Simultaneous Detection Method of 11 Respiratory Drug Substances Including Theobromine, Oxymetazoline, etc. in Adulterated Dietary Supplements Using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Analysis.

Recently, the demand for respiratory disease-related products has surged due to the influence of coronavirus disease 2019, prompting warnings about illegal dietary supplements containing unauthorized substances. Additionally, adulterated dietary supplements are continuously detected in open markets, posing significant public health safety problem. In this study, we developed and validated an analytical method for 11 respiratory drug substances using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and proposed optimal conditions for LC-quadrupole time-of-flight MS (LC-QTOF-MS) to determine the fragmentation patterns of each substance. This method underwent thorough validation considering specificity, linearity, limits of detection and quantification, accuracy, precision, matrix effect, stability, etc. All results met international guidelines. These validated methods were applied to 52 dietary supplements advertised for treating respiratory diseases and enhancing respiratory function, among which one sample was found to contain 313.7 mg/g of theobromine. This determination was made by comparing the product ion ratios with the standards and subsequent quantification. To re-confirm the detected substances, their fragmentation patterns were compared with those of the standards using LC-QTOF-MS. In conclusion, the mass-based information, coupled with the LC-ESI-MS/MS method development, can be successfully applied to rapidly identify 11 respiratory drug substances in illegal dietary supplements used for respiratory disease treatment. The developed simultaneous detection method contributes to public health and safety improvements.

Comparison between Early Clinical Results of Dual-Linear and Conventional Foot-Pedal Control in Phacoemulsification.

BACKGROUND: The aim of this study was to compare early clinical results regarding the safety and efficacy of dual-linear vs. conventional foot-pedal control in cataract surgery. METHODS: This was a paired-eye contralateral, retrospective, observational study. Each patient underwent cataract surgery in both eyes: one eye with dual-linear foot-pedal control (study group) and the other eye with conventional foot-pedal control (control group). Absolute phaco time (APT), average phaco power, effective phaco time (EPT), and surgical complications were analyzed and compared. Corneal endothelial cell count, corneal thickness, corneal volume, and best-corrected distance visual acuity (BCDVA) were measured preoperatively and at 1 week, 1 month, and 3 months postoperatively. RESULTS: A total of 94 patients (188 eyes) were enrolled. The respective APT, average phaco power, and EPT values were 7.05 ± 5.31 s, 28.4 ± 1.00, and 2.05 ± 1.56 s in the study group and 6.82 ± 6.48 s, 18.9 ± 1.74, and 1.35 ± 1.35 s in the control group. CONCLUSIONS: The average phaco power and EPT values were significantly higher in the study group. The safety of the dual-linear foot pedal was comparable to that of a conventional pedal in terms of endothelial cell loss, central corneal thickness, and surgical complications.

Visualizing Hand Force with Wearable Muscle Sensing for Enhanced Mixed Reality Remote Collaboration.

In this paper, we present a prototype system for sharing a user's hand force in mixed reality (MR) remote collaboration on physical tasks, where hand force is estimated using wearable surface electromyography (sEMG) sensor. In a remote collaboration between a worker and an expert, hand activity plays a crucial role. However, the force exerted by the worker's hand has not been extensively investigated. Our sEMG-based system reliably captures the worker's hand force during physical tasks and conveys this information to the expert through hand force visualization, overlaid on the worker's view or on the worker's avatar. A user study was conducted to evaluate the impact of visualizing a worker's hand force on collaboration, employing three distinct visualization methods across two view modes. Our findings demonstrate that sensing and sharing hand force in MR remote collaboration improves the expert's awareness of the worker's task, significantly enhances the expert's perception of the collaborator's hand force and the weight of the interacting object, and promotes a heightened sense of social presence for the expert. Based on the findings, we provide design implications for future mixed reality remote collaboration systems that incorporate hand force sensing and visualization.

Characteristics and Effectiveness of Mobile- and Web-Based Tele-Emergency Consultation System between Rural and Urban Hospitals in South Korea: A National-Wide Observation Study.

