BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients versus non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs (including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients,95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.

Allergic reactions are the most frequent adverse effects of blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The causes of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HPdel) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes of HPdel have an Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HPdel is found in East and Southeast Asian populations, but not in other populations, with a frequency of approximately 0.9% to 4%. Diagnosis of Hp deficiency due to HPdel prior to transfusion is desirable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administrating plasma products obtained from an Hp deficient donor pool. This review outlines the background of the identification of HPdel and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HPdel.

Cannabidiol, is the first cannabis-derived drug approved for the treatment of Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). The current study performed a descriptive analysis followed by a disproportionality analysis of potential adverse events caused by CBD extracted from the database VigiBase®. Further, biological plausibility of the association between CBD and the serotonin 5-HT1A receptor, as possible cause of adverse events was analyzed and discussed. Data were extracted from VigiBase® database using VigiLyze® signal detection and signal management tool. Adverse events in VigiBase® reports were coded using MedDRA, version 19 of Preferred Terms (PTs). Data were uploaded into SPSS software and analyzed via disproportionality analysis. Statistically significant disproportionality signals for CBD were found for “weight decreased” 5.19 (95% CI: 4.54 - 5.70), “hypophagia” 3.68 (95% CI: 3.22 - 5.27), and “insomnia” 1.6 (95% CI: 1.40 - 1.83). Positive IC025 values were found for “weight decreased” (2.2), “hypophagia” (1.3), and “insomnia” (0.5), indicating a surplus of reported cases. CBD’s interactions with 5-HT1A serotonin receptors may offer a potential biological explanation for the occurrence of insomnia in patients. It is noteworthy that the risk profiles mentioned in the prescribing information for CBD as antiepileptic agent by regulatory agencies showed disparities specifically related to the adverse event “insomnia”.

Hospital-based adverse drug reaction (ADR) monitoring and reporting programs intend to identify and quantify the risks associated with the use of drugs. To examine the causality, preventability and severity of ADR in a hospital setting; a prospective cohort study on spontaneous ADR reporting was conducted from December 2015 to May 2016. Incidence of ADRs, causality, type, severity and preventability were assessed using necessary assessment scales. The study included 3157 hospitalized individuals, in whom 51 ADRs were detected among 49 patients. The overall incidence of suspected ADRs was found to be 1.6%. According to the causality assessment, most of the ADRs reported were probable (n = 26, 51.0%), and type A (augmented/pharmacological) reactions (n = 39, 76%) were the most common type of ADR found. The majority of ADRs were moderate to severe (n = 35, 68.6%), of which 37.3% were found to be potentially preventable. Predictability was observed in 28 (54.9%) reported ADRs. The drugs most frequently associated with ADRs were antibiotics, antiepileptics and antihypertensives. This feasibility study was able to highlight the clinical pharmacist’s role in ADR monitoring service and create awareness about the way it could be done to promote safer drug use. Similar ADR reporting programs are necessary to educate and to improve awareness among the healthcare professionals in developing countries.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Background: Pleurotus ostreutus is one of the world’s most commonly consumed mushrooms. Cultivation of mushrooms using wood resources usually results in environmental issues of deforestation. Juncao grass Pennisetum sp, Arundo Donax, and Methodology: Miscanthus are the culture mediums used in this research which offered a composting system most particularly for a simple formulation, cheap and feasible for small farms in cultivating oyster mushrooms. Results: The present study assessed the different junco grass as a substrate for growing Pleurotus ostreatus given the enzyme activities, growth, and yields. In addition, on the other hand, Lignin peroxidase (LiP) was the most active enzyme in each culture material among the other enzyme activities expressed differently between substrate and growing stages. Fruiting bodies harvested on giant grass,Arundo donax,and miscanthus,substrate weighed 159.2g/bag,132g/bag, and 65.1g/bag on average respectively. The biological efficiency of pleurotus cultivated in three different substrates was 75.2%, 63.4%, and 28.7%, respectively. Lignin peroxidase (LiP) was the most active enzyme followed by Laccase in each substrate. At the same time, other enzyme activities were differently expressed between substrate and different developmental stages. Nutrient analysis revealed significant variations, with differences in polysaccharides, proteins, and amino acids among substrates as well as the presence of heavy metals as arsenic, lead, mercury, and cadmium content in all samples was within safe limits. Conclusion: Findings from this study will serve as a solid foundation for future studies aimed at characterizing different substrate responses on enzyme activity. This research provides a sustainable footprint for subsequent research promoting eco-friendly mushroom production. The obtained results indicate that Arundo donax should be a good substrate in place of giant grass, using miscanthus is not productive based on the results obtained in this research the juncao grasses offer a sustainable approach that reduces reliance on wood-based substrates and enhances environmental sustainability.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

Background: Although triptorelin acetate (TA) is generally considered a safe medication, severe adverse drug reactions (ADRs) to triptorelin have occurred. In this study, we present the largest retrospective analysis of ADRs related to TA during the treatment of pediatric central precocious puberty. Methods: We describe a total of 38 suspected cases of TA-induced ADRs reported to the pharma-covigilance center of Shenzhen Children’s Hospital from September 2015 to December 2022. Causality assessment was carried out using the validated Kramer’s algorithm. The severity of ADRs was evaluated using the Modified Hartwig and Siegel Scale. Results: The most common ADRs attributed to TA were damage to the cutaneous tissues (29.3%) and reactions affecting the systemic and digestive systems (20.7%). The majority (61.1%) of ADRs occurred within 2 hours of administration. Among the 12 patients with severe ADRs, the three most frequent symptoms were anaphylactic reactions, hip synovitis, and arthralgia. Additional-ly, six patients experienced ADRs due to a change in the manufacturing process. Conclusion: The majority of ADRs observed in pediatric cases were type I anaphylactic reactions, which are rare but life-threatening. It is advisable to perform skin prick tests and intradermal tests when switching pharmaceutical manufacturers.

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

There are many pollution and environment problem in the human ecosystem. There are different methods are used to removal of sulfur from sour gases for example Basic Claus process and Modified Claus process . There are different chemical software are used for simulation and optimization of Claus process for example Aspen Plus and Chemcad ECT. The Gibbs free energy method is introduced and model of Claus process. There are new parameter are introduced in reaction furnace to reduce the error from 33% to 7 %. The waste heat boiler is installed at the reaction furnace in which high pressure stream is produced and study the decomposition the hydrogen sulphide. The new rate of reaction is introduced of the enhancement of H2 production in chemical process. The simulation of reaction furnace in Aspen plus software is the maximum utilization of process. Due to suitable operating condition of reaction furnace is caused the maximum destruction of ammonia gas in the reactor. When we are increasing the oxygen concentration and temperature of feed is causing decreasing the ammonia production in reaction furnace. It is below than acceptance value of ammonia is 150 ppm in the reaction furnace. The presence of oxygen components, Sulfur oxide, hydroxide components are effect on decreasing the amount of ammonia in furnace and temperature is about at 1350⁰C. It is noted that when the production of sulfur recovery is decrease in Claus process and the production of carbon monoxide is increase in the thermal section at the existence. Now we are work on parametric studies of furnace that could be causes the production of ammonia destruction and CO emission in the Claus process. Due to optimize the reaction furnace parameter are help to get large of sulfur production, ammonia gas destruction, increased the catalyst life and decreased of dangerous gases.

Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In pervious review articles, we have presented 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalizations, and addition followed by cyclization reactions. Presents in this paper are radical cyclization followed by the second functionalization reactions. The second functionalization could be realized by atom transfer reactions, radical or transition metal-assisted coupling reactions, and reactions with neutral molecules, cationic and anionic species.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this special issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need of great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is sometimes overlooked with non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Radical reactions in water or aqueous media are important for organic synthesis, realizing high yielding processes under non-toxic and environmentally friendly conditions. This overview includes (i) a general introduction to organic chemistry in water and aqueous media, (ii) synthetic approaches in-, on- and with-water as well as in heterogeneous phase, (iii) reaction of carbon-centered radicals with water (or deuterium oxide) activated through coordination with various Lewis acids, (iv) photocatalysis in water and aqueous media, and (v) synthetic applications bioinspired from naturally occurring processes. A wide range of chemical processes and synthetic strategies under different experimental conditions have been reviewed that lead to important functional group translocation and transformation reactions, leading to the preparation of complex molecules. These results reveal how water as a solvent/medium/reagent in radical chemistry has matured over the last two decades and how further discoveries are foreseen to come in the near future.

News on the stock market contains positive or negative sentiments depending on whether the information provided is favorable or unfavorable to the stock market. This study aims to discover the news sentiment and classify news according to its sentiments with the application of PhoBERT, a Natural Language Processing model designed for the Vietnamese language. A collection of nearly 40,000 articles on financial and economic websites is used to train the model. After training, the model succeeds in assigning news to different classes of sentiments with an accuracy level of over 81%. The research also aims to investigate how investors concern about the daily news by testing the movements of the market before and after the news is released. The analysis results show that there is an insignificant difference in the stock price as a response to the news. However, investors tend to overreact to negative and positive news in the Vietnam stock market.

