Room-Temperature Phosphorescence Materials Featuring Triplet Hybrid Local Charge Transfer Emission.

Room-temperature phosphorescence materials have found important applications in dissolved oxygen sensing, temperature monitoring, anticounterfeiting, etc., because of their prolonged phosphorescence lifetime. However, the known systems mainly utilize the triplet local excited state emission, which is generally less sensitive to microenvironment perturbation. In this work, we designed a series of 4-phenyl-1,8-naphthalimide (NMI) derivatives containing different numbers of carbazole (Cz) units (denoted as NMI-Cz, NMI-2Cz, and NMI-3Cz). Steady state and time-resolved spectroscopy studies determined that the compounds undergo intramolecular through-space charge transfer in solution, yielding a triplet hybrid local charge transfer state. Room-temperature phosphorescence emission was observed in compound-doped poly(methyl methacrylate) thin films upon ammonia treatment. Interestingly, emission from different films exhibited different persistence times. We believe a film-based, time-resolved luminescent ammonia sensor could be developed by making a device of the emissive films as fabricated.

Nuciferine reduces inflammation induced by cerebral ischemia-reperfusion injury through the PI3K/Akt/NF-κB pathway.

BACKGROUND: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed. OBJECTIVE: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury. RESULTS: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue. CONCLUSION: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury.

Fast and Selective Luminescent Sensing by Langmuir-Schaeffer Films Based on Controlled Assembly of Perylene Bisimide Modified with A Cyclometalated AuIII Complex.

Condensed films of functional luminophores dominated by the magnitude and dimensionality of the intermolecular interactions play important roles in sensing performance. However, controlling the molecular assembly and regulating photophysical properties remain challenging. In this study, a new luminophore, ortho-PBI-Au, was synthesized by anchoring a cyclometalated alkynyl-gold(III) unit at the ortho-position of perylene bisimide. An unprecedented T-type packing model driven by weak Au-π interaction and Au-H bonds was observed, laying foundation for striking properties of the luminophore. Controlled assembly of ortho-PBI-Au at the air-water interface, realized using the classical Langmuir-Schaeffer technique, afforded the obtained luminescent films with different packing structures. With an optimized film, sensitive, selective, and rapid detection of a hazardous new psychoactive substance, phenylethylamine (PEA), was achieved. The detection limit, response time, and recovery time were <4 ppb, <1 s, and <5 s, respectively, surpassing the performance of the PEA sensors known thus far. The relationship between the characters of films and the sensing performance was systematically examined by grey relational analysis (GRA). The present study suggests that designing novel molecular aggregation with definite adlayer structure is a crucial strategy to enhance the sensing performance, which could be favorable for the film-based fluorescent sensors.

Comparative Observation of Distinct Dynamic Stokes Shifts in Diaryl BODIPY Triads with Broadband Two-Photon Absorption.

Time-resolved evolution of excited states in the twist-conjugated chromophores is of great fundamental interest for photoluminescent applications. The four diaryl BODIPY triads modified with diverse end-cappers at 2,6-positions were investigated properly, and considerable two-photon absorption capabilities in the first biological spectral window were obtained. Fast relaxations from the initially twisted conformation to the planarized conformation in the excited state were resolved spectrally and kinetically, accompanied by the discernible phenomenon of the fluorescence dynamic Stokes shift (DSS). Along with increasing electron donating capabilities and solvent polarities, the characteristics of structural rearrangement and intramolecular charge transfer have been estimated by enhanced DSS behaviors. Especially, the blue-shifted DSS was rationalized as the sequence conversion between the planarized state and the twisted charge transfer state. A molecular-level picture for relaxation pathways in different polarities was depicted and supported by the theoretical simulations. Significant and fast structural motions in this work contribute to the excited-state dynamics and rational development of versatile BODIPY chromophores.

ApoE4-mediated blood-brain barrier damage in Alzheimer's disease: Progress and prospects.

Late-onset Alzheimer's disease (AD), a neurodegenerative disease, is expected in the elderly population and adversely affects families and society. The extensive debate on the deposition of amyloid (Aß), abnormal phosphorylation of Tau protein, and neuroinflammation hypothesis in the pathogenesis of AD has been recognized by many scholars. The blood-brain barrier (BBB) is an essential physical barrier that protects the brain from external material interference, and its integrity affects the process of AD. Apolipoprotein E4 (ApoE4) has shown a critical regulatory role in many studies and is a crucial protein that affects AD. Numerous current studies on ApoE4 are based on complementary hypotheses to the three hypotheses above, ignoring the effect of ApoE4 on BBB constitutive cells and the role of the BBB in AD. In this review, we summarize the findings of the role of ApoE4 in the composition of the BBB and the value of ApoE4 for maintaining BBB integrity, which may play an essential role in changing the progression of the disease.

