Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

Chiropractors in Multidisciplinary Teams: Enablers of Colocation Integration in GP-Led Primary Healthcare.

The aim of this study was to explore and document the enablers and barriers of chiropractic care colocation in general practice at a large-scale private primary care centre in Australia. This study focused on the perceptions of healthcare professionals regarding this integration. The research setting was a large integrated primary care centre located in an outer metro, low-socioeconomic area in the City of Moreton Bay, Queensland, Australia. Participant inclusion criteria included general medical practitioners, practice nurses, and medical managers who self-reported interactions with the physically collocated and integrated chiropractic practice. Data was collected from 22 participants using face-to-face, qualitative, semi-structured interviews with an average duration of 32 min. The data collected included perceptions of chiropractic treatment, enablers to patient referral pathways, and views of the integrated chiropractic care model. A reflexive thematic analysis was conducted on the data set. All participants reported that this was their first exposure to the colocation of a chiropractor within a general medical practice. Four key enablers of chiropractic care integration were identified: (1) the practitioner [chiropractor], (2) the organisation [general practice], (3) consumer flow, and (4) the environment [shared spaces and tenant ecosystem]. The chiropractic integration enhanced knowledge sharing and interprofessional trust among healthcare providers. The formal reporting of patient outcomes and understanding of the chiropractor's scope of practice further enabled referrals to the service. Shared administrative and business processes, including patient records, booking systems, and clinical meetings, facilitated relationship development between the chiropractor and referring health providers. Colocation as part of a larger primary care centre created proximity and convenience for health providers in terms of interprofessional communication, and for patients, in terms of access to chiropractic services. Existing governance structures supported communication, professional education, and shared values related to the delivery of patient-centred care. Identified barriers included limited public funding for chiropractic services resulting in reduced access for patients of low-socioeconomic status. Additionally, scepticism or negativity towards the discipline of chiropractic care was identified as an initial barrier to refer patients. In most cases, this view towards the chiropractor was overcome by regular patient reporting of positive treatment outcomes to their GP, the delivery of education sessions by the chiropractor for the health providers, and the development of interprofessional trust between the chiropractor and referring health providers. This study provides preliminary evidence and a conceptual framework of factors influencing the successful integration of chiropractic care within an Australian large primary care centre. The data collected indicated that integration of chiropractic care into a primary care centre serving a low-socioeconomic region can be achieved with a high degree of health provider satisfaction.

Evaluation of water ecological health of Yanhe River based on benthic fauna integrity index.

Yanhe River Basin is located in the hilly gully area of the Loess Plateau with serious soil erosion. Strong human activities in the middle and lower reaches lead to fragile ecological environment. Soil erosion status varies among different geomorphic units within the watershed (loess liang hilly and gully region, loess mao hilly and gully region, and broken platform region). In this study, we surveyed the benthic community from the Yanhe River Basin in April (spring) and October (autumn) of 2021. To evaluate the water ecological health status of the watershed and investigate the effects of different geomorphic units on the benthic integrity of the benthos, we constructed the benthic-index of biotical integrity (B-IBI) based on the biological data. We identified a total of 113 species of 73 genera in 4 phyla of benthic fauna, with aquatic insects as the dominant taxa in both seasons. Through screening 26 candidate indicators, we found that the spring B-IBI consisted of three indicators: relative abundance of individuals of dominant taxonomic units, family biotic index (FBI), and relative abundance of predator individuals, and that autumn B-IBI was composed of the number of taxonomic units of Ephemeroptera, FBI value, and the relative abundance of predator individuals. Results of the B-IBI evaluation showed that 83.3% of the sampling sites in the upper mainstem and tributaries were at a healthy condition, while only 28.6% sampling sites in the middle and lower mainstem and tributaries were at a healthy condition. In addition, the health status of the watershed was better in spring than in autumn. The Kruskal-Wallis nonparametric tests showed that benthic density, species number, and B-IBI percentile scores in the fragmented loess area were significantly higher in spring than in autumn, and significantly lower in autumn than in the loess liang hilly and gully region and loess mao hilly and gully region, being mainly caused by the increasing erosion due to the concentrated rainfall in wet season. Results of the redundancy analysis showed that key environmental factors affecting benthic community structure in spring were boulder substrate, chlorophyll-a, oxidation reduction potential, turbidity, conductivity, and dissolved oxygen, and were nitrate-nitrogen, oxidation reduction potential, and pH in autumn.

