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Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for the preparation of di- or tri-substituted alkenyl nitriles. Related approaches that are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z- or E-di-substituted cyano-substituted alkenes or their corresponding tri-substituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy to apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to the synthesis of biologically active compounds.

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z- and E-selective olefin metathesis is introduced. Prior to the addition of a sensitive Mo- or Ru-based complex, treatment of a hydroxy- or a carboxylic-acid-containing olefin with commercially available HB(pin) or readily accessible HB(trip)2 (pin=pinacolato, trip=2,4,6-tri(isopropyl)phenyl) for 15 min is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection. A range of stereochemically defined Z- and E-alkenyl chlorides, bromides, fluorides, and boronates or Z-trifluoromethyl-substituted alkenes with a hydroxy or carboxylic acid group were thus prepared in 51-97 % yield with 93 to >98 % stereoselectivity. We also show that, regardless of whether a polar functional unit is present or not, a small amount of HB(pin) may be used to remove residual water, significantly enhancing efficiency.

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity-namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products-and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D.

The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations.

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization-a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib-a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis-was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.

A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules.

Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules.

Objectives To investigate the serum IL-6 levels and their rate of change in predicting the mortality of critically ill patients with COVID-19 in Vietnam.Design A single-centre, cross-sectional study.Setting An Intensive Care Centre for the Treatment of Critically Ill Patients with COVID-19 in Ho Chi Minh City, Vietnam.Participants We included patients aged 18 years or older who were critically ill with COVID-19 and presented to the study centre from 30 July 2021 to 15 October 2021. We excluded patients who did not have serum IL-6 measurements between admission and the end of the first day.Primary outcome measures The primary outcome was hospital all-cause mortality.Results Of 90 patients, 41.1% were men, the median age was 60.5 years (Q1–Q3: 52.0–71.0), and 76.7% of patients died in the hospital. Elevated IL-6 levels were observed on admission (41.79 pg/mL; Q1–Q3: 20.68–106.27) and on the third day after admission (72.00 pg/mL; Q1–Q3: 26.98–186.50), along with a significant rate of change in IL-6 during that period (839.5%; SD: 2753.2). While admission IL-6 level (areas under the receiver operator characteristic curve (AUROC): 0.610 (95% CI: 0.459 to 0.761); cut-off value ≥15.8 pg/mL) and rate of change in IL-6 on the third day of admission (AUROC: 0.586 (95% CI: 0.420 to 0.751); cut-off value ≥−58.7%) demonstrated poor discriminatory ability in predicting hospital mortality, the third day IL-6 rate of change from admission ≥−58.7% (adjusted OR: 12.812; 95% CI: 2.104 to 78.005) emerged as an independent predictor of hospital mortality.Conclusions This study focused on a highly selected cohort of critically ill COVID-19 patients with a high IL-6 level and mortality rate. Despite the poor discriminatory value of admission IL-6 levels, the rate of change in IL-6 proved valuable in predicting mortality. To identify critically ill COVID-19 patients with the highest risk for mortality, monitoring the serial serum IL-6 measurements and observing the rate of change in serum IL-6 levels over time are needed.

Introduction Older adults can face challenges when seeking care from emergency departments (EDs) due to presenting with multiple comorbidities and non-specific symptoms. Psychosocial care is a possible target to help improve ED care for this population. It is possible that digital health technologies can be implemented within emergency settings to improve the provision of psychosocial care. However, it is unclear what the barriers and facilitators are to implementing digital psychosocial interventions for older adults presenting to the ED. Therefore, the scoping review aims to determine what are these barriers and facilitators.Methods and analysis The scoping review will be conducted in line with the Joanna Briggs Institute guidelines and will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The databases Medline, Embase, PsycINFO and Scopus will be searched. The search strategy will be developed in consultation with a specialist research librarian and will cover three key concepts: EDs, digital health technologies and older adults. Additionally, the first 100 hits of a Google Scholar search will be screened for inclusion. We will include both qualitative and quantitative studies that investigate ED digital interventions for psychosocial care where the primary focus is the views, attitudes, experiences and perceptions of patients, families and staff. After extracting all data, analysis and synthesis will follow the ‘best-fit framework synthesis’ approach and the Theoretical Domains Framework will be used to identify barriers and facilitators.Ethics and dissemination Ethics approval is not required for this scoping review since only publicly available data will be analysed and appraised. The findings of the scoping review will be disseminated through peer-reviewed publications and conference presentations.

