Local Reactions Research Articles

Does black widow spider bite the heart?

BackgroundBlack widow spider (BWS) bites account for 0.5 % of global poisonings and 21 % of poisonings in North-East Iran. In addition to local reactions, systemic cardiovascular manifestations are likely to occur. ObjectiveThis study aims to present cases of patients who experienced cardiac symptoms after being envenomed by BWS. MethodsA descriptive retrospective cross-sectional evaluation was conducted on all patients who were bitten by a BWS in 2020 and presented with cardiac manifestations. They were referred to our tertiary pediatric cardiology center in Mashhad, Iran for evaluation. All accessible variables including history, physical examination, laboratory tests prioritizing cardiology, as well as electrocardiography and echocardiography findings were evaluated. ResultSix patients, ranging in age from 5.5 to 13 years old, were bitten by BWS. None of the patients had a past or drug history and were admitted due to pain complaints at various bite sites that radiated in different directions. Four patients showed signs of tachycardia and two showed hypertension, but no signs of infection were observed. Half of the patients experienced systemic complications. Upon arrival at the hospital, four patients showed elevated CKMB levels which decreased during their hospitalization. Troponin I and N-Terminal Pro B-type Natriuretic Peptide levels were high in all patients. One patient with unstable hemodynamics showed pro-BNP over 35,000. T wave inversion was observed in six patients, ST segment depression in three patients, and ST-segment elevation in one patient with overlap between them. ConclusionTaking notice of cardiovascular presentations after a BWS bite is considerable.

지방소멸대응기금 성과분석에 따른 개선 방향 고찰

Two years have passed since the local extension reaction Fund was introduced and the budget was allocated to overcome the problem of continuous population decline. The government expects that the annual budget of 1 trillion won, focusing on 89 population-decreasing areas, will alleviate the serious population decline problem, especially in non-capital areas. Therefore, this study analyzed based on statistical data on the extent to which the fund performed in the population-decreasing area. As a result of the analysis, it was confirmed that the population decline in the population-decreasing area was significantly alleviated and the net outflow of young people decreased in size compared to before the input of the fund. Nevertheless, it was also confirmed that there is a limit to responding to the population decline in South Korea with this fund, considering the fact that the population has turned to a decline in areas that are not designated as a population-decreasing area or the scale of net outflow of young people has expanded. In the end, in order to overcome the problem of rapid population decline in South Korea, there are certain limitations in establishing investment plans and discovering projects at the level of basic local governments, so it would be desirable to approach it through regional planning and project discovery based on inter-regional cooperation. In addition, in terms of the financial system, it is necessary to overcome the population crisis by efficient financial input to enable the linkage of this fund project with the Special Account for Balanced National Development or other budget projects.

Pre-treatment with topical 5-fluorouracil increases the efficacy of daylight photodynamic therapy for actinic keratoses – A randomized controlled trial

BackgroundDaylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance.This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses. MethodsSixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight. ResultsTwelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments. ConclusionsSequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction.

IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice.

Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (Il17ra) in mesenchymal progenitor cells was achieved by crossing Il17raF/F mice with Prx1-cre mice to generate Prx1-cre; Il17raF/F mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of Il17ra decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, Il17ra conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within Prx1+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing.

A Phase 1, Double-blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of HEV-239 (Hecolin®) Vaccine in Healthy US Adults.

Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality. We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine: placebo) trial of 30 µg HEV-239 (Hecolin®, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18-45 years. Participants were vaccinated on days 1, 29, and 180. Participants reported solicited local and systemic reactions for 7 days following vaccination and were followed through 12 months after enrollment for safety and immunogenicity (IgG, IgM). Solicited local and systemic reactions between treatment and placebo group were similar and overall mild. No participants experienced serious adverse events related to HEV-239. All participants receiving HEV-239 seroconverted at one month following the first dose and remained seropositive throughout the study. HEV-239 elicited a robust hepatitis E IgG response that peaked one month following the second dose (Geometric Mean Concentration (GMC) 6.16; 95% CI 4.40-8.63), was boosted with the third dose (GMC 11.50; 95% CI 7.90-16.75) and persisted through 6 months. HEV-239 is safe and elicits a durable immune response through at least 6 months after the third dose in healthy US adults. NCT03827395. Safety Study of Hepatitis E Vaccine (HEV239) - Full Text View - ClinicalTrials.gov.