Precise Manipulation of Excited-State Intramolecular Proton Transfer via Incorporating Charge Transfer toward High-Performance Film-Based Fluorescence Sensing.

Excited-state intramolecular proton transfer (ESIPT) has been widely employed for the design of a variety of functionality-led molecular systems. However, precise manipulation of the excited-state reaction is challenging. Herein, we report a new tactic for tuning ESIPT via incorporating an excited-state intramolecular charge transfer (ESICT) process. Specifically, three o-carborane derivatives, NaCBO, PaCBO, and PyCBO, were designed, where the 2-(2'-hydroxyphenyl)-benzothiazole is a typical ESIPT unit functioning as an electron acceptor, and the electron-donating units are naphthyl-(Na), phenanthrenyl-(Pa), and pyrenyl-(Py), respectively. The architectures of the molecules are featured with a face-to-face alignment of the two units. Spectroscopy and theoretical calculation studies revealed that the electron-donating capacity of the donors and solvent polarity continuously modulate the ESIPT/ESICT energetics and dynamics, resulting in distinct emissions. Moreover, the molecules depicted not only highly porous structures but also very different fluorescent colors in the solid state, enabling highly selective film-based fluorescence sensing of mustard gas simulant, 2-chloroethyl ethyl sulfide, with a detection limit of 50 ppb and a response time of 5 s. This work thus provides a reliable strategy for the creation of high-performance sensing fluorophores via ESIPT manipulation.

Molecular characteristics and antibiotic resistance mechanisms of clindamycin-resistant Streptococcus agalactiae isolates in China.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal infections with high morbidity and mortality, and clindamycin is the main antibiotic used to treat GBS infections in patients allergic to penicillin. We aimed to analyse the antibiotic sensitivity, sequence types, serotypes, virulence factors, and antibiotic resistance mechanisms of clinically isolated clindamycin-resistant S. agalactiae and provide basic data for the treatment, prevention, and control of clinical infection of S. agalactiae. A total of 110 strains of clindamycin-resistant S. agalactiae were collected from two tertiary hospitals in Hebei, China. We performed antibiotic sensitivity tests for 11 antibiotics on these strains and whole-genome sequencing analysis. All the strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, tigecycline, and quinupristin-dalfopristin. Resistance to erythromycin, levofloxacin, tetracycline, and chloramphenicol were also observed. Genome sequence analysis revealed that all strains belonged to 12 sequence types (STs) related to six cloning complexes (CCs), namely CC10, CC19, CC23, CC651, CC1, and CC17. Five serotypes were identified, including IA, IB, II, III, and V. The most prominent resistance genes were mreA (100%) and ermB (81.8%). Furthermore, cfb, cylE, pavA and the gene cluster related to the pili were 100% present in all strains, followed by lmb (95.5%) and srr1 (67.2%). This study found that clindamycin-resistant S. agalactiae showed polymorphisms in molecular types and serotypes. Furthermore, multiple virulence factor genes have been identified in their genomes.

Medicinal fungus Phellinus igniarius alleviates gout in vitro by modulating TLR4/NF-kB/NLRP3 signaling.

Background: Phellinus igniarius (P. igniarius) is a valuable medicinal and edible fungus with various biological activities such as anti-inflammation, antioxidation, and immune regulation. In this study, we explored the effects of P. igniarius on a gout model in vitro. Methods: The DPPH, ABTS, and FRAP methods were combined to determine and compare the antioxidant activities of wild P. igniarius total polyphenols (WPP) and cultivated P. igniarius total polyphenols (CPP) in vitro. Spectrophotometry was used to compare the inhibitory effect of WPP and CPP on xanthine oxidase (XO) activity to evaluate anti-hyperuricemia activity in vitro. HUVECs were stimulated with monosodium urate (MSU) crystals for 24 h to establish an acute gouty inflammation model in vitro. The protective effects were compared by measuring cell viability; the contents of ICAM-1, IL-1ß, IL-6 and VCAM-1; the protein expressions of TLR4 and NLRP3; reactive oxygen species production; and the nuclear translocation of NF-κB p65. UHPLC-QE-MS technology was used to explore the potential metabolic mechanism of P. igniarius against gout. Results: WPP and CPP had strong antioxidant capacity, and the antioxidant capacity of CPP was similar to that of WPP. In a comparative experiment of xanthine oxidase activity inhibition by WPP and CPP, the IC50 values were 88.19 µg/ml and 108.0 µg/ml, respectively. At a dose of 40 µg/ml, WPP and CPP significantly improved the decrease in cell viability induced by monosodium urate (150 µg/ml) and inhibited the increase in inflammatory factors such as ICAM-1, IL-1ß, IL-6, and VCAM-1. The increase in TLR4 and NLRP3 protein expression induced by MSU crystals in HUVECs was also significantly inhibited by total polyphenols from wild and cultivated P. igniarius. In addition, both significantly improved MSU-induced ROS overproduction and NF-κB p65 nuclear translocation. WPP and CPP may primarily be involved in phenylalanine metabolism and lysophosphatidylcholine metabolism in their role in the treatment of gout. Conclusion: CPP and WPP both showed good antioxidant activity and xanthine oxidase inhibitory activity and had good therapeutic effects on the gout model in vitro. Furthermore, this study indicated that cultivated P. igniarius had a protective effect similar to that of wild P. igniarius, which would be expected to improve the shortage of wild P. igniarius and promote the development of the cultivated P. igniarius industry and product development.