Diverse Genotypes of Cronobacter spp. Associated with Dairy Farm Systems in Jiangsu and Shandong Provinces in China.

Cronobacter spp. are the most concerning foodborne pathogen in infant formula milk powder. Currently, there are many reports on the prevalence of Cronobacter spp. in infant formula milk and its processing environment, but there are few studies on the prevalence of Cronobacter spp. on dairy farms. We have, therefore, undertaken this study to investigate and track genomic epidemiology of Cronobacter spp. isolates from Chinese dairy farms in the provinces of Jiangsu and Shandong. In this study, forty Cronobacter spp. strains, consisting of thirty Cronobacter sakazakii, eight Cronobacter malonaticus, and two Cronobacter dublinensis, were obtained from 1115 dairy farm samples (raw milk, silage, bedding, and feces), with a prevalence rate of 3.57%. These isolates were classified into 10 Cronobacter serotypes and 31 sequence types (STs), including three novel STs which were isolated for the first time. Notably, pathogenic Cronobacter STs 7, 8, 17, 60, and 64, which are associated with clinical infections, were observed. Antimicrobial susceptibility testing showed that all the Cronobacter spp. were highly resistant to cephalothin and fosfomycin, which was consistent with the antimicrobial genotype. All isolates carried core virulence genes related to adherence, invasion, endotoxin, immune evasion, secretion system, and regulation. Approximately half the isolates were also able to produce a strong biofilm. Twenty-one prophages and eight plasmids were detected, with the most common prophage being Cronobacter_ENT47670 and the most common plasmid being IncFIB (pCTU1). In addition, two isolates harbored the transmissible locus of stress tolerance (tLST) which confers high environmental persistence. Phylogenetic analysis showed strong clustering by species level and sequence types. Isolates from different sources or regions with a similar genomic background suggests the cross-contamination of Cronobacter spp. The presence of diverse genotypes of Cronobacter spp. in dairy farms in Jiangsu and Shandong provinces indicates that surveillance of Cronobacter spp. on dairy farms should be strengthened, to prevent and control transmission and ensure the quality and safety of raw dairy products.

Measuring Mental Health Service Accessibility for Indigenous Populations: a Systematic Review.

Indigenous populations have experienced inequality of accessing mental health services compared with their non-Indigenous counterparts, although the way of measuring mental health service accessibility for Indigenous populations is unclear. This systematic review examines measures of mental health service accessibility for Indigenous people, including the diversity of mental health services that are available to them and the barriers to accessing mental healthcare. Using a systematic search procedure, we identified 27 studies that explored Indigenous populations' mental health service access. Our review shows that 18 studies used interview-based methods to explore how Indigenous people use mental health services, and only nine studies used quantitative methods to measure the uptake of mental health services. While advanced methods for quantifying geographical access to healthcare services are widely available, these methods have not been applied in the current literature to explore the potential access to mental health services by Indigenous populations. This is partially due to limited understanding of how Indigenous populations seek mental healthcare, barriers that prevent Indigenous people from accessing diverse types of mental health services, and scarcity of data that are available to researchers. Future research could focus on developing methods to support spatially explicit measuring of accessibility to mental health services for Indigenous populations.

Dasatinib suppresses collective cell migration through the coordination of focal adhesion and E-cadherin in colon cancer cells.

