High-Throughput, Label-Free Detection of DNA Origami in Single-Cell Suspensions Using origamiFISH-Flow.

Structural DNA nanotechnology enables custom fabrication of nanoscale devices and promises diverse biological applications. However, the effects of design on DNA nanostructure (DN)-cell interactions in vitro and in vivo are not yet well-characterized. origamiFISH is a recently developed technique for imaging DNs in cells and tissues. Compared to the use of fluorescent tags, origamiFISH offers label-free and structure-agnostic detection of DNs with significantly improved sensitivity. Here, the origamiFISH technique is extended to quantify DNs in single-cell suspensions, including in nonadherent cells such as subsets of immune cells, via readout by flow cytometry. This method, referred to as origamiFISH-Flow, is high-throughput (e.g., 10 000 cells per second) and compatible with immunostaining for concurrent cell-type and cell-state characterization. It is shown that origamiFISH-Flow provides 20-fold higher signal-to-noise ratio for DN detection compared to dye labeling approaches, leading to the capture of >25-fold more DN+ cells under single-picomolar DN uptake concentrations. Additionally, the use of origamiFISH-Flow is validated to profile the uptake of various DN shapes across multiple cell lines and splenocytes, as well as to quantify in vivo DN accumulation in lymphoid organs. Together, origamiFISH-Flow offers a new tool to interrogate DN interactions with cells and tissues, while providing insights for tailoring their designs in bio-applications.

ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.

Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.

Functional outcomes in MRI-guided laser interstitial therapy for temporal lobe epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The use of MRI-guided laser interstitial thermal therapy (MRgLITT) has emerged as a promising treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). Although the minimally invasive approach holds promise as an effective treatment for achieving seizure freedom, a comprehensive review of its impact on functional outcomes is still warranted. To address this need, this review aims to summarize data pertaining to the functional and neurocognitive outcomes following MRgLITT for TLE. METHODS: Four primary electronic databases were screened following PRISMA guidelines by two independent reviewers. All functional data related to cognitive, behavioral, and emotional outcomes were gathered and analyzed as well as the neuropsychological tests issued to assess pre- and postoperative outcomes. The functional outcomes assessed were grouped into the 5 most common categories: verbal cognition, visual cognition, cognitive emotion, visual deficits, and other higher-order cognitive functioning. RESULTS: A total of 4184 studies were screened and ultimately 408 patients from 14 studies were included for analysis. Changes in functional areas were assessed by comparing pre- and postoperative scores across a comprehensive set of 31 different functional and cognitive assessments, and were tabulated as the percentage of patients whose status improved, declined, or was maintained, where possible. In verbal (n = 112) and visual (n = 42) cognition, the rates of patients experiencing a decline were 20.4% and 13.5%, respectively, and the rates of improvement were 24.9% and 16.7%, respectively. Other functional outcomes assessed, including cognitive emotion (n = 150), visual deficits (n = 325), and higher-order cognitive processes like attention/processing (n = 19), motor cognition (n = 18), and general executive function (n = 4), exhibited varying rates of decline, ranging from 10.5% to 25%. CONCLUSIONS: MRgLITT is an effective and minimally invasive surgical alternative treatment for TLE, but there is an observable impact on patient functioning and cognitive status. This review demonstrates the need for standardized methods that can accurately capture and quantify the associated risk of MRgLITT to optimize its effect on patient quality of life moving forward.

How are Oral Antibiotics Being Used in Total Joint Arthroplasty? A Review of the Literature.

While the role and benefit of perioperative intravenous (IV) antibiotics in patients undergoing total joint arthroplasty (TJA) is well-established, oral antibiotic use in TJA remains a controversial topic with wide variations in practice patterns. With this review, we aimed to better educate the orthopedic surgeon on when and how oral antibiotics may be used most effectively in TJA patients, and to identify gaps in the literature that could be clarified with targeted research. Extended oral antibiotic prophylaxis (EOAP) use in high-risk primary, aseptic revision, and exchange TJA for infection may be useful in decreasing periprosthetic joint infection (PJI) rates. When prescribing oral antibiotics either as EOAP or for draining wounds, patient factors, type of surgery, and type of infectious organisms should be considered in order to optimally prevent and treat PJI. It is important to maintain antibiotic stewardship by administering the proper duration, dose, and type of antibiotics and by consulting infectious disease when necessary.