Understanding Local Reactions Induced by Bothrops jararaca Venom: The Role of Inflammatory Mediators in Leukocyte-Endothelium Interactions.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte-endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte-endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom-induced alterations in leukocyte-endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Severely Painful and Pruritic Forearm Rash: A Case of Caterpillar Envenomation in South Florida

Introduction: The asp caterpillar (Megalopyge opercularis) is endemic to the southeastern United States, with most sightings in Florida, Texas, and Louisiana. A few hundred caterpillar envenomations are reported annually with most cases occurring in July–November. Asp caterpillars have hollow spines along their backs that contain venom. Contact with these spines is what produces the characteristic “sting” resulting in contact dermatitis and a localized hypersensitivity reaction collectively referred to as lepidopterism. Symptoms of lepidopterism may include severe burning pain, pruritis, edema, nausea, vomiting, abdominal pain, and headache. Symptoms are often self limited, and treatment should focus on expedited removal of implanted spines and aggressive symptom management.Case Report: We present the case of a patient presenting to the emergency department (ED) with acute-onset severe left forearm pain with associated pruritic rash incurred while working in a retail store. Initial therapeutic management included administration of analgesics, antihistamines, and steroids. After obtaining a comprehensive history and consulting with the Poison Control Center, we suspected an asp caterpillar envenomation. Following extraction of the caterpillar spines with silk tape, the patient’s symptoms improved. After a period of observation in the ED, the patient was discharged home without any known sequelae.Conclusion: Although asp caterpillars typically inhabit trees and foliage, human exposure to the caterpillar may occur in developed environments. Effective history-taking, prompt communication with toxicologic experts, and complete removal of intact spines are essential for early identification and effective clinical management of asp caterpillar envenomation.

Self-assembly of hyperbranched DNA network structure for signal amplification detection of miRNA

Catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) can achieve the high sensitivity and rapid reaction rate in detecting miRNA. However, the amplification efficiency by these methods are limited. Herein, an enzyme-free and label-free hyperbranched DNA network structure (HDNS) was designed, in which localized catalytic hairpin assembly (LCHA) and hybridization chain reaction occurred in the horizontal axis and longitudinal axis, respectively, exhibiting intensive signal dual-amplification. miRNA-122 was selected as the target on behalf of miRNA to design the HDNS sensor. The fluorescence signal change of HDNS showed good linearity for detecting miRNA-122 in the concentration range from 0.1 nM to 60 nM with a limit of detection (LOD) at 37 pM which was lower than those of the sensors based on separate CHA or HCR. Afterwards, the HDNS sensor was applied to detect miRNA-122 in serum samples with the recovery rate in the range of 97.2 %–107 %. The sensor could distinguish different kinds of miRNAs, even the family members with high sequence homology, exhibiting excellent selectivity. This method provided a novel design strategy for improving the sensitivity and selectivity of DNA sensor for miRNA detection.

The Human Health Impacts of the Red Imported Fire Ant in the Western Pacific Region Context: A Narrative Review.

Background: The red imported fire ant (RIFA) is one of the world's most destructive invasive species. RIFA stings are painful and can lead to allergic reactions, including life-threatening anaphylaxis, yet health impacts remain inadequately defined. Methods: We searched MEDLINE (Ovid) and Google Scholar (grey literature) from inception until 20 September 2023 for articles in English using search terms related to red imported fire ants and allergies, including anaphylaxis. Results: Approximately a third of the population in RIFA-infested areas are stung each year. The most frequent reaction is a sterile 1-2 mm pseudo pustule on the skin. Approximately 20% of stings cause a large local reaction and between about 0.5% and 2% stings cause a systemic allergic reaction which can range from skin symptoms to life-threatening anaphylaxis. Local biodiversity is also significantly disrupted by invading RIFA and may lead to complex adverse effects on human health, from agriculture losses to expanded ranges for pathogen vectors. Conclusions: The potential for red imported fire ants to establish themselves as an invasive species in the Western Pacific presents a substantial and costly health issue. Successful eradication and surveillance programs, to identify and eradicate new incursions, would avoid substantial health impacts and costs.

