Utilization and perceptions of language assistance services by medical trainees: a pathway to language certification.

Background: Access to language assistance is a patient's right under federal law. Despite this, underuse of language services persists. Objective: The aim of this study was to explore the interest in obtaining bilingual certification and to describe perspectives on language services by resident physicians. Methods: Between May and August 2021, we conducted a cross-sectional survey of residents at a public, urban hospital serving mostly patients with limited English proficiency (LEP). We assessed resident perspectives on language services, exposure to language-related trainings, non-English language (NEL) skills, and interest in bilingual certification. Results: A total of 214 residents of 289 completed the survey (a 74% response rate). Of the 95 residents who used their NEL for patient care, 65 (68%) would be interested in bilingual certification. Sixty-nine (33%), 65 (31%), and 95 (45%) residents disagreed or strongly disagreed with being satisfied with the language services available, convenience, and sufficient equipment, respectively. Furthermore, 28 (13%) disagreed or strongly disagreed that they could achieve bi-directional communication with LEP patients. Conclusions: Over a quarter of the residents expressed interest in bilingual certification and were likely to pass the certification exam. Many reported using their own NEL skills without certification and held negative views on services and trainings.

The discovery of indazapyroxamet: a novel 3-pyridinyl insecticide targeting piercing/sucking insectsa.

In recent years, the registrations for a number of commercial insecticides utilized for piercing/sucking insects have been cancelled or restricted. To meet this growing need for new hemipteran controlling agrochemicals, we discovered a 2-(pyridin-3-yl)-thiazole compound, with limited insecticidal activity against cotton/melon aphid (Aphis gossypii). The 2-(pyridin-3-yl)-thiazole moiety offered us a basis to pursue the bicyclic 2-(pyridin-3-yl)-2H-indazole carboxamides. Evaluation of such 2-(pyridin-3-yl)-2H-indazole carboxamides revealed that even analogs containing only simple alkyl amides attached at the 4 or 5 positions possess promising insecticidal activity. Extensive optimization of this novel class of 2-(pyridin-3-yl)-2H-indazole carboxamides led to identifying indazapyroxamet for commercial development. © 2024 Society of Chemical Industry.

Observer-based differential evolution constrained control for safe reference tracking in robots.

Big torque inputs in controls could increase energy consumption, and big estimated perturbations in observers could produce device damages. Therefore, it would be interesting to propose a constrained control for safe reference tracking and a constrained observer for safe perturbation estimation in robots. Furthermore, the best gains in controls produce a balance between safe reference tracking and save energy consumption. Therefore, it would be interesting to propose a method to find the best gains. In this paper, an observer-based differential evolution constrained control is proposed for safe reference tracking in robots. The contributions are described as follows: (1) a constrained observer is proposed for safe perturbation estimation in robots, (2) a constrained control is proposed for safe reference tracking in robots, (3) a differential evolution optimizer is used to find the best gains in an observer-based constrained control, (4) the robust stability in an observer-based constrained control is assured, (5) the pseudo-code of an observer-based differential evolution constrained control is detailed. The proposed observer-based differential evolution constrained control is applied for safe reference tracking in two robots.

Discovery of novel (N-aryl-4-methylpiperidinyl)pyrazoles: a new class of potent lepidopteran insecticides.

BACKGROUND: Insects of the order Lepidoptera are among the most destructive global pests, causing billions of dollars in damage annually. A new class of N-arylpyrazole-4-methylpiperidines with potent activity on lepidopteran species has been discovered. RESULTS: In a high-throughput insecticide screen compound 1 was identified to possess modest activity on the lepidopteran insect Plutella xylostella. Optimization of 1 to compound 42 resulted in a compound with excellent activity on Spodoptera exigua, Spodoptera frugiperda, and Helicoverpa zea with median lethal concentrations values of 2.8, 1.4, and 12.5 ppm respectively. Although the mode of action remains unknown, these compounds do not appear to work by many of the known biochemical mechanisms of insect control. CONCLUSION: N-Arylpyrazole-4-methylpiperidines represent a new class of insecticides with excellent activity on a broad spectrum of lepidopteran pests. Studies to date indicate the potential for a novel mode of action; however, the target site is unknown at present. © 2023 Society of Chemical Industry.