(1) Background: The government of South Korea has established a nationwide web- and mobile-based emergency teleconsultation network by designating urban and rural hospitals. The purpose of this study is to analyze the characteristics and effectiveness of the tele-emergency system in South Korea. (2) Methods: Tele-emergency consultation cases from May 2015 to December 2018 were analyzed in the present study. The definition of a tele-emergency in the present study is an emergency consultation between doctors in rural and urban hospitals via a web- and mobile-based remote emergency consultation system (RECS). Consultations through an RECS are grouped into three categories: medical procedure or treatment guidance, image interpretation, and transportation requests. The present study analyzed the characteristics of the tele-emergency system and the reduction in unnecessary transportation (RUT). (3) Results: A total of 2604 cases were analyzed in the present study from 2985 tele-emergency consultation cases. A total of 381 cases were excluded for missing data. Consultations for image interpretation were the most common in trauma cases (71.3%), while transfer requests were the most common in non-trauma cases (50.3%). Trauma patients were more frequently admitted to rural hospitals or discharged and followed up with at rural hospitals (20.3% vs. 40.5%) after consultations. In terms of disease severity, non-severe cases were statistically higher in trauma cases (80.6% vs. 59.4%; p < 0.001). The RUT was statistically highly associated with trauma cases (60.8% vs. 42.8%; p < 0.001). In an analysis that categorized cases by region, a statistically higher proportion of transportation was used in island regions (69.9% vs. 49.5%; p < 0.003). More RUT was associated with non-island regions (30.1% vs. 50.5%; p = 0.001). (4) Conclusions: The tele-emergency system had a great role in reducing unnecessary patient transportation in non-severe trauma cases and non-island rural area emergency cases. Further research is needed for a cost/benefit analysis and clinical outcomes.

Effects of Avatar Transparency on Social Presence in Task-Centric Mixed Reality Remote Collaboration.

Despite the importance of avatar representation on user experience for Mixed Reality (MR) remote collaboration involving various device environments and large amounts of task-related information, studies on how controlling visual parameters for avatars can benefit users in such situations have been scarce. Thus, we conducted a user study comparing the effects of three avatars with different transparency levels (Nontransparent, Semi-transparent, and Near-transparent) on social presence for users in Augmented Reality (AR) and Virtual Reality (VR) during task-centric MR remote collaboration. Results show that avatars with a strong visual presence are not required in situations where accomplishing the collaborative task is prioritized over social interaction. However, AR users preferred more vivid avatars than VR users. Based on our findings, we suggest guidelines on how different levels of avatar transparency should be applied based on the context of the task and device type for MR remote collaboration.

Simultaneous determination of 11 nootropic substances potentially adulterated in dietary supplements for improving brain function using ultra-performance liquid chromatography and liquid chromatography-quadrupole-time-of-flight mass spectrometry.

Recently, the demand for improved brain function and concentration has increased in the dietary supplement market. However, to artificially enhance their pharmacological efficacy, dietary supplements may be illegally adulterated with unauthorised substances. Therefore, we developed a rapid and accurate method to simultaneously determine 11 nootropic substances using an ultra-high-performance liquid chromatography (UPLC) system equipped with a photodiode array (PDA) detector. In addition, sample preparation procedures were semi-optimised for various types of matrices, including solid (hard capsule, tablet, powder, and pill) and liquid (oil and extract) samples. The method was validated to determine the limit of detection (LOD), limit of quantification (LOQ), method detection limit (MDL), method quantitation limit (MQL), specificity, linearity, precision, accuracy, recovery, stability, and matrix effects. The validation results satisfied international validation guideline requirements. To test the applicability of the method, 55 real samples advertised as effective brain health, memory, and cognition supplements were analysed. Among the real samples, vinpocetine (2.483 and 7.296 µg/g), and kavain (69-44.056 µg/g) were detected. In addition, the detected compounds were confirmed by comparing their fragmentation patterns with those of the reference standards using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF/MS). In conclusion, the UPLC-PDA method not only rapidly and accurately quantifies illegal nootropics but also enables the pre-emptive investigation and identification of 11 nootropic substances in illegal dietary supplements to protect public health.

Stereoscopic Vision Recalling Memory for Monocular 3D Object Detection.