Effect of antitumor therapy on microflora and oral mucosa in patients with malignant neoplasms

The present article investigates the relationship between the microbiota of the oral cavity and oral mucositis induced by systemic antitumor therapy in patients with malignant neoplasms. This article highlights modern ideas about the composition of the normal microbiota of the oral cavity and its changes during chemotherapeutic treatment.&#x0D; It has been shown that the normal oral microbiota includes representatives of such genera as Actinomyces, Corynebacterium, Fusobacterium, Leptotrichia, Neisseria, Prevotella, Streptococcus, and Veillonella. Moreover, it is emphasized that despite the existence of modern molecular genetic techniques and development of an oral microbiota database, determining the role of individual taxonomic units in oral homeostasis remains challenging.&#x0D; Existing studies of changes in the qualitative and quantitative composition of oral microflora against the background of drug antitumor therapy have demonstrated that treatment is associated with significant changes in the microbiological landscape of the oral cavity. An increase was noted in the number of Gram-negative anaerobic opportunistic flora and a decrease in the representation of protective commensal flora. It has been demonstrated that the components of a bacterial cell can modulate the local reactions of a macroorganism through a system of Toll-like receptors while acting in different directions.&#x0D; Several unresolved fundamental issues related to the role of oral microbiota in the pathogenesis of oral mucositis are highlighted.

A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.

The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.

Abstract 5386: Increased sprouting angiogenesis in a microphysiological model of cisplatin-resistant recurrent lung cancers

Abstract Non-small cell lung cancer (NSCLC) constitutes 85% of total lung cancer cases and first-line therapies still often employ the platinum-based agents. Cisplatin therapy for NSCLC often leads to relapse of aggressive tumors with high metastatic potential after a period of dormancy. We hypothesize that cisplatin-resistant tumor cell phenotypes will increase features of aggressivity including sprouting angiogenesis in microphysiological models of NSCLC. First, we engineered various TME configurations using A549 cell spheroids and cancer associated fibroblasts (CAF) to establish a baseline of tumor cell proliferation, ECM deposition, and expression of proangiogenic and proinflammatory genes. Next, we generated cisplatin-resistant (Cis-R) A549 sub-lines to test the hypothesis that 3D tumor models engineered using these drug-resistant cells will capture hallmarks of highly aggressive recurrent tumors such as increased expression of progression-associated genes, increased induction of local stromal reactions and more profound angiogenesis. We treated parent A549 with 25 μM cisplatin for 96 hours followed by at least 14 days of recovery to generate Cis-R A549 cells. Interestingly, Cis-R spheroids exhibited significantly lower rates of proliferation (P&amp;lt;0.01) relative to parent A549 spheroids as measured by Ki67 index. Cis-R cells and spheroids exhibit increased genetic expression for genes involved in inflammation, EMT, proliferation and chemoresistance. Furthermore, Cis-R cells in 2D displayed a mesenchymal-like morphology and further exhibited dysmorphic spheroid morphology in 3D. We then developed a membrane free microphysiological system (MPS) comprised of two adjacent and contiguous tissue layers to investigate cancer mediated angiogenesis. We seeded one layer with lung fibroblasts and endothelial cells, which formed a vascularized network, while the other lane was cultured with no cells (control), parent A549 spheroids, or Cis-R A549 spheroids. Media void of VEGF was used throughout the duration of the experiment to isolate the effect of TME-derived factors. We measured increased angiogenetic sprouting induced by Cis-R tissues relative to parent using the following metrics: sprout density (Cis-R = 49.86 ± 10.93 µm/µm2, parent = 13.73 ± 4.12 µm/µm2, blank = 14.76 ± 4.22 µm/µm2), sprout length (Cis-R = 15006 ± 5507 µm, parent = 2466 ± 639.1 µm, blank = 4749 ± 1547 µm), and sprout area fraction (Cis-R = 0.10 ± 0.028, parent = 0.041 ± 0.010, blank = 0.032 ± 0.0095). Thus, the creation of drug resistant tumor cell sub lines enables the construction of more aggressive engineered tumor microenvironments. Future iterations of our MPS model will be used to investigate angiogenesis in the context of additional cancers, including breast and colon, while transitioning to the use of patient-derived organoids. Citation Format: Elisabet Olsen, G. Wills Kpeli, Omar M.K. Ahmad, Mark Mondrinos. Increased sprouting angiogenesis in a microphysiological model of cisplatin-resistant recurrent lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5386.

