Interlaboratory Comparison of Extractable Organofluorine Measurements in Groundwater and Eel (Anguilla rostrata): Recommendations for Methods Standardization.

Research on per- and polyfluoroalkyl substances (PFAS) frequently incorporates organofluorine measurements, particularly because they could support a class-based approach to regulation. However, standardized methods for organofluorine analysis in a broad suite of matrices are currently unavailable, including a method for extractable organofluorine (EOF) measured using combustion ion chromatography (CIC). Here, we report the results of an international interlaboratory comparison. Seven laboratories representing academia, government, and the private sector measured paired EOF and PFAS concentrations in groundwater and eel (Anguilla rostrata) from a site contaminated by aqueous film-forming foam. Among all laboratories, targeted PFAS could not explain all EOF in groundwater but accounted for most EOF in eel. EOF results from all laboratories for at least one replicate extract fell within one standard deviation of the interlaboratory mean for groundwater and five out of seven laboratories for eel. PFAS spike mixture recoveries for EOF measurements in groundwater and eel were close to the criterion (±30%) for standardized targeted PFAS methods. Instrumental operation of the CIC such as replicate sample injections was a major source of measurement uncertainty. Blank contamination and incomplete inorganic fluorine removal may introduce additional uncertainties. To elucidate the presence of unknown organofluorine using paired EOF and PFAS measurements, we recommend that analysts carefully consider confounding methodological uncertainties such as differences in precision between measurements, data processing steps such as blank subtraction and replicate analyses, and the relative recoveries of PFAS and other fluorine compounds.

Fusion with CTP increases the stability of recombinant neuritin.

Neuritin is a vital neurotrophin that plays an essential role in recovery from nerve injury and neurodegenerative diseases and may become a new target for treating these conditions. However, improving neuritin protein stability is an urgent problem. In this study, to obtain active and stable neuritin proteins, we added a carboxyl-terminal peptide (CTP) sequence containing four O-linked glycosylation sites to the C-terminus of neuritin and cloned it into the Chinese hamster ovary (CHO) expression system. The neuritin-CTP protein was purified using a His-Tag purification strategy after G418 screening of stable high-expression cell lines. Ultimately, we obtained neuritin-CTP protein with a purity >90%. Functional analyses showed that the purified neuritin-CTP protein promoted the neurite outgrowth of PC12 cells, and stability experiments showed that neuritin stability was increased by adding CTP. These results indicate that neuritin protein-CTP fusion effectively increases stability without affecting secretion and activity. This study offers a sound strategy for improving the stability of neuritin protein and provides material conditions for further study of the function of neuritin.

Effect of neuromuscular electrical stimulation combined with early rehabilitation therapy on mechanically ventilated patients: a prospective randomized controlled study.

BACKGROUND: This study aimed to investigate the effectiveness of neuromuscular electrical stimulation (NMES) blended with early rehabilitation on the diaphragm and skeletal muscle in sufferers on mechanical ventilation (MV). METHOD: This is a prospective randomized controlled study. Eighty patients on MV for respiratory failure were divided into a study group (40 cases) and a control group (40 cases) randomly. The study group adopted a treatment method of NMES combined with early rehabilitation and the control group adopted the method of early rehabilitation only. The diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), variation of thickness of intercostal muscles (TIM), variation of thickness of rectus abdominis (TRA), and variation of the cross-sectional area of rectus femoris (CSA-RF) were measured to evaluate the therapeutic effect by ultrasound before and after intervention at the first day of MV, the 3rd and 7th day of intervention and the day discharged from ICU. RESULTS: No significant difference was found in the general demographic information and ultrasound indicators between the two groups before treatment (all P > 0.05). After treatment, the variation of DTF (0.15 ± 0.05% vs. 0.12 ± 0.04%, P = 0.034) was significantly higher in the study group than that in the control group on the day discharged from ICU. The variation of TRA (0.05 ± 0.09% vs. 0.10 ± 0.11%, P = 0.029) and variation of CSA-RF (0.13 ± 0.07% vs. 0.19 ± 0.08%, P < 0.001) in the study group were significantly lower than that in the control group. The duration of MV in the study group was significantly shorter than that in the control group [109.5 (88.0, 213.0) hours vs. 189.5 (131.5, 343.5) hours, P = 0.023]. The study group had better muscle strength score than the control group at discharge (52.20 ± 11.70 vs. 44.10 ± 15.70, P = 0.011). CONCLUSION: NMES combined with early rehabilitation therapy is beneficial in reducing muscle atrophy and improving muscle strength in mechanically ventilated patients. This treatment approach may provide a new option for patients to choose a rehabilitation program; however, more research is needed to fully evaluate the effectiveness of this treatment option.