Collective cell migration is an important process in cancer metastasis. Unlike single-cell migration, collective cell migration requires E-cadherin expression in the cell cohort. However, the mechanisms underlying cellular contact and focal adhesions remain unclear. In this study, Src was hypothesized to coordinate focal adhesion and Rab11-mediated E-cadherin distribution during collective cell migration. This study primarily used confocal microscopy to visualize the 3D structure of cell-cell contacts with associated molecules. These results demonstrate that the clinical Src inhibitor dasatinib was less toxic to HT-29 colon cancer cells; instead, the cells aggregated. 3D immunofluorescence imaging showed that Rab11 was localized with E-cadherin at the adherens junctions of the apical cell-cell contacts. In the transwell assay, Rab11 colocalized with a broad range of E-cadherin proteins in collectively migrated cells, and dasatinib treatment significantly suppressed collective cell migration. Transmission electron microscopy demonstrated that dasatinib treatment increased cell membrane protrusion contacts and generated spaces between cells, which may allow epidermal growth factor receptor activity at the cell-cell contacts. This study suggests that dasatinib treatment does not inhibit cell survival but targets Src at different cellular compartments in the coordination of focal adhesions and cell-cell contacts in collective cell migration through E-cadherin dynamics in colon cancer cells.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

Predictors of Psychological Distress among Post-Operative Cardiac Patients: A Narrative Review.

Following surgery, over 50% of cardiac surgery patients report anxiety, stress and/or depression, with at least 10% meeting clinical diagnoses, which can persist for more than a year. Psychological distress predicts post-surgery health outcomes for cardiac patients. Therefore, post-operative distress represents a critical recovery challenge affecting both physical and psychological health. Despite some research identifying key personal, social, and health service correlates of patient distress, a review or synthesis of this evidence remains unavailable. Understanding these factors can facilitate the identification of high-risk patients, develop tailored support resources and interventions to support optimum recovery. This narrative review synthesises evidence from 39 studies that investigate personal, social, and health service predictors of post-surgery psychological distress among cardiac patients. The following factors predicted lower post-operative distress: participation in pre-operative education, cardiac rehabilitation, having a partner, happier marriages, increased physical activity, and greater social interaction. Conversely, increased pain and functional impairment predicted greater distress. The role of age, and sex in predicting distress is inconclusive. Understanding several factors is limited by the inability to carry out experimental manipulations for ethical reasons (e.g., pain). Future research would profit from addressing key methodological limitations and exploring the role of self-efficacy, pre-operative distress, and pre-operative physical activity. It is recommended that cardiac patients be educated pre-surgery and attend cardiac rehabilitation to decrease distress.

Genomic epidemiology and characterization of Staphylococcus aureus isolates from raw milk in Jiangsu, China: emerging broader host tropism strain clones ST59 and ST398.

Staphylococcus aureus is highly pathogenic and can cause disease in both humans and domestic animals. The aim of this study was to investigate the genomic epidemiology of S. aureus isolates from raw milk in Jiangsu Province, China, to identify predominant lineages and their associated genomic and phenotypic characteristics. In this study, we identified 117 S. aureus isolates collected from 1,062 samples in Jiangsu Province between 2021 and 2022. Based on whole-genome sequencing (WGS) data from 117 S. aureus isolates, molecular analyses indicated CC1-ST1 (26.50%, 31/117), CC97-ST97 (18.80%, 22/117), CC398-ST398 (10.26%, 12/117), CC8-ST630 (7.69%, 9/117) and CC59-ST59 (2.56%, 3/117) were the major lineages. The prevalence of mecA-positive strains was 11.11%. Four methicillin-resistant S. aureus (MRSA) lineages were found, including MRSA-ST59-t172 (n = 3), OS-MRSA-ST398-t011 (n = 1), MRSA-ST630-t2196 (n = 2) and OS-MRSA-ST630-t2196 (n = 7). Phenotypic resistance to penicillin (30.77%, 36/117), ciprofloxacin (17.09%, 20/117) and erythromycin (15.38%, 18/117) was observed which corresponded with resistance genotypes. All of the isolates could produce biofilms, and 38.46% (45/117) of isolates had invasion rates in mammary epithelial cells (MAC-T) of greater than 1%. Interestingly, most biofilm-producing and invading isolates harbored ebp-icaA-icaB-icaC-icaR-clfA-clfB-fnbA-fnbB-sdrC-sdrD-sdrE-map-can (27.35%, 32/117) and ebp-icaA-icaB-icaC-icaD-icaR-clfA-clfB-fnbA-fnbB-sdrC-sdrD-sdrE-map (33.33%, 39/117) adherence-associated gene patterns and belonged to lineages CC1 and CC97, respectively. Virulence factor assays showed that 47.01% of the isolates contained at least enterotoxin genes. Isolates harboring the immune evasion cluster (IEC) genes (sea, sak, chp, and scn) were predominantly categorized as STs 464, 398, and 59. IEC-positive ST398 and ST59 isolates contained a very high proportion of virulence genes located on prophages, whereas most IEC-negative ST398 clade isolates carried broad-spectrum drug resistance genes. Meanwhile, the IEC-positive ST398 clade showed a close genetic relationship with isolates from the pork supply chain and hospital surgical site infections. MRSA-ST59 strains showed the closest genetic relationship with an isolate from quick-frozen products. High-risk livestock-associated strains ST398 and MRSA-ST59 were detected in raw milk, indicating a potential public health risk of S. aureus transmission between livestock and humans. Our study highlights the necessity for S. aureus surveillance in the dairy industry.