In this study, 12 organic waste materials were subjected to TG/DTG thermogravimetric analysis and DSC calorimetric analysis. These analyses provided basic information about thermochemical transformations and degradation rates during organic waste pyrolysis. Waste materials were chosen to cover the most abundant waste that can be found in the municipal solid waste stream. Based on TG results, kinetic parameters according to Coats–Redfern method were determined. The pyrolysis activation energy was the highest for cotton 134.5 kJ∙(mol∙K)-1 and the lowest for leather 25.2 kJ∙(mol∙K)-1. The DSC analysis showed number of transformations occurred during pyrolysis for each material. For each transformation, normalized energy required for transformation, or released during transformation were determined and then summarized to present energy balance. The study found that only for three waste materials: PET (-220.1 J⸱g-1), leather (-66.9 J⸱g-1), and chicken meat (-130.3 J⸱g-1) energy balance was negative, while the highest positive balance value was found for potato peelings (367.8 J⸱g-1). The obtained results may be applied for the modelling of energy and mass balance of municipal solid waste pyrolysis.

Motivated by the way animals react in nature, we introduce a fully-connected neural-network model, which incorporates the external pattern presented to the system as a fundamental tool of the recognition process. In this new scenario, in the absence of this external field, memories are not attractors inside basins of attraction, as in usual attractor neural networks, although basins may be created according to the external pattern, thus allowing storing a much larger number of memories. The key point consists in calibrating the influence of the external pattern such as to cancel the noise generated by those memories not correlated with the external pattern.We illustrate how this proposal works by including this new contribution in the standard Hopfield model, showing a significant increase in its recognition capacity (typically by a factor $10^{2}$). As an additional feature of this model, we show its ability to react promptly to changes in the external environment, a crucial attribute of living beings. This procedure can be applied to a wide variety of neural-network models to increase considerably their recognition and reaction capabilities.

In this short review paper we have assembled the main characteristics of partial oxidation reactions (oxidative dehydrogenation and selective oxidation to olefins or oxygenates, as aldehydes and carboxylic acids and nitriles), as well as total oxidation, particularly for depollution, environmental issues and wastewater treatments. Both gas-solid and liquid-solid media have been considered with recent and representative examples within these fields. We have also discussed about their potential and prospective industrial applications. Particular attention has been brought to new raw materials stemming from biomass and to liquid-solid catalysts cases. This review paper also summarizes the progresses made in the use of unconventional activation methods for performing oxidation reactions, highlighting the synergy of these technologies with heterogeneous catalysis. Focus has been centered on usual catalysts activation methods but also on less usual ones, such as the use of ultrasounds, microwaves, grinding (mechanochemistry) and photo-activated processes, as well as their combined use.

Weather-related risks in aviation are one of the main causes of accidents worldwide. This article aims to analyze aviation risks resulting from adverse weather conditions, using the case study of the Pucallpa accident that occurred on August 23, 2005, in eastern Peru. In this analysis, we have determined the relationship between meteorological information and aviation risks, presented a matrix of risks associated with the most predominant meteorological variables at Pucallpa airport, and drawn up three maps of meteorological risks indicating the month of the year in which their incidence is most relevant. Finally, we conclude that it is essential to emphasize the importance of considering the prevailing weather conditions at Pucallpa airport to help mitigate the potential risks that may occur during different phases of the flight.

Acrylates and methacrylates are widely used, especially in the dental industry, but can cause adverse skin reactions. These compounds, including 2-hydroxyethyl methacrylate, triethylene glycol dimethacrylate, and bisphenol A-glycidyl methacrylate, are strong contact irritants or allergens. Found in dental prostheses, composite resins, dentin bonding materials, and glass ionomers, they pose a higher risk of exposure for dental personnel. Clinically, acrylate allergies manifest as facial rashes, eczema with cracked skin on fingers (pulpitis), nail dystrophy, and periungual dermatitis. Recently, the highest frequency of allergic reactions to acrylates has shifted from dentistry to the beauty industry due to increased use in artificial nails, eyelashes, and hair extensions. This has led to greater sensitization. Acrylates are also used in medical applications, such as bone cement for orthopedic endoprostheses, soft contact lenses, hearing aids, histological preparations, and wound dressings, which can also cause allergic reactions. Severe dermatitis from surgical glue containing acrylates has been documented, and diabetic medical devices are potential sources of allergic contact dermatitis. Given the extensive use and prolonged skin contact of products containing acrylates and methacrylates, this review aims to present current knowledge and literature on reactions to these compounds across different industries.

Strangeness flavor is abundant and in chemical equilibrium in the primordial Quark-Gluon Plasma(QGP) filling the early Universe. Upon hadronization near to T=150 MeV one may think that relatively short lived massive strange hadrons decay rapidly and strangeness disappears. However, we show using detailed balance considerations for inverse decay reactions that the back reaction repopulate strangeness keeping it in chemical equilibrium at least to the time when strange antibaryons annihilate near T≃30-50 MeV. However, our present study is focused on the meson sector of the hadronic Universe. Specifically, we establish here the temperature range in which the expansion of the Universe becomes faster compared to the production processes which balance natural strangeness decay: In the temperature interval 33MeV<T<20MeV: μ±+νμ→K±, π+π→K and l−+l+→ϕ reactions in sequence become slower compared to the characteristic Hubble time.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

A new study for CH4 reforming to hydrogen and hydrogen storage was performed using magnesium-based alloy. MgH2-12Ni (with the composition of 88 wt% MgH2 + 12 wt% Ni) was prepared in a planetary ball mill by milling in hydrogen atmosphere (reaction-involved milling). X-ray diffraction (XRD) analyses were performed for the samples after reaction-involved milling and after reactions with CH4. The variation of adsorbed or desorbed gas with time was measured by a Sieverts’ type high-pressure apparatus at 773 K. The microstructures of the powders were observed using scanning transmission microscope (STEM) with energy-dispersive X-ray spectroscopy (EDS). The synthesized samples were also characterized using Fourier Transform Infrared (FT-IR) spectroscopy. XRD pattern of MgH2-12Ni after reaction with CH4 of 12 bar at 773 K and decomposition under 1.0 bar at 773 K exhibited phases of MgH2 and Mg2NiH4. This shows that reforming of CH4 was occurred, hydrogen produced after reforming of CH4 was then adsorbed on the particles, and hydrides were formed during cooling to room temperature. Ni and Mg2Ni formed during heating up to 773 K are believed to have brought about catalytic effects for reforming CH4. MgH2-12Ni adsorbed 0.8 wt% reformed CH4 within 1 min in a reaction with CH4 of 12 bar at 773 K and then desorbed 0.8 wt% reformed CH4 (hydrogen-containing mixture) within 1 min under 1 bar at 773 K. Attenuated total reflectance FT-IR spectroscopy (ATR-FTIR) spectra of MgH2-12Ni after reactions under 12 bar CH4 at 723 K and 773 K showed peaks of C-H bending, C=C stretching, O-H stretching, O-H bending, and C-O stretching.

This short review is aimed at giving an overview of catalytic carbonylative double cyclization reactions, which are processes in which suitable organic substrates and carbon monoxide are sequentially activated by a promoting catalyst to afford the formation of two new cycles with concomitant incorporation of carbon monoxide as a carbonyl function into the final product. Paradigmatic examples of this powerful synthetic methodology, which allows the one-step synthesis of complex molecular architectures from simple building blocks using the simplest and readily available C-1 unit (CO) are illustrated and discussed. The review is divided into five sections: 1) Introduction; 2) Functionalized Olefinic Substrates; 3) Functionalized Acetylenic Substrates; 4) Functionalized Halides; 5) Conclusions and Future Perspectives.

We search for limit cycles in the dynamical model of two-species chemical reactions that contain seven reaction rate coefficients as parameters and at least one third-order reaction step, that is, the induced kinetic differential equation of the reaction is a planar cubic differential system. Symbolic calculations were carried out using the Mathematica (or, Wolfram language) mathematical program package, and it was also used for the numerical verifications to show the following facts: the kinetic differential equations of these reactions each has two limit cycles surrounding the stationary point of focus type in the positive quadrant. In the case of Model 1, the outer limit cycle is stable and the inner one is unstable that appears in a supercritical Hopf bifurcation. Moreover, the oscillations in a neighborhood of the outer limit cycle are slow-fast oscillations. In the case of Model 2, the outer limit cycle is unstable and the inner one is stable. With another set of parameters, the outer limit cycle can be made stable and the inner one unstable.