Tinnitus as a Potential Risk Factor for Uveitis: A 14-Year Nationwide Population-Based Cohort Study in Taiwan.

BACKGROUND: Tinnitus and uveitis have shared commonality in pathophysiology in terms of autoimmunity. However, no studies that have linked any association between the conditions of tinnitus and uveitis. METHODS: This is a retrospective study conducted from the Taiwan National Health Insurance database in order to investigate whether tinnitus patients are at increased risk of uveitis. Patients newly diagnosed with tinnitus between 2001 and 2014 were recruited and followed up until 2018. The endpoint of interest was a diagnosis of uveitis. RESULTS: A total of 31,034 tinnitus patients and 124,136 matched comparisons were analyzed. Tinnitus patients were found to have a significantly higher cumulative incidence for uveitis than those without the diagnosis of tinnitus with incidence rate of 1.68 (95% CI 1.55-1.82) per 10 000 person-months for tinnitus group and 1.48 (95% CI 1.42-1.54) per 10 000 person-months for non-tinnitus group. CONCLUSION: Tinnitus patients were found to have increased risk of developing uveitis.

Corrigendum: The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

[This corrects the article DOI: 10.3389/fnhum.2023.1100320.].

Neuritin affects the activity of neuralized-like 1 by promoting degradation and weakening its affinity for substrate.

Neuritin plays a key role in neural development and regeneration by promoting neurite outgrowth and synapse maturation. Our previous research revealed the mechanism by which neuritin inhibits Notch signaling through interaction with neuralized-like 1 (Neurl1) to promote neurite growth. However, how neuritin regulates Notch signaling through Neurl1 has not been elucidated. Here, we first confirm that neuritin is an upstream regulator of Neurl1 and inhibits Notch signaling through Neurl1. Neurl1 is an E3 ubiquitin ligase that can promote ubiquitination and endocytosis of the Notch1 ligand Jagged1. Therefore, we observe the effect of neuritin on the ligase activity of Neurl1. The results indicate that neuritin inhibits Neurl1 activity by reducing the ubiquitination level and endocytosis of the target protein Jagged1. Moreover, we find that decreased activity of Neurl1 results in reduced expression of Notch receptor Notch intracellular domain (NICD) and downstream target gene hairy and enhancer of split-1 ( HES1). Furthermore, we investigate how neuritin affects Neurl1 enzyme activity. The results show that neuritin not only weakens the affinity between Neurl1 and Jagged1 but also promotes the degradation of Neurl1 by the 26S proteasome pathway. Taken together, our results suggest that neuritin negatively regulates Notch signaling by inhibiting the activity of Neurl1, promoting the degradation of Neurl1 and weakening the affinity of Neurl1 for Jagged1. Our study clarifies the molecular mechanisms of neuritin in regulating the Notch signaling pathway and provides new clues about how neuritin mediates neural regeneration and plasticity.

