Control of drinking water disinfection byproducts with a novel bromide-selective anion exchange resin: Design, mechanism, and performance.

In regions where drinking water sources containing elevated bromide levels, the formation of brominated disinfection byproducts (Br-DBPs) is enhanced, which may increase risks of cancer and birth defects. Anion exchange resin (AER) adsorption is a promising approach for reducing precursors of Br-DBPs (e.g., bromide and natural organic matter) due to its strong electrostatic force for reversible ion exchange process. However, high bromide water sources typically have high salinities, and the presence of co-existing ions (e.g., sulfate, nitrate, chloride) can significantly diminish the efficiency of conventional AERs, which use polyacrylic or polystyrene skeletons with trimethyl-ammonium functional groups. This study designed a novel AER with the polystyrene skeleton and tripentyl-ammonium functional group for the selective bromide removal, which resisted interferences from co-existing ions based on ion dehydration and ion-pairing electrostatic interactions. Column experiments with continuous high-bromide water flows demonstrated that the novel AER exhibited up to three times the operating capacity of conventional AERs, achieving reductions of 71.2 %, 44.6 %, and 67.7 % in bromide, dissolved organic carbon, and specific UV absorbance, respectively. Competitive experiments showed that the novel AER's strong sulfate interference resistance enhanced its bromide selectivity. The electrostatic interactions between AER fragments and bromide or sulfate particles were quantitatively evaluated using density functional theory calculations. Treatment with the novel AER led to reductions in total organic bromine, aliphatic Br-DBPs, and cyclic Br-DBPs by 76.7 %, 62.5 %, and 90.5 %, respectively. Notably, cytotoxicity assays using Chinese hamster ovary cells indicated a 39.7 % decrease in overall cytotoxicity of chlorinated drinking water following treatment with the novel AER.

Ecotoxicity of bromate and human health risks resulting from wastewater treatment units' effluents associated with some key physicochemical parameters in two hotspots connected to the Egyptian Mediterranean Sea.

This study is the first of its kind in terms of focusing on the seasonal monitoring of bromine species (bromide- and bromate) and some of the main physicochemical parameters in the surface water of stations inside and in front of the El Noubareya and El-Umum drains that flow directly or indirectly to the Egyptian Mediterranean coast at A (El Noubareya Drain) and B (El-Mex Bay) sites. Among the bromine species, bromate (BrO3-) is a disinfection byproduct considered by many international agencies to have a potential carcinogenic effect in humans and is also known to be ecologically toxic to aquatic organisms. Drain water samples collected from the studied sites A and B had a bromide/chlorinity ratio (3.85E-03 - 6.25E-03 and 3.27E-03 - 6.97E-03, respectively) significantly higher than the typical value for open seawater (3.50E-03), showing significant dilution with wastewater at drain stations in the investigated sites. The source and origin of bromine species and the major ions studied associated with the wastewater units were identified and tracked by calculating the ion/chlorinity ratio and multivariate analysis. The total hazard quotient (THQ) for bromate intake and dermal exposure in children, females, and males demonstrates negligible harm to human health. The toxic unit (TU) and the sum of toxic units (STU) values of the three trophic levels in the surface water for the two sites under investigation yielded approximately comparable values for risk quotient (RQ) and mixture risk characterization ratios (RCRmix(MEC/PNEC)), indicating that invertebrates are more sensitive to bromate dangers than fish and algae. The study highlights the importance of conducting large-scale laboratory tests on the effluents resulting from wastewater treatment units, including bromide levels, to prevent the formation of dangerous side compounds such as bromate, which may have negative effects on populations and may lead to the toxicity of trophic levels in ecosystems.

Evaluating Vacuum and Steam Heat to Eliminate Pinewood Nematodes in Naturally Infested Whole Pine Logs.