The method tsscds, recently developed in our group, discovers chemical reaction mechanisms with minimal human intervention. It employs accelerated molecular dynamics, spectral graph theory, statistical rate theory and stochastic simulations to uncover chemical reaction paths and to solve the kinetics at the experimental conditions. In the present review, its application to solve mechanistic/kinetics problems in different research areas will be presented. Examples will be given of reactions involved in photodissociation dynamics, mass spectrometry, combustion chemistry and organometallic catalysis. The source code can be downloaded from: http://forge.cesga.es/wiki/g/tsscds/HomePage

Zinc (Zn) is the second most abundant metal in the human body, and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself, and then the quantity of other food constituents such as phytate, protein and calcium (Ca). In cells, Zn is involved in regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. Cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, the Solute-Linked Carrier 30A and 39A (SLC30A and SLC39A), known as the ZnT and the Zrt-/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases, including those induced by COVID-19 infections, among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to the potential protective effects of Zn against bone, lung and heart diseases associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

(1) Background: Heat stress detrimentally restricted the economic in dairy farming production, therefore, this study was designed to investigate how automatic spraying method on alleviating heat stress on cows. (2) Methods: A total of 1208 multiparous dairy cows were randomly allocated into 6 barns, three barns were equipped with automatic sprinklers (SP), each barn was considered as a replicate. The other three barns were considered as control treatments (CON). Each barn was considered as a replicate. (3) Results: body temperature and milk somatic cell count were significantly decreased, while DMI, milk yield, and milk fat content significantly increased with spraying treatment. ICR was improved from 30% to 35%. Rumen fermentation was enhanced by the increased levels of total VFA, acetate, propionate, and butyrate with the spraying treatment. Rumen microbiota results showed at the phylum level, rumen Fibrobacters abundance significantly increased by the spraying treatment. At the genus level, Eubacterium, Shuttleworthia, Saccharofermentans, Lachnospira, Pseudobutyrivibrio, Selenomonas, and Succinivibrio abundance were significantly increased, while Ruminococcaceae and Rikenellaceae abundance were significantly decreased in the rumen with spraying treatment. (4) Conclusion: this study demonstrated automatic spraying modulated the rumen microbiota composition and fermentation function, and effectively meliorated side-effects of heat stress on dairy cows.

Adverse events associated with opioid use in palliative care have been extensively studied. However, predicting the occurrence of adverse events based on the specific opioid used remains unclear. This study aimed to comprehensively analyze the adverse events caused by µ receptor stimulation of opioids approved in Japan and investigate the tendencies of adverse event occur-rence among different opioids.We utilized the FDA Adverse Event Reporting System (FAERS) database to extract reported adverse events of opioids approved in Japan. Cluster analysis was performed on reporting odds ratios (RORs) of adverse event names among opioids to visualize relationships between opioids and adverse events, facilitating a comparative study of their clas-sifications.We calculated the RORs of adverse events for the target opioids. Based on these RORs, we performed a cluster analysis, which resulted in the classification of 11 target opioids into five distinct groups. we were able to comprehensively compare and examine the relationships between opioids and adverse events. This analysis helps in understanding and managing the risks and benefits of each drug in palliative care settings. By analyzing relationships between opioids and adverse events, clinicians can make informed decisions about opioid selection, dosage, and monitoring to maximize patient safety and comfort.

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhib-itors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines and bispecific an-tibodies are improving patients’ outcomes. However, stimulation of the immune system, benefi-cial in terms of fighting against cancer, generates the risk of harm to other cells in a patient's body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, su-perficially, are renal AEs in patients treated with ICIs. International guidelines issued by Euro-pean Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are scarce data concerning renal adverse drug reactions of other immunotherapeutic methods. This implicates the need for the collection of safety data during ongoing clinical trials and in the re-al-life world to characterize the hazard related to the use of new immunotherapies and manage-ment of irAEs.

Transcriptional regulations have been widely studied as one of the main bridges between biology and other basic sciences as well as medicine. The traffic across it has been mostly unidirectional: chemistry and physics provided a lot of tools for biology, although the supply is now saturating. The traffic in opposite direction, the supply of subjects to develop chemistry and physics, has been only a little. However, if there are any, the supply will be at least from transcription, because the notion of chemical reaction is the strongest. This topic is aimed to increase the opposite traffic by introducing the forefront of physicochemical studies of transcription.

This study presents a new kinetic scheme for the mass yield prediction of waste lignocellulosic biomasses treated by Hydrothermal Carbonization (HTC). The proposed reactions are based on the decomposition, solubilization, and polymerization of each main fraction of the biomass: cellulose, hemicellulose, and lignin. The ash content was assumed to be inert. The kinetic parameters have been obtained by non-linear adjustment using a data set with 220 experimental runs collected from the literature. The results indicate that the pre-exponential factors range was from 7.33 x10¹ to 1.412x10⁵ min^-1, and activation energies were between 33.75 y 225.3 kJ/mol. A good fit is achieved between the observed and predicted data with an R² of 0.81 and an RMSE of 7.7 %. The proposed scheme was validated with the experimental data obtained by the HTC of sawdust (Pinus radiata) and rapeseed (Brassica napus). The experiments were carried out at temperatures of 190, 220, and 250 ºC and reaction times of 0, 30, 60, 90, and 120 min. The predicted values showed an average error of 2.3 and 3.5 %, respectively. Therefore, the kinetic scheme is a useful tool in the conversion analysis of waste biomass treated by HTC.

Hydrogen is considered as an ideal substitute to the traditional fossil fuels because of its widespread sources, high calorific value of combustion, and zero carbon emissions. The electrocatalytic water-splitting to produce hydrogen is also deemed to be the best approach, however, it is a challenge to make high-efficient and low-cost electrocatalysts. Single-atom catalysts (SACs) are considered the most promising candidate to replace the traditional noble-metal catalysts. Compared with SACs, the dual-atom catalysts (DACs) are of greater attraction including higher metal loading, more versatile active sites, and excellent catalytic activity. In the review, several general synthetic strategies and structural characterization methods of DACs are introduced, and the mechanisms of hydrogen evolution reaction (HER) and oxygen evolution reactions (OER) are discussed. The authors hope that the review has given some insights and inspiration to the researchers about DACs in electrocatalytic water-splitting.

Addressing global environmental problem, water splitting to produce hydrogen fuel by solar energy is getting so much attention. In the water splitting, the essential problem to solve is the development of efficient　catalysts for oxygen production. In this paper, having the prospect for a practical application of photocatalysts to artificial photosynthesis, molecular mechanisms in the current literature are briefly reviewed. At first, recent progress in the function of Mn cluster at the natural photosystem II is briefly described. The kinds of devices in which oxygen evolution reaction (OER) catalysts are used were designated; water electrolyzers, photoelectrodes, and photocatalysts. Some methods for analyzing molecular mechanism in OER catalysis, emphasized by FTIR method, are shown briefly. After describing common OER mechanisms, the molecular mechanisms are discussed for TiO2 and BiVO4 photoelectrodes with our novel data, followed by presenting of co-catalysts IrO2, RuO2, NiO2, and other metal oxides for OER catalysts. Recent reports describing OER catalysts of perovskites, layered double hydroxides (LDH), metal-organic frameworks (MOF), single atom catalysts, as well as metal complexes are reviewed. Finally, by comparing with natural photosystem, the requiring factors to improve the activity of the catalysts for artificial photosynthesis will be discussed.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Nonmedical prescription stimulant use (NPSU) is an ongoing public health crisis in the United States. There exists, however, a dearth of research investigating specific childhood risk factors that may contribute to this illicit use. Adverse childhood experi-ences (ACEs) may be a significant risk factor to address in the prevention and treatment of NPSU, as research has provided evi-dence for increased substance use, potentially including prescription stimulant misuse, among individuals who have experienced trauma. A systematic review of the literature was conducted to gather and synthesize research articles specifically examining the relationship between nonmedical prescription stimulant use in adults and the experience of adverse childhood experiences (ACEs). Four studies met all inclusion criteria and were included in the review. The results demonstrated that nonmedical use of prescription stimulants in adults is significantly associated with ACEs, with a higher numerical count of ACEs associated with a greater likelihood of nonmedical prescription stimulant use. Gaps in the literature were identified, specifically noting a lack of information available regarding the relationship between ACEs and NPSU within gender- and racially-diverse populations. The findings have implications for informing interventions related to ACEs and the misuse of prescription stimulant medication in adults.