Backflow reduction in local injection therapy with gelatin formulations

The local injection of therapeutic drugs, including cells, oncolytic viruses and nucleic acids, into different organs is an administrative route used to achieve high drug exposure at the site of action. However, after local injection, material backflow and side effect reactions can occur. Hence, this study was carried out to investigate the effect of gelatin on backflow reduction in local injection. Gelatin particles (GPs) and hydrolyzed gelatin (HG) were injected into tissue models, including versatile training tissue (VTT), versatile training tissue tumor-in type (VTT-T), and broiler chicken muscles (BCM), using needle gauges between 23 G and 33 G. The backflow material fluid was collected with filter paper, and the backflow fluid rate was determined. The backflow rate was significantly reduced with 35 μm GPs (p value < .0001) at different concentrations up to 5% and with 75 μm GPs (p value < .01) up to 2% in the tissue models. The reduction in backflow with HG of different molecular weights showed that lower-molecular-weight HG required a higher-concentration dose (5% to 30%) and that higher-molecular-weight HG required a lower-concentration dose (7% to 8%). The backflow rate was significantly reduced with the gelatin-based formulation, in regard to the injection volumes, which varied from 10 μL to 100 μL with VTT or VTT-T and from 10 μL to 200 μL with BCM. The 35 μm GPs were injectable with needles of small gauges, which included 33 G, and the 75 μm GPs and HG were injectable with 27 G needles. The backflow rate was dependent on an optimal viscosity of the gelatin solutions. An optimal concentration of GPs or HG can prevent material backflow in local injection, and further studies with active drugs are necessary to investigate the applicability in tumor and organ injections.

Electron‐Donating Cu Atoms Induced High Proton Supply and Anti‐Poisoning Ruthenium Clusters for Superior Direct Seawater Hydrogen Production

AbstractDirect seawater hydrogen production via electrolysis would be a transformative technology for large‐scale pathways for future sustainable energy systems. However, prohibiting the formation of insoluble hydroxides and promoting proton supply at the electrode‐seawater interface are extremely desirable but remain challenging. Herein, inspired by the dual‐metal pair sites in natural enzyme, the de novo design of an efficient, robust, and precise electron‐donating Cu‐modulated ruthenium clusters on porous carbon matrix (Cu@Runc‐C) is reported as a high proton supply and anti‐poisoning cathode material for superior direct seawater hydrogen production. Benefitting from the unique Cu@Runc pair sites, the cathode exhibits particularly high hydrogen evolution activities with ultralow overpotentials to reach a high current density of 300 mA cm−2 in both alkaline (115 mV) and seawater (459 mV) electrolytes, and notably, the cathode can maintain superior long‐lasting stability in seawater electrolysis. The mechanism exploration demonstrates that the ruthenium cathode with Cu@Runc pair sites exhibits low oxophilic and fast proton‐transferring local reaction environments to prohibit the formation of insoluble precipitates and provide efficient proton supply within the electrode‐seawater interface. It is expected that the proposed bioinspired regulation strategy offers a new pathway for constructing efficient, robust, and selective cathode materials for scalable seawater hydrogen production.