Mitochondrial genome characteristics of six Phylloscopus species and their phylogenetic implication.

The mitochondrial genomes of six Phylloscopus species-small insectivores belonging to the Phylloscopidae family-were obtained using the Illumina sequencing platform. The mitogenomes were closed circular molecules 16,922-17,007 bp in size, containing 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions (CR1 and remnant CR2). The gene orders were conserved in 35 sampled Phylloscopus mitogenomes in the GenBank database, with a gene rearrangement of cytb-trnT-CR1-trnP-nad6-trnE-remnant CR2-trnF-rrnS. The average base compositions of the six Phylloscopus mitogenomes were 29.43% A, 32.75% C, 14.68% G, and 23.10% T, with the A+T content slightly higher than that of G+C. ATG and TAA were the most frequent initiating and terminating codons, respectively. Several conserved boxes were identified in CR1, including C-string in domain I; F, E, D, and C boxes, as well as bird similarity and B boxes, in domain II; and CSB1 in domain III. Tandem repeats were observed in remnant CR2 of the Phylloscopus fuscatus and Phylloscopus proregulus mitogenomes. A phylogenetic analysis with maximum likelihood (ML) and Bayesian inference (BI) methods, based on 13 protein-coding genes and two rRNA genes, indicated that the Phylloscopus species was divided into two larger clades, with a splitting time approximately 11.06 million years ago (mya). The taxa of Phylloscopus coronatus/Phylloscopus burkii and Phylloscopus inornatus/P. proregulus were located at the basal position of the different clades. The phylogenetic result of the cox1 gene showed that Seicercus was nested within Phylloscopus. The complete set of mitogenomes of the Phylloscopus species provides potentially useful resources for the further exploration of the taxonomic status and phylogenetic history of Phylloscopidae.

Livestock grazing is associated with the gut microbiota and antibiotic resistance genes in sympatric plateau pika (Ochotona curzoniae).

With the overuse of antibiotics in health care and animal husbandry, antibiotic resistance becomes a serious threat to public health. Antibiotic residues from veterinary medicine have increased the dissemination of antibiotic resistance genes (ARGs) by horizontal gene transfer globally, leading to the enrichment of ARGs in wildlife. Plateau pika (Ochotona curzoniae) is a small herbivore endemic to the Qinghai-Tibetan Plateau. Previous studies reveal that pika evolves a coprophagy behavior toward cohabitated yak, which makes the pika population a potential reservoir of ARGs. Yet, little is known about the resistome of pika under different grazing intensities. Here, we sampled the cecum content of pika from three different grazing intensity areas in the Qinghai-Tibetan Plateau to evaluate the effect of grazing on its gut microbiota and resistome. By using the 16S full-length amplicon and metagenomic sequencing, our study revealed that livestock grazing significantly altered the gut microbial community of plateau pika as compared to prohibited grazing areas. We found bacterial lineage Prevotellaceae, Lachnospirales, and RF39 increased in grazing areas. Analysis of the resistome revealed that pika from continuous grazing areas enriched a higher abundance of colistin (MCR) and streptogramin (vat) resistance genes. Moreover, we observed significant correlations between the gut microbial community, ARGs, and mobile genetic element profiles, hinting that pika gut microbiota was an important shaping force of the resistome. In future studies, the continuous monitoring of wildlife gut resistome and environmental antibiotic residues is imperative for a better understanding and for tackling the horizontal gene transfer of ARGs across the wildlife-livestock interface.