The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

Objective: We aimed to investigate the effects and mechanisms of swallowing-related brain regions using resting-state functional magnetic resonance imaging (rs-fMRI) in healthy subjects who underwent intermittent theta burst stimulation (iTBS) on dominant or non-dominant cerebellar hemispheres. Methods: Thirty-nine healthy subjects were randomized into three groups that completed different iTBS protocols (dominant cerebellum group, non-dominant cerebellum group and sham group). Before iTBS, the resting motor threshold (rMT) was measured by single-pulse transcranial magnetic stimulation (sTMS) on the cerebellar representation of the suprahyoid muscles, and the dominant cerebellar hemisphere for swallowing was determined. Forty-eight hours after elution, iTBS protocols were completed: in the dominant cerebellum group, iTBS was administered to the dominant cerebellar hemisphere, and the non-dominant cerebellar hemisphere was given sham stimulation; in the non-dominant cerebellum group, iTBS was administered to the non-dominant cerebellar hemisphere, and sham stimulation was delivered to the dominant cerebellar hemisphere; in the sham group, sham stimulation was applied to the cerebellum bilaterally. Rs-fMRI was performed before and after iTBS stimulation to observe changes in the fractional amplitude of low-frequency fluctuation (fALFF) in the whole brain. Results: Compared with baseline, the dominant cerebellum group showed increased fALFF in the ipsilateral cerebellum, and decreased fALFF in the ipsilateral middle temporal gyrus and contralateral precuneus after iTBS; the iTBS of the non-dominant cerebellum group induced increased fALFF in the ipsilateral superior frontal gyrus, the calcarine fissure and the surrounding cortex, and the contralateral inferior parietal lobule; and in the sham group, there was no significant difference in fALFF. Exploring the effects induced by iTBS among groups, the dominant cerebellum group showed decreased fALFF in the contralateral calcarine fissure, and surrounding cortex compared with the sham group. Conclusion: Intermittent theta burst stimulation of the dominant cerebellar hemisphere for swallowing excited the ipsilateral cerebellum, and stimulation of the non-dominant cerebellar hemisphere increased the spontaneous neural activity of multiple cerebrocortical areas related to swallowing. In conclusion, regardless of which side of the cerebellum is stimulated, iTBS can facilitate part of the brain neural network related to swallowing. Our findings provide supporting evidence that cerebellar iTBS can be used as a potential method to modulate human swallowing movement.

Optical Coherence Tomography Biomarkers in Predicting Treatment Outcomes of Diabetic Macular Edema after Ranibizumab Injections.

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 µm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 µm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes.

Association between triglyceride-glucose index and arterial stiffness reflected by carotid pulse-wave velocity in stage 1 hypertension and individuals with normal/elevated blood pressure.

Evidence of the triglyceride-glucose (TyG) index as an independent predictor of arterial stiffness in stage 1 hypertension patients is scarce. This study aimed to explore the association between TyG index and arterial stiffness in this population. A total of 1041 individuals from 32 centers with normal/elevated blood pressure (BP, <130/80 mmHg; 345 men (33%); median age, 37 years) and 585 stage 1 hypertension patients (BP ≥130/80 and <140/90 mmHg; 305 men (52%); median age, 47 years) were prospectively enrolled. Arterial stiffness was determined by measuring carotid ultrafast pulse-wave velocity (ufPWV). TyG index was calculated as ln (fasting triglyceride (TG) × fasting blood glucose/2). Patients with a higher TyG index tended to have higher ufPWV. The TyG index was positively associated with ufPWV at the end of systole in stage 1 hypertension patients after adjusting for confounding factors (ß for per unit .48), and restricted cubic spline analysis confirmed a linear association. Subgroup analyses in terms of age, sex, and body mass index yielded similar results. However, no significant relationship was observed between the TyG index and ufPWV in the population with normal/elevated BP. The fully adjusted ß between ufPWV and the TyG index was higher than the TG/high-density lipoprotein cholesterol ratio, TG, and pulse pressure. In conclusion, patients with a higher TyG index had greater arterial stiffness, and the TyG index independently and positively correlated with arterial stiffness in stage 1 hypertension patients. The TyG index may provide a simple and reliable marker to monitor arterial stiffness in hypertensive patients.

Removal and destruction of perfluoroalkyl ether carboxylic acids (PFECAs) in an anion exchange resin and electrochemical oxidation treatment train.