Pinewood nematodes threaten forest health and continue to interfere with international trade because they can be spread around the globe via nematode-infested wood. International Standards for Phytosanitary Measure (ISPM-15) requires that all pine wood be treated at 56°C for 30 min to ensure that all pests and pathogens are killed within sawn wood, whereas fumigation with methyl bromide is the currently approved practice and widely used in treating whole logs. A method of treatment that uses less energy and time or does not rely on environmentally damaging gases is urgently needed. Because vacuum with steam has shown promise in treating several different commodities, the purpose of this study was to use it to eradicate pinewood nematodes in whole logs. Three protocols were applied: 1) 48°C for 15 min., 2) 56°C for 30 min., and 3) 60°C for 60 min. The third protocol reduced the population to statistically zero; however, some samples contained at least 1 survivor. Unfortunately, these surviving nematodes increased in number one month after treatment, and one year later, they continued to reproduce in the wood. Therefore, this protocol needs to be further refined to remove pinewood nematodes completely. Explanation of the survival of individual nematodes within whole logs remains a matter for conjecture: 1) certain portions of the wood were somehow insulated from the heat and did not achieve the lethal temperature, and 2) survival stages may be able to survive temperatures that are deadly to the normal life stages.

Active-bromide and surfactant synergy for enhanced microfouling control.

Biofilms are structured microbial communities encased in a matrix of self-produced extracellular polymeric substance (EPS) and pose significant challenges in various industrial cooling systems. A nuclear power plant uses a biocide active-bromide for control of biological growth in its condenser cooling system. This study is aimed at evaluating the anti-bacterial and anti-biofilm efficacy of active-bromide against planktonic and biofilm-forming bacteria that are commonly encountered in seawater cooling systems. The results demonstrated that active-bromide at the concentration used at the power plant (1 ppm) exhibited minimal killing activity against Pseudomonas aeruginosa planktonic cells. The bacterial cell surface hydrophobicity assay using Staphylococcus aureus and P. aeruginosa indicated that Triton-X 100 significantly decreased the hydrophobicity of planktonic cells, enhancing the susceptibility of the cells to active-bromide. Biofilm inhibition assays revealed limited efficacy of active-bromide at 1 ppm concentration, but significant inhibition at 5 ppm and 10 ppm. However, the addition of a surfactant, Triton-X 100, in combination with 1 ppm active-bromide displayed a synergistic effect, leading to significant biofilm dispersal of pre-formed P. aeruginosa biofilms. This observation was substantiated by epifluorescence microscopy using a live/dead bacterial assay that showed the combination treatment resulted in extensive cell death within the biofilm, as indicated by a marked increase in red fluorescence, compared to treatments with either agent alone. These findings suggest that active bromide alone may be insufficient for microfouling control in the seawater-based condenser cooling system of the power plant. Including a biocompatible surfactant that disrupts established biofilms (microfouling) can significantly improve the efficacy of active bromide treatment.

Effect of bromide on the degradation kinetics of antibiotic resistance genes during water chlorination.

Degradation of antibiotic resistance genes (ARGs) in water chlorination can be influenced by bromide (Br-), a common component in water matrices; however, detailed kinetic information on this process is limited. This study investigated the degradation kinetics tetA and blaTEM-1 genes, contained within the plasmid pWH1266, when exposed to bromine, chlorine, and chlorine with varying concentrations of Br- across a pH range of 7.0-8.5. The degradation of four ARG amplicons, measured using quantitative polymerase chain reaction, was observed to pursue second-order kinetics with bromine, exhibiting k of 4.0 × 102 - 1.6 × 103 M-1 s-1 at pH 7.0 and 2.6 × 102 - 9.6 × 102 M-1 s-1 at pH 8.5. These k values increased linearly with the length of the ARG sequences (209-1136 bps), yielding sequence-independent k of 1.2 and 7.4 × 10-1 (M AT + GC)-1 s-1 at pH 7.0 and 8.5, respectively. The degradation rate of ARGs during chlorination increased with rising Br- concentration due to the bromine formation through the reaction between chlorine with Br-, which subsequently degrades ARGs more rapidly than chlorine. This behavior was successfully simulated using a kinetic model derived from the reaction kinetics of bromine and chlorine reactions with ARGs. The existence of dissolved organic matter extracts only marginally decreased the enhanced degradation of ARGs with Br-, while ammonia significantly inhibited this process during chlorination, both with and without Br-, due to the low reactivity of NH2Cl and NH2Br toward ARGs. These findings highlight the importance of Br- in ARG degradation during water chlorination and the need for further studies in diverse water matrices.

