A document by Camille Ziegler. Click on the document to view its contents.

Early in the 2022 Mpox (MPX) global outbreak, caseloads in the New York Metropolitan area climbed rapidly before other US urban areas. This case series summarizes the authors’ clinical experience detecting and treating MPX, during a quickly evolving outbreak. Clinical outcomes were recorded with a focus on varied clinical presentation and outcomes such as complications and response to experimental tecovirimat therapy. A focal or multifocal rash was the most common presenting symptom in 91% of patients. Almost two thirds (62%) of patients had anogenital involvement. Proctitis was one of the most painful presentations with 75% requiring antiviral treatment and 3 patients needing hospitalization for pain management. Most patients responded promptly to antiviral treatment with tecovirimat. Five out of 10 patients treated with tecovirimat reported symptom resolution within 48 – 72 hours of therapy and another 3 saw resolution within first 96 hours. Two patients had poor response to tecovirimat. This series includes the only reported case of an HIV positive, immunocompetent patient who experienced recurrent anal ulcers due to Mpox and required a second course of tecovirimat. Other unique presentations included urethritis, abscess formation and MPX infection post-vaccination. Control of this current Mpox outbreak was possible due to timely diagnosis and the availability of both a licensed vaccine and an investigational drug.

Interventions to promote deprescribing are an important focus of research. Key decisions for such interventions are whether to target one or multiple medicines, and whether the intervention scope is deprescribing, or also extends to other aspects of medicines optimisation. This article reflects on how these decisions impact on developing interventions and measuring outcomes. Many behavioural strategies are common to deprescribing and medicines optimisation, however operationalisation may differ. Aspects to consider include the burden of multiple simple interventions versus one complex intervention, the extent to which the approach to deprescribing can be specified as part of the intervention, and variability in how the intervention is delivered across patients and providers. Outcomes should be selected based on the intervention target and scope and the audience for whom evidence is being produced. These may include medication changes, and process outcomes to assess intervention delivery. Targeting single medications may allow for a focus on specific clinical or symptom-related outcomes, rather than more general outcomes such as adverse drug reactions. Cost-related outcomes are also important to inform implementation decisions, and modelling approaches may be more feasible for interventions targeting single medications.

Significant racial disparities in prostate cancer incidence and mortality have been reported between African American Men (AAM) who are at increased risk for prostate cancer, and European American Men (EAM). In most of the studies carried out on prostate cancer, this population is underrepresented. With the advancement of genome-wide association studies (GWAS), several genetic predictor models of prostate cancer risk have been elaborated, as well as numerous studies that identify both germline and somatic mutations with clinical utility. Despite significant advances, the AAM population continues to be underrepresented in genomic studies, which can limit their generalizability and potentially widen disparities. Here we outline racial disparities in currently available genomic applications that are used to estimate the risk of individuals developing prostate cancer and to identify personalized oncology treatment strategies. While the incidence and mortality of prostate cancer are different between AAM and EAM. the biological features and differences of prostate tumors in AAM and EAM are still being described. Samples from AAM remain to be unrepresented in different studies. This disparity impacts the available genomic data on prostate cancer. As a result, the disparity can limit the predictive utility of the genomic applications that have been developed and may lead to widening disparities. More studies with substantially higher recruitment and engagement of African American patients are necessary to overcome this disparity.

Water plays a vital role in all aspects of life. In recent years, water pollution has increased due to various organic and inorganic pollutants caused by human activities. Organic pollutants are hard to degrade in nature. Henceforth cost-effective and sustainable approaches are needed to degrade these organic pollutants to purify wastewater. Organic dye is a major source of organic pollutants from coloring industries, which must be removed during water treatment. The photoactive metal-organic frameworks (MOFs) offer an ultimate strategy to construct catalysts to degrade pollutants present in wastewater. Tuning the metal ions/cluster and organic ligands for better photocatalytic activity of MOFs is the need for an hour. This review comprehensively reported various MOFs, their composites, and POM-based MOF materials for the ultimate photo-degradation of various pollutants in the aqueous phase. Furthermore, special mention has been given to POM-based MOF material, which has an advantage over other materials due to their conducting behavior and high stability. A brief discussion on MOF-based photocatalysts is explored using various theoretical approaches such as density functional theory (DFT) and machine learning (ML). Although there are various article dealing with the basic concept of MOF-based photocatalyst but the area of combining design structure-activity with high-performance theoretical analysis have not been discussed in detail yet. Thus, this article eventually paved the way for applying different structural features to modulate hazardous materials’ photodegradation properties toward organic pollutants.

