Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

Objective Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.

Effects of ozone on sickness and depressive-like behavioral and biochemical phenotypes and their relations to serum amyloid A and kynurenine in blood

Ozone (O3) is an air pollutant which primarily damages the lungs, but growing evidence supports that O3 exposure can also affect the brain. Serum amyloid A (SAA) and kynurenine have been identified as circulating factors that are upregulated by O3, and both can contribute to depressive-like behaviors in mice. However, little is known about the relations of O3 exposure to sickness and depressive-like behaviors in experimental settings. In this study, we evaluated O3 dose-, time- and sex- dependent changes in circulating SAA in context of pulmonary inflammation and damage, sickness and depressive-like behavioral changes, and systemic changes in kynurenine and indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates kynurenine production and contributes to inflammation-induced depressive-like behaviors. Our results in Balb/c and CD-1 mice showed that 3ppm O3, but not 2 or 1ppm O3, caused elevations in serum SAA and pulmonary neutrophils, and these responses resolved by 48 hours. Sickness and depressive-like behaviors were observed at all O3 doses (1-3ppm), although the detection of certain behavioral changes varied by dose. We also found that Ido1 mRNA expression was increased in the brain and spleen 24 hours after 3ppm O3, and that kynurenine was increased in blood. Together, these findings indicate that acute O3 exposure induces transient symptoms of sickness and depressive-like behaviors which may occur in the presence or absence of overt pulmonary neutrophilia and systemic increases of SAA. We also present evidence that the IDO/kynurenine pathway is upregulated systemically following an acute exposure to O3 in mice.

B- and N-doped carbon dots by one-step microwave hydrothermal synthesis: tracking yeast status and imaging mechanism

Background Carbon dots (CDs) are widely used in cell imaging due to their excellent optical properties, biocompatibility and low toxicity. At present, most of the research on CDs focuses on biomedical application, while there are few studies on the application of microbial imaging. Results In this study, B- and N-doped carbon dots (BN-CDs) were prepared from citric acid, ethylenediamine, and boric acid by microwave hydrothermal method. Based on BN-CDs labeling yeast, the dead or living of yeast cell could be quickly identified, and their growth status could also be clearly observed. In order to further observe the morphology of yeast cell under different lethal methods, six methods were used to kill the cells and then used BN-CDs to label the cells for imaging. More remarkably, imaging of yeast cell with ultrasound and antibiotics was significantly different from other imaging due to the overflow of cell contents. In addition, the endocytosis mechanism of BN-CDs was investigated. The cellular uptake of BN-CDs is dose, time and partially energy-dependent along with the involvement of passive diffusion. The main mechanism of endocytosis is caveolae-mediated. Conclusion BN-CDs can be used for long-term stable imaging of yeast, and the study provides basic research for applying CDs to microbiol imaging. Graphical Abstract

Cyanobacterial Biomass as a Potential Biosorbent for the Removal of Recalcitrant Dyes from Water

The accumulation of cyanobacteria produced due to eutrophication processes and the increment of different pollutants in water as a result of industrial processes affects aquatic environments such as the ocean, rivers, and swamps. In this work, cyanobacterial biomass was used as a biosorbent for the removal of a commercial dye, methylene blue (MB). Thus, MB was removed from biomass obtained from cyanobacterial samples collected from the swamp located in the Colombian Caribbean. Spectroscopical techniques such as FTIR, SEM, EDX measurements were used for the physico-chemical characterization of the bio-adsorbent material. Furthermore, we present the effect of various adsorption parameters such as pH, MB dose, time, and adsorbent concentration on the adsorbent equilibrium process. Three different isotherm models were used to model the MB adsorption on biomass. The functional groups identified on biomass suggest that these models are suitable for the characterization of the sorption of cationic dyes on the surfaces of the biomass; in addition, an SEM assay showed the heterogeneous surface of the biomass’ morphology. The equilibrium tests suggested a multilayer type adsorption of MB on the biomass surface. The kinetics results show that a pseudo-second order kinetic model was suitable to describe the MB adsorption on the biomass surface. Finally, the herein obtained results give an alternative to resolve the eutrophication problems generated by cyanobacterial growth in the swamp “Ciénaga de Malambo”.