Insight into didecyl dimethyl ammonium bromide toxicity following acute exposure in pullets (Gallus gallusdomesticus).

Didecyl dimethyl ammonium bromide (DDAB) is a quaternary ammonium compound used for the sanitation of drinking water of poultry and water pipelines in farms. There is scarcity of information on the toxicology of DDAB in poultry. This study set out to profile the acute toxicity of DDAB in poultry. Issa brown pullets (n = 34) as experimental birds were orally administered varying doses of DDAB, using a syringe, after 12 h fasting, and observed for toxicity over 14 days. Control birds (n = 10) were similarly given normal saline orally. Toxic signs in the experimental birds were depression, anorexia, adipsia, vocalization with foamy salivation, later emaciation and death. The LD50 was calculated as 458.00 mg/kg. Birds given 2151 mg/kg DDAB died within 24 h, while those treated with 516 mg/kg succumbed on Day 14. At necropsy, grossly, there were necrosis and sloughing of the oesophagus and intestines, pale and friable liver, congested and necrotic lungs, friable popped out kidneys and emaciated carcasses. Microscopically, desquamation and necrosis of the oesophagus, crop, proventriculus and intestines and disruption of the koilin membrane of the gizzard were observed. The lungs, liver and kidneys were congested with mononuclear cellular infiltration plus loss of architecture in the lungs and liver. In conclusion, at high doses, DDAB caused significant toxicity in chickens and these findings provide new information which could serve as a guide in the diagnosis of quaternary ammonium toxicity in chicken. The results could be extrapolated to other quaternary ammonium toxicities in related avian species.

Blue Light-Emitting Diodes Based on Pure Bromide Perovskites.

Blue perovskite light-emitting diodes (LEDs) are essential for the creation of full-color displays and white-light illumination, and some significant progress is made in recent years. However, most high-performance blue perovskite LEDs are currently based on mixed-halide perovskites and suffer from unstable spectra due to inevitable halide phase segregation, which is unfavorable for the application of blue perovskite LEDs. In contrast, blue emissions from pure bromide perovskites generally exhibit stable spectra (consistent emission peak positions and spectral shapes) and are worthy of attention. In this review, the recent advances in blue LEDs based on pure bromide perovskites according to different strategies are classified and summarized. Moreover, the challenges related to poor charge injection, high defect-state density, lack of high-performance in the deeper blue region, and inferior operational stability are addressed. Finally, an outlook is provided on feasible future research directions for highly bright, efficient, and stable blue perovskite LEDs.

Occurrence, toxicity, and control of halogenated aliphatic and phenolic disinfection byproducts in the chlorinated and chloraminated desalinated water.

Seawater desalination is widely used to overcome the freshwater shortage worldwide. However, even after three-stage reverse osmosis treatment, the desalinated water still contained 14.6 µg/L of aliphatic disinfection byproducts (DBPs), 384.2 ng/L of bromophenolic DBPs, 3.5 ng/L of iodophenolic DBPs, 1024.7 µg/L of Br-, 2.8 µg/L of I-, and 2.4 mg C/L of dissolved organic carbon (DOC). After the desalinated water was disinfected with chlor(am)ine, the concentrations of halogenated aliphatic and phenolic DBPs further increased, and bromophenolic DBPs were the toxicity forcing agents. When surface water was mixed with desalinated water and then chlorinated, the yield of aliphatic and phenolic DBPs significantly elevated. Separately chlorinating desalinated water and surface water before mixing could mitigate this adverse situation. Chloramine disinfection was more conducive to reducing the total calculated toxicity of disinfected desalinated waters and mixed waters compared to chlorine disinfection. The treatment of desalinated water with granular activated carbon could effectively remove DOC and UV254, leading to a reduction in the content of total organic halogen after chlor(am)ination. Although anion exchange resin could adsorb Br-, it also released the organic precursors of DBPs, ultimately increasing the yield of DBPs. The results of this study can provide a reference for the seawater desalination industry to improve seawater pre-treatment and desalination processes and thus minimize the DBPs.