Perfluoroalkyl ether carboxylic acids (PFECAs) are a group of emerging recalcitrant contaminants that are being developed to replace legacy per- and polyfluoroalkyl substances (PFAS) in industrial applications and that are generated as by-products in fluoropolymer manufacturing. Here, we report on the removal and destruction of four structurally different PFECAs using an integrated anion exchange resin (AER) and electrochemical oxidation (ECO) treatment train. Results from this work illustrated that (1) flow-through columns packed with PFAS-selective AERs are highly effective for the removal of PFECAs and (2) PFECA affinity is strongly correlated with their hydrophobic features. Regeneration of the spent resin columns revealed that high percentage (e.g., 80%) of organic cosolvent is necessary for achieving 60-100% PFECA release, and regeneration efficiency was higher for a macroporous resin than a gel-type resin. Treatment of spent regenerants showed (1) >99.99% methanol removal was achieved by distillation, (2) >99.999% conversion of the four studied PFECAs was achieved during the ECO treatment of the still bottoms after 24 hours with an energy per order of magnitude of PFECA removal (EE/O) <1.03 kWh/m3 of total groundwater treated, and (3) >85% of the organic fluorine was recovered as inorganic fluoride. Trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), and perfluoro-2-methoxyacetic acid (PFMOAA) were confirmed via high-resolution mass spectrometry as transformation products (TPs) in the treated still bottoms, and two distinctive degradation schemes and four reaction pathways are proposed for the four PFECAs. Lastly, dissolved organic matter (DOM) inhibited uptake, regeneration, and oxidation of PFECAs throughout the treatment train, suggesting pretreatment steps targeting DOM removal can enhance the system's treatment efficiency. Results from this work provide guidelines for developing effective separation-concentration-destruction treatment trains and meaningful insights for achieving PFECA destruction in impacted aquatic systems.

MULTIMODAL IMAGING OF ACUTE MULTIFOCAL HEMORRHAGIC RETINAL VASCULITIS: A CASE REPORT.

PURPOSE: To report a case of acute multifocal hemorrhagic retinal vasculitis and demonstrate the multimodal imaging. METHODS: Interventional case report. RESULTS: A 54-year-old woman without significant past medical history complained of redness and blurred vision in both eyes. Her visual acuity was counting fingers and 20/60. Mild conjunctival injection, anterior chamber cells, and vitreous haze were noted. Fundus showed multifocal intraretinal hemorrhages. Fluorescein angiography revealed vasculitic process with intraretinal hemorrhage blocking defects and retinal ischemic changes in both eyes. Anterior chamber tap fluid polymerase chain reaction for varicella zoster virus, herpes simplex virus I/II, cytomegalovirus, and Epstein-Barr virus was unremarkable. Rheumatology was consulted and systemic vasculitis was ruled out. Her vision improved to 20/50 and 20/20 after pulse methylprednisolone therapy, oral methotrexate, and prednisolone treatment. CONCLUSION: Acute multifocal hemorrhagic retinal vasculitis can occur in an immunocompetent patient. Multimodal Imaging is useful in the diagnosis and follow-up. Patients could benefit from early and aggressive immunosuppressive therapy.

Short-Term Effects of Brolucizumab in the Treatment of Wet Age-Related Macular Degeneration or Polypoidal Choroidopathy Refractory to Previous Anti-Vascular Endothelial Growth Factor Therapy.

Background and objectives: To report the initial response to a single intravitreal brolucizumab (IVI-B) injection in wet age-related macular degeneration (wAMD) or polypoidal choroidopathy (PCV) complicated with either persistent subretinal fluid (SRF) or pigment epithelial detachment refractory to previous anti-vascular endothelial growth factor (anti-VEGF) therapy. Material and methods: In this retrospective study, all eyes received a single IVI-B (6 mg/0.05 mL) for wAMD or PCV with treatment-resistant SRF or PED. Outcome measures included assessment in central retinal thickness (CRT), visual acuity, and evaluation for changes in the SRF or PED on OCT. Follow-up was prior to the first brolucizumab injection, then at 1 week and 5 weeks afterwards. Results: In total, 10 eyes of 10 patients (6 women [60%]) were enrolled. Five patients had wAMD and five patients had PCV. Average age of participants was 67.6 years. All patients received one IVI-B. All patients were not treatment-naïve to anti-VEGF agents. At the first week and fifth week following the first IVI-B, seven out of seven patients (100%) had resolved SRF. However, seven out of nine patients (78%) had no improvement of their PED at 5 weeks follow-up. Mean PED height and width before the first IVI-B was 339.77 µm and 2233.44 µm, respectively. Mean PED height and width at the fifthweek following the first IVI-B was 328.125 µm and 2129.5 µm, respectively. Overall mean visual acuity before the first IVI-B was 0.224; and 5 weeks following the first IVI-B was 0.38. Conclusions: Treatment with brolucizumab resulted in anatomical improvement for all patients with persistent SRF. Limited efficacy was seen for persistent PED. Brolucizumab appears to be a safe and effective option for treatment-resistant SRF. Future multicenter collaborative studies are warranted.