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in woman and is a high cause of mortality of them in reason to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy and inhibit distant metastases so potentially acts on tumor micro-environment; (2) Methods: Ferroptosis/Extracellular matrix remodeling literature text-mining results were integrated in breast cancer transcriptome cohort according their distant relapse free survival (DRFS) under adjuvant therapy (anthracyclin+taxanes) and also in MDA-MB-231 transcriptome functional experiments with ferroptosis activations (GSE173905); (3) Results: Ferroptosis/Extracellular matrix remodeling text-mining identified 910 associated genes in at list 10 articles. Univariate Cox analyses censored on breast cancer (GSE25066) selected 252 individual significant genes and 171 of them found with an adverse expression. Functional enrichment of these 171 adverse genes predicted basal breast cancer signatures. By text-mining some ferroptosis significant adverse selected genes shared citations in domain of ECM remodeling such as: TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, TLR4. A molecular score based on expression the eleven genes was found predictive of worst prognosis breast cancer at univariate level: basal subtype, short DRFS, high grade values 3 and 4, estrogen and progesterone receptors negative and nodal stages 2 and 3. This eleven gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in triple negative breast cancer cellular model MDA-MB-231.; (4) Conclusions: Crosstalk between ECM remodeling-Ferroptosis functionalities allowed to define a molecular score which have been characterized as an independent adverse parameter in prognosis of breast cancer patients. Gene signature of this molecular score have been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate ECM impact of ferroptosis target therapies in breast cancer.

Endoscopic retrograde cholangiopancreatography (ERCP) is a routinely used therapeutic procedure for the biliary and pancreatic diseases. Population aging may increase the typical indications of ERCP and come with more complexity and difficulties, especially in cannulation. This study aimed to evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in super-aged patients and the role of difficult cannulation as a risk factor for adverse events. A total of 614 patients, underwent ERCP, were prospectively studied as a cohort and divided into two groups based on their age. There were 146 patients aged 80 years or older in group A and 468 patients aged less than 80 years in group B. The primary outcome measures were the difficulty grade of papilla cannulation, clinical outcomes, and ERCP-related complications in the two groups. The adverse events were analyzed using logistic regression for patient age, co-morbidities, indications, and cannulation difficulty grade variables. There was no difference in the incidence of difficult cannulation between the two groups (32.9% vs. 34.4%, p=0.765) though, as expected, super-aged Group A had a higher prevalence of periampullary diverticulum (29.5% vs. 16.7%, p=0.001). The technical cannulation success rate was (96.6% vs. 96.8%, p= 0.54). All used cannulation techniques in the elderly group were efficient and safe. Logistic regression showed that age ≥80 was not associated with increased adverse events; however, difficult cannulation (adjusted odds ratio [AOR]=3.478; 95% confidence interval [CI]=1.877, 6.442; p<0.001) and CCI ≥2 (AOR=1.824; 95% CI=0.993, 3.349; p=0.045) were more likely to have adverse events. Age ≤65 (AOR=3.460; 95% CI=1.511, 7.922; p=0.003), female gender (AOR=2.362; 95% CI=1.089, 5.124; p=0.030), difficult cannulation (AOR=4.527; 95% CI=2.078, 9.860; p<0.001), and patients with cholangitis (AOR=3.261; 95% CI=1.204, 8.832; p=0.020) were strongly associated with increasing Post-ERCP Pancreatitis (PEP). Advanced age has not proved to be a risk factor of difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized for this group. CCI ≥2 and difficult cannulation are associated with increased overall adverse events rate while age ≥80 factor is not.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk‐reducing salpingo‐oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT alleviated menopausal symptoms in BRCA2 carriers and women who were physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in those with a history of cancer. MBSR, on the other hand, was associated with increased intensity of most menopausal symptoms. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level while their need for extensive measures to optimize their psychological wellbeing is ongoing. Adverse effects of MBSR, which are captured in the present study imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in those women.

Multicomponent reactions (MCRs) have been used for more than a century; since their discovery in 1850 by Strecker. To date, MCRs route is regarded as a beneficial strategy due to its capacity to quickly produce molecular diversity and structural complexity of interest for a variety of applications. Despite having famous MRCs such as the Ugi, Passerini, Biginelli, and Hantzsch, this re-view portrays the importance of MCRs in the synthesis of desired products towards applications such as medicinal purposes, sustainable chemistry, and polymerisation. MCRs provide ad-vantages such as reducing the number of sequential multiple reactions to one step, atom economy, recyclable catalysts, mild conditions, preventing waste and reduce solvent use.

We present a formalism to assess the safety of the COVID19 vaccines and infer a causal relation between vaccine administration and adverse effects, in particular death. We use data on adverse effects from VAERS covering the time interval [01-10-2020, 31-12-2021] (downloaded on 1 Feb 2022). We measure a vaccine fatality rate of order 0.01 for all vaccine manufacturers and identify a strong heterogeneity in the vaccine toxicity across vaccine lots, spanning up to four orders of magnitude. We compute the correlation between vaccination dates and death dates, and produce an estimate of the time lag that maximises the correlation, finding that the onset of adverse effects happened statistically (i.e. 32-41 percentiles) within one day after the vaccine administration and that death happened statistically (i.e. 22-50 percentiles) within about two weeks after the vaccine administration. These results provide data-based insights that can guide public health measures and health insurance policies.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of N,N-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen)^† reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates S­_N1 and S_N2 reactivity at the amide nitrogen.

The influence of humic aggregates in water solution upon the chemical stability under basic conditions of different substrates has been reviewed. The kinetic behavior of each substrate has been modelized in terms of micellar pseudophase model.

Construction safety is especially important because the construction industry is so important to a country's development. Significant research and practice have been conducted to mitigate potential risks during construction and improve worker efficiency. With the rapid advancement of cognitive neuroscience and the incorporation of medical technology in recent years, various wearable monitoring devices have been widely used in the construction field for real-time monitoring of workers' physical and mental status. Among these, the use of EEG (Electroencephalogram) in construction environment research allows researchers to gain insight into the physical and mental states of construction workers while performing construction tasks. This review introduces EEG technology and portable EEG devices, followed by an overview of their use in both monitoring workers' adverse reactions and identifying hazards on construction sites, providing an effective guide for EEG research in the construction field and on-site safety management.

For autonomous driving, perception is a primary and essential element that fundamentally deals with the insight into the ego vehicle’s environment through sensors. Perception is a challenging task suffering from dynamic objects and continuous environmental changes. The issue gets worse due to interrupting the quality of perception by adverse weather like snow, rain, fog, night light, sand storm, strong daylight, etc. In this work, we have tried to improve camera-based perception accuracy, such as autonomous driving-related object detection in adverse weather. We proposed the improvement of YOLOv8-based object detection in adverse weather through transfer learning using merged data from various harsh weather datasets. Two prosperous open-source datasets (ACDC and DAWN) and their merged dataset were used to detect primary objects on the road in harsh weather. A set of training weights were collected from training on the individual datasets, their merged version, and several subsets of those datasets according to their characteristics. A comparison between the training weights also occurred by evaluating the detection performance on the above-mentioned datasets and their subsets. The evaluation revealed that using custom datasets for training significantly improves the detection performance compared to the YOLOv8 base weights. And using more images through the feature-related data merging technique steadily increases the object detection performance.

A sustainable green one pot procedure for the synthesis of dihydropyrimidinones (DHPMs) derivatives by a three-component reaction of β-ketoester derivatives, aldehyde and urea or thiourea over the alkali-treated H-ZSM-5 zeolite under ball-milling has been developed. The product was isolated by simple washing of the crude reaction residue with ethyl acetate followed by evaporation of solvent. The hierachical zeolite catalyst (MFI27_6) showed high yield (86–96%) of dihydropyrimidinones (DHPMs), in very short time (10-30 min). The catalyst is recycled for subsequent reactions in four runs without appreciable loss of activity and high yields of products provide efficient protocol for Biginelli reactions.

The use of hydrogen fuel cells as a mobile source of electricity might prove to be a keystone in future decarbonization of heavy duty road and marine transport. Due to complex interplay of various physicochemical processes in the fuel cells, further development of these devices will rely on concerted effort of researchers from various fields, e.g. chemistry, physics, electric and mechanical engineering. This results in knowledge gaps which are filled by the information, dispersed in wide range of literature, but rarely covered in a short and condensed form. To address this issue and with the aim of providing a concise and simple explanation of fuel cell operation, we propose a simple educational model of the most relevant processes in the fuel cell, aimed at proper description of causal relations. The derivation of model equations provides an intuitive understanding of electric potentials acting on protons on the microscopic level and relates this knowledge to the common terminology in fuel cell research community, such as catalyst electric overpotential and internal membrane resistance. The results of the model fit well with experimental data, indicating that a simple description, provided in the paper, is sufficient for intuitive understanding of fuel cell operation.

Foods are mixed with saliva in the oral cavity and swallowed. During staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component nitrite is protonated to produce active nitrous acid at acidic pH, the redox reactions of nitrous acid with phenolic compounds in foods become possible in the stomach. In the reactions, nitrous acid is reduced to nitric oxide (•NO), producing various products from phenolic compounds. In the products, stable hydroxybezoyl benzofuranone derivatives, which are produced from quercetin and its 7-O-glucoside, are included. Caffeic acid, chlorogenic acid, and rutin are oxidized to quinones and the quinones can react with thiocyanic acid derived from saliva producing stable oxathiolone derivatives. 6,8-Dinitrosocatechis are produced from catechins by the redox reaction, and the dinitrocatechins are oxidized further by nitrous acid producing the quinones, which can make charge transfer complexes with the dinitrosocatechin and can react with thiocyanic acid producing the stable thiocyanate conjugates. In this way, various products can be produced by the reactions of salivary nitrite with dietary phenolic compounds, and reactive and toxic quinones formed by the reactions are postulated to be removed in the stomach by thiocyanic acid derived from saliva.