Anti-arthritic effect of spirocyclopiperazinium bromide DXL-A-24 in CFA-induced arthritic rats and its mechanism.

This study aimed to investigate the effect of spirocyclopiperazinium bromide DXL-A-24 on complete Freund's adjuvant (CFA)-induced arthritis and its underlying mechanism in rats. A rheumatoid arthritis model was established by the intradermal injection of CFA into the paws of rats. Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), ankle swelling and paw edema were used to evaluate the effects of DXL-A-24. Bone erosion and bone mineral density (BMD) were observed using micro-computed tomography. Receptor blocking test, western blotting, and enzyme-linked immunosorbent assay were performed to explore the mechanisms. Administration of DXL-A-24 (1, 0.5, 0.25 mg/kg, i.g.) dose-dependently increased the MWT and TWL, while alleviating ankle and paw swelling in CFA rats. The effects were blocked by peripheral α7 nicotinic or M4 muscarinic receptor antagonists. DXL-A-24 improved bone erosion and BMD, as well as downregulated the overexpression of Cav3.2, pJAK2, pSTAT3, pIκBα, pNF-κB p65, c-Fos and TNF-α proteins that were induced by CFA. In conclusion, this study shows, for the first time, that DXL-A-24 improves bone erosion and BMD and exhibits obvious anti-arthritic effects in CFA rats. The mechanism may be related to activating the peripheral α7 nicotinic and M4 muscarinic receptors, reducing Cav3.2 expression, and suppressing JAK2/STAT3 and IκBα/NF-κB p65 inflammatory signaling pathways, ultimately inhibiting inflammation-related proteins TNF-α and c-Fos.

Degradation of ambroxol by UV/chloramine process: Kinetics, degradation pathway, and control of the risk of highly toxic disinfection by-products.

Ambroxol (AMB) is a commonly used bromine-containing organic compound in medical applications and has been frequently found in water environments, which might pose risks of forming brominated disinfection by-products (Br-DBPs) in water treatment systems. The degradation kinetics as well as the degradation mechanism of AMB in the UV/chloramine process were investigated in this study. It was determined that reactive chlorine species (RCS) and the reactive nitrogen species (RNS) were the dominant free radicals for AMB degradation. Debromination occurred mainly in the initial stage of the degradation process, with a debromination rate of 34.5% at 10 min. Four possible degradation pathways of AMB were proposed based on liquid chromatography mass spectrometry (LC-MS) analysis as well as density functional theory (DFT) calculations, meanwhile the ECOSAR model was used to predict the toxicity risk of AMB and its degradation intermediates. Furthermore, after assessing the formation of DBPs during the UV/chloramine pre-oxidation process and conducting a toxicity risk analysis based on the results, it has been verified that this method can effectively remove AMB while reducing the formation potential of DBPs in the water environment. This suggests that the UV/chloramine process shows promise for treating bromine-containing organic compounds in real-world water treatment applications.

Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness.