Reference values of the carotid elastic modulus using shear wave elastography and arterial stiffness change in coronary slow flow.

PURPOSE: Shear wave elastography (SWE) accurately and sensitively evaluates arterial wall stiffness by quantifying the elastic modulus (EM); however, the absence of reference values has precluded its widespread clinical application. This prospective cohort study aimed to establish reference values for the carotid EM using SWE; investigate the main determinants of the EM; and evaluate EM changes in coronary slow flow (CSF), which is characterized by delayed coronary opacification without evident obstructive lesion in epicardial coronary artery on angiography. METHOD: This study enrolled 169 healthy volunteers and 30 patients with CSF. The carotid maximum EM (EMmax), mean EM, and minimum EM were measured using SWE. CSF was diagnosed by thrombolysis in the myocardial infarction frame count during coronary angiography. RESULTS: No differences were found in the EM between the left and right carotid arteries and between men and women. Multiple linear regression analysis revealed that age was independently correlated with the EMmax, which progressively increased with age. Moreover, smoking had an independent influence on the EM after adjusting for age; smokers had higher EM than non-smokers. Age-specific reference values for the carotid EM were established. The EM was higher in patients with CSF than in controls after adjusting for age and smoking status. CONCLUSIONS: This study first established the reference values for the carotid EM using SWE. Age and smoking status were the main determinants of the EM. Patients with CSF had high EM. SWE can effectively and noninvasively evaluate arterial stiffness in patients with CSF.

Use of Ultra-Widefield Fluorescein Angiography to Guide the Treatment to Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis-Case Report and Literature Review.

PURPOSE: To review the clinical features, diagnosis, and treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and to report a case with the use of ultra-widefield fluorescein angiography (UWFA) for confirming the precise staging of IRVAN and aid in early treatment. The patient improved after being treated with intravitreal aflibercept injection. RESULTS: A 26-year-old female complained of progressive blurred vision OD for one week. Her BCVA was 0.6 OD and 1.0 OS. Fundus examination showed vitritis, retinal hemorrhage, and vasculitis over bilateral eyes. Fluorescein angiography (FA) with a 55 degree of view revealed aneurysmal dilations of the peripapillary arteriole, peripapillary focal leakage, venous leakage, and capillary nonperfusion area. Stage 2 IRVAN was impressed OU. Oral prednisolone was administered. After four months, she experienced decreased visual acuity OS. Optical coherence tomography (OCT) revealed subretinal and intraretinal fluid with hyperreflective material. One posterior subtenon triamcinolone and one intravitreal aflibercept injection were performed OS, and macular edema subsided. A 105-degree ultra-widefield fluorescein angiography (UWFA) showed multiple peripheral background hypofluorescence areas corresponding to capillary nonperfusion. Retinal neovascularization (NV) was found OS, which had not been revealed by the previous 55-degree FA. Stage 3 IRVAN was made OS and panretinal laser photocoagulation (PRP) was performed. Oral prednisone and cyclosporine were prescribed. Her vision improved to 1.0 OU. CONCLUSION: UWFA provides visualization of peripheral retinal pathology and for precise staging. It also had direct implications in the follow-up and treatment strategy.

Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death­related ceRNA network.