Incidence of Discharge Against Medical Advice in Queensland Hospital Emergency Departments Among Indigenous Patients from 2016 to 2021.

BACKGROUND: The incidence of discharge against medical advice (DAMA) in emergency departments (EDs) among Indigenous people is a growing concern in Australia. This study aimed to determine the incidence of ED DAMA in public hospitals in Queensland (QLD) from 2016 to 2021 and investigate the disparities in ED DAMA between Indigenous and non-Indigenous patients. The study also assessed the impact of the COVID-19 pandemic on the incidence of ED DAMA. METHODS: A descriptive epidemiological study was conducted using aggregated data from QLD public hospital EDs. The data was retrieved from Clinical Excellence QLD, Healthcare Improvement Unit, in the QLD Health Open Data Portal for the period 1 January 2016 to 31 December 2021. Incidence rates and unadjusted odds ratios were calculated and compared using the chi-square test to identify differences between Indigenous and non-Indigenous patients. RESULTS: The annual incidence of DAMA in EDs was 7.7% among Indigenous patients, compared to 4.8% among non-Indigenous patients, with the highest rate (8.9%) reported in 2021 among Indigenous patients. The incidence of ED DAMA was higher for Indigenous patients in major cities (20.0%) than in very remote areas (7.4%). Patients in triage categories 4 (10.0%) and 3 (7.3%) accounted for the vast majority of ED DAMA events among Indigenous patients. The acute group A hospitals had the highest incidence of ED DAMA (10.9% for Indigenous patients and 6.5% for non-Indigenous patients). The COVID-19 pandemic had no impact on the incidence of ED DAMA. CONCLUSION: Indigenous patients experience a disparity in ED DAMA incidence. Addressing this issue requires collaborative efforts from healthcare providers, policymakers, and community organizations.

Threshold control strategy for a Filippov model with group defense of pests and a constant-rate release of natural enemies.

In this paper, we establish an integrated pest management Filippov model with group defense of pests and a constant rate release of natural enemies. First, the dynamics of the subsystems in the Filippov system are analyzed. Second, the dynamics of the sliding mode system and the types of equilibria of the Filippov system are discussed. Then the complex dynamics of the Filippov system are investigated by using numerical analysis when there is a globally asymptotically stable limit cycle and a globally asymptotically stable equilibrium in two subsystems, respectively. Furthermore, we analyze the existence region of a sliding mode and pseudo equilibrium, as well as the complex dynamics of the Filippov system, such as boundary equilibrium bifurcation, the grazing bifurcation, the buckling bifurcation and the crossing bifurcation. These complex sliding bifurcations reveal that the selection of key parameters can control the population density no more than the economic threshold, so as to prevent the outbreak of pests.

Facile synthesis of phosphorus and nitrogen co-doped carbon dots with excellent fluorescence emission towards cellular imaging.