Abstract: Background: With the growing trends in recreational marijuana use, our study aims at analyzing the association between Acute coronary syndromes (ACS) and Ventricular Fibrillation (Vfib) and cannabis use disorder in young adults (18 – 45) Methods: National In-patient Sample was used for population analysis. Probit logistic regression was used for analyzing the associations between diagnosis of ACS/ Vfib and documented cannabis use disorder. Propensity Score matched samples were made from the ACS/Vfib admissions with Cannabis use disorder to analyze the in-hospital outcomes. Results: Statistically significant association was found between admission diagnosis of ACS/ vfib, and documented cannabis use disorder in the study population. The association remained sig-nificant after accounting for potential confounders. Documented race as black, documented di-agnosis of uncontrolled hypertension and diabetes were found to have significant association with admissions for ACS among the population with documented Cannabis use disorder. No difference in mortality were found between ACS admissions with and without documented cannabis use disorder in the propensity matched cohorts. Conclusions: Documented diagnosis of Cannabis use disorder has statistically significant associ-ation with admission diagnosis of ACS/Vfib even after accounting for confounders. Documented race as black, and co existing diagnosis of uncontrolled hypertension and diabetes had significant association with admission diagnosis of ACS in population with documented cannabis use dis-order. Keywords: Cannabis use disorder; ACS; Ventricular fibrillation

Abstract: (1) Background: to find out how COVID-19 infection during pregnancy affects the outcome of the pregnancy; (2) Methods: 166 SARS-CoV-2-positive pregnant women formed the study group. 128 SARS-CoV-2-negative pregnant women formed the control group. Anatomopathological study of the placenta was performed in all cases; (3) Results: Placental insufficiency appeared in 38 patients (22.9%) of the study group and in 17 patients (13.2%) in the control group (p=0.016). Villitis appeared in 50 patients (30.1%) of the study group and in 16 (12.6%) in the control group (p=0.000). 166 COVID-19 positive patients were further subdivided, into those with anatomopathological affection of the placenta, and those without. When gestational age between patients with placental insufficiency and those without it are compared, a difference of 4.38 days is obtained (p=0.0393). If we compare neonatal weight between patients with placental insufficiency and those without it, a difference of 406.4 grams is obtained (p=0.0000). When gestational age between patients with villitis and those with-out it are compared, a difference of 3.2 days is found (p=0.0919). When neonatal weight between patients with villitis and those without it are compared, a difference of 242.2 grams is obtained (p=0.0018). (4) Conclusions: COVID-19 infection during pregnancy may produce lower fetal weight and shorter gestational length.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

The clinical application of Phentolamine Mesylate (PM) as an anaesthetic reversal agent has been documented in paediatric patients and in conservative dentistry, but no studies have been found in implant surgery. A prospective randomised study was conducted in 60 patients eligible for mandibular implant treatment, randomly divided between the Control Group (CG) and Experimental Group (EG), who were administered PM. Haemodynamic changes, adverse effects and patient satisfaction were assessed. No statistically significant differences in haemodynamic changes and postoperative pain were found between CG and EG (p&lt;0.05), except for Systolic Blood Pressure (SBP) which increased slightly in EG, without posing a risk to the patient. There were no differences in the presence of adverse effects between the two groups, except in the CG which presented greater difficulty in chewing and biting (p&lt;0.05) and the EG with greater pain in the injection area (p=0.043). 83.3% of the EG patients would request PM again for future dental treatment. The use of PM offers an alternative in implant surgery, without increasing the risks and increasing the patient's quality of life.

Findings from studies of prenatal exposure to pesticides and adverse birth outcomes have been equivocal so far. We examined prenatal exposure to agricultural pesticides in relation to preterm birth and term low birthweight, respectively, in children born between 1998 and 2010 randomly selected from California birth records. We estimated residential exposures to agriculturally applied pesticides within 2 km of residential addresses at birth by pregnancy trimester for 17 individual pesticides and 3 chemical classes (organophosphates, pyrethroids, and carbamates). Among maternal addresses located within 2 km of any agricultural pesticide application, we identified 24,693 preterm and 220,297 term births, and 4,412 term low birthweight and 194,732 term normal birthweight infants. First or second trimester exposures to individual pesticides (e.g., glyphosates, paraquat, imidacloprid) or exposures to 2+ pesticides in the three chemical classes were associated with small increases (3-7%) in risk for preterm birth; associations were stronger for female offspring. We did not find associations between term low birthweight and exposures to pesticides other than for myclobutanil (OR: 1.11; 95% CI: 1.04-1.20) and possibly pyrethroids as a class. Our improved exposure assessment revealed that first and second trimester exposures to pesticides were associated with preterm delivery but few affected term low birthweight.

The article presents the trends in penitentiary work with convicts of different cultures, focuses on their activation, individualisation of work, and organizational difficulties. The purpose of the research has been to discover the ways in which prison staff react to situations requiring flexibility justified by cultural differences of the inmates. The research questions have included: How does prison staff respond to the needs of culturally different inmates? How do the respondents’ reactions correlate with professional experience? Based on the literature, a hypothesis has been established that prison staff avoids individualized treatment of convicted foreigners. Despite the perceived differences in culture, religion, and their different mentality, prison procedures aim at uniformity. Tendencies towards resistance and stiffness to the needs of culturally different people become prevailing. The research method used has included a diagnostic survey (n = 232, F: 40, M: 192) conducted in prison officers in Poland. The written interview technique has been used, where the respondents has reacted to 3 situations of convicts, reflecting their national, religious, and cultural distinctiveness. In their responses, the respondents have decided on the way of action in the situation, as well as their motivation. The operationalization of the source material has been performed in two ways. There has been applied the content analysis method according to the grounded theory (B.G. Glaser, A.L. Strauss), resulting in the creation of categories marking actions and motives. A multiple correspondence analysis (MCA) of the built categories has been carried out using the Statistica program, as well as the correlation analysis of variables with the Cramer's V coefficient. The results of the analysis show statistically created, indicated manners of reacting that have occurred in the studied sample. Additionally, they point out an independent variable - seniority, which has correlated with the quality of the response.

The increased global incidence of myopia requires the establishment of therapeutic approaches. Previous studies have suggested that inflammation plays an important role in the development and progression of myopia. We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJE and PVE lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. Expression levels of IL-6, IL-8, and TNF-α were upregulated in retinal pigment epithelium (RPE) cells treated with IL-6 and TNF-α. FJ extract (FJE) + PV extract (PVE) reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-β1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type Ⅰ collagen expression. Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with 1-naphthyl- or 1-anthracenylamine, respectively. Due to steric bulk and high electron density ring closure to benzo[h]quinolines takes place, exclusively. Such highly substituted annelated pyridine systems can be modified in subsequent, selective reactions to build up new N-heterocycles with promising microbiological properties. Antibacterial and antiproliferative assays against four cell mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinolines analogs display potent phenotypic bioactivities in the single-digit micromolar range.

The steady-state multiplicity of the porous, non-isothermal, catalyst pellet when two parallel and consecutive chemical reactions take place was analysed in this work. The geometry selected for the catalyst pellet is finite hollow cylinder. A numerical multigrid continuation technique with the preconditioned conjugate gradient squared as coarse grid solver was used. The continuation parameter is the dimensionless adiabatic heat rise (Prater number) for the first chemical reaction. The effect of the other governing parameters was analysed and the results are compared to those provided by the single chemical reaction.

Current paper reviews applications of luminescence bioassays for monitoring low-intensity factors, namely, radioactivity of different types (alpha, beta and gamma), and bioactive compounds (humic substances and fullerenols). Luminescence intensity is taken as a physiological parameter of luminous organisms. High rates of luminescence response can provide (1) a proper number of experiments under comparable conditions and, therefore, proper statistical processing, with this being highly important for ‘noisy’ low-dose exposures; (2) non-genetic, i.e. biochemical and physicochemical mechanisms of cellular response, in accordance to “exposome” concept. Bioassays based on luminous marine bacteria, their enzymes, and fluorescence coelenteramide-containing proteins were used to compare results of low-intensity exposures at cellular, biochemical and physicochemical levels, respectively. Results of the cellular exposures were discussed in terms of hormesis concept. Bioluminescence time dependence under low-dose radiation exposures corresponded to hormesis or threshold models; no bioluminescence monotonic dependency on intensity of exposure (dose rate, radioactivity, concentration) was found. Bioluminescence activation and absence of its dependency on intensity of exposure can be accepted as features of cellular adaptive response. Changes of biological luminescence were analyzed and discussed for bioassays of lower organization level – enzymes and florescent protein.

