Association of weather variables with pathogens contributing to conjunctivitis worldwide.

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally. METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus). RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type. CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

Arabidopsis transcription factor ANAC102 predominantly expresses a nuclear protein and acts as a negative regulator of methyl viologen-induced oxidative stress responses.

Plants, being sessile organisms, constantly need to respond to environmental stresses, often leading to the accumulation of reactive oxygen species (ROS). While ROS can be harmful, they also act as second messengers guiding plant growth and stress responses. Because chloroplasts are sensitive to environmental changes and are both a source and a target of ROS during stress conditions, they are important in conveying environmental changes to the nucleus, where acclimation responses are coordinated to maintain organellar and overall cellular homeostasis. ANAC102 has previously been established as a regulator of ß-cyclocitral-mediated chloroplast-to-nucleus signaling, protecting plants against photooxidative stress. However, debates persist about where ANAC102 is located-in chloroplasts or in the nucleus. Our study, utilizing the genomic ANAC102 sequence driven by its native promoter, establishes ANAC102 primarily as a nuclear protein, lacking a complete N-terminal chloroplast-targeting peptide. Moreover, our research reveals the sensitivity of plants overexpressing ANAC102 to severe superoxide-induced chloroplast oxidative stress. Transcriptome analysis unraveled a dual role of ANAC102 in negatively and positively regulating genome-wide transcriptional responses to chloroplast oxidative stress. Through the integration of published data and our own study, we constructed a comprehensive transcriptional network, which suggests that ANAC102 exerts direct and indirect control over transcriptional responses through downstream transcription factor networks, providing deeper insights into the ANAC102-mediated regulatory landscape during oxidative stress.

Effects of Dye Addition on the Rheological Properties of Aqueous Polymer Solutions.

In many commercial applications, polymer-dye interactions are frequently encountered from food to wastewater treatment, and while shear rheology has been well characterized, the extensional properties are not well known. The extensional viscosity ηE and relaxation time λE are the extensional rheological parameters that provide valuable insights into how aqueous polymers respond during deformation, and this study investigated the effect of dyes on the extensional rheology of three different aqueous polymer solutions (e.g., anionic, cationic, and neutral) paired with two different dye salts (e.g., anionic and cationic) using drop pinch-off experiments. We have found that the influence of dyes on the pinch-off dynamics is complex but generally leads to a decrease in, for example, the apparent extensional relaxation time. We have utilized the dripping-onto-substrate method to probe the uniaxial deformation of widely used polymers such as xanthan gum (XG), poly(diallyldimethylammonium chloride) (PDADMAC), and poly(ethylene oxide) (PEO) as the anionic, cationic, and neutral polymers, respectively, paired with either fluorescein (Fl) or methylene blue (MB) as the anionic and cationic dyes, respectively. Polymer-dye pairs with opposite charges (e.g., XG-MB and PDADMAC-Fl) displayed a pronounced decrease in pinch-off times, but even PEO, which is a neutral polymer, resulted in decreased pinch-off times, which was restored by the addition of NaCl. The pinch-off times for the Boger fluid (mixture of poly(ethylene glycol) and PEO), however, were surprisingly uninfluenced by dyes. These results showed that not only did the small addition of dyes strongly decrease the polymer relaxation times, but the relative importance of the dye salts on the polymer pinch-off dynamics was also different from that of pure salts such as NaCl.

The impacts of telemedicine on assisted reproduction: a systematic review and meta-analysis.

Telemedicine is being applied in assisted reproduction technology (ART) to provide remote consultations, monitoring and support for patients. This study aimed to evaluate the potential advantages of telemedicine in ART treatment in the form of virtual consultations. Studies in which patients were using telemedicine during ART treatment were identified from four scientific databases (PudMed, EMBASE, Scopus, Web of Science). The success of fertility treatments was compared between telemedicine and in-office care, and patient satisfaction with ART through telemedicine was assessed. Eleven studies, comprising 4697 patients, were identified. Quality assessment (Joanna Briggs Institute Critical Appraisal and revised Cochrane risk-of-bias tools) revealed an acceptable risk of bias for both randomized controlled trials and observational studies. Using a fixed-effects model, telemedicine was comparable to in-person care regarding the pregnancy rate achieved (odds ratio 1.02, 95% confidence intervals 0.83-1.26, P = 0.83). A Q-test suggested that all the included studies were homogeneous. Patients who received telemedicine during fertility treatment reported a high level of satisfaction (91%, 95% confidence intervals 80-96%). Egger's test confirmed that no publication bias was found. Telemedicine could serve as a complementary tool during fertility treatment to facilitate patients' satisfaction and overcome some practical problems without compromising treatment outcomes. Future studies should continue exploring the potential applications of telemedicine in assisted reproduction.