Emerging advances in identifying signal transmission molecules involved in the interaction between Mycobacterium tuberculosis and the host.

Tuberculosis caused by Mycobacterium tuberculosis (MTB) is an ancient chronic infectious disease and is still the leading cause of death worldwide due to a single infectious disease. MTB can achieve immune escape by interacting with host cells through its special cell structure and secreting a variety of effector proteins. Innate immunity-related pattern recognition receptors (PPR receptors) play a key role in the regulation of signaling pathways. In this review, we focus on the latest research progress on related signal transduction molecules in the interaction between MTB and the host. In addition, we provide new research ideas for the development of new anti-tuberculosis drug targets and lead compounds and provide an overview of information useful for approaching future tuberculosis host-oriented treatment research approaches and strategies, which has crucial scientific guiding significance and research value.

Fast and Selective Detection of Trace Chemical Warfare Agents Enabled by an ESIPT-Based Fluorescent Film Sensor.

Reliable detection of airborne chemical warfare agents (CWAs) at the site and in real-time remains a challenge due to the rarity of miniaturized analytical tools. Herein, an o-carborane-functionalized benzothiazole derivative (PCBO) with excited-state intramolecular proton transfer (ESIPT) and AIE characteristics was synthesized. The PCBO-based film sensor showed a highly sensitive response to representative simulants of CWAs, and detection limits were found to be 1.0 mg·m-3 for triphosgene, 6.0 mg·m-3 for chloroethyl ethyl sulfide, and 0.2 mg·m-3 for diethyl chlorophosphite. Moreover, the sensor showed great reusability (>100 cycles) and unprecedented response speed (<0.5 s). The excellent sensing performance was ascribed to the microenvironmental sensitivity of the sensing fluorophore, the porous adlayer structure of the film, and the specific binding of the fluorophore to the analytes. Furthermore, discrimination and identification of the examined CWA simulants were realized via the introduction of another fluorophore (HCBO)-based film. Importantly, a portable fluorescent CWA detector was built with the sensor as the key component, and its applicability was demonstrated by the successful detection of a typical CWA sample (Sarin). The present study indicates that fluorescent film sensors could satisfy reliable onsite and real-time detection of harmful chemicals.

One Fluorophore-Two Sensing Films: Hydrogen-Bond Directed Formation of a Quadruple Perylene Bisimide Stack.

Elaborately designed π-stacked molecular aggregates are significant for modulation of photophysical properties of polycyclic aromatic hydrocarbons (PAHs). Herein, a double hydrogen-bonds trussed di(pyridyl)pyrrole-perylene bisimide (HDPP-PBI) was designed and its dimerization behavior was studied. HDPP-PBI tends to form a quadruple PBI stack with a dimerization constant of ∼5.56×106  M-1 . The dimerization was ascribed to synergistic intramolecular double hydrogen-bonds formation and intermolecular π-π stacking. Addition of CF3 COOH, a hydrogen bond blocker, promotes the dimer to monomer transition. Accordingly, two distinct fluorescent films were prepared by drop-casting of the dimerized or the monomeric HDPP-PBI onto a substrate surface. Interestingly, the less-emissive PBI quadruple stack-based film showed a turn on response to acetone vapor, while the highly emissive HDPP-PBI-based film exhibited fluorescence quenching upon exposure to triethylamine vapor. We believe that the discovered synergistic effect in the PBI aggregates would enlighten the design of new PAHs aggregates with defined structures.