One of the research priorities in atmospheric chemistry is to advance our understanding of heterogeneous reactions and their effect on the composition of the troposphere. Chemistry on aqueous surfaces is particularly important in this regard because of their ubiquity and expanse. They range from the surfaces of oceans (360 million km²), cloud and aerosol drops (~10 trillion km²) to the fluids lining the human lung (~200 m²). Typically, ambient air contains reactive gases that may affect human health, influence climate and participate in biogeochemical cycles. Despite their importance, reactions between gases and solutes at air-aqueous interfaces are not well understood. New, surface-specific techniques are required that detect and identify the intermediates and products of such reactions as they happen on liquids. This is a tall order because genuine interfacial reactions are faster than mass diffusion into bulk liquids, and may produce novel species at low concentrations. Herein, we review evidence that validates online pneumatic ionization mass spectrometry of liquid microjets dosed by reactive gases as a technique meeting such requirements. Next, we call attention to results obtained by this approach on reactions of ozone, nitrogen dioxide and hydroxyl radicals with various solutes on aqueous surfaces. The overarching conclusion is that the outermost layers of aqueous solutions are unique media, where equilibria shift and reactions proceed faster than, in some cases along different pathways from the bulk liquids. The fact that the rates and mechanisms of reactions at air-aqueous interfaces may not be deduced from experiments in bulk liquids opens new conceptual frameworks and lines of research, and adds an overlooked dimension to atmospheric chemistry.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives gave significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This means an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Background: Few studies examined the contributions of childhood adversities, intimate partner violence and social support to antenatal depression (AD). This study aims to 1) evaluate association of these psychosocial factors with AD symptoms in early pregnancy; and 2) examine the mediating effect of social support on the relationship between psychosocial stressors and AD symptoms.Methods: Participants were 120 pregnant women aged from 18 to 49 in less than 16 gestational weeks and attending at Antenatal Care Center at Khon Kaen hospital, Thailand. AD symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS). Childhood adversities, intimate partner violence and social support were measured using the Adverse Childhood Experiences Questionnaire (ACE questionnaire), Abuse Assessment Screen (AAS), and Multidimensional Scale of Perceived Social Support (MSPSS). Results: We found that the EPDS score was significantly and positively associated with adverse childhood experiences (ACEs) and negatively with social support. Partial Least Square analysis showed that 49.1% of the variance in the depressive subdomain of the EPDS score was predicted by ACEs, namely psychological and physical abuse and neglect, emotional or physical abuse by the partner, unplanned pregnancy, and no satisfaction with their relationship. The effects of adverse childhood experience due to neglect on the EDPS score was mediated by social support by friends. Limitations: ACEs were assessed retrospectively and, therefore, may be susceptible to recall bias.Conclusion: Prenatal depression scores are to a large extent predicted by psychological distress as indicated by early lifetime trauma, abuse by partner, relation satisfaction, and implications of unintended pregnancy.

The ionic Diels-Alder (I-DA) reactions of a series of six iminium cations with cyclopentadiene have been studied within the Molecular Electron Density Theory (MEDT). The superelectrophilic character of iminium cations,  > 8.20 eV, accounts for the high reactivity of these species participating in I-DA reactions. The activation energies are found between 13 and 20 kcal·mol-1 lower in energy than those associated to the corresponding Diels-Alder (DA) reactions of neutral imines. These reactions are low endo selective as a consequence of the cationic character of the TSs, but highly regioselective. Solvents have poor effects on the relative energies, and an unappreciable effect in the geometries. In dichloromethane the activation energies increase slightly as a consequence of the better solvation of the iminium cations than the cationic TSs. ELF topological analysis of the bonding changes along the I-DA reactions shows that they are very similar to those in polar DA reactions. The present MEDT study makes it possible establishing that the global electron density transfer (GEDT) taking place at the TSs of I-DA reactions, and not steric (Pauli) repulsions such as have been recently proposed, are responsible for the features of these type of DA reactions.

Underpinned by the new world Kirkpatrick model and in the context of a community-based, sport psychology program (My Strengths Training for Life™) for young people experiencing homelessness, this process evaluation investigated: (1) young peoples’ reactions (program and facilitator evaluation, enjoyment, attendance, and engagement) to and learning (mental skills and transfer intention), (2) the relationship between reaction and learning variables, and (3) the mediators underpinning this relationship. 301 young people living in a West Midlands housing service completed questionnaires on demographics, reaction and learning variables. Higher levels of program engagement were positively associated with more favorable reactions to the program. Enjoyment positively predicted learning outcomes, which was mediated by transfer intention. Recommendations are made for: (1) a balance between rigor and flexibility for evaluation methods with disadvantaged youth, (2) including engagement as well as attendance for indicators of meaningful program participation, (3) measuring program experiences (e.g., enjoyment) to understand program effectiveness, and (4) providing opportunities for skill transfer during and after program participation. Findings have implications for researchers, program commissioners, and policy makers working designing and evaluating programs in community-based settings.

Objectives: The aim of this study was to assess the knowledge, attitude and practice of healthcare professionals regarding adverse drug reaction [ADR] monitoring and pharmacovigilance [PV] in India. Materials and Methods: It was a questionnaire based cross sectional observational study. Data was collected with the help of data collection Google form that included the demographics and twenty two survey based questions. Data were analysed by using Microsoft Excel sheet, further analysed for results, including frequency, percentage, mean and standard deviation. Result: The questionnaire was filled by two hundred ten healthcare professionals in which 52.9 % were male and 47.10% of female. Most of the respondents were pharm d students (50.47%). Out of the total 91.4% responded to the definition of pharmacovigilance correctly. 87.6% participants said all ADR should be reported. 86.20% participants think Pharmacovigilance should be taught in detail to healthcare professionals. Most of the respondents (43.8%) always informed the patients about ADR while prescribing the medicines. Conclusion: Study revealed most of the participants have good knowledge about ADR and pharmacovigilance. Difficult to decide whether ADR occur or not and extra work load being major factors responsible for under reporting.

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798, had shown the highest level of evidence about their association with FPs response. The EMA and FDA-approved drug labels for FPs, recommend genotyping these variants before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still find patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the association with the response to FPs of DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595; as explanatory candidates of the interindividual differences for the FP-related toxicities. We also studied the impact of DPYD*2A, *13, *HapB3, and rs67376798 genotype for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found that FP dose lowering based on DPYD genotype does not affect the treatment efficacy. Also, the DPYD*4 (defined by rs1801158) allele was associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R.= 5.66; 95% C.I.= 1.35 – 23.67; p= 0.014) and multivariate analyses (O.R.= 5.73; 95% C.I.= 1.41 – 28.77; p= 0.019). This makes it a candidate variant for implementation in clinical practice.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

Adverse childhood experiences are known to program children for disrupted biological cycles, premature aging, microbiome dysbiosis, immune-inflammatory misregulation, and chronic disease multimorbidity. To date, the microbiome has not been a major focus of deprogramming efforts despite its emerging role in every aspect of ACE-related dysbiosis and dysfunction. This article examines: 1) the utility of incorporating microorganism-based, anti-aging approaches to combat ACE-programmed chronic diseases (also known as noncommunicable diseases and conditions, NCDs) and 2) microbiome regulation of core systems biology cycles that affect NCD comorbid risk. In this review microbiota influence over three key cyclic rhythms (circadian cycles, the sleep cycle, and the lifespan/longevity cycle) as well as tissue inflammation and oxidative stress are discussed as an opportunity to deprogram ACE-driven chronic disorders. Microbiota, particularly those in the gut, have been shown to affect host-microbe interactions regulating the circadian clock, sleep quality, as well as immune function/senescence and regulation of tissue inflammation. The microimmunosome is one of several systems biology targets of gut microbiota regulation. Furthermore, correcting misregulated inflammation and increased oxidative stress is key to protecting telomere length and lifespan/longevity and extending what has become known as the healthspan. This review article concludes that to reverse the tragedy of ACE-programmed NCDs and premature aging, managing the human holobiont microbiome should become a routine part of healthcare and preventative medicine across the life course.