Abstract Background Older people experiencing depression and anxiety have higher rates of health service utilisation than others, but little is known about whether these influence their seeking of emergency care. The aim was to examine the associations between symptoms of depression and the use of emergency health care, in an Australian context, among a population of people aged 70 years and over initially free of cardiovascular disease, dementia or major physical disability. Methods We undertook secondary analyses of data from a large cohort of community-dwelling Australians aged $$ \ge $$ 70 years. Multivariable logistic regression was used to compare the association of symptoms of depression (measured using the Center for Epidemiological Studies Depression Scale 10 question version, CESD at baseline) with subsequent episodes of emergency care, adjusting for physical and social factors of clinical interest. Marginal adjusted odds ratios were calculated from the logistic regression. Results Data were available for 10,837 Australian participants aged at least 70 years. In a follow-up assessment three years after the baseline assessment, 17.6% of people self-reported an episode of emergency care (attended an ED of called an emergency ambulance) in the last 12 months. Use of emergency healthcare was similar for men and women (17.8% vs. 17.4% p = 0.61). A score above the cut-off on the CESD at baseline was associated with greater use of emergency health care (OR = 1.35, 95% CI 1.11,1.64). When modelled separately, there was a greater association between a score above the cut-off on the CESD and emergency healthcare for women compared with men. Conclusions This study is unique in demonstrating how depressive symptoms among healthy older persons are associated with subsequent increased use of emergency healthcare. Improved understanding and monitoring of mental health in primary care is essential to undertake effective healthcare planning including prevention of needing emergency care.

This study aimed to establish evidence of the psychometric properties of the Centre for Epidemiologic Studies Depression Scale Revised – Vietnamese Version (CESDR-V) for use among adolescents in Vietnam. We selected 1084 Grade-10 students in Hanoi using a multiple-stage sampling method. The factorial structure of the CESDR-V was evaluated using exploratory factor analysis. Internal consistency was tested using Cronbach's alpha coefficient. Measurement invariance between male and female participants was tested using multiple group confirmatory factor analysis. Convergent and divergent validity were tested using Pearson's correlation coefficients between CESDR-V and the Depression Anxiety and Stress Subscales of Depression (DASS21-D), Anxiety (DASS21-A), and Stress (DASS21-S) and a measure of mental well-being, Mental Health Continuum Short Form (MHC-SF). The CESDR-V was found to be unidimensional. Cronbach's alpha coefficient of CESDR-V was 0.92. All levels of measurement invariance between male and female participants for the CESDR-V were supported well. The CESDR-V was positively correlated with DASS21-D at stronger levels (convergent pattern) than with DASS21-A/DASS21-S (discriminant pattern). The CESDR-V was negatively correlated with MHC-SF at a lower level than with the DASS21 subscales (discriminant pattern). This study strongly supports the use of the CESDR-V to screen for depression in adolescents in Vietnam who are attending school.

Các quan hệ thứ tự tập dùng trong bài toán tối ưu tập đóng vai trò quan trọng trong áp dụng vào các bài toán trong thực tế. Việc xây dựng giải thuật nhằm so sánh các tập hợp theo các quan hệ thứ tự tập là thiết thực và là tiền đề cho việc đi sâu nghiên cứu về giải thuật cho lớp bài toán tối ưu tập. Nghiên cứu này tập trung vào việc xây dựng giải thuật so sánh hai tập hợp cùng với liên hệ vận dụng vào các mô hình kinh tế, xã hội trong thực tế.

Abstract Background Gestational diabetes mellitus is associated with perinatal mental disorders. Effective management may reduce this risk, but there is little evidence on effects of different glycaemic treatment targets. We assessed whether tight glycaemic treatment targets compared with less-tight targets reduce the risk of poor mental health outcomes in women with gestational diabetes. Methods This was a secondary analysis of data from women who consented to complete perinatal mental health questionnaires as participants in the TARGET Trial, a stepped-wedge cluster randomized trial in 10 hospitals in New Zealand. All hospitals initially used less tight glycaemic targets for management of gestational diabetes and were sequentially randomized, in clusters of two at 4-monthly intervals, to using tighter glycaemic targets. Data were collected from 414 participants on anxiety (6-item Spielberger State Anxiety scale), depression (Edinburgh Postnatal Depression Scale), and health-related quality of life (36-Item Short-Form General Health Survey) at the time of diagnosis (baseline), 36 weeks of gestation, and 6 months postpartum. The primary outcome was composite poor mental health (any of anxiety, vulnerability to depression, or poor mental health-related quality of life). Generalized linear mixed models were used to determine the main treatment effect with 95% confidence intervals using an intention-to-treat approach. Results We found no differences between randomised glycaemic target groups in the primary outcome at 36 weeks’ (relative risk (RR): 1.07; 95% confidence interval 0.58, 1.95) and 6 months postpartum (RR: 1.03; 0.58, 1.81). There were similarly no differences in the components of the primary outcome at 36 weeks’ [anxiety (RR: 0.85; 0.44, 1.62), vulnerability to depression (RR: 1.10; 0.43, 2.83), or poor mental health-related quality of life (RR: 1.05; 0.50, 2.20)] or at 6 months postpartum [anxiety (RR:1.21; 0.59, 2.48), vulnerability to depression (RR:1.41; 0.53, 3.79), poor mental health-related quality of life (RR: 1.11; 0.59, 2.08)]. Conclusion We found no evidence that adoption of tighter glycaemic treatment targets in women with gestational diabetes alters their mental health status at 36 weeks’ gestation and at 6 months postpartum. Trial registration The Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12615000282583 (ANZCTR—Registration). Date of registration: 25 March 2015.