Gulf War Illness (GWI) affects nearly 30% of veterans from the 1990-1991 Gulf War (GW) and is a multi-symptom illness with many neurological effects attributed to in-theater wartime chemical overexposures. Brain-focused studies have revealed persistent structural and functional alterations in veterans with GWI, including reduced volumes, connectivity, and signaling that correlate with poor cognitive and motor performance. GWI symptomology components have been recapitulated in rodent models as behavioral, neurochemical, and neuroinflammatory aberrations. However, preclinical structural imaging studies remain limited. This study aimed to characterize the progression of brain structural alterations over the course of 12 months in two established preclinical models of GWI. In the PB/PM model, male C57BL/6 J mice (8-9 weeks) received daily exposure to the nerve agent prophylactic pyridostigmine bromide (PB) and the pyrethroid insecticide permethrin (PM) for 10 days. In the PB/DEET/CORT/DFP model, mice received daily exposure to PB and the insect repellent DEET (days 1-14) and corticosterone (CORT; days 7-14). On day 15, mice received a single injection of the sarin surrogate diisopropylfluorophosphate (DFP). Using a Varian 7 T Bore MRI System, structural (sagittal T2-weighted) scans were performed at 6-, 9-, and 12-months post GWI exposures. Regions of interest, including total brain, ventricles, cortex, hippocampus, cerebellum, and brainstem were delineated in the open source Aedes Toolbox in MATLAB, followed by brain volumetric and cortical thickness analyses in ImageJ. Limited behavioral testing 1 month after the last MRI was also performed. The results of this study compare similarities and distinctions between these exposure paradigms and aid in the understanding of GWI pathogenesis. Major similarities among the models include relative ventricular enlargement and reductions in hippocampal volumes with age. Key differences in the PB/DEET/CORT/DFP model included reduced brainstem volumes and an early and persistent loss of total brain volume, while the PB/PM model produced reductions in cortical thickness with age. Behaviorally, at 13 months, motor function was largely preserved in both models. However, the GWI mice in the PB/DEET/CORT/DFP model exhibited an elevation in anxiety-like behavior.

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats.

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and ß-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

Halogenation of Anilines: Formation of Haloacetonitriles and Large-Molecule Disinfection Byproducts.

Aniline-related structures are common in anthropogenic chemicals, such as pharmaceuticals and pesticides. Compared with the widely studied phenolic compounds, anilines have received far less assessment of their disinfection byproduct (DBP) formation potential, even though anilines and phenols likely exhibit similar reactivities on their respective aromatic rings. In this study, a suite of 19 aniline compounds with varying N- and ring-substitutions were evaluated for their formation potentials of haloacetonitriles and trihalomethanes under free chlorination and free bromination conditions. Eight of the aniline compounds formed dichloroacetonitrile at yields above 0.50%; the highest yields were observed for 4-nitroaniline, 3-chloroaniline, and 4-(methylsulfonyl)aniline (1.6-2.3%). Free bromination generally resulted in greater haloacetonitrile yields with the highest yield observed for 2-ethylaniline (6.5%). The trihalomethane yields of anilines correlated with their haloacetonitrile yields. Product analysis of aniline chlorination by liquid chromatography-high-resolution mass spectrometry revealed several large-molecule DBPs, including chloroanilines, (chloro)hydroxyanilines, (chloro)benzoquinone imines, and ring-cleavage products. The product time profiles suggested that the reaction pathways include initial ring chlorination and hydroxylation, followed by the formation of benzoquinone imines that eventually led to ring cleavage. This work revealed the potential of aniline-related moieties in micropollutants as potent precursors to haloacetonitriles and other emerging large-molecule DBPs with the expected toxicity.

Colloidal Quasi-2D Methylammonium Lead Bromide Perovskite Nanostructures with Tunable Shape and High Chemical Stability.

Control over the lateral dimensions of colloidal nanostructures is a complex task which requires a deep understanding of the formation mechanism and reactivity in the corresponding systems. As a result, it provides a well-founded insight to the physical and chemical properties of these materials. In this work, the preparation of quasi-2D methylammonium lead bromide nanostripes and discuss the influence of some specific parameters on the morphology and stability of this material is demonstrated. The variation in the amount of the main ligand dodecylamine gives a large range of structures beginning with 3D brick-like particles at low concentrations, nanostripes at elevated and ultimately nanosheets at large concentrations. The amount of the co-ligand trioctylphosphine can alter the width of the nanostripe shape to a certain degree. The thickness can be adjusted by the amount of the second precursor methylammonium bromide. Additionally, insights are given for the suggested formation mechanism of these anisotropic structures as well as for stability against moisture at ambient conditions in comparison with differently synthesized nanosheet samples.