Monocular 3D object detection has drawn increasing attention in various human-related applications, such as autonomous vehicles, due to its cost-effective property. On the other hand, a monocular image alone inherently contains insufficient information to infer the 3D information. In this paper, we propose a new monocular 3D object detector that can recall the stereoscopic visual information about an object, given a left-view monocular image. Here, we devise a location embedding module to handle each object by being aware of its location. Next, given the object appearance of the left-view monocular image, we devise Monocular-to-Stereoscopic (M2S) memory that can recall the object appearance of the right-view and depth information. For this purpose, we introduce a stereoscopic vision memorizing loss that guides the M2S memory to store the stereoscopic visual information. Furthermore, we propose a binocular vision association loss to guide the M2S memory that can associate the information of the left-right view about the object when estimating the depth. As a result, our monocular 3D object detector with the M2S memory can effectively exploit the recalled stereoscopic visual information in the inference phase. The comprehensive experimental results on two public datasets, KITTI 3D Object Detection Benchmark and Waymo Open Dataset, demonstrate the effectiveness of the proposed method. We claim that our method is a step-forward method that follows the behaviors of humans that can recall the stereoscopic visual information even when one eye is closed.

Visual outcomes of epiretinal membrane removal after diffractive-type multifocal intraocular lens implantation.

BACKGROUND: To assess visual outcomes of epiretinal membrane (ERM) removal in multifocal intraocular lens (MIOL)-implanted eyes, according to ERM stage. METHODS: Retrospective chart reviews were undertaken in patients with diffractive-type MIOL implants, each undergoing pars plana vitrectomy and ERM removal between February 2018 and November 2020 at Gyeongju St. Mary's Eye Clinic and KEYE Eye Center. Assessments focused on monocular uncorrected and corrected values of distant visual acuity (UDVA and CDVA) and uncorrected near visual acuity (UNVA) at postoperative 12 months according to the stage of ERM. RESULTS: The present study included a total of 49 MIOL-implanted eyes from 49 enrollees, 25 undergoing pars plana vitrectomy for ERM removal (11 eyes with Stage 2 and 14 eyes with Stage 3), and 24 acting as age-matched controls. There was a significant difference in UDVA and UNVA between control and Stage 3 ERM (UDVA; 0.01 ± 0.04 for control, and 0.07 ± 0.08 for stage 3 ERM, p = 0.035, UNVA; 0.03 ± 0.05 for control, and 0.13 ± 0.16 for Stage 3 ERM, p = 0.029). There were no significant differences in CDVA between groups (p = 0.121, ANOVA test). CONCLUSIONS: Eyes with Stage 3 ERM did not achieve visual acuity comparable to control eyes, suggesting the necessity of an early intervention for ERM in eyes with diffractive type MIOL. A meticulous preoperative retinal evaluation for ERM development is mandatory when planning diffractive-type MIOL implantation.

Effects of Brain Factor­7® against motor deficit and oxidative stress in a mouse model of MPTP­induced Parkinson's disease.

Oxidative stress is strongly implicated in the pathogenesis of Parkinson's disease (PD) through degeneration of dopaminergic neurons. The present study was designed to investigate the underlying mechanisms and therapeutic potential of Brain Factor-7® (BF-7®), a natural compound in silkworm, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP (20 mg/kg) was intraperitoneally injected into mice to cause symptoms of PD. Mice were orally administered BF-7® (a mixture of silk peptides) before and after MPTP treatment. Rotarod performance test was used to assess motor performance. Fluoro-Jade B staining for neurons undergoing degeneration and immunohistochemistry of tyrosine hydroxylase for dopaminergic neurons, 4-hydroxy-2-nonenal (4HNE) for lipid peroxidation, 8-hydroxy-2'-deoxyguanosine (8OHdG) for DNA damage and superoxide dismutase (SOD) 1 and SOD2 for antioxidative enzymes in the pars compacta of the substantia nigra were performed. Results showed that BF-7® treatment significantly improved MPTP-induced motor deficit and protected MPTP-induced dopaminergic neurodegeneration. Furthermore, BF-7® treatment significantly ameliorated MPTP-induced oxidative stress. Increased 4HNE and 8OHdG immunoreactivities induced by MPTP were significantly reduced by BF-7®, whereas SOD1 and SOD2 immunoreactivities decreased by MPTP were significantly enhanced by BF-7®. In conclusion, BF-7® exerted protective and/or therapeutic effects in a mouse model of PD by decreasing effects of oxidative stress on dopaminergic neurons in the substantia nigra pars compacta.