Fluorescent carbon nanomaterials have attracted increasing attention owing to their unique photoluminescence properties, good biocompatibility and low toxicity in bioimaging as well as biosensing. Heteroatom doping is usually used to improve photoluminescence properties by tuning the functional groups and the particle size domain effect, thus leading to redshifted emission. Here, we report a straightforward strategy for the fabrication of a mixture of fluorescent phosphorus and nitrogen carbon nanodots (P,N-CDs) followed by separating two kinds of fluorescent fractions based on their different negative charges. Such a one-pot hydrothermal method using formamide, urea and hydroxyethylidene diphosphonic acid as the precursor yields fluorescent P,N-CDs. Specifically, blue-emitting CDs (bCDs) and green-emitting CDs (gCDs) were separated by using column chromatography. The quantum yields of bCDs and gCDs were 20.33% and 1.92%, respectively. And the fluorescence lifetimes of bCDs and gCDs were 6.194 ns and 2.09 ns, respectively. What is more, the resultant P,N-CDs exhibited low toxicity and excellent biocompatibility. Confocal fluorescence microscopy images were obtained successfully, suggesting that P,N-CDs have excellent cell membrane permeability and cellular imaging. This work provides a promising fluorescent carbon nanomaterial with tunable emission as a probe for versatile applications in bioimaging, sensing and drug delivery.

Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1-b][1,3,4]thiadiazole moiety.

Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.

MOFs-based Fe@YAU-101/GCE electrochemical sensor platform for highly selective detecting trace multiplex heavy metal ions.

The construction of sensors with specific recognition functions can easily, sensitively and efficiently detect heavy metal ions, which is a demand in the field of electrochemical sensing and an important topic in the detection of environmental pollutants. An electrochemical sensor based on MOFs composites was developed for sensing of multiplex metal ions. The large surface area, adjustable porosities and channels in MOFs facilitate successful loading of sufficient quantities highly active units. The active units and pore structures of MOFs are regulated and synergetic with each other to enhance the electrochemical activity of MOFs composites. Thus, the selectivity, sensitivity and reproducibility of MOFs composites have been improved. Fortunately, after characterization, Fe@YAU-101/GCE sensor with strong signal was successfully constructed. In the presence of target metal ions in solution, the Fe@YAU-101/GCE can efficiently and synchronously identify Hg2+, Pb2+, and Cd2+. The detection limits (LOD) are 6.67 × 10-10 M(Cd2+), 3.33 × 10-10 M(Pb2+) and 1.33 × 10-8 M (Hg2+), and are superior to the permissible limits set by the National Environmental Protection Agency. The electrochemical sensor is simple without sophisticated instrumentation and testing processes, hence promising for practical applications.

Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes.

ConspectusAlkenes are versatile compounds that are readily available on a large scale from industry or through organic synthesis. The widespread occurrence of alkenes provides the continuous impetus for the development of catalytic asymmetric alkene hydrofunctionalizations, which enables expeditious construction of complex chiral molecules from readily available starting materials. Catalytic asymmetric hydrofunctionalization of internal alkenes presents a notable challenge, due to their low reactivity, many potential side reactions, and the simultaneous control of the regio-, diastereo-, and enantioselectivities.Dehydroamino acids and enamides are among the first substrates that provide notable enantioselectivities in catalytic asymmetric hydrogenation. The crucial importance of an amide coordinating group is established by a series of classical mechanistic studies. This initial success greatly stimulated further development for catalytic hydrogenation and hydrofunctionalization. Building on these pioneering works in asymmetric hydrogenation as well as related hydrofunctionalizations, we have adopted coordination assistance as a powerful tool to address the challenges associated with the asymmetric hydrofunctionalization of internal alkenes. Using a functional group on the alkene substrate as a native coordinating group, a two-point binding mode of the substrate to the metal center effectively enhances the reactivity and facilitates the control of regio-, diastereo- and enantioselectivities. Through this strategy, we have developed a number of alkene hydrofunctionalization methods with excellent regio-, diastereo-, and enantiocontrols.In this Account, we summarize the recent advance in our lab using coordination assistance as a key element to achieve regio- and enantioselective hydroalkynylation of internal alkenes. First, we describe our early work aimed at controlling the regio- and enantioselectivity of hydroalkynylation using disubstituted enamide as the substrate. Both α- and ß-alkynylation were achieved by channeling the reaction pathway into a Chalk-Harrod or modified Chalk-Harrod mechanism. Next, we discuss the further development of catalysts to achieve regiodivergent and enantioselective hydroalkynylation of trisubstituted enamide to access vicinal stereocenters and quaternary carbon stereocenters. We also discuss the hydroalkynylation of α,ß-unsaturated amides to achieve unconventional site-selectivity through a combination of alkene isomerization and regioselective hydroalkynylation. This provides the basis for the construction of a remote quaternary carbon stereocenter through catalytic hydroalkynylation of trisubstituted ß,γ-unsaturated amides. We further show that this controlling principle is applicable to terminal alkene with a coordinating group as well. A ligand-controlled mechanism shift is discussed for the enantioselective alkynylation at the terminal and internal position of 1,1,-disubstituted alkenes. Finally, we briefly mention the application of coordination assistance to other hydrofunctionalizations such as hydroboration and hydrosilylation, where previously inaccessible reactivity and selectivity were achieved. Collectively, these catalytic methods demonstrate the power of coordination assistance for enantioselective hydrofunctionalizations. We anticipate that this strategy will create a platform to enable diverse enantioselective alkene transformations.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Factors Influencing Medication Errors in the Prehospital Paramedic Environment: A Mixed Method Systematic Review.

