Small Doses Research Articles

Development of high-dispersion CLDH/carbon dot composites to boost chloride binding of cement

Chloride-induced corrosion of steel reinforcement significantly contributes to the durability deterioration for reinforced concrete (RC) structures. Calcined layered double hydroxide (CLDH) possesses a distinctive structure memory effect to adsorb anions and a nucleation effect to facilitate cement hydration, thereby demonstrating a promising potential for chloride binding enhancement of cementitious materials. However, CLDH suffers from severe agglomeration in cement composites, limiting its performance efficacy. To tackle this problem, novel high-dispersity CLDH/carbon dots (CDs) composites (CC) only at small dosages are applied to greatly improve the chloride binding behavior of cement pastes for the first time. In detail, the specific surface area of CC synthesized by simply stirring CDs and CLDH improves by 166.4 % than that of pure CLDH. Remarkably, cement pastes containing CC display a preferable chloride binding capacity; And the chloride binding substantially increases by 52.41 % when the incorporation of CC (by weight of cement) is 0.8 wt%. More importantly, according to the phase composite and microstructure analyses, the chloride binding enhancement mechanism of CC-containing cement pastes is reasonably ascribed to two effects of CC: providing nucleation sites to accelerate cement hydration and exerting the inherent chloride adsorption capacity. This boosts the formation of C–S–H gels and improves the structure memory effect and anions exchange-induced chloride adsorption, thus significantly strengthening the chloride binding of cement. This work provides a novel approach to improve the dispersity of CLDH, effectively strengthening the chloride binding of cement, thereby conductive to prolonging the service life of RC structures.

Investigating in VigiBase over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia

ABSTRACT Background The literature associates clozapine with pneumonia/aspiration pneumonia. Research design and methods The international pharmacovigilance database (VigiBase™) uses the information component (IC) as statistical signal. VigiBase clozapine reports were analyzed for pneumonia/aspiration pneumonia from introduction to 10 May 2023. Results There were 6392 cases of all types of pneumonia (5572 cases of pneumonia, 775 of aspiration pneumonia, and 45 combined). The IC was 3.52 for aspiration pneumonia, introduced as a VigiBase label in 2003, and 1.91 for pneumonia. Patients were reclassified as 3628 with no signs of aspiration and 1533 with signs. Signs of aspiration were strongly associated with some co-medications: olanzapine, odds ratio (OR) = 23.8, 95% confidence interval (CI), 14.9–38.0; risperidone OR = 18.6, CI, 11.4–30.4; valproic acid, OR = 5.5, CI, 4.5–6.6; and benzodiazepines OR = 5.5, CI, 4.5–6.6. In 2415 cases with completed data, fatal outcomes made up 45% (signs of aspiration made no difference), but there was wide variability from 0% (females <45 years of age; duration ≤30 days) to 76% (males >64 years of age; duration >1 year). During the first week, pneumonia was associated with 1) very high titration doses, 2) very small doses in Parkinson’s disease, and 3) Japan vs other countries. Conclusions In clozapine-treated patients: 1) at least 30% of pneumonia cases may be aspiration pneumonia, 2) stopping some co-medications may decrease the risk of aspiration pneumonia, 3) average lethality in pneumonia was 45% but may be around 75% in geriatric patients with long-term treatment, and 4) safer titrations may sometimes require 5-mg tablets.

Analgesic Effect of Intrathecal Nalbuphine versus Intrathecal Fentanyl as Adjuvant to 0.5% Bupivacaine for Cesarian Section under Spinal Anaesthesia