Entropy-Aware Model Initialization for Effective Exploration in Deep Reinforcement Learning.

Effective exploration is one of the critical factors affecting performance in deep reinforcement learning. Agents acquire data to learn the optimal policy through exploration, and if it is not guaranteed, the data quality deteriorates, which leads to performance degradation. This study investigates the effect of initial entropy, which significantly influences exploration, especially in the early learning stage. The results of this study on tasks with discrete action space show that (1) low initial entropy increases the probability of learning failure, (2) the distributions of initial entropy for various tasks are biased towards low values that inhibit exploration, and (3) the initial entropy for discrete action space varies with both the initial weight and task, making it hard to control. We then devise a simple yet powerful learning strategy to deal with these limitations, namely, entropy-aware model initialization. The proposed algorithm aims to provide a model with high initial entropy to a deep reinforcement learning algorithm for effective exploration. Our experiments showed that the devised learning strategy significantly reduces learning failures and enhances performance, stability, and learning speed.

Intercomparison study of fragmentation pathways and fragment ion structures for screening of illegal drugs and their novel analogues used to adulterate dietary supplements using liquid chromatography/quadrupole time-of-flight mass spectrometry.

RATIONALE: As public interest in health and immunity has increased in recent years, so has the demand for dietary supplements. However, supplements adulterated with illegal drugs and their novel analogues are being sold even as the pharmacological efficacies of these drugs are being advertised. Since the use of these illegal compounds can have serious side effects, they pose a risk to public health. Hence, in this study, we propose a strategy for proactively testing drugs and novel analogues that may be added to dietary supplements illegally. METHODS: The optimal conditions for liquid chromatography/quadrupole time-of-flight mass spectrometry were explored to determine the fragmentation patterns for 60 compounds. The optimal conditions were established by comparing the areas and heights of the precursor ion peaks at a fragmentor voltage of 125 or 175 V. Furthermore, the optimized spectra were acquired using collision energies of 1 to 50 eV. The energy value was selected based on the condition that the mass error of the precursor ions is 10 ppm or lower. RESULTS: The fragmentation pathway of each product ion and its chemical structure were predicted and determined. In addition, the obtained structural information was used to screen 18 seized samples. Based on the precursor ions and the corresponding fragmentation patterns, the unknown compounds present in the samples were identified as desulfonylchlorosildenafil and propoxyphenylthiohydroxy homosildenafil. CONCLUSIONS: We obtained mass spectrometry-based information for various compounds by predicting the fragmentation pathways and chemical structures of their fragment ions. Subsequently, based on the obtained structural information, we tested several seized samples and were able to detect two novel analogues in four of the samples. Therefore, the proposed approach is suitable for quickly and accurately identifying the unknown compounds detected in real-world samples.

Development of a method for simultaneous screening of four natural-derived steroids and their analogues used as dietary supplements via liquid chromatography-quadrupole-time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry.

Natural-derived steroids and their analogues are present in various plants and insects. To minimize the chance of missing a positive doping test and avoiding potentially serious health problems, adequate screening methods are necessary for the detection of a wide range of natural-derived steroids and their analogues in dietary supplements. In this study, an accurate and simple liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine and quantify the natural-derived steroids and their analogues according to the International Conference on Harmonization of technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The validation results indicating excellent extraction efficiency and low matrix effects show that the LC-MS/MS method is reliable for the detection of natural-derived steroids and their analogues. In addition, we established the ion fragmentation of turkesterone and ion fragmentation of four natural-derived steroids and their analogues. The validated method was applied to 60 dietary supplements purchased online and in person from international vendors in 2020. Ecdysterone and 5α-hydroxylaxogenin were detected respectively in 3 and 14 of 60 dietary supplements. Especially, a high amount of 5α-hydroxylaxogenin, an FDA-unapproved ingredient, was detected in two of dietary supplements (44.4 and 32.3 mg/g). This component should be controlled since it may cause unexpected side effects if administered excessively. Thus, this method will be helpful for the continuous control and supervision of unlicensed dietary supplements containing natural-derived steroids and their analogues.