In the last decade and a half, the world has experienced the outbreak of a range of viruses such as COVID-19, H1N1, flu, Ebola, Zika Virus, Middle East Respiratory Syndrome (MERS), Measles, and West Nile Virus, just to name a few. During these virus outbreaks, the usage and effectiveness of social media platforms increased significantly as such platforms served as virtual communities, enabling their users to share and exchange information, news, perspectives, opinions, ideas, and comments related to the outbreaks. Analysis of this Big Data of conversations related to virus outbreaks using concepts of Natural Language Processing such as Topic Modeling has attracted the attention of researchers from different disciplines such as Healthcare, Epidemiology, Data Science, Medicine, and Computer Science. The recent outbreak of the MPox virus has resulted in a tremendous increase in the usage of Twitter. Prior works in this field have primarily focused on the sentiment analysis and content analysis of these Tweets, and the few works that have focused on topic modeling have multiple limitations. This paper aims to address this research gap and makes two scientific contributions to this field. First, it presents the results of performing Topic Modeling on 601,432 Tweets about the 2022 Mpox outbreak, which were posted on Twitter between May 7, 2022, and March 3, 2023. The results indicate that the conversations on Twitter related to Mpox during this time range may be broadly categorized into four distinct themes - Views and Perspectives about MPox, Updates on Cases and Investigations about Mpox, MPox and the LGBTQIA+ Community, and MPox and COVID-19. Second, the paper presents the findings from the analysis of these Tweets. The results show that the theme that was most popular on Twitter (in terms of the number of Tweets posted) during this time range was - Views and Perspectives about MPox. It is followed by the theme of MPox and the LGBTQIA+ Community, which is followed by the themes of MPox and COVID-19 and Updates on Cases and Investigations about Mpox, respectively. Finally, a comparison with prior works in this field is also presented to highlight the novelty and significance of this research work.

Sequential reactions of aminoalkynes represent a powerful tool to easily assembly biologically important polyfunctionalized nitrogen heterocyclic scaffolds. Metal catalysis often plays a key role in terms of selectivity, efficiency, atom economy and green chemistry of these sequential approaches. This review examines the existing literature on the applications of reactions of aminoalkynes with carbonyls which are emerging for their synthetic potential. Aspect concerning the features of the starting reagents, the catalytic systems, alternative reaction conditions and the pathways as well as the possible intermediates are provided.

Background: The aim of the study is to present the process of monitoring the changes in the effi-ciency of equilibrium reactions in the children with postural disorders, in the course of the thera-peutic process. Methods: The shape of spine and the efficiency of equilibrium reactions in standing posture and during gait were assessed in all the subjects. The subjects were put in 2 groups: with the shape of spine disorder and without one. The recommended set of therapeutic activities in home conditions lasted about 20 minutes and was performed by the child with parent’s supervision. The therapeutic program was based on elements of the PNF and Vojta methods. The following parameters were measured: maximum movement of the center of presure (CoP) in the frontal plane during gate, maximum movement of the CoP in the sagittal plane, movement of the CoP in the frontal plane in static conditions, movement of the CoP in the sagittal plane in static conditions. Results: Six statistically significant differences were recorded, all of them were related to measurement I. The Friedman test result was statistically significant for all the indexes. Post-hoc analyzes were performed using the Dunn-Bonferroni test. Conclusions: 1. The children with shape of spine disorders are featured by lower efficiency of equivalent reactions in relation to the children without disorders. 2. The therapy with the application of neurophysiological methods in the treatment of shape of spine disorders improves equilibrium reactions in these patients. 3. Long-lasting and thorough observations of the therapeutic process in the children with shape of spine disorders should include the monitoring of the efficiency of equilibrium reactions

The intramolecular ionic Diel-Alder (IIDA) reactions of two dieniminiums have been studied within the Molecular Electron Density Theory (MEDT) at the B97XD/6-311G(d,p) computational level. ELF topological analysis of dieniminiums shows that its electronic structure can been seen as the sum of those of butadiene and ethaniminium. The superelectrophilic character of dieniminiums accounts for the high intramolecular global electron density transfer taking place between the diene and iminium frameworks at the transition state structures (TSs) of these IIDA reactions. The activation enthalpy associated to the IIDA reaction of the experimental dieniminium, 8.7 kcal·mol-1, is closer to that of the ionic Diels-Alder (I-DA) reaction between butadiene and ethaniminium, 9.3 kcal·mol-1. However, the activation Gibbs free energy of the IIDA reaction is 12.7 kcal·mol-1 lower than that of the intermolecular I-DA reaction. The strong exergonic character of the IIDA reaction, higher than 17 kcal·mol-1, makes the reaction irreversible. These IIDA reactions present a total re/exo and si/endo diastereoselectivity, which is controlled by the most favourable chair conformation of the tetramethylene chain. Electron localization function (ELF) topological analysis of the single bond formation indicates that these IIDA reactions take place through a non-concerted two-stage one-step mechanism. Finally, ELF and atoms-in-molecules (AIM) topological analyses of the TS associated to inter and intramolecular processes show the great similitude among them.

The etiology of ‘dual harm’ (the co-occurrence of self-harm and externalized violence in the same individual) is under-researched. Risk factors have mostly been investigated for each behavior separately. We aimed to examine adversities experienced between birth and age 15 years among adolescents and young adults with histories of self-harm and violent criminality, with a specific focus on dual harm. Three nested case-control studies were delineated using national interlinked Danish registers; 58,409 cases in total aged 15-35 were identified: 28,956 with a history of violent criminality (but not self-harm), 25,826 with a history of self-harm (but not violent criminality), and 3987 with dual harm history. Each case was matched by date of birth and gender to 20 controls who had not engaged in either behavior. We estimated exposure prevalence for cases vs. controls for each of the three behavior groups, and incidence rate ratios (IRRs). Experiencing 5 or more childhood adversities was more prevalent among individuals with dual harm history (19.3%; 95% CI 18.0, 20.8%) versus self-harm (10.9%; 10.5, 11.3%) and violence (11.4%; 11.0%, 11.8%) histories. The highest IRRs for dual harm were linked with parental unemployment (5.15; 95% CI 4.71, 5.64), parental hospitalization following self-harm (4.91; 4.40, 5.48) or assault (5.90; 5.07, 6.86), and parental violent criminality (6.11; 5.57, 6.70). Growing up in environments that are characterized by poverty, violence and substance misuse, and experiencing multiple adversities in childhood, appear to be especially strongly linked with elevated dual harm risk. These novel findings indicate potential etiologic pathways to dual harm.

This study was conducted to recover valuable metals (silicon and silver) using acid leaching and substitution reactions with copper powder from the pulverized solar cell separated from the PV ribbon. Leaching experiments were conducted according to nitric acid concentration by molar solution as 1M, 2M, and 3M using an ultrasonic cleaner at a reaction temperature of 60 °C for the leaching times of 30 to 120 minutes. Si phases were detected at all leaching reaction times, it was confirmed that the aluminium was removed effectively if the nitric acid leaching time was more than 30 minutes, and silicon with a purity above 99% could be recovered. The silver was precipitated by adding copper, which has greater reducibility than Cu, Al, Si, Pb, and Sn. When the addition of copper powder was 0.75 and 1.0 g, precipitate was produced 0.23 and 0.55 g, respectively. The optimal condition for the recovery of silver by the addition of copper powder was 1 g, where is recovery rate reached 93.3%.

The control of stereo-, regio-, and chemo-selectivity in transition-metal-catalyzed coupling reactions is a key topic in organic synthesis. Several methods for controlling selectivity have been reported thus far. On the other hand, the reduction of the catalyst loading in the reaction is one of the most important issues in organic synthesis from the standpoint of green sustainable chemistry. As another advantage of reducing the catalyst loading, the expression of the reaction selectivity and the substituent effect caused by the reduction of the catalyst loading to the parts-par-million (ppm) level in various catalytic reactions is presented herein.

The 32CA reactions of a series of pairs of bent three-atom-components (B-TACs) and linear TACs (L-TACs) towards electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory in order to understand their different reactivity. ELF analysis indicates that while pseudodiradical B-TACs change their electronic structure to pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs experience no remarkable change. Analysis of the CDFT indices indicates that five of the nine studied TACs have a strong nucleophilic character, thus participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions of the nine TACs towards electrophilic DCE range from 0.6 to 22.0 kcal·mol-1, which are by between 2.0 and 10.1 kcal·mol-1 lower than those involved in the non-polar 32CA reactions with ethylene. In general, B-TACs are more reactive than their L-TAC counterparts. A change of the regioselectivity is found in these polar 32CA reactions; in general, while B-TACs are meta regioselective, L-TACs are ortho regioselective. Analysis of the geometrical parameters indicates that at all TSs, the formation of the single bond involving the most electrophilic C4 carbon of DCE is more advanced than that involving the C5 one. A change of the asynchronicity in the reactions involving B-TACs and L-TACs is also found.

Homogeneous and heterogeneous chemical reactions in partially ionized magneto-nano-liquid are investigated theoretically using finite element method (FEM). The effects of ions and electrons collisions on the transport of heat and mass are analyzed for both the cases of heterogeneous and homogeneous chemical reactions. The simultaneous effects of dispersion of nanosized particles in partially ionized nano-liquid in the presence of magnetic field are also investigated. Through numerical experiments, it is noted that the temperature of partially ionized nano-liquid increases when electrons collision rate and ion collisions are increased. The transport rate of reacting species decreases when heterogeneous and homogeneous chemical reactions strengths are increased. It is also observed that the effect of electron collisions on the flow in y-direction is the same to that of ion collisions on the flow in y-direction. Homogeneous and heterogeneous chemical reactions have similar effects on concentration of chemically reacting species in qualitative sense. However, in quantitative sense, homogeneous chemical reaction has more significant effect on the concentration reacting species as compared to heterogeneous chemical reaction.