Abstract Background One of the main objectives of anesthesia is to alleviate the patient’s pain and agony, by ensuring the performance of surgical procedures without any discomfort. Elimination of postoperative pain is indispensable due to the central, peripheral and immunological stress response to tissue injury. So there is a need for extended analgesia without any side effects to achieve this goal. The use of opioids in intrathecal or epidural anesthesia has become common to increase postoperative analgesia. However, opioid-induced side effects, such as respiratory depression, nausea, vomiting, urinary retention and pruritus, limit their use. Objective To assess the postoperative analgesic requirements and the spinally mediated analgesic effects of intrathecal nalbuphine as an adjuvant to intrathecal bupivacaine after cesarean section in comparison to intrathecal bupivacaine with fentanyl. Methods This randomized comparative clinical trial was conducted in Ain Shams University Hospitals’ operating rooms on 48 patients undergoing cesarean section within a period of six months after approval of ethical committee of Faculty of Medicine, Ain Shams University. Results This study showed that the addition of a small dose of nalbuphine or fentanyl to bupivacaine in spinal anesthesia prolonged the time of postoperative analgesia. In this study, there was no significant difference regarding the demographic data, duration of operation, maximum sensory level, and maximum motor blockade level. Adding to this, there was also no significant changes regarding the vital data of the patients. On the other hand, there was a significant difference regarding the duration of analgesia which was longer with nalbuphine. It was also noticed that with nalbuphine less patients required rescue analgesia in comparison to fentanyl. There was higher number of side effects recorded with fentanyl in comparison to nalbuphine. Conclusion Either intrathecal nalbuphine (0.8 mg) or intrathecal fentanyl (25 μg) combined with Bupivacaine improves intraoperative analgesia and prolongs post- operative analgesia in cesarean section. There was statistically significant difference between them, intrathecal nalbuphine had a prolonged duration of post-operative analgesia, lesser amount of rescue analgesia needed and fewer side effects than intrathecal fentanyl.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

Optimizing the number, locations, and chlorine dosages of booster chlorination stations in water distribution networks

ABSTRACT Safe and reliable drinking water is essential for sustaining life. Chlorination is widely used for disinfection in water distribution networks (WDNs). A higher dose of chlorine is required in an overhead service reservoir to maintain minimum residual chlorine at the farthest end in WDNs. However, delivering high dosages of chlorine from storage tanks can pose public health issues, especially for the residents living near overhead service reservoirs due to the formation of trihalomethanes, haloacetic acids, and chlorophenols. In addition, a higher dosage will lead to increased chlorine consumption and will accelerate pipe corrosion. Booster chlorination (BC) stations with smaller dosages are a solution to this problem. However, identifying the optimal number, locations, and dosage of each BC station in a cost-effective manner is challenging. This study proposes a methodology for determining the optimal number, locations, and chlorine dosages of BC stations in WDNs using a mixed integer linear programming problem. The methodology is illustrated through a simplified WDN in Holeta town, Ethiopia. The results indicate that if one adds two BC stations beyond the three dosage stations at the source, it will lead to a 49% reduction in chlorine use and a 27% decrease in the life cycle cost.

Clinical impact of DVH uncertainties

Dose-volume histograms (DVH), along with dose and volume metrics, are central to radiotherapy planning. As such, errors have the potential to significantly impact the selection of appropriate treatment plans. Dose distributions that pass tests in one TPS may fail the same tests when transferred to another, even if using identical structures and dose grid information. This work shows the design and implementation of methods for assessing the accuracy of dose and volume computations performed by treatment planning systems (TPS), and other analytical tools. We demonstrate examples where differences in calculations between systems can change the assessment of a plan’s clinical acceptability. Our work also provides a more detailed DVH analysis of single targets than earlier published studies. This is relevant for SRS plans and small structure dose assessments. Very small structures are a particular problem because of their coarse digital representation, and the impact of this is thoroughly examined.Reference DVH curves were derived mathematically, based on Gaussian dose distributions centered on spherical structures. The structures and dose distributions were generated synthetically, and imported into RayStation, MasterPlan, and ProKnow. Corresponding DVHs were analytically derived and taken as ground truth references, for comparison with the commercial DVH calculations. Two commonly used dose metrics PCI and MGI were used to determine the limit of calculation accuracy for small structures. In addition, to measure the DVH differences between a larger range of commercial DVH calculators, the D95 metric from a set of real clinical plans was compared across both the 3 DVH calculators under test, and across a further six TPSs from other hospitals.We show that even slight deviations between the results of DVH calculators can lead to plan check failures, and we illustrate this with the commonly used D95 planning metric. We present clinical data across eight planning systems that highlight instances where plan checks would pass in one software and fail in another due to DVH calculation differences. For the smallest volumes tested, errors of up to 20% were observed in the DVHs. RayStation was tested down to a 3 mm radius sphere (≈0.1 cc) and this showed close to 10% error, reducing to 1% for 10 mm radius (≈4.0 cc) and 0.1% for 20 mm radius (≈33 cc). In clinical plans, the variation in D95 was up to 9% for the smallest volumes, and typically around 2% in the range 0.5 cc-20 cc, and 1% in 20 cc-70 cc, falling to <0.1% for large volumes. Paddick Conformity Index (PCI) and Modified Gradient Index (MGI) are commonly used plan quality indicators for very small volumes. For volumes ≈0.1 cc we observed errors of up to 40% in PCI, and up to 75% in MGI.Our study extends the range of tested DVH calculators in published work, and shows their performance over a wider range of volume sizes. We provide quantitative evidence of the critical need to test the accuracy of DVH calculators in the TPS before clinical use. This work is particularly relevant for both stereotactic plan evaluation and for assessment of small volume doses in published dose constraint recommendations. We demonstrate that significant errors can occur in DVHs for volumes less than 1 cc, even if the volumes themselves are calculated accurately. Even for large structures, deviations between the outputs of DVH calculators can lead to indicated or reported plan check failures if they do not include appropriate tolerances. We urge caution in the use of DVH metrics for these very small volumes and recommend that appropriate DVH uncertainty tolerances are set in organ dose constraints when using them to evaluate clinical plans.