A Counter Prechop Technique Using a Modified Universal Prechopper in Combination with or without Using a Universal Chopper.

PURPOSE: To introduce an alternative prechop technique without or with the use of a modified universal chopper (AE-2591, HI Kim chopper, ASICO, Inc. USA). METHODS: Patients who underwent cataract surgery using the phaco-chop technique and the modified prechop technique have been grouped and reviewed retrospectively. Endothelial cell count (ECC) and central corneal thickness (CCT) measured 7 days pre-operatively, and 1 month and 3 months post-operatively, were compared between the two groups. In modified prechop technique, a narrow 1.7 mm neck prechopper (AE-4298, HI Kim-Inamura chopper, ASICO, Inc., USA) was used with universal chopper (AE-2591, HI Kim chopper, ASICO, Inc., USA) as an additional device for grade 4 and above cataracts or without it for grade 2 to 3 cataracts. Details of the surgical technique is further described in the Method section. RESULTS: A total of 104 eyes in the modified prechop group and 97 eyes in the phaco-chop group were enrolled in the study. Pre-operative nuclear opacity, ECC, and CCT as well as post-operative ECC (absolute value and the loss) and CCT (absolute value and the change) throughout the follow-up between the two groups did not show statistically significant differences. CONCLUSION: Counter prechop technique using the modified prechopper and universal chopper is a safe, easy, and versatile surgical technique that can be applied broadly in a wide range of cases with various complexities, including LOCS lll N1 to N6 nuclei, hypermature cataracts, small pupils, and fragile suspensory zonular ligaments, with post-operative result not inferior to that of the conventional technique.

Application of predicted fragmentation pathways and fragment ion structures for detecting steroids and selective androgen receptor modulators in dietary supplements using liquid chromatography-quadrupole time-of-flight mass spectrometry.

RATIONALE: Dietary supplements advertised to strengthen muscles have earned fame among athletes. However, several products containing unauthorized compounds are often detected, which can cause a public health risk. Particularly, steroids and selective androgen receptor modulators (SARMs) can cause serious side effects as hormone modulators. In this study, we analyzed 15 steroids and 20 SARMs using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/QTOFMS) to provide fundamental information about fragmentation pathways and fragment ion structures. METHODS: The optimal conditions of LC/QTOFMS were explored to obtain fragmentation patterns for each compound. The optimal conditions were established by comparing the area and height of the precursor ion peak at 125 or 175 V as a fragmentor energy. Furthermore, the optimized spectra were acquired by applying collision energy ranging from 1 to 50 eV. The energy value was selected under the condition that the mass error of precursor ions was less than 10 ppm. RESULTS: The 35 compounds were classified on the basis of their chemical core structures: arylpropionamide (3 compounds), quinolinone (2), pyrrolidinylbenzonitrile (1), indole (2), tropanol (2), phenylaxadaizole (1), hydantoin (2), phenylthiazole (1), nitrothiophene (1) and steroidal derivative (20). Fragmentation pathways and the chemical structure of each product ion were predicted and identified. Furthermore, the obtained structural information was applied to screen seized samples. As a result, 10 seized samples were confirmed to contain one or more SARMs by comparing each precursor ion and fragmentation pattern. CONCLUSIONS: The application to real samples for accurate screening indicated that the same fragmentation patterns and product ions as one or more SARM standards were detected and identified in the seized samples advertised as muscle building. Therefore, this study can contribute to ensuring the safety of public health through providing fundamental information about the risk of illegal adulteration.

Assessing Distraction Potential of Augmented Reality Head-Up Displays for Vehicle Drivers.