Gut micriobiota have important roles in the immune, nutrition, and physiology of animals. To study the cause of gut microbiota change in black-necked cranes, we collected 9fresh Black-necked cranes’ fecal samples from Dashanbao Reserve. High throughput Illumina sequencing technology was used to analyze the microbial community structure of the collected samples for the V4 region of the 16S rRNA gene. Proteobacteria (44.14%) followed by Firmicutes (17.95%) and Bacteroidetes (9.97%) were the core dominant groups, and all of them play a role in the degradation of cellulose in Black-necked cranes. Bacteroidetes and Firmicutes contain glycan degrading enzymes, play a vital role in polysaccharide fermentation, and could help the host obtain more energy and materials. Higher Proteobacteria were unusual in birds. To explain this phenomenon, we analyzed the genus abundance of Proteobacteria in detail, found that Psychrobacter has the highest abundance and can grow at sub-zero temperatures. Through comparison, it was show that there were certain differences in the abundance of gut microbiota in different period The significance of this study was to provide a reference for understanding the function of intestinal microbiota and factors of gut microbiota structure change of Black-necked cranes and other migratory waterbirds.

Bacterial species display unique and common molecular mechanisms for nutrient acquisition depending on their habitat. Molecular details of xylan utilization by plant pathogens and human commensal bacteria have been reported but no significant reports can be found for environmental bacteria. Caulobacter crescentus is a gram-negative, oligotrophic, environmental bacterium with unique adaptations for growth in low-nutrient conditions. C. crescentus’ genome codes for a repertoire of genes that can facilitate xylan utilization as a carbon source for growth. Polymeric xylan and xylan-derivative use by C. crescentus was investigated in this work. Growth, enzyme, metabolite, and gene expression analyses show possible membrane-bound enzymes for xylan deconstruction on the cell surface while enzymes for further deconstruction of xylan-derived oligosaccharides are concentrated in the periplasm. TonB-dependent transporter (TBDT) inhibition data suggest that TBDT may be involved in the transport of xylo-oligosaccharides across the outer membrane. Collectively, data suggest xylan binding onto the bacterial surface and deconstruction and the xylan fragment uptake across the outer membrane. A comprehensive model for xylan utilization by C. crescentus develops to show features of previously proposed gut and plant pathogenic bacterial models. This study further advances the molecular level understanding of xylan derived nutrient acquisition in environmental bacteria.

Understanding the characteristics of long-term changes in the water use efficiency (WUE) of grassland ecosystems is vital for WUE improvement on the Qinghai-Tibet Plateau. In this study, five vegetation types, namely alpine shrub, desert, grassland, meadow, and swamp, were evaluated. The changes in WUE over the past 16 years were calculated using the total primary productivity and latent heat flux data of the ecosystem from 2006 to 2021. In addition, meteorological data were used to further explore the relationship between WUE and environmental factors. The WUE of alpine desert, meadow, and swamp showed an increasing trend. In contrast, alpine shrub and grassland WUE showed a decreasing trend, with the WUE of shrub being significantly higher than that of grassland on the interannual scale. The WUE of all vegetation types showed seasonal maximum and minimum values in July and January, respectively, and the WUE of shrubs was significantly higher than that of the other vegetation types. The structural equation model showed that precipitation, temperature, and relative humidity were the main positive influences on the WUE of grasslands on the Qinghai-Tibet Plateau, whereas net radiation had a negative influence. Climate factors may substantially impact future changes in the WUE of various ecosystems. The results of this study provide a theoretical basis for further study of WUE changes in the grasslands of the Qinghai-Tibet Plateau.