Anti-Inflammation Effectiveness of Ginger (Kaemferia galanga l.) and Shallots (Allium ascalonicum l.) Extract Combination on Sprague-Dawley Male Rat

Inflammation can be caused by various stimuli which include physical injury, infection, heat and antigen antibody interactions. Ginger (Kaempferia galanga L.) and Shallots (Allium ascalonicum L.) are medicinal plants that are often used by Indonesians as an alternative to natural medicine and have been studied to have good anti-inflammatory properties because they contain quercetin. This study aims to determine the effective dose of the combination of Ginger ethanol extract and Shallots as anti-inflammatory with a smaller dose. This study was carried out using male rats in 5 treatment groups, consisting of negative control (CMC-Na 0.5 %), control positive (diclofenac Na tablets 0,1 mg/kg body weight rat), and 3 combination doses of Ginger extract: Shallots extract, dose combination I (3 mg/kg body weight Rat: 2 mg / kg body weight Rat), dose combination II (6 mg / kg body weight Rat : 1 mg/kg body weight Rat), and the dose combination III (6 mg/kg body weight Rat: 2 mg kg body weight Rat) using Carrageenan Method on Rat's Feet. The results of the anti-inflammatory activity test showed that all the dose combination treatment groups had anti-inflammatory. The dose combination III was significantly different from the negative control group and showed the most effective dose of combination. The formulated combination shows a synergistic effect between ginger and shallots as an anti-inflammatory. Average percentage (%) of edema inhibition combination III is 71,08 %.

A Case of Fatal Poisoning: Use of 2-4 Dinitrophenol for Weight Loss

Aim: 2,4-dinitrophenol (DNP®) causes rapid weight loss. Therefore, this drug is used for weight loss, is mostly sold on internet sites, and is banned for sale owing to its deadly side effects. In this case report, we aimed to report a patient who was admitted to our hospital with DNP poisoning. Case: In the present study, we present a 29-year-old patient who took 200-mg DNP® once a day for 5 days and who applied to our emergency department approximately 6 hours after taking two tablets on the last day. He developed cardiopulmonary arrest 8 hours after admission despite all supportive treatments and died despite effective and adequate cardiopulmonary resuscitation. Conclusion: DNP poisoning can be fatal even in small doses. It is difficult to control because the drug is freely available on the internet, and urgent diagnosis and treatment is critical. In recent times, where sedentary life and obesity are on the rise, people should be better informed about healthy living and the risks associated with weight loss drugs that can be obtained illegally. Preventing the unauthorized sale of these products, which have a limited response to treatment and a high mortality rate, over the internet and early recognition of poisoning by emergency room physicians is the most important preventive measure in DNP poisonings and the most important step in treatment.