Setting up EEG Source Imaging in Practice.

SUMMARY: Adding EEG source imaging to a clinical practice has clear advantages over visual inspection of EEG. This article offers insight on incorporating EEG source imaging into an EEG laboratory and the best practices for producing optimal source analysis results.

Management of soybean cyst nematode and sudden death syndrome with nematode-protectant seed treatments across multiple environments in soybean.

As soybean (Glycine max) production continues to expand in the U.S. and Canada, so do pathogens and pests which directly threaten soybean yield potential and economic returns for farmers. One such pathogen is the soybean cyst nematode (SCN; Heterodera glycines). SCN has traditionally been managed using SCN-resistant cultivars and rotation with non-host crops, but the interaction of SCN with sudden death syndrome (SDS; caused by Fusarium virguliforme) in the field makes management more difficult. Nematode-protectant seed treatments have become options for SCN and SDS management. The objectives of this study were to evaluate nematode-protectant seed treatments for their effects on: (i) early and full season SCN reproduction, (ii) foliar symptoms and root-rot caused by SDS, and (iii) soybean yield across environments accounting for the above factors. Using a standard protocol, field trials were implemented in 13 U.S. States and 1 Canadian Province from 2019 to 2021 constituting 51 site-years. Six nematode-protectant seed treatment products were compared to a fungicide + insecticide base treatment and a non-treated check. Initial (at soybean planting) and final (at soybean harvest) SCN egg populations were enumerated and SCN females were extracted from roots and counted at 30 to 35 days post-planting. Foliar disease index (FDX) and root rot caused by the SDS pathogen were evaluated, and yield data were collected for each plot. No seed treatment offered significant nematode control versus the non-treated check for in-season and full season nematode response, no matter the initial SCN population or FDX level. Of all treatments, ILEVO (fluopyram) and Saltro (pydiflumetofen) provided more consistent increases in yield over the non-treated check in a broader range of SCN environments, even when FDX level was high.

The application of synthetic antibacterial minerals to combat topical infections: exploring a mouse model of MRSA infection.

The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to be effective in killing antibiotic resistant bacteria. However, these natural clays are too variable to be used in clinical settings. Our study shows that synthetic antibacterial minerals exhibit potent antibacterial activity against topical MRSA infections and increase the rate of wound closure relative to controls. The antibacterial minerals maintain a redox cycle between Fe2+/Fe3+ and the surfaces of pyrite minerals, which act as a semiconductor and produce reactive oxygen species (ROS), while smectite minerals act as a cation exchange reservoir. Acidic conditions are maintained throughout the application of the hydrated minerals and can mitigate the alkaline pH conditions observed in chronic non-healing wounds. These results provide evidence for the strategy of 'iron overload' to combat antibiotic resistant infections through the maintained release of Fe2+ and generation of ROS via distinct geochemical reactions that can break the chronic wound damage cycle.

The Unique Lived Experiences of LGBQ Athletes: A Collegiate Women's Rugby Club Team as an Inclusive & Empowering Community.

There is ongoing debate regarding the culture of competitive women's sports. On one hand, women who participate in sports are viewed as adhering to and reinforcing heteronormative stereotypes and hegemonic masculinity. Conversely, women's sports are viewed as an inherently supportive environment for those involved. The current study explored the latter phenomena, specifically related to factors that promote an inclusive and empowering community for LGBTQ+ women. Eleven individual semi-structured interviews and one follow-up focus group with six participants were conducted with women from a collegiate women's rugby club team. All participants described their sexual identities as Lesbian, Gay, Bisexual, and/or Queer (LGBQ). A reflexive thematic analysis was used to analyze the data collectively. Participants described their collegiate rugby team as being one of their first encounters with a safe and inclusive LGBTQ+ environment. Membership on the team also was viewed as an important experience that helped participants come to terms with their sexual identity. Specifically, findings indicate the supportive actions of teammates, an inclusive team culture, and unique factors related to the sport of rugby helped promote an inclusive and empowering community for LGBTQ+ women. Indeed, from a critical positive youth development perspective, social justice life skills (e.g., allyship) provided actionable behaviors that promote an inclusive and empowering community for LGBTQ+ women. However, future research must seek to understand the lived experiences of all women's rugby participants, particularly transgender and athletes of color.