INTRODUCTION: There is limited research available on safe medication management practices in emergency medical services (EMS) practice, with most evidence-based medication safety guidelines based on research in nursing, operating theater and pharmacy settings. Prevention of errors requires recognition of contributing factors across the spectrum from the organizational level to procedural elements and patient characteristics. Evidence is inconsistent regarding the incidence of medication errors and multiple sources also state that errors are under-reported, making the true magnitude of the problem difficult to quantify. Definitions of error also vary, with the specific context of medication errors in prehospital practice yet to be established. The objective of this review is to identify the factors influencing the occurrence of medication errors by EMS personnel in the prehospital environment. METHODS AND ANALYSIS: The review included both qualitative and quantitative research involving interventions or phenomena related to medication safety or medication error by EMS personnel in the prehospital environment. A search of multiple databases was conducted to identify studies meeting these inclusion criteria. All studies selected were assessed for methodological quality; however, this was not used as a basis for exclusion. Each stage of study selection, appraisal and data extraction was conducted by two independent reviewers, with a third reviewer deciding any unresolved conflicts. The review follows a convergent integrated approach, conducting a single qualitative synthesis of qualitative and "qualitized" quantitative data. RESULTS: Fifty-six articles were included in the review, with case reports and qualitative studies being the most frequent study types. Qualitative analysis revealed seven major themes: organizational factors (with reporting as a sub-theme), equipment/medications, environmental factors, procedure-related factors, communication, patient-related factors (with pediatrics as a sub-theme) and cognitive factors. Both contributing factors and protective factors were identified. DISCUSSION: The body of evidence regarding medication errors is heterogenous and limited in both quantity and quality. Multiple factors influence medication error occurrence; knowledge of these is necessary to mitigate the risk of errors. Medication error incidence is difficult to quantify due to inconsistent measure, definitions and contexts of research conducted to date. Further research is required to quantify the prevalence of identified factors in specific practice settings.

Indigenous Australians' Experiences of Cancer Care: A Narrative Literature Review.

To provide the latest evidence for future research and practice, this study critically reviewed Indigenous peoples' cancer care experiences in the Australian healthcare system from the patient's point of view. After searching PubMed, CINAHL and Scopus databases, twenty-three qualitative studies were included in this review. The inductive approach was used for analysing qualitative data on cancer care experience in primary, tertiary and transitional care between systems. Three main themes were found in healthcare services from Indigenous cancer care experiences: communication, cultural safety, and access to services. Communication was an important theme for all healthcare systems, including language and literacy, understanding of cancer care pathways and hospital environment, and lack of information. Cultural safety was related to trust in the system, privacy, and racism. Access to health services was the main concern in transitional care between healthcare systems. While some challenges will need long-term and collective efforts, such as institutional racism as a downstream effect of colonisation, cultural training for healthcare providers and increasing the volume of the Indigenous workforce, such as Indigenous Liaison Officers or Indigenous Care Coordinators, could effectively address this inequity issue for Indigenous people with cancer in Australia in a timely manner.