Photoluminescence of L-Valine Irradiated with Small Doses

The measurement technique and the results obtained by optical spectroscopy during excitation of L-valine molecules by photons described. The photoluminescence spectra of L-valine studied in the wavelength range 400-700 nm during excitation by photons of different energies 3.26-4.51 eV. Peculiarities were found in the luminescence spectra (radiation intensity, positions of maxima), indicating the excitation of the OH, CO and CH molecules as fragments of the valine molecule by photon impact. The same results obtained for the samples of L-valine irradiated by electrons with the dozes 0.2, 0.5, 2 and 5 Gy. Irradiation of L-valine leads to fragmentation of carboxyl COOH group. The biggest changes in photoluminescence spectra observed for the sample with 0.2 Gy irradiation doze. Also X-ray powder diffraction spectra measured, which showed absence of any structural changes for the irradiated samples. The results (photoluminescence and XRay structural spectra) of melted at 330o C L-valine sample are presented.

IN VITRO STUDY OF THE DOSE-DEPENDENT EFFECT OF JANUS KINASE INHIBITORS

Background. One of the most promising means of targeting the mechanisms of autoimmune processes and hyperimmune reactions associated with cytokine imbalance are Janus kinase inhibitors. However, these chemicals in the used doses have a number of undesirable side effects. The effect of small and ultra-low doses in relation to this group of substances has not been studied. Purpose. To study the effect of low and ultra-low concentrations of Janus kinase inhibitors on the synthesis of cytokines by human mononuclear cells in vitro. Materials and methods. The concentrations of tumor necrosis factor alpha (TNFα), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon alpha (IFNα), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8) and interleukin 10 (IL-10) after stimulation with phytohemagglutinin were determined in the culture of mononuclear cells of healthy donors. Also the effect on the production of these cytokines of ruxolitinib and baricitinib in various doses, including ultra-low ones, was determined. Results. It was found that baricitinib, as well as ruxolitinib, at normal concentrations significantly decreased, and at ultra-low concentrations they significantly increased the level of synthesis of all cytokines studied in this experiment. Conclusion. The stimulating, but not suppressive effect of ultra-low concentrations of Janus kinase inhibitors has been demonstrated using the example of ruxolitinib and baricitinib. In relation to inhibitors of Janus kinase functions, this phenomenon has been discovered for the first time, which opens up ways to search for new means of regulating immunity, in particular, the production of cytokines.

Volume of detonation determination based on gaseous products of energetic materials by time resolved LIPS combined with schlieren image.

The safe and fast measurement of volume of detonation (VoD) is always a hard task for macroscale explosion even though it is one of the important parameters to evaluate the explosion performance. Therefore, a promising technology to determine the VoD is highly desirable for evaluation of energetic materials. Herein, a new method of VoD determination based on gaseous products via small dose energetic materials by time correlated laser induced plasma spectroscopy (LIPS) combined with schlieren image was proposed. Hydrodynamics of products after laser ablation on a time scale ranging from microsecond to millisecond was investigated. Based on the analysis of hydrodynamics of products after laser ablation, the effective spectra of gaseous products of each energetic material are obtained. Subsequently, a high-accuracy quantitative analysis model of VoD based on gaseous products using the method of principal component analysis - partial least squares (PCA-PLS) with small sample modeling algorithm has been developed( R2>0.96). The VOD model accurately predicts the detonation parameters with the average relative error of test set (ARET) < 3% and the maximum relative error of test set (MRET) < 5%. Moreover, the results without spectra selection of the relative error of blind data show the max relative error is less than 7%. The results of variable importance in projection (VIP) identification indicate a robust association between the spectral signatures of carbon (C), nitrogen (N), hydrogen (H), oxygen (O) and VoD. Furthermore, the N lines exert the most substantial influence on the VoD model. This method provides a new safe and fast determination technology for the evaluation of VoD and clarification of the related mechanism.

Rotation from methadone to buprenorphine using a micro-dosing regime in patients with opioid use disorder and serious mental illness: A case series.