Differences in Tic Severity Among Adolescent Girls and Boys with Tourette Syndrome During the Pandemic.

Limited data are available regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents with Tourette syndrome (TS). We sought to compare sex differences in tic severity experienced by adolescents before and during the COVID-19 pandemic. We extracted from the electronic health record and retrospectively reviewed Yale Global Tic Severity Scores (YGTSS) from adolescents (ages 13 through 17) with TS presenting to our clinic before (36 months) and during (24 months) the pandemic. A total of 373 unique adolescent patient encounters (prepandemic: 199; pandemic: 173) were identified. Compared with prepandemic, girls accounted for a significantly greater proportion of visits during the pandemic (p < 0.001). Prepandemic, tic severity did not differ between girls and boys. During the pandemic, compared with girls, boys had less clinically severe tics (p = 0.003). During the pandemic, older girls, but not boys, had less clinically severe tics (ρ =- 0.32, p = 0.003). These findings provide evidence that, regarding tic severity assessed with YGTSS, the experiences of adolescent girls and boys with TS have differed during the pandemic.

Universal, label-free, single-molecule visualization of DNA origami nanodevices across biological samples using origamiFISH.

Structural DNA nanotechnology enables the fabrication of user-defined DNA origami nanostructures (DNs) for biological applications. However, the role of DN design during cellular interactions and subsequent biodistribution remain poorly understood. Current methods for tracking DN fates in situ, including fluorescent-dye labelling, suffer from low sensitivity and dye-induced artifacts. Here we present origamiFISH, a label-free and universal method for the single-molecule fluorescence detection of DNA origami nanostructures in cells and tissues. origamiFISH targets pan-DN scaffold sequences with hybridization chain reaction probes to achieve 1,000-fold signal amplification. We identify cell-type- and DN shape-specific spatiotemporal distribution patterns within a minute of uptake and at picomolar DN concentrations, 10,000× lower than field standards. We additionally optimize compatibility with immunofluorescence and tissue clearing to visualize DN distribution within tissue cryo-/vibratome sections, slice cultures and whole-mount organoids. Together, origamiFISH enables the accurate mapping of DN distribution across subcellular and tissue barriers for guiding the development of DN-based therapeutics.

Structural Connectivity of the Human Piriform Cortex: an Exploratory Study.

BACKGROUND AND OBJECTIVES: The piriform cortex (PC) is part of the primary olfactory network in humans. Recent findings suggest that it plays a role in pathophysiology of epilepsy. Therefore, studying its connectivity can further our understanding of seizure propagation in epilepsy. We aimed to explore the structural connectivity of PC using high-quality human connectome project data coupled with segmentation of PC on anatomic MRI. METHODS: Twenty subjects were randomly selected from the human connectome project database, and PC was traced on each hemisphere. Probabilistic whole-brain tractography was then used to visualize PC connectivity. RESULTS: The strongest connectivity was noted between PC and ipsilateral insula in both hemispheres. Specifically, the posterior long gyrus of each insula was predominantly connected to PC. This was followed by connections between PC and basal ganglia as well as orbital frontal cortices. CONCLUSION: The PC has the strongest connectivity with the insula bilaterally. Specifically, the posterior long gyri of insula have the strongest connectivity. This finding may provide additional insight for localizing and treating temporo-insular epilepsy.

The Seated Trunk Control Test: Investigation of Reliability and Known-Groups Validity Using Individuals Post-Anterior Cruciate Ligament Reconstruction.