Bioconvective flows have attracted attention in recent years due to actual and potential applications. In this paper, we consider a steady and laminar convective MHD flow of a nanofluid with heat, mass and microorganism transfer with a heat source/sink present. In addition, we assume there exists a first order chemical reaction. The governing partial differential equations (PDEs) are reduced to ordinary differential equations (ODEs) using the scaling group transformation and the associated boundary value problem is then solved. The influences of selected governing parameters on the dimensionless velocity, temperature, nanoparticle concentration, density of motile microorganisms, skin friction, heat transfer, mass transfer, and motile microorganism density rates are computed and discussed

The role of initial state (ISI) and final state (FSI) ion–ion interactions in heavy ion double charge exchange (DCE) reactions A(Z,N)→A(Z±2,N∓2) are studied in the context of double single charge exchange (DSCE) reactions given by sequential actions of the isovector nucleon–nucleon (NN) T–matrix. The second order DSCE reaction amplitude is investigated in momentum representation in a formulation, focused on the extraction of nuclear matrix elements under the conditions of strong initial state (ISI) and final state (FSI) interactions. In closure approximation and using the momentum representation, the reaction amplitude is finally separated into ISI/FSI distortion coefficients and reaction kernels and nuclear matrix elements. The ISI/FSI reaction kernels emerge as the result of the repeated scattering on the avoided volume, introduced by the imaginary parts of the ion–ion optical potential and acting as sinks for the quantal probability current. The closure approximation allows derive a set of induced effective two–body isotensor interactions, given by products of spin–scalar, spin–vector central and rank–2 spin–tensor interactions. The intermediate propagator plays a key role in establishing correlation between the DCE transitions in the projectile and target nucleus. The presented approach emphasizes the special features of DSCE reaction dynamics as proceeding like a system of two coupled isospin dipoles whose strengths are determined by the momentum-space form factors of the NN isovector interaction. The properties of the DSCE interaction form factors are investigated and the approach is applied to data.

The COVID-19 pandemic caused many enduring changes in everyday life of families with negative effects on parents’ and children well-being. However, literature lacks of studies exploring emotional reactions and coping strategies of both mothers and children of different ages. Furthermore, most studies used only self-reports. This study aimed to identify the emotions and coping strategies of children, adolescents and their mothers and to verify the association between maternal and children well-being. A mixed-method design using interviews and questionnaires was applied to collect information on well-being (emotional reactions, behavioral/emotional problems) and coping strategies of both mothers (n=65), and their children (n=35, 8-10 year; n=30, 11-13 year) during the second wave of the pandemic (December 2020). No differences between the groups emerged concerning the emotional reactions reported. In contrast, mothers and children of different ages reported different self-regulation and other-regulation strategies. Moreover, maternal strategies had different effects on children well-being. The integration of qualitative and quantitative results was informative to understand how families adapted to the radical changes of everyday life caused by the pandemic. Implications for developing interventions in such similar stressful situations to promote family well-being are discussed.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

: Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is limited. Therefore, we used the Japanese Adverse Drug Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency (PMDA) to analyze the risk factors associated with glaucoma and the trends and characteristics of corticosteroid-induced glaucoma. We did not find sex or age differences associated with the onset of glaucoma. Hierarchical clustering and principal component analysis revealed that triamcinolone acetonide and betamethasone sodium phosphate, which are used around the eyes in Japan, are more likely to induce intraocular pressure (IOP) elevation compared with other corticosteroids. Increased IOP is a direct cause of glaucoma. Based on these findings, it may be necessary to limit or avoid the use of these corticosteroids.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires comprehensively address the adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable for assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their well-being is affected and to identify children at risk.

The immunization of healthcare workers in the early stages of the rollout of COVID-19 vaccines was prioritized in order to ensure uninterrupted medical care provision. At the same time the increasing number of available COVID-19 vaccines may trigger hesitancy towards the decision to get vaccinated. Thus, accumulating reliable information on the adverse events following immunization may educate and urge the general population to receive a COVID-19 vaccine. The present study aimed to evaluate the adverse events (AEs) following immunization with any of the available COVID-19 vaccine among Bulgarian healthcare workers (HCWs). A cross-sectional study among HCWs in Plovdiv, Bulgaria was conducted in the period March – September 2021. Through a semi-structured online questionnaire, the participants reported the adverse events following the administration of the first and second dose of a COVID-19 vaccine. A total of 253 respondents, vaccinated with one of the available vaccines against COVID-19 took part in the study. Of them 71.9% were females, and 75.9% received mRNA-based vaccines, while 24.1% received a viral-vector based vaccine. Overall 91.6% and 82.6% of all participants reported at least one local AE after the first and second dose of a COVID-19 vaccine. The share of respondents reporting at least one systemic AE after the first and second dose of a COVID-19 vaccine was 59.7% and 62.4% respectively. The most common local AE was pain at the injection spot (84.0%), while the most common systemic AEs were fatigue (54.9%), chills (43.2%), and headache (41.7%). The mRNA-based vaccines versions seem to cause higher prevalence of local AEs, while the vector-based vaccines were linked with increased prevalence of systemic AEs. Female HCWs and the younger age group were associated with an increased risk of adverse events generally. Our results added more evidence that mRNA-based and viral-vector based vaccines are generally safe. The reported adverse events were mild, although they occurred in a high share of the respondents. No serious AEs attributable to the vaccines were reported.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI &lt; 18.5 kg/m2. This study was based on observational routinely-collected data from a University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥ 12.5 kg and &lt; 12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 135 participants with a median age of 28±8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.2±45.4 vs 42.6±48.8 %; P&lt;0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (28.1% vs 11.3%; P=0.017). Our study also showed increased risks of premature rupture of membranes, anaemia and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Adverse Outcome Pathways (AOP) provide structured frameworks for systematic organization of research data and knowledge. The AOP framework follows a set of key principles that allow for broad application across diverse disciplines related to human health, including toxicology, pharmacology, virology and medical research. The COVID-19 pandemic engages a great number of scientists world-wide and data is increasing with exponential speed. Diligent data management strategies are employed but approaches for systematically organizing the data-derived information and knowledge are lacking. We believe AOPs can play an important role in improving interpretation and efficient application of scientific understanding of COVID-19. Here, we outline a newly initiated effort to streamline collaboration between scientists across the world towards development of AOPs for COVID-19, and describe the overarching aims of the effort, as well as the expected outcomes and research support that they will provide.

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from October 27, 2022, to January 19, 2023, the research examines AEs in 441 out of 1711 second booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings reveal incidence rates (IR) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster 5 times more likely to report them again (Incidence rat rato, 5.02, P&lt;0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. The study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

The impact of early maternal age on several outcomes (e.g. mental health issues, delinquency, aggression, impulsivity, victimization and interpersonal difficulties) has been studied since the late 1980s. Research has demonstrated links between exposure to adverse childhood experiences (ACEs) and trauma related outcomes such as substance abuse, interpersonal and self-directed violence, and sexual risk-taking, to name a few. The current study analyzed the incidence of ACE exposure and mental health outcomes (e.g. suicidal behaviors or self-harm, psychiatric hospitalizations, and substance use) as related to early maternal age in youth known to have experienced trafficking or sexual abuse. General demographics and incidence of various experiences and clinical presentations (e.g. ACE exposure, age of mother at birth of youth and age at first birth), and history of self-harm, substance use and psychiatric hospitalization were examined in a sample of 225 youth referred for services subsequent to experiences of sex trafficking or exploitation. Relationships between ACE exposure and maternal age related to mental health outcomes was also examined. Trafficked and exploited youth reported rates of ACE exposure and poor mental health outcomes at far greater rates than the general population. Significant findings were related to early maternal age and engaging in self-harm or suicidal behaviors. Previously anticipated mediational analyses were not conducted due to the sample size and lack of correlations. Findings highlight the significant ACE exposure and high needs of exploited, trafficked and abused youth and related mental health outcomes, emphasizing the need for early and comprehensive preventive and therapeutic interventions.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display an off-target distribution in tissues that are terminally differentiated, triggering autoimmune reactions. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesizes non-self antigens becomes inevitably the target of the immune system, and since the human body is not a strictly compartmentalized system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities on the critical need of bio-distribution studies for the genetic vaccines against COVID-19, as well as of rational harm-benefit assessments by age group.

Multicomponent reactions (MCR) have been used to synthesis a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in discovery of drug . The understanding of structure-activity correlations that drive the development of new goods and technology, requires structural variety in these libraries. In current world, antibiotic resistance is a major ongoing problem which is developing a problematic scenario in public health. The implementation of isocyanide based multicomponent reactions uphold a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and fight against such concerns. This study discusses recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs in the near future.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.