OBJECTIVE: To develop a framework for quantifying the visual and cognitive distraction potential of augmented reality (AR) head-up displays (HUDs). BACKGROUND: AR HUDs promise to be less distractive than traditional in-vehicle displays because they project information onto the driver's forward-looking view of the road. However, AR graphics may direct the driver's attention away from critical road elements. Moreover, current in-vehicle device assessment methods, which are based on eyes-off-road time measures, cannot capture this unique challenge. METHOD: This article proposes a new method for the assessment of AR HUDs by measuring driver gaze behavior, situation awareness, confidence, and workload. An experimental user study (n = 24) was conducted in a driving simulator to apply the proposed method for the assessment of two AR pedestrian collision warning (PCW) design alternatives. RESULTS: Only one of the two tested AR interfaces improved driver awareness of pedestrians without visually and cognitively distracting drivers from other road elements that were not augmented by the display but still critical for safe driving. CONCLUSION: Our initial human-subject experiment demonstrated the potential of the proposed method in quantifying both positive and negative consequences of AR HUDs on driver cognitive processes. More importantly, the study suggests that AR interfaces can be informative or distractive depending on the perceptual forms of graphical elements presented on the displays. APPLICATION: The proposed methods can be applied by designers of in-vehicle AR HUD interfaces and be leveraged by designers of AR user interfaces in general.

Simultaneous screening of 21 potential adulterants in dietary supplements for the treatment of prostate diseases using ultra-performance liquid chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry.

Reports of the number of adulteration cases using illegal therapeutic substances in dietary supplements have increased. In recent years, various dietary supplements are being distributed that exaggerate the efficacy of treatment for prostate-related diseases. To develop the preemptive monitoring method, we selected 21 prostate-related therapeutic substances and optimized the simultaneous ultra-performance liquid chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry and pretreatment procedures for various types of matrices including solid, liquid, and soft capsule samples. The methods were validated by determining the specificity, linearity, limit of detection, limit of quantification, method detection limit, method quantitation limit, precision, accuracy, recovery, stability, and matrix effect. The simultaneous methods were validated according to the international guidelines. In addition, using the validated methods, 81 real samples, which were searched and purchased by focusing on promotional phrases, such as prostate and prostatic hyperplasia, were successfully screened. As a result, sildenafil and tadalafil were detected in one seized capsule sample (5.15 and 14.6 mg/g, respectively). Synthetically, our approach could be useful for the determination of illegal therapeutic substances potentially adulterated in various types of dietary supplements.

Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation.

Cardiac arrest (CA) causes severe spinal cord injury and evokes spinal cord disorders including paraplegia. It has been reported that risperidone, an antipsychotic drug, effectively protects neuronal cell death from transient ischemia injury in gerbil brains. However, until now, studies on the effects of risperidone on spinal cord injury after asphyxial CA (ACA) and cardiopulmonary resuscitation (CPR) are not sufficient. Therefore, this study investigated the effect of risperidone on hind limb motor deficits and neuronal damage/death in the lumbar part of the spinal cord following ACA in rats. Mortality, severe motor deficits in the hind limbs, and the damage/death (loss) of motor neurons located in the anterior horn were observed two days after ACA/CPR. These symptoms were significantly alleviated by risperidone (an atypical antipsychotic) treatment after ACA. In vehicle-treated rats, the immunoreactivities of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1ß), as pro-inflammatory cytokines, were increased, and the immunoreactivities of IL-4 and IL-13, as anti-inflammatory cytokines, were reduced with time after ACA/CPR. In contrast, in risperidone-treated rats, the immunoreactivity of the pro-inflammatory cytokines was significantly decreased, and the anti-inflammatory cytokines were enhanced compared to vehicle-treated rats. In brief, risperidone treatment after ACA/CPR in rats significantly improved the survival rate and attenuated paralysis, the damage/death (loss) of motor neurons, and inflammation in the lumbar anterior horn. Thus, risperidone might be a therapeutic agent for paraplegia by attenuation of the damage/death (loss) of spinal motor neurons and neuroinflammation after ACA/CPR.

Populus tomentiglandulosa Extract Is Rich in Polyphenols and Protects Neurons, Astrocytes, and the Blood-Brain Barrier in Gerbil Striatum Following Ischemia-Reperfusion Injury.