CONTEXT: Decreased trunk neuromuscular control is a risk factor for both upper- and lower-extremity injuries, yet there are few reliable and valid clinical tests to identify deficits. OBJECTIVE: The purpose of this study was to determine the reliability and known-groups validity of a novel clinical test, the seated trunk control test (STCT). DESIGN: Cross-sectional reliability and known-groups validity study. SETTING: Laboratory. PARTICIPANTS: 89 unique participants: 34 were 3 months postoperative anterior cruciate ligament reconstruction (ACLR) and 55 healthy controls. METHODS: For the STCT, participants sat on a balance board with their eyes closed for three 30-second trials while investigators counted balance errors. Intraclass correlations (ICCs) were used to assess interrater reliability (N = 20) and test-retest reliability (N = 40). To assess known-groups validity, independent t tests were used to compare STCT errors at 3 months post-ACLR with healthy matched controls (N = 34/group). Area under a receiver operating characteristic curve identified an optimal cutoff for distinguishing between groups. RESULTS: The STCT had perfect interrater reliability (ICC2,3 = 1.00) and good test-retest reliability (ICC3,3 = .79; 95% confidence interval = .61-.89). The ACLR group made significantly more errors on the STCT (mean [SD] = 15.5 [5.4]) than controls (mean [SD] = 8.2 [4.1]; P < .001, Cohen d = 1.52). The STCT's ability to distinguish between groups was excellent (area under a ROC curve = 0.86). A cutoff of 12 errors maximized sensitivity (76%) and specificity (85%). CONCLUSIONS: The STCT is reliable between raters and across days. It also has excellent ability to distinguish between individuals with a recent ACLR and healthy matched controls, which provides initial evidence to suggest that the STCT may be clinically useful for identifying deficits in trunk neuromuscular control.

The effects of early-life and intergenerational stress on the brain.

Stress experienced during ontogeny can have profound effects on the adult phenotype. However, stress can also be experienced intergenerationally, where an offspring's phenotype can be moulded by stress experienced by the parents. Although early-life and intergenerational stress can alter anatomy, physiology, and behaviour, nothing is known about how these stress contexts interact to affect the neural phenotype. Here, we examined how early-life and intergenerational stress affect the brain in eastern fence lizards (Sceloporus undulatus). Some lizard populations co-occur with predatory fire ants, and stress from fire ant attacks exerts intergenerational physiological and behavioural changes in lizards. However, it is unclear if intergenerational stress, or the interaction between intergenerational and early-life stress, modulates the brain. To test this, we captured gravid females from fire ant invaded and uninvaded populations, and subjected offspring to three early-life stress treatments: (1) fire ant attack, (2) corticosterone, or (3) a control. Corticosterone and fire ant attack decreased some aspects of the neural phenotype while population of origin and the interaction of early-life stress and population had no effects on the brain. These results suggest that early-life stressors may better predict adult brain variation than intergenerational stress in this species.

Robotic Total Knee Arthroplasty is Associated with Earlier Return of Postoperative Range of Motion.

INTRODUCTION: Postoperative range of motion (ROM) is an important measure for the functional outcome and overall success after total knee arthroplasty (TKA). While robotic knee systems have been shown to reduce pain and improve early function, the return of postoperative ROM specifically has not been adequately studied. The purpose of this study was to compare postoperative ROM in robotic and conventional TKA. We hypothesized that robotic TKA leads to an improvement in postoperative ROM. MATERIALS AND METHODS: A retrospective cohort study of 674 primary TKAs by a single surgeon between January 2018 and February 2023 was completed. Patients that did not have both a two-week follow up and eight-week follow up were excluded. Revision/conversion TKAs were excluded. The population was divided into two cohorts based on technique utilized: robotic versus conventional. Preoperative extension/flexion data, postoperative extension/flexion data at two-week and eight-week follow ups, and manipulation under anesthesia data were collected. ROM was defined as flexion minus extension. Chi-square tests were used to examine for differences between categorical variables and t-tests for continuous variables. RESULTS: A total of 307 robotic and 265 conventional knees were included. There were no differences in demographics, mean follow up, or preoperative ROM between groups. The robotic group had significantly more flexion (99.20° vs. 96.98°; p=0.034) and ROM (97.81° vs. 95.56°; p=0.047) at the two-week follow up. The loss in ROM at the two-week follow up from preoperative ROM was significantly less for the robotic group (-11.21° vs. -14.16°; p=0.031). There were no significant differences in extension at either follow up, in flexion at the eight-week follow up, or in ROM at the eight-week follow up. CONCLUSION: Robotic TKA leads to an improvement in postoperative flexion and ROM when compared to preoperative ROM at two-week follow up. These findings could partially explain the quicker recovery associated with robotic TKA.