Claisen Self-Condensation of Lactones in the Synthesis of Ionizable Lipids.

The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence of TiCl4 and triethylamine. The primary Claisen products can be elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for the synthesis of ionizable lipids for the delivery of nucleic acid therapeutics and can now be accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.

Polygenic Risk Score Informed Clinical Model for Improving Abdominal Aortic Aneurysm Screening.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRSs) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening. METHODS: PRSAAA was calculated using 911,440 SNVs and PRS of coronary artery disease was calculated using 2,324,683 SNVs derived from mixed ancestry genome-wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at the time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS-informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA. RESULTS: Four hundred eighty-one thousand one hundred 5 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30 to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23 to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (hazard ratio 2.06 [1.70-2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (hazard ratio 1.92 [1.69-2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Among males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA. CONCLUSIONS: Prob-AAA, a PRS-informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor-informed, screening guidelines for AAA.

Comparison between cycloplegic and noncycloplegic refraction in young adult myopes.

SIGNIFICANCE: This study explores the difference between cycloplegic and noncycloplegic refraction in young adult myopes. PURPOSE: From the available literature, it is unclear whether cycloplegia is necessary when refracting young adults. This study investigates the agreement between noncycloplegic autorefraction and cycloplegic autorefraction and investigates factors affecting the agreement between the two methods. METHODS: In total, 125 myopes with ages ranging between 18 and 26 years were included from Australia and Vietnam. Each participant underwent noncycloplegic autorefraction and cycloplegic autorefraction. Cycloplegia was induced with 1% ophthalmic tropicamide. RESULTS: The mean spherical equivalent difference (95% confidence interval) between noncycloplegic autorefraction and cycloplegic autorefraction was -0.20 D (-0.25 to -0.14 D; t124 = -7.18, p<0.0001 ) . A mean difference of >0.25 D was seen in 46.8% of eyes. The lower and upper limits of agreement were -0.80 and 0.41 D, respectively. With univariate analysis, factors including age, degree of refractive error, accommodation amplitude, and distance phorias showed no impact on the average difference between cycloplegic autorefraction and noncycloplegic autorefraction. Yet, eyes with near exophoria ( F2,120 = 6.63, p=0.0019) and Caucasian eyes ( F3,121 = 2.85, p=0.040) exhibited the smallest paired differences. However, in the multivariate analysis, only near exophoria was associated with a lower mean difference. A significantly smaller proportion (34.9%) of eyes with near exophoria had a paired difference of -0.25 D or more compared with esophoria (50%) and orthophoria (65%; χ2 = 6.6, p=0.038). CONCLUSIONS: Noncycloplegic autorefraction results in more myopic refractive error than cycloplegic autorefraction in young adults.

CRK2 and C-terminal Phosphorylation of NADPH Oxidase RBOHD Regulate Reactive Oxygen Species Production in Arabidopsis.

Reactive oxygen species (ROS) are important messengers in eukaryotic organisms, and their production is tightly controlled. Active extracellular ROS production by NADPH oxidases in plants is triggered by receptor-like protein kinase-dependent signaling networks. Here, we show that CYSTEINE-RICH RLK2 (CRK2) kinase activity is required for plant growth and CRK2 exists in a preformed complex with the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) in Arabidopsis (Arabidopsis thaliana). Functional CRK2 is required for the full elicitor-induced ROS burst, and consequently the crk2 mutant is impaired in defense against the bacterial pathogen Pseudomonas syringae pv tomato DC3000. Our work demonstrates that CRK2 regulates plant innate immunity. We identified in vitro CRK2-dependent phosphorylation sites in the C-terminal region of RBOHD. Phosphorylation of S703 RBOHD is enhanced upon flg22 treatment, and substitution of S703 with Ala reduced ROS production in Arabidopsis. Phylogenetic analysis suggests that phospho-sites in the C-terminal region of RBOHD are conserved throughout the plant lineage and between animals and plants. We propose that regulation of NADPH oxidase activity by phosphorylation of the C-terminal region might be an ancient mechanism and that CRK2 is an important element in regulating microbe-associated molecular pattern-triggered ROS production.

