sociodemographic characteristics, clinical, laboratory, and echocardiography findings, treatments given, and clinical course of all patients included in the study were evaluated.ResultsThe median age was 30 months (7–84) in KD and 96 months (6-204) in MIS-C, and it was significantly higher in the MIS-C group (p = 0.000). Symptom duration was significantly longer in the MIS-C group (p = 0.000). In terms of clinical features, gastrointestinal syndrome findings (nausea, vomiting, abdominal pain) and respiratory findings (dyspnea) were significantly higher in the MIS-C group (p = 0.007, p = 0.000, p = 0.002, respectively). Regarding cardiovascular system involvement, coronary involvement was significantly higher in the KD group. However, valvular involvement, left ventricular systolic dysfunction, and pericardial effusion were significantly higher in the MIS-C group (p = 0.000, p = 0.001, p = 0.003, p = 0.023, respectively). In terms of laboratory findings, white blood cell count was higher in KD (p = 0.000), absolute lymphocyte count, platelet level, blood sodium, and albumin levels were lower in MIS-C group (p = 0.000, p = 0.000, p = 0.000, p = 0.000, p = 0.003, respectively), ferritin and troponin levels were significantly higher in MIS-C group. These results were statistically significant (p = 0.000, p = 0.000, respectively). D-dimer and fibrinogen levels were high in both groups, and no significant statistical difference was detected between the two groups. There was no significant difference between the two groups regarding the length of hospitalization and mortality, but steroid use was significantly higher in the MIS-C group (p = 0.000).ConclusionIn conclusion, this study has demonstrated the similarities and differences between MIS-C and KD regarding clinical findings, organ involvement, and laboratory and imaging results. The results of our study have important implications in terms of contributing to the data in the existing literature on these two diseases and for the correct diagnosis and better management of pediatric patients presenting with these disorders.What is knownMultisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings.What is newAlthough MIS-C and KD have many similarities, their symptoms, disease processes, possible complications, and treatment regimens may differ.

Assessing the Mental Model State of Emergency Responders in the Context of Radiological Dispersal Device (RDD) Incidents: A Multi-state Study.

Hazardous Materials (HAZMAT) Technicians' notions of mental model, or cognitive representations of their understanding and beliefs regarding Radiological Dispersal Devices (RDDs) incidents, have not been previously explored. A prior study developed an Expected Mental Model State (EMMS) framework specific to RDD incident response for HAZMAT technicians. The work herein presents the development of a derivative of this framework, the EMMS Diagnostic Matrix, to evaluate the actual Mental Model State (MMS) of HAZMAT technicians in the context of RDD incidents. The EMMS Diagnostic Matrix was administered via a survey and simulation activity in four U.S. states representing the Northeast, West, South, and Midwest regions. Data were collected and coded using grounded theory methodology. Reflexive thematic analysis was employed to identify themes across related areas where the notions of mental model for the HAZMAT technician responders' actual MMS differed from the EMMS. The analysis of the collected data revealed four significant themes representing incomplete notions of the mental model spanning various EMMS conceptual domains: Overestimation of Radiation Dose and Health Effects, indicating misunderstandings about the health impacts of radiation exposure, Acute Radiation Syndrome (ARS), particularly in the lower range of radiation doses; Overreliance on Responder Protection [personal protective equipment (PPE)/self-contained breathing apparatus (SCBA)], highlighting gaps in understanding radiation principles and radioactive material dispersal properties from a radiological dispersal device; Misunderstanding Radiation Detection and Units, signifying confusion about radiation units and differentiation between dose rate and accumulated dose; and Incomplete Understanding of Radiation Characteristics and Dispersal Properties, outlining a limited grasp of inhalation risks from radiation and the dispersal traits of a radiological dispersal device. The interconnectedness of these technical misunderstandings can guide the development of a strategic plan to evaluate and modify existing training, aiming at these specific themes to improve the efficiency of HAZMAT technicians in emergency situations and to identify areas for further research.

Biomarkers for Radiation Biodosimetry and Correlation with Hematopoietic Injury in a Humanized Mouse Model.