Ancient whole-genome duplication (WGD) or polyploidization is prevalent in plants and has played a crucial role in plant adaptation. However, the underlying genomic basis of ecological adaptation and subsequent diversification after WGD are still poorly understood in most plants. Here, we report a chromosome-scale reference genome assembly for the genus Orinus (Orinus kokonorica as representative) and preformed comparative genomics with its closely related genus Cleistogenes (Cleistogenes songorica as representative), both belonging to a newly named subtribe Orininae of the grass subfamily Chloridoideae. The two genera may share one paleo-allotetraploidy event before 10 million years ago, and their two subgenomes display neither fractionation bias nor global homoeolog expression dominance. Recent expansion of transposable elements and enormous contraction in gene families in O. kokonorica have maintained a similar genome size compared to C. songorica. Further comparative genomic analyses reveal substantial genome rearrangements and extensive structural variations (SVs) between the two species. With comparative transcriptomics, we demonstrate that functional innovations of orthologous genes have played an important role in promoting adaptive evolution and diversification of the two genera after polyploidization. In addition, copy number variations in flower and rhizome development related genes and extensive SVs between orthologs may contribute to the morphological differences between the two genera. Our results provide significant new insights into the adaptive evolution and subsequent diversification of the two genera after polyploidization.

This work addresses the applicability of a local criterion incorporating the coupling of critical stress and a critical hydrogen concentration to predict hydrogen embrittlement effects on the fracture strength of high strength steels using notched round specimens with different notch root radii. The numerical simulations incorporating a relatively simple hydrogen transport model provide strong support to the adoption of a failure criterion in terms of achieving a critical level of tensile stress coupled to the local hydrogen concentration, which, in turn, enable the construction of a failure locus for the material. For the cases analyzed here, construction of such a failure locus based on a critical combination of maximum principal stress and hydrogen concentration enabled predictions of fracture strength for hydrogen-charged tensile specimens which are in very good agreement with experimental data. Overall, the results presented here lend additional support for further developments of a local stress-based criterion to predict hydrogen embrittlement effects on the fracture strength of high strength steels.

Chemotherapy induced nephrotoxicity is one of the most common complications in cancer patients, especially under treatment with cisplatin containing regimens, which may require cisplatin dose reduction and in some cases discontinuation of the treatment, which interferes with treatment process. Curcumin is an antioxidant and anti-inflammatory compound and the most important active component of curcuma longa. In this study, the preventive effect of nano-curcumin oral formulation on cisplatin-induced nephrotoxicity in cancer patients was investigated. In this triple-blind clinical trial 30 cancer patients were randomly divided into the treatment group, receiving 40 mg nano-curcumin capsules (15 patients) and the placebo group (15 patients) twice a day for four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course. (P value>0.05) and was not effective in preventing the cisplatin induced nephrotoxicity in cancer patients in comparison with the placebo. Additional studies with different doses and durations of administration are recommended.

Lead-acid battery system is designed to perform optimally at ambient temperature (25 °C) in terms of capacity and cyclability. However, varying climate zones enforce harsher conditions on the automotive lead acid batteries. Hence, they age faster and exhibit low performance when operated at either extremity of the optimum ambient conditions. In this work, a systematic study was conducted to analyze the effect of varying temperatures (-10, 0, 25 and 40 °C) on the sealed lead acid. Enersys® Cyclon (2V, 5Ah) cells were cycled at C/10 rate using battery testing system. The environmental aging results in shorter cycle life due to the degradation of electrode, and grid materials at higher temperature (25 and 40 °C), while at lower temperature (-10 and 0 °C) negligible degradation was observed due to slower kinetics and reduced available capacity. Electrochemical impedance spectroscopy, X-ray diffraction and Energy-dispersive X-ray spectroscopy analysis were used to evaluate the degradation mechanism, chemical and morphological changes.