Inducting buprenorphine from methadone has traditionally involved initial opioid withdrawal, with risk of mental state deterioration in patients with serious mental illness (SMI). Micro-dosing of buprenorphine, with small incremental doses, is a novel off-label approach to transitioning from methadone and does not require a period of methadone abstinence. Given the limited literature about buprenorphine microdosing, we aimed to evaluate the feasibility and safety of inducting buprenorphine in a series of patients on methadone with SMI. For this retrospective case series, we reviewed the records of 16 patients with SMI at a Melbourne addiction treatment centre, from January 2021 to July 2022, who transitioned via micro-dosing, from high-dose methadone (>30 mg) to buprenorphine and depot-buprenorphine. Psychiatric diagnoses, mental state, other substance withdrawal, transfer success, transition time, opioid withdrawal symptoms and overall patient experience were collected via objective and subjective reporting. Methadone to buprenorphine transfer was completed by 88% of patients. Mental health measures remained stable with the exception of mildly increased anxiety. Median transfer time was 6.5 days for inpatients, 9 days for mixed setting and 10 days for outpatients. Most patients (93%) rated their experience 'manageable' reporting mild withdrawal symptoms. One patient met study criteria for precipitated withdrawal. This retrospective case series provides evidence that the use of a micro-dosing buprenorphine induction for methadone to buprenorphine transitions, including to depot-buprenorphine, has negligible risk, is tolerated by patients with SMI and is unlikely to precipitate an exacerbation of their mental illness.

Ayurvedic poisonous plants and their medicinal values

A poisonous plant is one that, when touched or consumed in large enough quantities, can be hazardous or lethal to humans or other animals. These plants can be utilized as herbal medicines with therapeutic effects when used in the right proportions and in small doses. Many plants are harmful to people when consumed or through skin contact with plant chemicals. Poisonous medicinal herbs are used to treat a variety of illnesses, including diabetes, cancer, infections, and fungal growth. According to the review, numerous phytochemical components that have diuretic, purgative, laxative, anti-allergic, and other significant therapeutic effects have been identified in a variety of medicinal plants. If utilized appropriately, poison can be life-giving, calming to the three Doshas, encouraging, and regenerating. The poisonous plants are categorized as Visha and Upvisha in Ayurvedic texts. Agadtantra is an important branch of Ashtanga Ayurveda. The importance of this branch has been described in our Vedas, Epics, and Samhita. Proper description, classification, clinical features, and management of any kind of Visha have been described in this branch. Some poisonous plants are Dhatura, Bhallataka, Vatsanabha, Bhanga, Vach, Kuchala, and Gunja, etc. The Shodhana process is the only bridge between Visha and Aushadhi. Shodhana is the process by which physical, chemical, and natural impurities are removed. It will intensify the potency and effectiveness of the drug and nullify its toxicity. The aim of this review article is to provide a brief overview of the numerous medicinal uses of some poisonous plants.

The use of low doses of gabapentin in patients with neuropathic pain and with thrombocytopenia