IMMUNOLOGICAL ANALYSIS OF ORAL FLUID IN PATIENTS WITH GENERALIZED PERIODONTITIS

The objective of this study is to conduct an immunological analysis of oral fluid, specifically focusing on determining the interleukin status among patients with generalized periodontitis and underlying metabolic syndrome. Materials and methods. For immunological studies, 3 groups were formed: main group, comparative and control groups. The main group included 30 individuals with generalized periodontitis and metabolic syndrome, the comparison group included 30 people with generalized periodontitis without somatic pathology; 20 healthy individuals with intact periodontium made up the control group. The content of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and anti-inflammatory cytokines IL-4, TGF-β1 in the oral fluid of the subjects of the examination groups was determined by the method of solid-phase enzyme immunoassay using reagents of the company "Simko" (Ukraine).&#x0D; Results. According to average values obtained, the highest levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were found in individuals with periodontal pathology and metabolic syndrome. The value of the IL-1β content in the oral fluid of the main group was 1.1 times higher than the similar indicator of the comparison group, and 1.4 times higher than the indicator of the control group. The mean IL-6 content in the oral fluid of patients with metabolic syndrome was 1.3 times higher compared to individuals without the systemic disease. Interestingly, the disparity was more pronounced in healthy individuals, with IL-6 levels differing by 2 times.&#x0D; Conclusion. Patients with metabolic syndrome and periodontal pathology have significant disturbances in cytokine regulation. Cytokines are key factors in the formation of a local inflammatory reaction, therefore, an increase in the concentration of pro-inflammatory IL-1 β can be considered an immune response to the inflammatory process in periodontal tissues.

VP-102 Tolerability Evaluated by Concomitant Analgesic Medication Usage in Two Phase 3 Trials for Molluscum Contagiosum

Background: Drug tolerability is the degree to which a patient can tolerate a drug's adverse effects. VP-102, a drug-device combination product containing cantharidin (0.7%), a vesicant, is approved for treatment of molluscum contagiosum (molluscum) in patients &gt;2. Local skin reactions (LSRs) are expected, including pain. In Phase 3 trials, 97% of LSRs were mild to moderate. The discontinuation rate due to an adverse reaction was 2.3%:0.5% (drug:vehicle) treated subjects, respectively. This post-hoc analysis evaluated VP-102 tolerability based on analgesic usage over the study course.&#x0D; Methods: VP-102 or vehicle was applied to all baseline and new lesions once every 21 days until complete clearance, or up to a maximum of 4 applications. Acetaminophen or ibuprofen were permitted for application site pain and/or other Adverse Reactions.&#x0D; Results: Overall incidence of pain at any time for a VP-102 subject was 62.7% (195/311), with the majority [(60.5%),188/311] as mild to moderate. 18.6% (58/311) of VP-102 and 1.4% (3/216) of vehicle treated subjects received an analgesic, including 15.8% (49/311) for an LSR after the first VP-102 application.&#x0D; &#x0D; Median VP-102 analgesic use for LSR pain (range) was 2 (1-14) days for the entire study, and 2 (1-9) days after the first application. 29% of participants who reported analgesic usage took medication ≤1 day. Analgesic usage for AEs other than LSR pain (≥ 5% of participants) included 6% (19/311) for application site vesicles. There were no treatment-related SAEs reported.&#x0D; &#x0D; Conclusions: In this largely pediatric population, VP-102 was well-tolerated, with a short duration of elective analgesic use.&#x0D;

Research on the destroy characteristics of PTFE/Cu composite liner to explosive reactive armor

The jet generated through PTFE based inert material liner has the characteristics of low energy, low density, and large aspect ratio, which can effectively achieve the “penetration without explosion” of explosive reactive armor. PTFE/Cu composite material liner with various densities is prepared, to research the roles of preparation procedure and density in the destroy effect of jet on reactive armor. Through numerical simulation research, it was found that there was no reaction at all in the explosive layer penetrated by the jet generated by the sinter liner molded, while the explosive layer penetrated by the jet generated through the hot-pressing sintering and extrusion molding liner experienced local reactions on the jet impact channel, and the overall explosive layer did not undergo any reaction. Through experimental verification, it has been proven that all three types of jets have achieved “penetration without explosion” on explosive reactive armor.