Transient ischemia in brains causes neuronal damage, gliosis, and blood-brain barrier (BBB) breakdown, which is related to ischemia-induced brain dysfunction. Populus species have various pharmacological properties including antioxidant and anti-inflammatory activities. In this study, we found that phenolic compounds were rich in Populus tomentiglandulosa extract and examined the effects of Populus tomentiglandulosa extract on neuronal damage/death, astrogliosis, and BBB breakdown in the striatum, which is related to motor behavior, following 15-min transient ischemia in the forebrain in gerbils. The gerbils were pre-treated with 50, 100, and 200 mg/kg of the extract. The latter showed significant effects against ischemia-reperfusion injury. Ischemia-induced hyperactivity using spontaneous motor activity test was significantly attenuated by the treatment. Striatal cells (neurons) were dead at five days after the ischemia; however, pre-treatment with the extract protected the striatal cells from ischemia/reperfusion injury. Ischemia-induced reactive astrogliosis was significantly alleviated, in particular, astrocyte end feet, which are a component of BBB, were significantly preserved. Immunoglobulin G, which is not found in intact brain parenchyma, was apparently shown (an indicator of extravasation) in striatal parenchyma at five days after the ischemia, but IgG leakage was dramatically attenuated in the parenchyma by the pre-treatment. Based on these findings, we suggest that Populus tomentiglandulosa extract rich in phenolic compounds can be employed as a pharmaceutical composition to develop a preventive material against brain ischemic injury.

Refractive Outcomes of Retropupillary Fixated Iris-Claw Lens for Exchange of the Dislocated Intraocular Lens Using Modified Scleral Incisions.

PURPOSE: To evaluate refractive outcomes after retropupillary iris-claw intraocular lens (IOL) implantation and to compare postoperative astigmatism from (1) a conventional 5.5-mm sclerocorneal incision, (2) an L-shaped scleral tunnel incision, and (3) a frown scleral tunnel incision. METHODS: This was a retrospective study of eyes undergoing dislocated IOL exchange for a retropupillary iris-claw IOL. Uncorrected and corrected distance visual acuity (UDVA and CDVA) and postoperative complications were evaluated until postoperative months 24. The refractive outcomes and the surgically induced astigmatism (SIA) vector were compared between groups. RESULTS: The medical records of 107 eyes from 107 patients with mean age of 65.31 ± 12.15 years were reviewed. Eyes with a frown incision showed the best UDVA, followed by those with L-shaped and conventional incisions (P = 0.003). Eyes with an L-shaped incision or frown incision had a lower SIA than that of the conventional incision group at postoperative 6 months (mean ± standard deviation [SD] SIA, 0.86 ± 0.85 D, 0.63 ± 0.37 D, and 1.70 ± 1.27 D for frown incision, L-shaped incision, and conventional incisions, respectively; P = 0.004). CONCLUSION: The frown incision and L-shaped incision induced a significantly smaller SIA than the conventional incisions, which was associated with better UDVA postoperatively.

Development and validation of liquid chromatography-tandem mass spectrometry method for screening six selective androgen receptor modulators in dietary supplements.

Selective androgen receptor modulators (SARMs) are compounds with specific androgenic properties that have been investigated for the treatment of conditions such as muscle wasting disease. The reported androgenic properties have resulted in their use by athletes, and consequently they have been on the World Anti-Doping Agency prohibited list for more than a decade. To minimise the chance of an unattended positive doping test and to avoid potential serious health problems, adequate screening methods for the detection of a wide range of SARMs in these supplements is necessary. In this study, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated simultaneously to screen and quantify six SARMs in dietary supplements, with confirmation by liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF/MS). The validated method was applied to 60 dietary supplements obtained by on-line and direct purchase from international vendors in 2020. Various SARMs were detected at high concentrations in 20 products which were advertised as having androgenic properties. For example, andarine was present at 7.2% in one product, and GW501516 was found at 3.49% in the another product. Furthermore, MK-677 and YK-11, not disclosed on the label, were detected in some products. YK-11 is easily hydrolysed in just a few hours. Although YK-11 is particularly unstable, such that the protonated ion [M + H]+ at m/z 431 for YK-11 was not detected, mass fragmentation, and a [M+ Na]+ ion at m/z 453.3 confirmed the presence of YK-11. Additionally, hydrolysed YK-11 under acidic conditions was confirmed by NMR spectral data, and 1H NMR and 13C NMR spectral data for YK-11 were in good agreement with literature data. This rapid and accurate LC-MS/MS method can therefore be successfully applied to screen and identify SARMs for the continuous control and supervision of dietary supplements.