A Case of Cardiac Arrest Due to Transcatheter Aortic Valve Infolding.

Prosthetic valvular infolding during transcatheter aortic valve implantation (TAVI) is an under-recognized yet significant complication that can occur. Here, we describe the case of a 61-year-old male with a history of heart failure with reduced ejection fraction (HFrEF) and low-flow, low-gradient severe aortic valve stenosis of a bicuspid aortic valve who presented to undergo TAVI. During the procedure, repositioning of the valve resulted in prosthetic valvular infolding and resultant severe aortic regurgitation (AR), culminating in cardiac arrest. Swift balloon valvuloplasty corrected the valve geometry and eliminated any AR, allowing hemodynamic recovery and completion of the procedure. Our case and review highlight methods, both angiographic and echocardiographic, to recognize prosthetic valvular infolding the moment it presents, as well as strategies to correct the infolding with minimal detriment to the patient.

Identity development, attraction, and behaviour of heterosexually identified men who have sex with men: scoping review protocol.

BACKGROUND: Heterosexually identified men who have sex with men (H-MSM) are distinct from other heterosexual men and from gay, bisexual, and other sexual minority men. Specifically, H-MSM experience discordance between their sexual identity (i.e., heterosexual) and behaviours (i.e., sexual encounters with other men). This sexual identity-behaviour discordance can create barriers to obtaining healthcare and social support. Understanding and accepting H-MSM as they self-identify may be necessary to implement effective public health and psychosocial interventions. The aim of the present study is to provide an overview of research on H-MSM. METHODS: A scoping review will be conducted to identify and describe the identity development, attraction, and behaviour of H-MSM. This scoping review will also identify and describe current trends related to the recruitment of H-MSM and recommend directions for future research. Searches will be conducted in Academic Search Complete, APA PsychInfo, CINAHL Plus with full text, Education Research Complete, Gender Studies Database, GenderWatch, Health Source: Nursing/Academic Edition, LGBTQ + Source, MEDLINE, Psychology and Behavioral Sciences Collection, SocINDEX with full text, Sociological Collection, Social Work Abstracts, ProQuest Dissertations and Theses, and ResearchGate. Primary research studies published in peer-reviewed journals will be included. Dissertations and theses that include primary research on H-MSM will also be included. Reference lists, experts in the field, preprint servers, and relevant conferences will also be consulted for extant and in-progress literature. Two reviewers will independently pilot the data extraction form and conduct the title and abstract screening, with consultation from a research librarian. Seven reviewers will then conduct the full-text article screening. Thematic content analysis will guide the review; through independent review and reviewer meetings, themes and subthemes will be identified and reported from the extracted literature. DISCUSSION: This is the first known knowledge synthesis on H-MSM, seeking to better understand sexual identity-behaviour discordance amongst cisgender men. We anticipate that a theoretical framework of H-MSM's sexuality, internal processes, and behaviours will be constructed from this review. Alongside implications for further research with H-MSM, this review may be relevant to sexually transmitted infection public health and to clinicians working in the field of male sexuality. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework: https://doi.org/10.17605/OSF.IO/MVY9H.

A Case of Cutibacterium acnes Pericardial Effusion After Coronary Artery Bypass Surgery.

Cutibacterium acnes is a gram-positive, anaerobic rod commonly found on the skin and mucosal membrane. It is mostly associated with its role in acne formation, but here we present a case of purulent pericarditis secondary to C. acnes after coronary artery bypass graft surgery (CABG). A 58-year-old male presented for CABG after a coronary angiogram showed severe multivessel disease. The procedure was performed successfully. He had minimal complications until postop day seven, when he developed a fever and hypoxia. The transthoracic echo (TTE) was largely unrevealing. Due to further declining status the following day, a transesophageal echo (TEE) was performed and revealed a loculated pericardial effusion not visualized on TTE. This was subsequently drained, and fluid cultures grew C. acnes. The patient received five weeks of antibiotic therapy, which improved his condition.

Is It Necessary to Wake Patients for Overnight Vital Signs Following Total Joint Arthroplasty?