Biomarkers of in vivo limbal stem cell function.

PURPOSE: To evaluate in vivo parameters as biomarkers of limbal stem cell function and to establish an objective system that detects and stage limbal stem cell deficiency (LSCD). METHODS: A total of 126 patients (172 eyes) with LSCD and 67 normal subjects (99 eyes) were included in this observational cross-sectional comparative study. Slit-lamp biomicroscopy, in vivo laser scanning confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT) were performed to obtain the following: clinical score, cell morphology score, basal cell density (BCD), central corneal epithelial thickness (CET), limbal epithelial thickness (LET), total corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and tortuosity coefficient. Their potential correlations with the severity of LSCD were investigated, and cutoff values were determined. RESULTS: An increase clinical score correlated with a decrease in central cornea BCD, limbal BCD, CET, mean LET, maximum LET, CNFL, CNFD, CNBD, and tortuosity coefficient. Regression analyses showed that central cornea BCD, CET and CNFL were the best parameters to differentiate LSCD from normal eyes (Coef = 3.123, 3.379, and 2.223; all p < 0.05). The rank correlation analysis showed a similar outcome between the clinical scores and the central cornea BCD (ρ = 0.79), CET (ρ = 0.82), and CNFL (ρ = 0.71). A comprehensive LSCD grading formula based on a combination of these parameters was established. CONCLUSIONS: A comprehensive staging system combining clinical presentation, central cornea BCD, CET, and CNFL is established to accurately and objectively diagnose LSCD and stage its severity.

Cytokeratin 13 Is a New Biomarker for the Diagnosis of Limbal Stem Cell Deficiency.

PURPOSE: The purpose of this study was to evaluate the expression of cytokeratin (K) 13 on the corneal surface and to validate its application in the diagnosis of limbal stem cell deficiency (LSCD). METHODS: This prospective comparative study included 26 corneal impression cytology (IC) specimens from patients diagnosed with LSCD. Twenty-three IC specimens from normal donors served as controls. K12 and K13 expression were detected on the IC specimens by immunohistochemistry study. The number of K12 + or K13 + cells in all areas of the IC was quantified using ImageJ software. RESULTS: The epithelial cells harvested from IC specimens from control corneas were all K12 + . In eyes with LSCD, K13 + and K12 + /K13 + cells accounted for 93.8% and 2.6%, respectively, in the cornea. In eyes with sectoral LSCD, the median number of K13 + cells in the clinically affected area was higher than that in the unaffected area (810.0 vs. 115.0 cells/mm 2 ; P < 0.001). No significant correlation was found between the LSCD severity and the number of K12 + cells (r = -0.284, P = 0.16) or K13 + cells (r = -0.011, P = 0.95). The presence of at least 16 K13 + cells/mm 2 was suggestive of LSCD. CONCLUSIONS: Identification of K13 + cells on IC specimens provides a simple and reliable method to detect conjunctival epithelial cells on the cornea. K13 is a marker for diagnosing LSCD and localizing the involved area in sectoral LSCD.

Pyrrole-2 carboxamides - A novel class of insect ryanodine receptor activators.

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based screening of an informer library led to discovery of a novel class of RyR activators, pyrrole-2-carboxamides. Efforts to optimize receptor activity resulted in analogs with potency comparable to that of commercial diamides when tested against RyR of the fruit fly, Drosophila melanogaster. Surprisingly, testing of pyrrole-2-carboxamides in whole-insect screens showed poor insecticidal activity, which is partially attributed to differential selectivity among insect receptors and rapid detoxification. Among various lepidopteran species field resistance to diamide insecticides has been well documented and in many cases has been attributed to a single point mutation, G4946E, of the RyR gene. As with diamide insecticides, the G4946E mutation confers greatly reduced sensitivity to pyrrole-2-carboxamides. This, coupled with findings from radioligand binding studies, indicates a shared binding domain between anthranilic diamides and pyrrole-2-carboxamides.