Nonwoven membranes are highly engineered fibrous materials that can be manufactured on a large scale from a wide range of different polymers, and their surfaces can be modified using a large variety of different chemistries and ligands. The fiber diameters, surface areas, pore sizes, total porosities, and thicknesses of the nonwoven mats can be carefully controlled, providing many opportunities for creative approaches for the development of novel membranes with unique properties to meet the needs of the future of downstream processing. Fibrous membranes are already finding use in ultrafiltration, microfiltration, depth filtration, and, more recently, in membrane chromatography for product capture and impurity removal. This article summarizes the various methods of manufacturing nonwoven fabrics, and the many methods available for the modification of the fiber surfaces. It also reviews recent studies focused on the use of nonwoven fabric devices in membrane chromatography and provides some perspectives on the challenges that need to be overcome to increase binding capacities, decrease residence times, and reduce pressure drops so that eventually they can replace resin column chromatography in downstream process operations.

Severe BPD can be associated with clinical and histologic features that are similar to ACD without evidence of FOXF1 genetic disease.  Importantly, lung FOXF1 and TMEM100 gene expression is markedly decreased in severe BPD, suggesting that impaired FOXF1 signaling may contribute to abnormal lung growth and refractory pulmonary hypertension in BPD.

Background: Repositioning a traumatized tooth involves, first, replacing and second stabilizing it. Stabilization, on the other hand, usually requires flexible splints. Occasionally the immediate replacement may be impossible being necessary to use other procedure. Methods: When complete replacement is not possible,

Every year, rice planthoppers (main brown planthopper, BPH, Nilaparvata lugens Stål), one of the most important pests in rice production, cause huge yield losses worldwide. The identification of resistance genes and exploration of insect resistance mechanisms are some of the most fundamental and effective methods to manage the pest. Here, the aspartic protease (AP) gene OsAP79 was transcriptionally expressed in all organs tested, particularly in the roots at the adult stage. The knockout of OsAP79 impaired rice resistance to BPH, whereas overexpression (OE) of OsAP79 improved rice resistance by increasing plant survival rates, and reducing BPH weight gain and honeydew excretion. Observation of the transverse section of rice shoots indicated that OE lines of OsAP79 can significantly enhance sclerenchyma layer thickness. Meanwhile, a significantly longer or shorter root was detected in the knockout or OE lines, respectively, which was positively correlated with the indole acetic acid (IAA) content. Hormone measurement and metabolomic analysis suggested that IAA biosynthesis, the citric acid cycle, and glycolysis biosynthesis contributed greatly the OsAP79-induced resistance of rice against BPH. Collectively, OsAP79 was continuously induced to express and enhance BPH resistance by reducing the IAA content, which restricts root growth and increases shoot sclerenchyma layer thickness. This study demonstrates the previously unappreciated importance of the AP gene in rice for combating piercing-sucking insect herbivores.

We present a case of synchronous dual hematological malignancies: multiple myeloma (MM) and masked essential Thrombocythemia (ET). Excessive thrombocytosis due to bone marrow recovery occurred during anti-myeloma therapy. Treatment for MM had no effect on ET; concomitant ET did not decrease the efficacy of anti-myeloma therapies in this frail patient.

Objectives: Despite its low sensitivity for the interstitial syndrome, chests X-Ray (XR) have been used on COVID-19 patients to exclude alternative diagnoses. Computed tomography (CT) scans can both exclude other pathological conditions and display a high level of sensitivity for the COVID-19 pneumonia. We therefore decided to compare the performance of lung ultrasonography (LUS) with that of lung CT scans in suspect or confirmed COVID-19 patients for the presence of interstitial pneumonia and the degree of lung injury. Methods: In a cross-sectional clinical study, LUS an CT were compared for the presence of interstitial pneumonia and the degree of lung injury in COVID-19 patients. Pearson’s and Spearman correlations analysis were performed to measure the degree of association between two methods. Bland–Altman plot was generated to provide a graphical visualization of the agreement between the two measurement methods. All statistical tests in this study were two-sided and p-values ≤ 0.05 were considered as statistically significant. Results: A good correlation between LUS and CT scan was obtained for estimates of lung injury in pneumonia in a group of COVID-19 suspect and diagnosed patients (R 2= 0.7613; p <0.01). Agreement between LUS and CT values is assessed by constructing Bland-Altman plot. Conclusions: LUS, as compared to CT scans, is an effective method to estimate degrees of lung injury in COVID-19 patients in the emergency department.