Benefits of sleep are well-established in postoperative recovery; however, patients undergoing total joint arthroplasty (TJA) often experience poor sleep during hospitalization. While multifactorial, among the major reasons are the frequent and ritualized overnight vital sign checks. In the absence of data in support of or against this practice, we asked whether it remains necessary. We retrospectively analyzed a cohort of 419 primary TJA patients. Demographics, comorbidities, operative, and vital sign data were collected through postoperative Day 3. Correlation between daytime (6:00 a.m. to 10:00 p.m.) and nighttime (10:01 p.m. to 5:59 a.m.) vitals was examined. The vast majority of nighttime vitals fell within normal ranges, including O2 saturation (O2; 99.4%), temperature (TEMP; 97.8%), heart rate (HR; 87.5%), systolic blood pressure (SBP; 85.8%), and diastolic blood pressure (DBP; 84.4%). Predictors of abnormal nighttime vitals included American Society of Anesthesiologists (ASA) score (abnormal SBP; odds ratio [OR] 1.64, p = .045), obesity (abnormal DBP; OR: 0.37, p = .011), and smoking status (elevated temperature; OR: 2.79, p = .042). Estimated blood loss was predictive of an abnormal nighttime TEMP (OR: 1.002; p < .001). Postoperatively, there were several correlations between abnormal daytime and nighttime vitals, including SBP (OR: 6.23, p < .001), DBP (OR: 4.31, p < .001), and HR (OR: 10.35; p < .001). Of the 419 patients, only 9 (2.1%) received any intervention based on abnormal nighttime vitals. Each exhibited daytime vital sign abnormalities prior to the abnormal nighttime readings. Patients with abnormal nighttime vitals can be predicted on the basis of medical comorbidities and abnormal daytime vitals. These findings suggest that healthy post-TJA patients with normal daytime vitals may not need to be routinely woken at night.

Current Trends in Head and Neck Trauma.

The practicing otolaryngologist frequently encounters consultation for injuries in the head and neck. Restoration of form and function is essential to normal activities of daily living and quality of life. This discussion intends to provide the reader with an up-to-date discussion of various evidence-based practice trends related to head and neck trauma. The discussion focuses on the acute management of trauma with minor emphasis on secondary management of injuries. Specific injuries related to the craniomaxillofacial skeleton, laryngotracheal complex, vascularity, and soft tissues are explored.

Efficacy and Profitability of Fungicides for Managing Frogeye Leaf Spot on Soybean in the United States: A 10-Year Quantitative Summary.

Frogeye leaf spot (FLS), caused by Cercospora sojina, is an economically important disease of soybean in the United States. Data from 66 uniform fungicide trials (UFTs) conducted from 2012 to 2021 across eight states (Alabama, Arkansas, Illinois, Iowa, Kentucky, Louisiana, Mississippi, and Tennessee) were gathered and analyzed to determine the efficacy and profitability of the following fungicides applied at the beginning pod developmental stage (R3): azoxystrobin + difenoconazole (AZOX + DIFE), difenoconazole + pydiflumetofen (DIFE + PYDI), pyraclostrobin (PYRA), pyraclostrobin + fluxapyroxad + propiconazole (PYRA + FLUX + PROP), tetraconazole (TTRA), thiophanate-methyl (TMET), thiophanate-methyl + tebuconazole (TMET + TEBU), and trifloxystrobin + prothioconazole (TFLX + PROT). A network meta-analytic model was fitted to the log of the means of FLS severity data and to the nontransformed mean yield for each treatment, including the nontreated. The percent reduction in disease severity (%) and the yield response (kg/ha) relative to the nontreated was the lowest for PYRA (11%; 136 kg/ha) and the greatest for DIFE + PYDI (57%; 441 kg/ha). A significant decline in efficacy over time was detected for PYRA (18 percentage points [p.p.]), TTRA (27 p.p.), AZOX + DIFE (18 p.p.), and TMET + TEBU (19 p.p.) by using year as a continuous covariate in the model. Finally, probabilities of breaking even were the greatest (>65%) for the most effective fungicide DIFE + PYDI and the lowest (<55%) for PYRA. Results of this meta-analysis may be useful to support decisions when planning fungicide programs.