Formal Synthesis of (±)-Salvinorin A via Gold(I) Catalysis.

The formal synthesis of (±)-salvinorin A is presented. Our approach utilizes two distinct gold(I) catalytic processes. The combination of a gold(I)-catalyzed reaction with an intermolecular Diels-Alder reaction followed by a gold(I)-catalyzed photoredox reaction generated in eight steps the framework of the natural product with high diastereoselectivity.

Interplay of Drop Shedding Mechanisms on High Wettability Contrast Biphilic Stripe-Patterned Surfaces.

To improve the rate of DWC, numerous studies have adjusted the distribution of drops through biphilic surface patterning and wettability gradients to control the nucleation and drop shedding rates on the condensing surface, yet the connection between drop shedding mechanisms and surface wettability patterning remains unclear. Moreover, wettability patterning places geometric bounds on the governing forces (i.e., gravity, capillary, and inertia), which drive the droplet shedding mechanisms. Thus, the subsequent influence of droplet distribution along the DWC regions on the shedding mechanisms may not be known a priori. In this study, the area fraction, ADWC, of the DWC and also the DWC region width, LN, were varied between 10 and 50% and 0.5-1.5 mm, respectively, to probe the dominant droplet shedding mechanisms on a high wettability contrast surface (i.e., the contact angle on the DWC was 159 ± 3.4° and the hysteresis 9 ± 3.6°, whereas the FWC was nearly perfectly wetting). Humid air was introduced inside a custom-built chamber with the upright steady-state condensation imaged by both real-time and high-speed imaging techniques. We found that the droplet shedding mechanisms changed with increasing LN where the sliding drop radii are reduced with LN while the jumping drop radii remained unchanged with LN. The maximum drop size for shedding also decreased by 13%, which we attribute to the secondary droplet inertia, which helps gravity overcome the capillary retention force. Lastly, although many studies have probed DWC enhancements via surface wettability patterning, an optimal combination of ADWC and LN provided in this study significantly aids in the improvement of future DWC-based condensers and water collector applications.

Clinical benefit of AI-assisted lung ultrasound in a resource-limited intensive care unit.

BACKGROUND: Interpreting point-of-care lung ultrasound (LUS) images from intensive care unit (ICU) patients can be challenging, especially in low- and middle- income countries (LMICs) where there is limited training available. Despite recent advances in the use of Artificial Intelligence (AI) to automate many ultrasound imaging analysis tasks, no AI-enabled LUS solutions have been proven to be clinically useful in ICUs, and specifically in LMICs. Therefore, we developed an AI solution that assists LUS practitioners and assessed its usefulness in  a low resource ICU. METHODS: This was a three-phase prospective study. In the first phase, the performance of four different clinical user groups in interpreting LUS clips was assessed. In the second phase, the performance of 57 non-expert clinicians with and without the aid of a bespoke AI tool for LUS interpretation was assessed in retrospective offline clips. In the third phase, we conducted a prospective study in the ICU where 14 clinicians were asked to carry out LUS examinations in 7 patients with and without our AI tool and we interviewed the clinicians regarding the usability of the AI tool. RESULTS: The average accuracy of beginners' LUS interpretation was 68.7% [95% CI 66.8-70.7%] compared to 72.2% [95% CI 70.0-75.6%] in intermediate, and 73.4% [95% CI 62.2-87.8%] in advanced users. Experts had an average accuracy of 95.0% [95% CI 88.2-100.0%], which was significantly better than beginners, intermediate and advanced users (p < 0.001). When supported by our AI tool for interpreting retrospectively acquired clips, the non-expert clinicians improved their performance from an average of 68.9% [95% CI 65.6-73.9%] to 82.9% [95% CI 79.1-86.7%], (p < 0.001). In prospective real-time testing, non-expert clinicians improved their baseline performance from 68.1% [95% CI 57.9-78.2%] to 93.4% [95% CI 89.0-97.8%], (p < 0.001) when using our AI tool. The time-to-interpret clips improved from a median of 12.1 s (IQR 8.5-20.6) to 5.0 s (IQR 3.5-8.8), (p < 0.001) and clinicians' median confidence level improved from 3 out of 4 to 4 out of 4 when using our AI tool. CONCLUSIONS: AI-assisted LUS can help non-expert clinicians in an LMIC ICU improve their performance in interpreting LUS features more accurately, more quickly and more confidently.