Understanding how bird species from white sand ecosystems (WSEs) have managed to inhabit and specialize in insular environment in the middle of the Amazon Rainforest is fundamental to understand the evolutionary processes in birds restricted to one type of habitat. We sought to evaluate the diversification processes of the specialist bird species of the white sand ecosystems of the Rio Negro basin by comparing them with the pool of bird species of riparian environments. Many WSEs may be ancient riverbeds, which may favor current riparian species to be potential colonizers and settle within the WSEs. For this, we used an extension of biogeographic evolutionary models to verify state-dependent speciation and extinction models that specifically explain the presence of unmeasured factors that can affect the estimated diversification rates for the states of any observed trait. Thus, it was possible to evaluate the evolutionary processes that most acted in the formation of bird communities of WSEs. The results showed that WSEs specialist bird species have different functional diversity to what was expected on a random basis and evolutionary models have higher extinction and speciation rates in WSEs specialist bird communities. This evidences that source-sink processes maintain WSEs over time, and that they receive generalist and specialist species from riparian ecosystems. According to the models analyzed, once the species have the high degree of adaptation required by an ecosystem with severe conditions, they cannot colonize other ecosystems. Extinction is an important process for the dynamics of biodiversity in the Amazon since, as many species are lost, there is also speciation and high adaptation. This work is one of the first to use local evolutionary analyses in Amazonian ecosystems and was effective in showing that extinction is recurrent, which is a cause for concern due to the severe and rapid ecological changes currently occurring.