A Resident-Led Quality Improvement Initiative to Optimize Care for Children and Young Adults with Sickle Cell Disease Vaso-Occlusive Pain with Intranasal Fentanyl in the Emergency Department

Background: Sickle cell disease (SCD) is an inherited blood condition that predisposes affected patients to severe vaso-occlusive (VOC) pain events. The NHLBI (last revised in 2014) and ASH guidelines (last revised 2020) recommend a door-to-first dose should be within 60 minutes vs. 30 minutes from registration, and reassessment and re-administration of medications should be every 30 minutes. Non-IV routes of administration, i.e. intranasal (IN) can facilitate rapid analgesic treatment. Recent studies have shown IN Fentanyl as an effective pharmacological strategy to treat vaso-occlusive pain episodes. Methods: This resident-led Quality Improvement specific aim was to reduce the meantime from check-in to first analgesic delivery to SCD patients with VOC presenting to the Pediatric Emergency Department (PED) by at least 20% during 12 months and to improve the overall care of SCD VOC in accordance to best practices. PDSA cycle methodology was utilized to identify root causes, countermeasures, and key drivers (Figure 1A). We implemented a SCD VOC clinical pathway for PED providers to utilize our enhanced and updated version of an electronic order set named "PED Sickle Cell Crisis Power Plan" that includes IN Fentanyl as first-line therapy for SCD VOC. IRB approval was obtained. PED nursing staff was trained to administer IN Fentanyl with a nasal mucosa atomizer. Exclusion criteria of patients with SCD with other ICD-10 diagnosis codes, i.e pain not associated with VOC. The main indicators were assessment-to-dose time; registration-to-discharge time; first dose-to-discharge time, and rate of VOC admissions. Data was collected by discrete-time stamps and statistically analyzed using Excel 365. The analysis compared baseline with initial PDSA cycles from December 2019 to February 2020, and from September 2020 to March 2021. Results: From September 2020 to February 2021, a total of 54 encounters for SCD VOC qualified clinically to receive IN Fentanyl. A total of 49 of these encounters received this medication, while 5 refused its administration. Patient demographics: Male-to-female ratio was 53% and 47%, respectively. The majority of the patients seen were adolescents (63% with ages between 12-21 years). African-American participants represented 88% and non-Hispanics 84%. After our interventions, 94% of encounters have documented pain reassessment in their electronic medical records. IN Fentanyl was first introduced in the PED in September 2020, and became the first medication to be administered in 94% of the encounters. The average length of stay in the PED was 269 minutes (4 hrs. with 29 minutes). The SCD VOC Clinical Pathway was used in 90% of the encounters and the SCD VOC Power Plan was used in 80% of them. From the total of encounters, 59% required admission to the floor for further pain management strategies. As shown in the control chart (Figure 1.B), the meantime from check-in to first analgesic delivery to patients with VOC presenting to the PED was reduced to under 40 minutes by February 2021. After the implementation of IN Fentanyl, there is an overall improvement of the waiting time for administration of medications of more than 70 minutes (from 138 min down to 67 minutes). Most importantly, 37% (18/49) of SCD VOC events were discharged after successful VOC pain management in the PED. Discussion: PED staff surveys demonstrated a lack of familiarity with current VOC guidelines and a standardized pathway. Medication refusal of IN Fentanyl was found to be related mostly to patient preference, poor knowledge about side effects, and parental fear for oversedation before our interventions. Conclusion: A multi-disciplinary team was formed to assist health care providers in the ED to deliver optimal care to patients with SCD based on the current evidence-based SCD VOC clinical pathway and efficient pharmacological intervention with IN Fentanyl. Standardized procedures to treat and reassess pain for SCD VOC patients in the PED resulted in check-in to first-dose time reduction by 47%. There was a consistent improvement in Length of Stay in the PED, which decreased more than 60 minutes (from 5 hrs. 21 min. to 4 hrs. 29 min). There is a significant improvement of quality in the care of VOC including 1. Pain scoring system. 2. Documented pain reassessment. 3. Use of a multidisciplinary reviewed protocol that includes PED SCD VOC clinical pathway, and an updated order set power plan with IN Fentanyl as the first line. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Comparative Analysis The Effect of Iodine, Ozone, and Peracetic Acid as A Disinfectant of Cantang Grouper Egg

Problems in the fish hatchery sector often occur such as high egg mortality or low quality of fish eggs. Optimizing biosecurity is one of the efforts to improve the quality of fish eggs, for example by adding disinfectants such as iodine, ozone, and peracetic acid. The use of chemical disinfectants will produce good results if the right dose, time, and commodity are used. In this study. This research aims (1) to determine whether the use of chemicals including iodine, ozone, and peracetic acid had an effect as a disinfectant to increase the hatching rate of grouper fish, (2) to determine the level of effectiveness and efficiency of the use of chemicals as a disinfectant. This research is an experimental research type. The research subjects included in the study were cantang grouper fish eggs at PT. Pakarti Daksa Segara who used the exploratory sampling method. The conclusion of this study indicates that there is an influence on the growth rate of the use of iodine, ozone and, peracetic acid chemicals as disinfectants of cantang grouper eggs and there is a comparison of the effectiveness and efficiency of the use of the three chemicals which includes the percentage of the hatching rate, the cost of the disinfectant material and the time, which is needed in the use of the disinfectant. Iodine has the best level of effectiveness from the comparison of hatching eggs of cantang grouper and peracetic acid is the most efficient type of chemical.