A Phase 3, Single-arm Trial to Evaluate the Safety and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine in Healthy Children 15 Months Through

A 20-valent pneumococcal conjugate vaccine (PCV20), containing 13-valent PCV (PCV13) components and 7 additional polysaccharide conjugates, was developed to extend protection for pneumococcal disease. This phase 3 study assessed the safety and immunogenicity of PCV20 in children. In this single-arm study, children (≥15 months-<18 years of age) received 1 dose of PCV20. Children <5 years of age had ≥3 prior doses of PCV13; children ≥5 years were recruited regardless of previous PCV receipt. Serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers were measured before and 1 month after PCV20. Local reactions and systemic events, adverse events (AEs), serious AEs, and newly diagnosed chronic medical conditions were collected. Of 839 enrolled participants, 831 (>99%) were vaccinated, and 819 (>97%) completed all study visits. Local reactions and systemic events were mostly mild to moderate in severity. No serious AEs were considered PCV20-related. IgG geometric mean fold rises (GMFRs) from before to 1 month after PCV20 ranged from 27.9-1847.7 (7 additional serotypes) and 2.9-44.9 (PCV13 serotypes) in children <5 years of age, and 10.5-187.7 (7 additional serotypes) and 4.3-127.9 (PCV13 serotypes) in children ≥5 years old. OPA GMFRs from before to 1 month after PCV20 ranged from 12.4-983.6 to 2.8-52.9 in children <5 years of age and from 11.5-499.0 to 5.3-147.9 in children ≥5 years of age. Among children ≥15 months through <18 years of age, PCV20 was well tolerated and induced robust responses to all 20 serotypes, supporting the use of PCV20 in children.

Donor Haemovigilance: A South Indian experience

Blood Donation from healthy screened donors is a well-tolerated procedure. However a small percentage may experience adverse donor reactions. Donor haemovigilance aims at identifying and documenting these reactions for donor safety.: This prospective cross-sectional study conducted at the Department of Transfusion Medicine &amp; Immunohaematology, Govt. Medical College, Kozhikode, Kerala for a one year study period from January 1st 2018 to December 31st 2018 included all adverse donor reactions and donor determinants in vasovagal reactions in allogenic whole blood donors. Donors were assessed as per the Standard Operating Procedure (S.O.P) based on national guidelines. 350ml collection bags were used. Vasovagal reactions were also graded as per the Blood Donation Reactions Inventory scale (B.D.R.I).: During the 1 year study period, 1.79% of 27,800 donors experienced adverse reactions. The most common symptoms were pre-syncopal 1.33% with syncope forming only 0.3% and local reactions 0.16%. Correlation with donor characteristics using Pearsons chi square test showed significance for female gender, first timers and lack of adequate sleep (&amp;#60;5 hrs). In our study there was no association with age (S.O.P guidelines) or food intake &amp;#60;4hrs.Our study reinforces the safety of blood donation with a very low prevalence of adverse reactions. Proper donor counseling and examination noting donor characteristics like adequate sleep, food intake and alleviation of fears and doubts of first timers can play a major role in further reducing the reaction rate and ensuring repeat donors, the need of the hour.

A grain boundary model of metamorphic reaction

A model is presented whereby metamorphic parageneses are governed by local, nano-scale reactions among adjacent phases along grain boundaries that are driven by local disequilibrium between the solid phases and the grain boundary composition. These reactions modify the grain boundary composition setting up compositional gradients that drive diffusion and change the grain boundary composition elsewhere in the rock, which drive local reactions in these locations. The process may be triggered by the nucleation of a new phase that is out of equilibrium with the existing assemblage and an example is presented based on the transformation of kyanite (Ky) to sillimanite (Sil). Model results reveal that a simple polymorphic transformation (Ky→Sil) can result in local reactions among all phases in the rock and some phases may grow in one locale and be consumed in another. An implication of these results is that interpretation of metamorphic parageneses based on growth or resorption and compositional changes of phases requires careful evaluation of nano-scale processes.