Skeletal muscle activity affects the deformity of long bone morphology in lathyritic chick embryo.

Embryonic muscle activity is involved in various aspects of bone morphogenesis and growth. Normal mechanical stimuli of muscle contraction are important in most cases, and when the muscles are immobilized, the developing bones are abnormally shaped. In chick embryos, a characteristic curved deformity is reproducibly induced in the developing tibiotarsus using the bone-weakening agent, beta-aminopropionitrile (bAPN). In this study, we applied decamethonium bromide (DMB), a well-established neuromuscular blocking agent, to embryos treated with bAPN, to test the hypothesis that the deformity is triggered and formed depending on the balance between the decrease in stiffness of the bAPN-affected tibiotarsus and the normal physiological increase in embryonic skeletal muscle activity. The occurrence of curved morphology induced by bAPN administered at 4 or 8 days of incubation (embryonic day [ED]) was temporally consistent with the posterior displacement of the leg muscles, which occurred just before ED8. The displaced muscles were assumed to exert a contraction force comparable to that of untreated normal muscles. When treated with DMB at ED8, the muscles atrophied and exhibited degenerative changes, and the degree of curved morphology was alleviated and reduced to 50% or more in the morphometric evaluation at ED10. These findings indicated that the coordinated development of skeletal element stiffness and muscle activity must be temporally regulated, particularly during the early stages of skeletogenesis.

Pinaverium bromide.

The structure of pinaverium bromide (systematic name: 4-[(2-bromo-4,5-di-meth-oxy-phen-yl)meth-yl]-4-{2-[2-(6,6-dimethyl-2-bi-cyclo-[3.1.1]hepta-nyl)eth-oxy]eth-yl}morpholin-4-ium bromide; C26H41Br2NO4), was determined at 110 K. It has monoclinic (P21) symmetry. It is of inter-est with respect to its anti-inflammatory properties. The asymmetric unit contains two independent mol-ecules, one of which exhibits disorder of the bi-cyclo terminal group (occupancy factors: 0.78 and 0.22).

Advancement in SARS-CoV-2 diagnosis: A new and stable electrochemical biosensor for genomic RNA detection.

Coronavirus disease (COVID-19) is caused by infection with the SARS-CoV-2 virus, having already caused more than seven million deaths worldwide. Conventional techniques for SARS-CoV-2 detection have limitations, as high cost, low specificity, and longer analysis time, among others. Biosensors emerge as a necessary alternative to overcome the difficulties of current diagnostics. This paper reports a sensor platform where silver-doped zinc oxide nanomaterial (Ag:ZnONp) was used onto carbon screen-printed electrode and ethidium bromide as indicator for development of a specific electrochemical genosensor for COVID-19. This genosensor demonstrated good linearity between the concentrations of 5.62 × 104-5.62 copies/mL and a detection limit of 5 copies/mL with gRNA in patient's samples, with a response time within 30 min. Molecular modeling and morphological analysis are in agreement with obtained electrochemical results. Additional techniques such as AFM, SEM, and EIS were conducted to characterize the morphological and electrochemical properties of the biosensor's surface. The biosensor was also capable of detecting the target presence in spiked samples and demonstrated a stability of 60 days, higher than other similar biosensors for SARS-CoV-2.

Effect of different doses of Budesonide combined with Tiotropium bromide inhalation on elderly patients with chronic obstructive pulmonary disease.