ObjectivesWe investigated changes over time in mental and social wellbeing indicators for vulnerable population subgroups during the pandemic. These groups were younger people, people with disabilities, low-income groups, unemployed, culturally, and linguistically diverse communities (CaLD), and Aboriginal and Torres Strait Islander peoples.MethodsA series of four repeated population representative surveys were conducted in June 2020, September 2020, January 2022, and June 2022. Questions included items on psychological distress, financial hardship, social connection, and life satisfaction.ResultsFor most groups, social connection and life satisfaction improved in 2022 relative to 2020. Psychological distress and financial hardship showed the opposite pattern, with some groups having worse results in 2022 relative to 2020. People without any vulnerability had better mental health and social wellbeing outcomes at each time point relative to the vulnerable population subgroups.ConclusionPandemic-related policies had differential effects over time and for different population groups. Future policies and research need to closely monitor how they impact population subgroups, and the overall results clearly demonstrate the inequity in mental health and social wellbeing outcomes for vulnerable population cohorts.

Introduction: To decrease the risk of complications from ventilator-associated pneumonia, it is essential to implement preventative measures in all ICU patients. Since 2018, with the help of Japanese experts, we have applied a ventilator-associated pneumonia care bundle with 10 basic standards in patient care and monitoring. Therefore, we conducted a study to evaluate the results of applying 10 solutions to prevent ventilator-associated pneumonia over 24 months. Methods: A cross-sectional descriptive study with longitudinal follow-up for 24 months on 170 mechanically ventilated patients at the Center for Critical Care Medicine, Bach Mai Hospital. According to the Centers for Disease Control (CDC, 2021), the diagnosis of ventilator-associated pneumonia is when pneumonia appears 48 h after intubation by confirmation by at least two doctors. Evaluate compliance with each solution in the care bundle through camera monitoring, medical records, and directly on patients daily. Results: The rate of ventilator-associated pneumonia is 12.9%, the frequency of occurrence is 16.54 of 1000 days. The compliance rate for complete compliance with a 10-item ventilator-associated pneumonia was only 1.8%, while the average value was 84.1%. Average values of compliance with each solution for hand hygiene, head elevation 30–45 degrees, oral hygiene, stopping sedation, breathing circuit management, cuff pressure management, hypoplastic suction, Spontaneous breathing trial (SBT) daily and assessed extubation, mobilization and early leaving bed, ulcer and thrombosis prevention were 96.9%, 97.3%, 99.4%, 81.5%, 99.9%, 99.9%, 86.3%, 83.5%, 49.3%, and 46.4%, respectively. The time to appear ventilator-associated pneumonia in the high compliance group was 46.7 ± 5.0 days, higher than in the low compliance group, 10.3 ± 0.7 days, p

Aim: To synthesize the evidence about the relationships between parents’ mental health and the social-emotional development of their children aged 24 to 59 months in low and middle-income countries (LMICs). Methods: We used a systematic strategy to search six databases for studies from LMICs, published between 2010 and 2021, of mental health problems experienced by parents and the social-emotional development of their children. We followed the standard methods for systematic reviews and meta-analyses set down in the PRISMA, MOOSE and COSMOS-E guidelines. Data were reported in a narrative synthesis. Meta-analysis was undertaken to calculate pooled odds ratios (ORs) and standard mean differences (SMD). Results: Overall, 26 papers reporting 15 cross-sectional studies and secondary analyses and 11 prospective cohort studies, from seven LMICs met inclusion criteria. The parent mental health problems studied were depression, anxiety, common mental disorders, stress, and mood disorders. Almost all the studies that assessed either perinatal or contemporaneous exposure to parental mental health problems found a significant association with increased child social-emotional development problems when aged 24 to 59 months. The use of harsh discipline in parenting mediated the relationship between maternal depression and higher prevalence of child’s externalizing behaviours. The children of parents with mental health problems were at nearly twice the odds of having social-emotional development problems (OR: 1.92, 95% CI: 1.47, 2.37), compared to children of parents without them. The pooled size of the effect (SMD) of parents' symptoms of mental health problem on child social-emotional development scores was 0.14 (95% CI: 0.04; 0.24). Conclusion: In LMICs, interventions to optimize early childhood social-emotional development need to address the mental health of parents. Rigorous prospective studies are needed to identify mechanisms and causal pathways, including modifiable risk and protective factors in the many LMICs which lack evidence to inform local policies, programs, and practices.