Insecticides, biologics and nematicides: Updates to IRAC's mode of action classification - a tool for resistance management.

Insecticide resistance has been and continues to be a significant problem for invertebrate pest control. As such, effective insecticide resistance management (IRM) is critical to maintain the efficacy of current and future insecticides. A technical group within CropLife International, the Insecticide Resistance Action Committee (IRAC) was established 35 years ago (1984) as an international association of crop protection companies that today spans the globe. IRAC's focus is on preserving the long-term utility of insect, mite, and most recently nematode control products through effective resistance management to promote sustainable agriculture and improved public health. A central task of IRAC has been the continual development and documentation of the Mode of Action (MoA) Classification scheme, which serves as an important tool for implementing IRM strategies focused on compound rotation / alternations. Updates to the IRAC MoA Classification scheme provide the latest information on the MoA of current and new insecticides and acaricides, and now includes information on biologics and nematicides. Details for these new changes and additions are reviewed herein.

Corneal Epithelial Thickness Measured Using Anterior Segment Optical Coherence Tomography as a Diagnostic Parameter for Limbal Stem Cell Deficiency.

OBJECTIVE: Using anterior segment optical coherence tomography (AS-OCT), we investigated the epithelial thickness (ET) of the central cornea and limbal regions in patients with limbal stem cell deficiency (LSCD) as a diagnostic and staging parameter. DESIGN: Prospective, cross-sectional study. METHODS: The central corneal epithelium thickness (CET) and maximum limbal epithelium thickness (mLET) were measured in the superior, inferior, nasal, and temporal limbus on AS-OCT images of the normal and eyes with LSCD. CET was obtained by 1-point (OCT-CET1) and 3-point measurement (OCT-CET3). The values of OCT-CET1 and OCT-CET3 were compared to the CET obtained with in vivo confocal microscopy (IVCM-CET). RESULTS: Sixty-eight eyes of 50 patients with LSCD and 52 eyes of 34 normal subjects were included. The mean (±standard deviation) OCT-CET3 was 55.0 ± 3.0 µm (range, 50.6-62.0 µm) in the control group and 41.6 ± 10.8 µm (range, 0-56.3 µm) in the LSCD group (P < .001). OCT-CET3 had a better correlation with IVCM-CET (r = 0.91) than did OCT-CET1 (r = 0.87, P = .001). The degree of reduction in OCT-CET3 increased in more advanced clinical stages of LSCD (all P < .001). The OCT-CET3 cutoff value that suggests LSCD was 46.6 µm. Compared with the control group, the LSCD group had decreases in mLET in all 4 limbal regions (all P < .001). The sensitivity and specificity of OCT-CET3 is the highest among all mLET in detecting LSCD. CONCLUSIONS: Both CET and mLET were thinner in patients with LSCD than in normal subjects. OCT-CET3 appears to be a reliable parameter to confirm LSCD when there is clinical suspicion.

In Vivo Evaluation of the Limbus Using Anterior Segment Optical Coherence Tomography.

PURPOSES: To investigate the limbal structure using anterior segment optical coherence tomography (AS-OCT) and compare the difference between a Chinese Han population and a Caucasian population. METHODS: Sixty healthy Chinese Han subjects (109 eyes, Chinese group) and 32 healthy Caucasian subjects (51 eyes, Caucasian group) were included in this comparative cross-sectional study. The central cornea and the superior, inferior, nasal, and temporal limbal regions of each subject underwent Fourier-domain AS-OCT. The following parameters were measured: corneal epithelial thickness (CET), maximum limbal epithelial thickness (LET), the mean LET, the width of limbus, distance between scleral spur and the location where limbal epithelium was the thickest (S-T), and limbal epithelial area between scleral spur and the end of Bowman's layer (LEA). RESULTS: CET was similar in both groups (P = 0.577). The width of limbus was more than 32.8% greater in all limbal quadrants in the Caucasian group (range, 1.25-2.20 mm) than in the Chinese group (range, 0.81-1.40 mm). S-T and LEA were also significantly higher in all limbal quadrants in the Caucasian group (all P < 0.001). The maximum LET and mean LET were 7.8% and 6.9% thicker at the nasal limbus and 8.1% and 8.7% thicker in the temporal limbus in Caucasian subjects than in Chinese subjects. CONCLUSIONS: The limbal structures can be visualized using AS-OCT and differ significantly between the Caucasian and Chinese eyes. TRANSLATIONAL RELEVANCE: Research of the limbus and surgeons performing procedures involving the limbal area should take into consideration of the anatomic differences especially when limbus is used as an anatomic reference.