Multifunctional Fe3O4 Nanoparticles Filled Polydopamine Hollow Rods for Antibacterial Biofilm Treatment.

This work reports the use of mesoporous silica rods as templates for the step-wise preparation of multifunctional Fe3O4 NPs filled polydopamine hollow rods (Fe3O4@PDA HR). The capacity of as-synthesized Fe3O4@PDA HR as a new drug carrier platform was assessed by its loading and the triggered release of fosfomycin under various stimulations. It was found that the release of fosfomycin was pH dependent with ~89% of fosfomycin being released in pH 5 after 24 h, which was 2-fold higher than that in pH 7. The magnetic properties of Fe3O4 NPs and the photothermal properties of PDA enabled the triggered release of fosfomycin upon the exposure to rotational magnetic field, or NIR laser irradiation. Additionally, the capability of using multifunctional Fe3O4@PDA HR to eliminate preformed bacterial biofilm was demonstrated. Upon exposure to the rotational magnetic field, the biomass of a preformed biofilm was significantly reduced by 65.3% after a 20 min treatment with Fe3O4@PDA HR. Again, due to the excellent photothermal properties of PDA, a dramatic biomass decline (72.5%) was achieved after 10 min of laser exposure. This study offers an alternative approach of using drug carrier platform as a physical mean to kill pathogenic bacteria along with its traditional use for drug delivery.

Treatment outcomes of EGFR-TKI with or without locoregional brain therapy in advanced EGFR-mutant non-small cell lung cancer patients with brain metastases.

Introduction: This study aimed to evaluate the treatment outcomes of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy alone or in combination with locoregional brain therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC) patients with brain metastases. Material and methods: A retrospective study involving 72 advanced EGFR-mutant NSCLC patients with brain metastases at the Vietnam National Cancer Hospital were conducted. Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy). Evaluation criteria included clinical and laboratory characteristics, central nervous system (CNS) progression time, progression-free survival (PFS), overall survival (OS), T790M mutation rate, and adverse events. Results: Epidermal growth factor receptor tyrosine kinase inhibitor monotherapy patients had better performance status (PS), fewer CNS symptoms, and significantly fewer brain metastases (p < 0.05). Median PFS and OS were 11 and 25 months, respectively, in both groups. Patients with PS 0-1 had longer median PFS (15 months) than those with PS 2 (7 months) (p = 0.039). Exon 19 deletion patients in both groups had longer median OS (26 months) than those with L858R exon 21 (15 months) (p = 0.023). Patients with T790M mutation who received osimertinib after progression had longer median OS (41 months vs. 23 months, p = 0.0001). Median time to CNS progression was 13.9 months (48 patients). Longer time to CNS progression correlated with longer OS (R2 = 0.89). Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor therapy, with or without locoregional therapy, is effective for advanced EGFR-mutant NSCLC patients with brain metastases. Exon 19 deletion patients had better prognosis.

Oscillation Dynamics of Drops on Immiscible Thin Liquid Films.

While drop oscillation dynamics has been widely studied for many decades, the influence of a moving contact line on the oscillation modes of drops remains underexplored. Herein, we report the oscillation dynamics of drops on thin liquid films with different viscosities where lower viscosities provide a slipping surface and higher viscosities immobilize the contact line. A gently deposited drop onto an oil film undergoes shape oscillations due to capillarity, where the frequency, amplitude, and apparent contact angle are tracked via a high-speed camera. This study demonstrates that restraining the mobility of the drop contact line by increasing the viscosity of a thin oil film underneath the drop increases the extent of the drop oscillation time as well as affecting the natural frequency of the drop oscillation. The drop oscillation time was defined by the time at which the changes in the drop height dropped to values less than 1% of the equilibrium height. The experimental results for the first longitudinal mode oscillation frequencies as a function of the equilibrium contact angles for the pinning and slipping contact lines were in good agreement with previously reported numerical simulations and model predictions.