After a large-scale radiological or nuclear event, hundreds of thousands of people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure to moderate doses (2-6 Gy) of radiation can lead to the hematopoietic acute radiation syndrome, in which the bone marrow (BM) is severely compromised, and severe hemorrhage and infection are common. Previously, we have developed a panel of intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 and TSPYL2), designed to reconstruct absorbed radiation dose from human peripheral blood (PB) leukocyte samples in humanized mice up to 3 days after exposure. The objective of this work was to continue to use the humanized mouse model to evaluate biomarker dose-/time- kinetics in human PB leukocytes invivo, at an earlier (day 2) and later (day 7) time point, after exposure to total-body irradiation (TBI) doses of 0 to 2 Gy of X rays. In addition, to assess hematological sensitivity and radiation-induced injury, PB leukocyte cell counts, human BM hematopoietic stem cell (HSC) and progenitor cell [multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte myeloid progenitor (GMP), megakaryocyte/erythrocyte progenitor (MEP) and multi-lymphoid progenitor (MLP)] levels were measured, and their correlation was also examined as the BM damages are difficult to assess by routine tests. Peripheral blood B-cells were significantly lower after TBI doses of 0.5 Gy on day 2 and 2 Gy on days 2 and 7; T-cells were significantly reduced only on day 2 after 2 Gy TBI. Bone marrow HSCs and MPP cells showed a dose-dependent depletion after irradiation with 0.5 Gy and 2 Gy on day 2, and after 1 Gy and 2 Gy on day 7. Circulating B cells correlated with HSCs, MPP and MLP cells on day 2, whereas T cells correlated with MPP, and myeloid cells correlated with MLP cells. On day 7, B cells correlated with MPP, CMP, GMP and MEP, while myeloid cells correlated with CMP, GMP and MEP. The intracellular leukocyte biomarkers were able to discriminate unirradiated and irradiated samples at different time points calculated by receiver operating characteristic (ROC) curve. Using machine learning algorithm methods, combining ACTN1, p53, TSPYL2 and PB-T cell and PB-B cell counts served as a strong predictor (area under the ROC >0.8) to distinguish unirradiated and irradiated samples independent of the days after TBI. The results further validated our biomarker-based triage assay and additionally evaluated the radiation sensitivity of the hematopoietic system after TBI exposures.

A clinical case of acute polyneuropathy, with the onset of bilateral facial nerve palsy in an early childhood

BACKGROUND: The differential diagnosis of peripheral nervous system damage depends on a thorough collection of history, comprehensive assessment of clinical manifestations, and dynamic examination of the patient. This article describes a clinical case of acute polyneuropathy in a young child, which began with gastrointestinal symptoms and bilateral facial neuropathy. CLINICAL CASE DESCRIPTION: The article presents a case of a child with an atypical course of acute polyneuropathy, which began with bilateral facial neuropathy combined with gastrointestinal complaints and pain syndrome. Features of the clinical presentation of the disease required extended laboratory and instrumental testing. Protocols for instrumental verification of diagnosis included nerve conduction studies examining neural conduction and axonal excitability of the affected facial nerve and the healthy side. Additionally, the functional status of the peripheral nerves in the upper and lower limbs was assessed. Polyneuropathic alterations revealed through nerve conduction studies confirmed diagnostic lumbar puncture to determine the presence of neuroinfectious processes. Magnetic resonance imaging of the brain, brachial, and lumbosacral plexuses using intravenous contrast showed the nature and prevalence of a lesion. Based on the overall clinical, laboratory, and instrumental examination data of the patient, “acute inflammatory demyelinating polyneuropathy” was diagnosed; timely etiopathogenetic treatment was initiated. CONCLUSION: In children, the course of a neuroinfection may be atypical. Sometimes, when dissociating the clinical manifestations of the disease from the results of a standard laboratory and instrumental test, expert diagnostic techniques should be used for differential diagnosis purposes.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components

BackgroundHeart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. MethodsThe active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model.ResultsWe initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated.ConclusionsMechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.Graphical