Meglumine gadoterate induces immunoglobulin-independent human mast cell activation and MRGPRX2 internalizationTo the Editor,Gadolinium-based contrast agents (GBCA) are intravenous drugs used to enhance resolution in magnetic resonance imaging. They can induce immediate hypersensitivity reactions, yet their pathogenic mechanisms remain poorly characterized. This hampers the ability to predict which patients are at risk of developing them.1 In fact, affected patients usually show negative skin-tests and can react upon the first known GBCA exposure, which implies that IgE-independent mechanisms might be driving this inflammatory response.The Mas-related G protein-coupled receptor member X2 (MRGPRX2) has been recently associated with non-IgE mediated immediate hypersensitivity reactions.2 Some drugs, such as fluoroquinolones, vancomycin, neuromuscular blockade agents, icatibant, morphine, leuprolide and iodinated contrast media, have been reported to activate MRGPRX2, which is highly expressed in mast cells (MCs).3To assess the ability of GBCA to induce non-IgE-mediated hypersensitivity reactions, we stimulated the human MC line LAD2 with several commercial GBCA, namely, meglumine gadoterate, gadobutrol, gadoxetate disodium and gadoteridol. Then, we determined cell viability and degranulation by flow cytometry4 (see a detailed material and methods section in this article´s online supplementary ).Of the GBCA tested, only meglumine gadoterate was able to induce significant MC activation (Figure 1A ) without compromising cell viability (Figure 1B ), as compared to unstimulated MCs. We further assessed MRGPRX2 expression on LAD2 cells by flow cytometry, as well as changes in its expression following stimulations with either meglumine gadoterate or vancomycin (a known agonist of MRGPRX2).5 Under basal conditions, LAD2 cells expressed high levels of MRGPRX2 (Figure 1C ). Following incubation with vancomycin, the level of MRGPRX2 expression was reduced, as compared to untreated LAD2 cells. Interestingly, we observed a similar decrease in MRGPRX2 expression levels upon meglumine gadoterate and vancomycin challenges, as compared to controls, suggesting both the signaling and the internalization of this receptor (Figure 1D ).Meglumine gadoterate is an ionic macrocyclic paramagnetic contrast media. It is composed by gadolinium, which together with the chelating agent tetraxetan (also known as DOTA), yields gadoteric acid. The base meglumine and gadoteric acid form the salt meglumine gadoterate (Figure 2A ). Given that MRGPRX2 has affinity for cationic amphiphilic compounds,6 we ascertained the ability of meglumine to induce MC activation. Meglumine itself induced MC degranulation without affecting cell viability, as compared to untreated cells (Figure 2B ), although a reduction in MRGPX2 expression could not be confirmed (data not shown). Interestingly, meglumine caused MC activation at lower concentrations than meglumine gadoterate, according to the half maximal effective concentration (EC50) of both substances (Figure 2C ). The logarithmically transformed EC50 for meglumine gadoterate was 2.04 (R2= 0.75), and for meglumine was about one order of magnitude lower (1.06; R2= 0.71). Considering the EC50 for meglumine and its proportion in meglumine gadoterate (~26%), meglumine could be its main component responsible for MC degranulation.In conclusion, our study demonstrates the ability of meglumine gadoterate to induce MC activation, by an immunoglobulin-independent mechanism that is likely mediated by MRGPRX2. Furthermore, we have delved into the meglumine gadoterate components that are involved in MC activation, and identified meglumine as a potential causative of non-IgE mediated hypersensitivity reactions. These data raise the possibility that immediate hypersensitivity reactions following intravascular administration of ionic iodinated contrast media may be at least partly mediated by meglumine. Further studies should be performed to define clinically relevant interactions between diverse radiological contrast media and MRGPRX2.Authors: Paula H. Ruiz de Azcárate,1#Rodrigo Jiménez-Saiz,1-4 #* Celia López-Sanz,1 Azahara López-Raigada,5Francisco Vega,5 Carlos Blanco,5*# First authors* Corresponding authorsAffiliations: 1Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain.2Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain.3Faculty of Experimental Sciences, Universidad Francisco de Vitoria (UFV), Madrid, Spain.4Department of Medicine, McMaster Immunology Research Centre (MIRC), Schroeder Allergy and Immunology Research Institute (SAIRI), McMaster University, Hamilton, ON, Canada.5Department of Allergy, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain.*Co-correspondence to :1) Rodrigo Jiménez-Saiz, Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Diego de León 62, 28006, Madrid, Spain. Email address: rodrigo.jimenez@ufv.es2) Carlos Blanco, Department of Allergy, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Diego de León 62, 28006, Madrid, Spain. Email address: cblague@gmail.com Funding information: RJS reports grants by the FSE/FEDER through the Instituto de Salud Carlos III (CP20/00043; PI22/00236; Spain), The Nutricia Research Foundation (NRF-2021-13; The Netherlands), New Frontiers in Research Fund (NFRFE-2019-00083; Canada) and SEAIC (BECA20A9; Spain). PHR is supported by the INVESTIGO Program of the Community of Madrid (Spain), which is funded by “Plan de Recuperación, Transformación y Resiliencia” and “NextGenerationEU” of the European Union (09-PIN1-00015.6/2022).Conflict of interest : All the authors have no significant conflicts of interest to declare in relation to this manuscript.References1. Vega F, Lopez-Raigada A, Mugica MV, Blanco C. Fast challenge tests with gadolinium-based contrast agents to search for an alternative contrast media in allergic patients. Allergy.2022;77(10):3151-3153.2. Kolkhir P, Ali H, Babina M, et al. MRGPRX2 in drug allergy: What we know and what we do not know. J Allergy Clin Immunol. 2022.3. Foer D, Wien M, Karlson EW, Song W, Boyce JA, Brennan PJ. Patient Characteristics Associated With Reactions to Mrgprx2-Activating Drugs in an Electronic Health Record-Linked Biobank. J Allergy Clin Immunol Pract. 2022.4. López-Sanz C, Sánchez-Martínez E, Jiménez-Saiz R. Protocol to desensitize human and murine mast cells after polyclonal IgE sensitization. STAR Protocols. 2022;3(4):101755.5. Navines-Ferrer A, Serrano-Candelas E, Lafuente A, Munoz-Cano R, Martin M, Gastaminza G. MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia. Sci Rep.2018;8(1):11628.6. Wolf K, Kühn H, Boehm F, et al. A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice. J Allergy Clin Immunol. 2021;148(2):506-522.e508.