Through-Space Charge Transfer: A New Way to Develop a High-Performance Fluorescence Sensing Film towards Opto-Electronically Inert Alkanes.

New strategies are in high demand for fast, sensitive, selective, on-site and real-time detection of the important but challenging alkane vapors owing to their opto-electronic inertness. Herein, we report, for the first time, a high-performance fluorescent film sensor (FFS) for the alkanes with a rationally designed through-space charge transfer (TSCT) molecule as the sensing fluorophore. Steady-state fluorescence, femto-second transient absorption spectroscopy and theoretical studies revealed continuous TSCT dynamics in the excited U-shaped molecule with increasing medium polarity. Furthermore, the interlocked, face-to-face alignment between the donor and acceptor favors mass transport of the analyte molecules in the film state. As anticipated, the compound-based FFS showed an experimental detection limit of ≈10 ppm for n-pentane, less than 5 s for a full detection, negligible interference and super-stability, revealing the effectiveness of the design strategy. Notably, the sensor is small (≈3.7 cm3 ), power-saving, and workable at room temperature.

Processing tactics for low-cost production of pure nuciferine from lotus leaf.

Nuciferine is an important drug candidate for the treatment of many diseases. However, there is no general method for its low - cost production. In this work, a feasible method for the production of nuciferine from lotus leaf, using ultrasonic-assisted extraction-solid phase extraction (UAE-SPE) as extraction and cleanup procedure, was developed. Petroleum ether and silica gel have been successfully used as extraction solvent and adsorbent to integrate UAE with SPE, respectively. Except for filtration, no treatment (e.g. concentration and redissolution, etc) was needed on UAE extract before SPE and the effluents obtained in the loading process of SPE could be used as UAE extraction solvent without purification. No obvious decline in the extraction efficiency of UAE and adsorption capacity of SPE was observed at least for 5 runs, which provides a feasible way for the continuous production of nuciferine in industry, i.e. Cyclic UAE-SPE. Moreover, SPE column could be conveniently regenerated and reused without significant decline in its adsorption capacity at least for 5 cycles, which can be used to reduce the cost of the whole system further. In comparison with other cleanup procedures, Cyclic UAE-SPE showed apparent advantages in energy conservation and emission reduction. LLE and crystallization were applied to separate nuciferine from other impurities further. Under optimum conditions, the total recovery rate of nuciferine with a purity over 90.0% from lotus leaf reached 50.1%. All in all, the developed method has advantages in convenient operation, low cost, and high efficiency, thus, is fitting for the production of high purity nuciferine.

Rapid network meta-analysis using data from Food and Drug Administration approval packages is feasible but with limitations.

OBJECTIVE: To test rapid approaches that use Drugs@FDA (a public database of approved drugs) and ClinicalTrials.gov to identify trials and to compare these two sources with bibliographic databases as an evidence base for a systematic review and network meta-analysis (NMA). STUDY DESIGN AND SETTING: We searched bibliographic databases, Drugs@FDA, and ClinicalTrials.gov for eligible trials on first-line glaucoma medications. We extracted data, assessed risk of bias, and examined the completeness and consistency of information provided by different sources. We fitted random-effects NMA models separately for trials identified from each source and for all unique trials from three sources. RESULTS: We identified 138 unique trials including 29,394 participants on 15 first-line glaucoma medications. For a given trial, information reported was sometimes inconsistent across data sources. Journal articles provided the most information needed for a systematic review; trial registrations provided the least. Compared to an NMA including all unique trials, we were able to generate reasonably precise effect estimates and similar relative rankings for available interventions using trials from Drugs@FDA alone (but not ClinicalTrials.gov). CONCLUSIONS: A rapid NMA approach using data from Drugs@FDA is feasible but has its own limitations. Reporting of trial design and results can be improved in both the drug approval packages and on ClinicalTrials.gov.

Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND.: Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. METHODS.: Among children aged 1-59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). RESULTS.: Among 4232 cases with World Health Organization-defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). CONCLUSIONS.: Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

BACKGROUND.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. METHODS.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. RESULTS.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. CONCLUSIONS.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.

Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study.

In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case-control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case-control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.

Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study.

BACKGROUND.: The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization-defined severe and very severe pneumonia and age-matched community controls. METHODS.: In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. RESULTS.: The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. CONCLUSIONS.: Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma.

BACKGROUND: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. PURPOSE: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. STUDY SELECTION: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. DATA EXTRACTION: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. DATA SYNTHESIS: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: ß-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). LIMITATION: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. CONCLUSION: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis. PRIMARY FUNDING SOURCE: National Eye Institute, National Institutes of Health.