Defluoridation of Groundwater Using Formaldehyde-Treated Agricultural Waste - Wheat, Oats, And Pea Straw

The present study investigates the potential of acid-treated agricultural waste (Wheat, Oat, and Pea straw) for the defluoridation of groundwater following the chemical treatment using formaldehyde in 1:5 w/v ratio at 50℃. The effects of operational parameters (pH, dose, time, and initial fluoride concentration) were investigated in the batch mode. Response surface methodology (RSM) was employed to predicted and validated the experimental findings. The efficiency of developed adsorbents was compared with commercially available activated carbon (CAC) and found suitable for working at neutral pH conditions. The better applicability of Langmuir isotherm on adsorption data reflects monolayer adsorption over the homogeneous surface of adsorbents. Further, the experimental data can better be modeled by the pseudo-second-order kinetics (R2 = 0.996). The simple synthesis technique and massive raw material availability made these adsorbents a promising and cost-effective tecnhiqe for removing the fluoride from groundwater.

Comparative Characteristics of Cerebral Neuronal Patterns after Single and Prolonged Radiation Exposure

The aim of the study was to conduct a comparative assessment of radiation-induced patterns in cerebral neurons after a single and prolonged exposure to radiation.Material and methods. The experiment was carried out in compliance with the rules of bioethics, on 240 white outbred male rats at the age of 4 months, exposed to a single or prolonged exposure to γ-quanta of 60Со in total doses of 0.1; 0.2; 0.5 and 1.0 Gy. Neuromorphological and histochemical methods were used to assess morphometric and tinctorial parameters of nerve cells, the content of protein and nucleic acids, as well as the activity of some dehydrogenases in the early (1st day) and long-term periods (up to 18 months) of the postradiation period. Statistical processing of the results was carried out using Statistica 6.1 software packages, parametric methods were used (Student's t-test, regression and variance analysis), the significance level was 95%.Results. Despite a number of features of neuromorphological indicators dynamics, these irradiation regimes do not cause functionally significant changes in neurons. Among the influencing factors (radiation dose and time elapsed after irradiation), the radiation dose has a greater effect on the structural and functional state of neurons, but the elapsed time levels the resulting changes and most neuromorphological parameters do not have significant differences with the control. The revealed changes, as a rule, have a borderline character, and the level of their significance fluctuates around the indicators of age control within insignificant limits. One can find out a certain instability of the structural and functional organization and tension of the functioning of neurons under the irradiation regimes under consideration. At the same time, in the early periods of observation, more pronounced fluctuations in neuromorphological parameters occur with prolonged radiation exposure, and in later periods – with a single one. In general, no significant differences in the response of neurons to single and prolonged irradiation at the same total dose were found.Conclusion. No significant radiation-induced changes in the state of neurons have been established for all dose-time parameters and modes of exposure. The irradiation dose has a greater effect on neurons, but the time elapsed after irradiation regimens the resulting changes and the majority of neuromorphological parameters have no significant differences from the control. The considered modes of irradiation do not have significant differences among themselves by the response of neurons.

OS03.5.A Corelation between longitudinal t2 MRI radiomic primary texture feature values and radiation dose in non-tumoral regions of the brain in paediatric brain tumours

BACKGROUND Paediatric brain tumour survivors may have treatment toxicity associated with signal change on follow-up MRI. Quantitative MRI texture features can potentially be used as surrogates of the underlying tissue changes following radiation therapy. MATERIAL AND METHODS Longitudinal retrospective study in 51 paediatric primary brain tumours treated with photon (N=30) and proton (N=21) radiotherapy (RT). T2 MRI scans at baseline and multiple time point from the date of surgery to 2 years following radiotherapy were selected for the textural analysis. Scans were bias corrected, registered with the CT dose maps and with baseline scan for each patient using 3Dslicer. Regions of interest (ROI) of fixed diameter were drawn in 11 predetermined non-tumoral regions of brain including in peri-tumoural region (PTV). ROIs were placed in homogenous white/grey matter. Radiation dose was calculated in each of these 11 ROIs and texture features were extracted using pyradiomics. Data were analysed using machine learning and statistical analysis. General linear multivariate model was used to corelate primary texture features over period of 24 months and radiation dose, time, effect of dose*time together at each ROI separately. RESULTS There were Brainstem 4, Cerebellar19, Hemispheric cerebral 7 and Supratentorial midline 10 tumours. Median age at diagnosis was 8.26 years (range: 0–20). Median RT treatment dose was 28.52Gy (0-60Gy). Multivariate analysis shows significant corelation (p &lt; 0.001) between radiation dose and longitudinal primary texture features in all 11ROIs. Time showed corelation with feature values only in 3 ROIs and dose* time showed corelation in 5ROIs. Primary (statistical) feature values showing consistent correlation with dose in all 11 ROIs over 24 months are total energy, 10%, 90%, energy, entropy, mean, median, and minimum. CONCLUSION Radiomic texture analysis is a promising modality to understand dose related textural changes in the normal part of brain in paediatric brain tumour patients treated with radiation therapy. Radiomic changes need to be related to neurological outcomes in future research.