Introduction. Approximately 21–27% of patients with blood system diseases receive opioid analgesics, with neuropathic pain being one of the most common reasons for prescription. Gabapentin is used as a first-line drug for neuropathic pain (NP), but has been poorly studied in patients with blood system diseases.The objective was to study the effectiveness and safety of gabapentin in patients with blood system diseases with chronic pain.Materials and methods. A single-center, prospective observational study included 24 patients with thrombocytopenia and pain between October 2017 and October 2022. The patients’ age ranged from 18 to 71 years (median 40 years). All patients with blood system diseases: non-tumor blood system diseases (aplastic anemia) in 8% (n = 2), myeloid tumor blood system diseases (acute myeloid leukemia) in 34% (n = 8), lymphoid tumor blood system diseases (acute lymphoblastic leukemia, follicular lymphoma, diffuse B – large cell lymphoma, T-cell lymphomas, multiple myeloma) in 58% (n = 14). All patients had thrombocytopenia less than 150∙109/l, 66% (n = 16) had less than 90∙109/l. All patients were diagnosed with neuropathic pain (NP), localized according to the neuroanatomical distribution and accompanied by sensory disturbances typical of NP. The localization of pain was different, pain predominated in the lower extremities (63% (n = 15), 95% CI: 43 – 79%), caused by peripheral polyneuropathy of predominantly toxic origin (vincristine, bortezomib), and pain was also caused by the course of the underlying disease: cephalalgia and neck pain, this pain was caused by compression of the nerve structures by the lymph nodes, postherpetic neuralgia, trigeminal neuralgia caused by tumor growth. All patients had intractable, high-intensity pain requiring trimeperidine at a dose of 20–40 mg/day. All patients were prescribed gabapentin therapy at a dose of 900–1200 mg/day.Results. When taking gabapentin in the study group of patients (n = 24), already on the 3rd day, there was a clinically and statistically significant decrease in pain intensity: 1) by median: from the initial 6 to 4 points, p = 0.01 (and up to 3 points by 7th day of therapy) and 2) on average: from initial 6.5 to 3.9 points, p = 0.01 (and up to 3.2 points by the 7th day). Stratification of the dynamics of pain intensity reduction by type of blood system disease (BSD) shows that the decrease by day 3 (sustained and further by day 7) was clinically and statistically significant (p = 0.01) for groups of patients with lymphoid and myeloid BSD, and clinically and approximately statistically significant in patients (n = 2) with non-tumor BSD. Analgesic therapy using small doses of gabapentin gave a pronounced, stable positive effect (pain intensity statistically significantly decreased by an average of 50%). After 7 days of gabapentin therapy, a decrease in the opioid dose was noted in 52% of patients. Side effects were dominated by drowsiness 67% (n = 16), dizziness 32% (n = 8).Conclusion. The results of this study indicate that gabapentin is effective in the treatment of chronic neuropathic pain in patients with BSD and is safe when used in minimal/average therapeutic doses within the daily dosing ranges established by the official instructions for use.

Facile synthesis of Ag/AgCl/PAF-54 heterojunction photocatalysts for TC degradation

Photocatalysis plays an increasingly important role in the field of water treatment. Among the catalysts, Ag nanoparticles (NPs), a type of noble metal NP, show extraordinary potential for photocatalysis. Nevertheless, the aggregation caused by high surface energy limits their applications. The simple synthesis of Ag NPs with uniform size remains a challenge. In this work, a nitrogen-rich porous organic polymer (POP) with reduction ability, porous aromatic framework (PAF)-54, was chosen as the carrier for the in-situ synthesis of Ag NPs. By virtue of the reducing framework of PAF-54 and the formation of the AgCl/PAF-54 heterojunction, the in-situ reduction of Ag(I) was realized, and thus Ag NPs with the particle size of 20-25 nm were uniformly distributed on PAF-54, which exhibit a strong localized surface plasmon resonance (LSPR) effect. Furthermore, the Ag/AgCl/PAF-54 heterojunction effectively suppresses the recombination of photogenerated electrons and holes, leading to the enhanced photocatalytic ability of the composite material. Even with a small catalyst dosage, rapid tetracycline (TC) degradation can be achieved, and the degradation rate of TC reached 94.8% in 30 min. This study offers a facilitated approach for fabricating Ag-based POP composites with superior photocatalytic properties.

Therapeutic potential of fungally derived psilocybin extract in morphine-dependent mice: A research protocol

Introduction: Psilocybin is a naturally occurring tryptamine derivative psychedelic compound potently produced by fungi members of the genus Psilocybe. Previous literature has highlighted psilocybin as a serotonin 2A receptor agonist with striking effects on neural plasticity and cognition. Recent studies explore the usage of psilocybin in addressing addictive behaviours and substance abuse. Small psilocybin doses have shown promising anti-addictive and withdrawal-minimizing properties in alcohol-dependent mice. This study will further investigate this emerging field through a novel lens. We propose a novel study to elucidate psylobicin’s effect on opioid addiction in mouse models. Methods: Morphine-dependent mice will be administered either saline vehicle or differing doses of psilocybin during a morphine-available period to monitor consumption. Though mechanistically ambiguous, psilocybin’s hypothesized entry into serotonin-dependent stress-conciliating pathways supports the hypothesis that mean morphine consumption will decrease in a dose-dependent manner to similar levels to popular opioid receptor agonist therapeutics, such as methadone. Furthermore, we will examine psilocybin's impact on withdrawal behaviour. After morphine deprival on dependent mice, sustained doses of psilocybin, methadone, and positive and negative controls will be administered. Results: By analyzing stress-indicative behaviours in mice, the efficacy of psilocybin as a withdrawal assistance agent can be elucidated. Results from the morphine-dependent mice are expected to consume less morphine than controls, and minimize withdrawal symptoms at a similar level to popular therapeutic options like methadone. Discussion: If successful, psilocybin’s anti-addictive potential will help provide a cheaper, more accessible therapeutic option in addressing the growing opioid crisis. Furthermore, controlled psilocybin dosages have been shown to have lesser dependence potential compared to modern opioid addiction therapeutics. Conclusion: This study’s novel approach will provide meaningful support in exploring the growing field of mycology and its potential to address other substance use disorders. Future research may explore outside the limitations of the mouse model, like the oral administration of the compounds rather than intraperitoneal injection.