Objective: To explore the clinical effect of various doses of Budesonide combined with Tiotropium bromide in the treatment of elderly patients with chronic obstructive pulmonary disease (COPD). Methods: Clinical data of elderly patients with COPD, admitted to Affiliated Hospital of Shaoxing University from April 2021 to February 2023, were retrospectively analyzed. Based on the dosage of Budesonide combined with Tiotropium bromide, patients were divided into Low-dose group (Budesonide = 1mg), Medium-dose group (Budesonide = 2mg), and High-dose group (Budesonide = 3mg). All groups were matched for age, gender, course of disease, and BMI. Patients treated with Tiotropium bromide alone were assigned to the Control group. The clinical effect, pulmonary function index level, symptom improvement, inflammatory factor index level and adverse reactions in all groups were analyzed and compared. Results: A total of 88 patients were included in this study with 22 patients in each group. The total efficacy of Medium-dose (90.91%) and High-dose group (90.91%) was significantly higher than that of Low-dose group (63.64%) and the Control group (59.09%) (P<0.05). After the treatment, levels of pulmonary function, symptom improvement and inflammatory factors in the High-dose and the Medium-dose groups were better than those in the Low-dose group and the Control group. Pulmonary function, symptom improvement and levels of inflammatory factors was significantly better in the Low-dose group compared to the Control group (P<0.05). Conclusions: Budesonide combined with tiotropium bromide is better than tiotropium bromide alone in the treatment of elderly patients with COPD. Compared with low (1mg) dosage, medium (2mg) and high (3mg) dosage of budesonide are more effective in improving lung function, alleviating symptoms, reducing inflammatory response,, and are not associated with increased rate of adverse reactions.

[Epilepsy with PCDH19 mutation: polypharmacy as a consequence of the complexity and diversity of pathogenesis mechanisms]. / Epilepsiya pri mutatsii gena PCDH19: polipragmaziya kak sledstvie slozhnosti i mnogoobraziya mekhanizmov patogeneza.

Mutations in the human PCDH19 gene lead to epileptic encephalopathy of early childhood. It is characterized by the early onset of serial seizures, cognitive impairment and behavioral disorders (including autistic personality traits). In most cases, difficulties arise in selecting therapy due to pharmacoresistance. The pathogenesis of the disease is complex. The data available to us at the moment from numerous studies present the pathogenesis of «PCDH19 syndrome¼ as multi-level, affecting both the epigenetic support of cell life, and development of stem cells and progenitor cells in the process of neuroontogenesis, and the influence on the neurotransmitter mechanisms of the brain, and disruption of the formation of neural networks with an inevitable increase in the excitability of the cerebral cortex as a whole, and local changes in the highly labile regulatory structures of the hippocampal region. And it is not surprising that all these changes entail not only (and perhaps not so much) epileptization, but a profound disruption of the regulation of brain activity, accompanied by autism spectrum disorders, more profound disorders in the form of schizophrenia or cyclothymia, and the formation of delayed psychomotor development. A «side branch¼ of these pathogenetic processes can also be considered the participation of PCDH19 dysfunctions in certain variants of oncogenesis. The need for polypharmacy (in most cases) confirms the diversity of mechanisms involved in the pathogenesis of the disease and makes the prospects for the development of effective and rational treatment regimens very vague. Cautious optimism is caused only by attempts at relatively specific treatment with ganaxolone.

Precursor Chemistry of Lead Bromide Perovskite Nanocrystals.

We investigate the early stages of cesium lead bromide perovskite formation through absorption spectroscopy of stopped-flow reactions, high-throughput mapping, and direct synthesis and titration of potential precursor species. Calorimetric and spectroscopic measurements of lead bromide complex titrations combined with theoretical calculations suggest that bromide complexes with higher coordination numbers than previously considered for nonpolar systems can better explain observed behaviors. Synthesis mapping of binary lead halides reveals multiple lead bromide species with absorption peaks higher than 300 nm, including a previously observed species with a peak at 313 nm and two species with peaks at 345 and 370 nm that also appear as reaction intermediates during the formation of lead bromide perovskites. Based on theoretical calculations of excitonic energies that match within 50 meV, we give a preliminary assignment of these species as two-dimensional magic-sized clusters with side lengths of 2, 3, and 4 unit cells. Kinetic measurements of the conversion of benzoyl bromide precursor are connected to stopped-flow measurements of product formation and demonstrate that the formation of complexes and magic-sized clusters (i.e., nucleation) is controlled by precursor decomposition, whereas the growth rate of 2D and 3D perovskites is significantly slower.