The discovery of fluazaindolizine: A new product for the control of plant parasitic nematodes.

Fluazaindolizine is a new highly effective and selective product for the control of plant parasitic nematodes. Specificity for nematodes coupled with absence of activity against the target sites of commercial nematicides suggests that fluazaindolizine has a novel mode of action. The discovery, structure-activity development and biological properties for this new class of nematicides are presented.

Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of dicloromezotiaz as a lepidoptera insecticide acting on nicotinic acetylcholine receptors1,2.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program that led to the identification of dicloromezotiaz as a potent insecticide to control a broad range of lepidoptera. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.

Mesoionic insecticides: a novel class of insecticides that modulate nicotinic acetylcholine receptors.

BACKGROUND: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance. RESULTS: A novel class of mesoionic compounds has been discovered, with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera. These compounds bind to the orthosteric site of the nicotinic acetylcholine receptor and result in a highly potent inhibitory action at the receptor with minimal agonism. The synthesis, biological activity, optimization and mode of action will be discussed. CONCLUSION: Triflumezopyrim insect control will provide a powerful tool for control of hopper species in rice throughout Asia. Dicloromezotiaz can provide a useful control tool for lepidopteran pests, with an underexploited mode of action among these pests. © 2016 Society of Chemical Industry.

Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of triflumezopyrim as a potent hopper insecticide1.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program which led to the discovery of triflumezopyrim as a highly potent insecticide controlling various hopper species. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.

Mesoionic pyrido[1,2-a]pyrimidinones: A novel class of insecticides inhibiting nicotinic acetylcholine receptors.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we report the discovery, evolution, and preparation of this class of chemistry. Our efforts in structure-activity relationship elucidation and biological activity evaluation are also presented.

Mode of action of triflumezopyrim: A novel mesoionic insecticide which inhibits the nicotinic acetylcholine receptor.

Triflumezopyrim, a newly commercialized molecule from DuPont Crop Protection, belongs to the novel class of mesoionic insecticides. This study characterizes the biochemical and physiological action of this novel insecticide. Using membranes from the aphid, Myzus persicae, triflumezopyrim was found to displace (3)H-imidacloprid with a Ki value of 43 nM with competitive binding results indicating that triflumezopyrim binds to the orthosteric site of the nicotinic acetylcholine receptor (nAChR). In voltage clamp studies using dissociated Periplaneta americana neurons, triflumezopyrim inhibits nAChR currents with an IC50 of 0.6 nM. Activation of nAChR currents was minimal and required concentrations ≥100 µM. Xenopus oocytes expressing chimeric nAChRs (Drosophila α2/chick ß2) showed similar inhibitory effects from triflumezopyrim. In P. americana neurons, co-application experiments with acetylcholine reveal the inhibitory action of triflumezopyrim to be rapid and prolonged in nature. Such physiological action is distinct from other insecticides in IRAC Group 4 in which the toxicological mode of action is attributed to nAChR agonism. Mesoionic insecticides act via inhibition of the orthosteric binding site of the nAChR despite previous beliefs that such action would translate to poor insect control. Triflumezopyrim is the first commercialized insecticide from this class and provides outstanding control of hoppers, including the brown planthopper, Nilaparvata lugens, which is already displaying strong resistance to neonicotinoids such as imidacloprid.

Tubulin modulating antifungal and antiproliferative pyrazinone derivatives.

A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.

The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH. MATERIAL AND METHODS: Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRα, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot. RESULTS: Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRα did not show differences between groups. CONCLUSIONS: The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.