Multi-objective optimization of molten salt microreactor shielding perturbations employing machine learning

Nuclear reactor shielding is a requirement for all reactors to prevent radiation from escaping the core. Shielding design can be an arduous process that requires significant computational resources to model even a single concept, for either deterministic and stochastic computations. As such, many developed shield concepts are under-optimized and unnecessarily large and/or expensive. Machine learning models have been previously trained and paired with advanced optimizers to assist in this process, providing a low-cost estimate of neutronic codes like MCNP. However, traditional models often require a large quantity of data, usually hundreds or thousands of iterations, to be accurately trained and deployed. Additionally, many neutronic modelers do not have the optimization background to build or deploy an effective shielding optimizer and would benefit from a simple Python framework.A molten salt reactor shielding problem is presented for optimization, utilizing a predictive machine learning model requiring only 21 iterations for training. This model is paired with a closed-loop optimizer using the Gekko Optimization Suite for Python. A baseline shield around the core is presented, and mass and cost constraints are applied at 172 metric tons and $1.4 million, respectively. An optimal shield is generated using the closed-loop optimizer (0.0377mREM/hr), allowing a similarly small dose to that of the baseline, but at a 10.8% reduced mass, a 11.9% reduced material cost, and 61 times computational cost reduction (98.4% improvement). The simple shield optimization framework resulting from this work offers acceleration and simplification of work for shield designers, allowing them to create improved designs in a fraction of the time.

Density of lymphocytes in cortex and medulla substance of thymus particles of white rats in normal conditions and under influence of heavy metal salts during three months

The consumption of clean water is the most relevant today, but natural water is delivered to our homes through plastic, iron and galvanized pipes. Metal ions, which are part of the pipe material, can get into drinking water and affect the human body, in particular the thymus. That is why the aim of the work was to determine the density of large, medium and small lymphocytes in the cortex and medulla of the thymus lobules of outbred white male rats of reproductive age when consuming small doses of heavy metal salts with water for three months. The study was conducted on 40 outbred white male rats of reproductive age, which were divided into 4 groups: 1 group – control animals that consumed distilled water; 2 group of animals that consumed aqueous solutions – CuSO4·5H2O at a dose of 0.247 mg/dm3; 3 group – aqueous solution of ZnSO4·7H2O at a dose of 1.505 mg/dm3; group 4 – aqueous solution of FeSO4·7H2O at a dose of 0.5 mg/dm3. Histological, electron microscopic and morphometric research methods were used to study the density of large, medium and small lymphocytes in different zones of the thymus lobules. It was found that in the control group of rats, the density of large lymphocytes is the highest in the subcapsular zone, and the lowest in the medulla. The density of medium lymphocytes is the lowest in the subcapsular zone. The density of small lymphocytes is the lowest in the medulla, and the highest in the cortico-medullary zone. When using CuSO4·5H2O salts with drinking water for three months, there were no significant changes in the density of lymphocytes compared to the control group, except for a slight decrease in the density of large lymphocytes in the cortex of the thymus lobules. The density of lymphocytes in the third group of animals that consumed zinc salts (ZnSO4·7H2O) with drinking water changes significantly: the density of large lymphocytes in the subcapsular zone decreases by 2.3 times, in the cortico-medullary zone it increases by 4.7 times, and in the medulla it increases by 2.7 times; the density of medium lymphocytes decreases in the subcapsular zone by 2 times; the density of small lymphocytes decreases by 1.5 times in the subcapsular zone, in the cortex and cortico-medullary zone – decreases by 1.2 times, and in the medulla by 1.1 times. When using FeSO4·7H2O salts with drinking water for three months, no special changes in the density of lymphocytes were noted: a decrease in the density of large lymphocytes in the subcapsular zone by 1.5 times and by 1.3 times in the cortex was observed; the density of medium lymphocytes decreases by 1.2 times in the cortex, and the density of small lymphocytes decreases by 1.2 times in the subcapsular zone and cortex, and increases by 1.2 times in the medulla, compared to the control group of animals. Ultrastructural changes in the structure of lymphocytes and reticuloepithelial cells were not detected when heavy metal salts were consumed with water. Thus, the study showed that the most toxic for the body are zinc salts (ZnSO4·7H2O), the consumption of which with drinking water in small doses for three months led to significant changes in the density of lymphocytes, compared to the control group experimental animals.