A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials.

BACKGROUND: Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. METHODS: We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. RESULTS: The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. CONCLUSIONS: The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children.

First report of foodborne botulism due to Clostridium botulinum type A(B) from vegetarian home-canned pate in Hanoi, Vietnam.

Even one case of foodborne botulism constitutes a public health emergency. We report a series of cases with delayed treatment due to delayed diagnosis. Clostridium botulinum type A(B) was isolated from vegetarian home-canned pate, but not from stool samples. These are the first recorded cases of foodborne botulism in Hanoi.

A Conformal Frequency Reconfigurable Antenna with Multiband and Wideband Characteristics.

A compact flexible multi-frequency antenna for smart portable and flexible devices is presented. The antenna consists of a coplanar waveguide-fed slotted circular patch connected to a rectangular secondary resonator (stub). A thin low-loss substrate is used for flexibility, and a rectangular stub in the feedline is deployed to attain wide operational bandwidth. A rectangular slot is etched in the middle of the circular patch, and a p-i-n diode is placed at its center. The frequency reconfigurability is achieved through switching the diode that distributes the current by changing the antenna's electrical length. For the ON state, the antenna operates in the UWB region for -10 dB impedance bandwidth from 2.76 to 8.21 GHz. For the OFF state of the diode, the antenna operates at the ISM band (2.45/5.8 GHz), WLAN band (5.2 GHz), and lower X-band (8 GHz) with a minimum gain of 2.49 dBi and a maximum gain of 5.8 dBi at the 8 GHz band. Moreover, the antenna retains its performance in various bending conditions. The proposed antenna is suitable for modern miniaturized wireless electronic devices such as wearables, health monitoring sensors, mobile Internet devices, and laptops that operate at multiple frequency bands.

Dynamic Instability of Individual Carbon Nanotube Growth Revealed by In Situ Homodyne Polarization Microscopy.

Understanding the kinetic selectivity of carbon nanotube growth at the scale of individual nanotubes is essential for the development of high chiral selectivity growth methods. Here we demonstrate that homodyne polarization microscopy can be used for high-throughput imaging of long individual carbon nanotubes under real growth conditions (at ambient pressure, on a substrate) and with subsecond time resolution. Our in situ observations on hundreds of individual nanotubes reveal that about half of them grow at a constant rate all along their lifetime while the other half exhibits stochastic changes in growth rates and/or switches between growth, pause, and shrinkage. Statistical analysis shows that the growth rate of a given nanotube essentially varies between two values, with a similar average ratio (∼1.7) regardless of whether the rate change is accompanied by a change in chirality. These switches indicate that the nanotube edge or the catalyst nanoparticle fluctuates between different configurations during growth.

Divergent and Modular Synthesis of Terpenoid Scaffolds via a AuI Catalyzed One-Pot Cascade.

A one-pot cascade sequence to generate synthetically challenging polycyclic scaffolds is reported utilizing a novel Lewis acid gold catalyst for the key cyclization step, enabling the divergent synthesis of both 6,6,5-tricyclic and 6,6,6,5-tetracyclic cores through both ligand and reaction condition control. We have combined the intrinsic complexity and stereoselectivity of cycloadditions with the electronic and steric properties of gold complexes to selectively generate complex polycyclic scaffolds in a single operation.

What are the most effective community-based antimicrobial stewardship interventions in low- and middle-income countries? A narrative review.

Antimicrobial resistance (AMR) is a major global issue and antimicrobial stewardship is central to tackling its emergence. The burden of AMR disproportionately impacts low- and middle-income countries (LMICs), where capacity for surveillance and management of resistant pathogens is least developed. Poorly regulated antibiotic consumption in the community is a major driver of AMR, especially in LMICs, yet community-based interventions are neglected in stewardship research, which is often undertaken in high-income settings and/or in hospitals. We reviewed the evidence available to researchers and policymakers testing or implementing community-based antimicrobial stewardship strategies in LMICs. We critically appraise that evidence, deliver recommendations and identify outstanding areas of research need. We find that multifaceted, education-focused interventions are likely most effective in our setting. We also confirm that the quality and quantity of community-based stewardship intervention research is limited, with research on microbiological, clinical and economic sustainability most urgently needed.