In this paper, an enclosing control problem is investigated for nonholonomic mobile agents with a moving target of unknown velocity. An adaptive observer containing two internal variables is first designed for each agent to compensate for the lack of the target velocity information. One variable is designed to estimate the unknown target velocity and further its estimation error is assessed by the other internal variable to subsequently guarantee the control performance. Then using the estimated information from the adaptive observer, a dynamic control law for circular formation of nonholonomic agents around the moving target is designed by a backstepping process. The global asymptotical stability of the closed-loop system is achieved under the proposed dynamic control law with the adaptive observer. Finally, a simulation is conducted to demonstrate the effectiveness of the proposed approach.

Herein, we have developed a strategy of Rh(III)-catalyzed C–H activation of N-nitrosoanilines and iodonium ylides to construct novel tetralydrocarbzol-4-one scaffolds, which provided valuable templates for sequential C-H functionalization such as alkylation, alkenyla-tion, amidation and (hetero)arylation at C5-position of tetralydrocarbzol-4-one with different coupling partners. Gram-scale synthesis and further transformation of tetralydrocarbzol-4-one derivatives to Ondansetron and its analogues demonstrated the utility of this protocol, which enabled the concise and diverse construction of biologically active molecules.

Objective: To identify factors contributing to maternal mortality in Kazakhstan. Design: A retrospective study of the health and demography data set of Kazakhstan from 2000 to 2020. Setting and population: The data from the annual statistical report “Population health and healthcare organizations’ performance in the Republic of Kazakhstan from 2000 to 2020”. Kazakhstan and its 14 regions and 3 main cities for the period 2019-2020. Methods: We analyzed the MMR trend in Kazakhstan and in all 14 regions and 3 main cities for the period 2000-2020. We applied Univariate Linear Regression Models with Logarithmic Transformation of the outcome and predictors to detect determinants of MMR for 2019 and 2020 in Kazakhstan. Main Outcome Measures: Maternal mortality ratio and determinants. Results: Trends in MMR in many regions of Kazakhstan show a steady decline starting from 2000 until 2010-2015 with a subsequent increase by 2020. MMR was associated with factors such as socio-economic, health service-related, and population health indicators. An increase in most of these indicators leads to a decrease in maternal mortality, except obstetric beds per 1000 births, number of inpatient facilities, and population median age, which leads to an increase in MMR. Conclusions: Maternal mortality is a complex issue that is influenced by various socio-economic factors, healthcare system factors, and disease burden. Despite Kazakhstan’s alignment with the SDG goals, including reducing maternal mortality, the country’s middle-income status may have led to fluctuations in MMR.

Microbial infections are considered as one of the most important concerns of the world community. Developing drug delivery systems based on formulation of nanoparticles with antimicrobial agents have shown beneficial effectiveness against microbial infections and related antimicrobial resistance. In this study we prepared and characterized a chitosan based hydrogel loaded with zinc oxide nanoparticles for controlling the release of vancomycin and also improving its antibacterial effect. Characterization studies demonstrated that the developed biopolymeric hydrogel was able to sustained and controlled the release of vancomycin in response to acidic media for 96 hours. Furthermore, antimicrobial studies showed siginificant and efficient antibacterial activity of prepared hydrogel against S. aureus and P. aeruginosa. Based on obtained results, it can be concluded that the prepared chitosan hydrogel containing ZnO nanoparticles has a desirable activity for controlling the release of vancomycin and improving its antibacterial properties.