A new application of Cu2+ on differential modification to promote copper-molybdenum separation with a novel chalcopyrite depressant amidinothiourea

The separation of chalcopyrite and molybdenite has always been a challenge in mineral processing because of their similar floatability and close association. This study proposes a new chalcopyrite depressant named amidinothiourea (ADT) and a new application of Cu2+ on differentially modifying chalcopyrite and molybdenite. It is found that small dosage of ADT is insufficient to depress chalcopyrite, although there is ADT adsorption on chalcopyrite surface at this time. While after Cu2+ modification on chalcopyrite and molybdenite, a small dosage of ADT can strongly depress chalcopyrite, and has no effect on molybdenite. The largest difference of grade and recovery between chalcopyrite and molybdenite were 45.32 and 70.79 % in mixed-mineral flotation with 2.0 × 10−4 mol/L of Cu2+ and 1.6 × 10−4 mol/L of ADT. The mechanisms of ADT depression and Cu2+ modification were investigated through LEIS, XPS, ToF-SIMS and ICP-OES tests. LEIS experiments show that ADT can adsorb on chalcopyrite surface, and particularly pronounced after the modification of Cu2+ on chalcopyrite. XPS and ToF-SIMS confirm that N is the site of action for ADT, and Cu is the site of action for minerals. XPS, ToF-SIMS and ICP-OES tests reveal that Cu2+ modifies chalcopyrite by promoting the dissolution of iron ions and firmly binding with the exposed unsaturated S. While Cu2+ modifies molybdenite by binding with saturated S atoms weakly.

Effects of levothyroxine treatment on serum thyroid hormone levels in euthyroid patients with papillary thyroid microcarcinoma

We recently reported that lowering serum thyroid stimulating hormone (TSH) levels with levothyroxine (LT4) may be associated with decreased tumor growth during active surveillance (AS) of papillary thyroid microcarcinoma (PTMC). Most clinicians might believe that low serum TSH levels following LT4 therapy indicate subclinical thyrotoxicosis. This study aimed to evaluate the effects of TSH-lowering therapy using small doses of LT4 on serum thyroid hormone levels in euthyroid patients with PTMC. We retrospectively analyzed data from 28 patients with low-risk PTMC who had undergone measurement of both FT4 and FT3 consecutively and received LT4 to achieve serum TSH levels of < 0.5 μIU/mL and > 0.05 μIU/mL between January 2012 and May 2018 at Kuma Hospital. There were 24 females and 4 males (aged 55 ± 12 years [mean ± standard deviation {SD}]). We compared their serum FT4 and FT3 levels at diagnosis with those following TSH-lowering therapy with LT4. Following LT4 therapy, the patients’ serum FT4 levels were significantly increased (P < 0.001). Serum FT3 levels, however, remained unchanged (P = 0.10). The proportions of patients whose FT3 levels increased by more than 1 SD, remained unchanged, and decreased by more than 1 SD were 11 %, 57 %, and 32 %, respectively. Our study indicated that mild TSH-lowering doses of LT4 for euthyroid patients with PTMC increased serum FT4 levels but did not increase serum FT3 levels in most cases, suggesting that a mild TSH-lowering therapy for euthyroid patients may not necessarily cause thyrotoxicosis.