The present study aimed to uncover the underlying mechanisms and potential intervention targets of ischemic stroke (IS). An immune cell infiltration analysis using CIBERSORT was performed on two stroke-related datasets from the Gene Expression Omnibus database to generate a competitive endogenous RNA (ceRNA) network. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict potential biological functions of the network. Differentially expressed genes in the ceRNA network and programmed cell death-related genes were intersected to obtain common genes for a stroke ceRNA network related to programmed cell death. These genes were further verified through a middle cerebral artery occlusion rat model using reverse transcription-quantitative PCR. This built a ceRNA regulatory network based on bioinformatic analysis. In addition to the biological functions extracted from the GO and KEGG enrichment analyses, it was discovered that long non-coding (lnc)RNA-mediated ceRNA regulatory pathways were associated with programmed cell death. This included five for apoptosis (lncRNA deleted in lymphocytic leukemia 2 like (DLEU2L)/micro (miR)-4500/sulfite oxidase, lncRNA DLEU2L/miR-4500/transforming growth factor ß receptor III, lncRNA DLEU2L/miR-4500/BTB and CNC homology 1 (BACH1), lncRNA DLEU2L/miR-4500/zinc finger and BTB domain containing 5 and lncRNA LINC00266-1/miR-363-3p/zinc finger protein 354B and two for ferroptosis (lncRNA DLEU2L/miR-4500/ribo-nucleotide reductase regulatory subunit M2 and lncRNA DLEU2L/miR-4500/BACH1). Based on the aforementioned results, the present study provided potential approaches for bridging programmed cell death, immune infiltration and ceRNA regulatory networks in IS. The present study may provide novel insights into the clinical diagnosis and treatment of IS, and may improve the knowledge of the regulation of pathophysiological processes for IS.

High-Frequency Cerebellar rTMS Improves the Swallowing Function of Patients with Dysphagia after Brainstem Stroke.

Objective: To explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the swallowing motor area of the cerebellum in patients with dysphagia after brainstem stroke. Methods: A total of 36 patients with dysphagia after brainstem stroke were recruited and divided into 3 groups. Before stimulation, single-pulse transcranial magnetic stimulation (TMS) was used to determine the swallowing dominant cerebellar hemisphere and the representation of the mylohyoid muscle. The three groups of patients received bilateral cerebellar sham stimulation, dominant cerebellar rTMS + contralateral sham stimulation, or bilateral cerebellar rTMS. The stimulus plan for each side was 10 Hz, 80% resting movement threshold (rMT), 250 pulses, 1 s per stimulus, and 9 s intervals. Sham rTMS was performed with the coil held at 90° to the scalp. The changes in the motor evoked potential (MEP) amplitude and the clinical swallowing function scales of the patients after stimulation were compared among the three groups. Results: 34 patients were finally included for statistical analysis. The scores of penetration aspiration scale (PAS) and functional dysphagia scale (FDS) of the patients after 2 weeks of rTMS in the unilateral stimulation group and bilateral stimulation group were better than that in the sham stimulation group, and there was no significant difference between the two groups. The increase in the MEP amplitude of the cerebral hemisphere in the bilateral stimulation group was higher than that in the other two groups, and the increase in the MEP amplitude in the unilateral stimulation group was higher than that in sham stimulation group. There was no correlation between the improvement in patients' clinical swallowing function (PAS scores and FDS scores) and the increase in MEP amplitude in either the unilateral stimulation group or the bilateral stimulation group. Conclusion: High-frequency rTMS in the cerebellum can improve swallowing function in PSD patients and increase the excitability of the representation of swallowing in the bilateral cerebral hemispheres. Compared with unilateral cerebellar rTMS, bilateral stimulation increased the excitability of the cerebral swallowing cortex more significantly, but there was no significant difference in clinical swallowing function.

Optical Coherence Tomography Biomarkers in Predicting Treatment Outcomes of Diabetic Macular Edema After Dexamethasone Implants.

Purpose: To identify optical coherence tomography (OCT) biomarkers that may predict functional and anatomical outcomes in diabetic macular edema (DME) patients treated with intravitreal dexamethasone (DEX) implant. Materials and Methods: Sixty-four eyes from 50 patients with DME were enrolled. Best-corrected visual acuity (BCVA) and OCT biomarkers including central retinal thickness (CRT), subretinal fluid (SRF), intraretinal cysts (IRC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudate (HE), hyperreflective foci (HRF), epiretinal membrane (ERM), and vitreomacular interface (VMI) changes were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate each OCT biomarker as a predictive factor for functional and anatomical improvement at the end of treatment. Results: The presence of SRF at baseline was associated with a favorable outcome, with CRT improving by more than 100 µm after treatment from multivariate logistic regression analysis [odds ratio 6.16 (1.75-21.6)]. In addition, baseline SRF predicted a greater CRT improvement from multiple regression analysis (model R-square 0.11, p = 0.006). The reduction of DRIL, SRF, LONLC, IRC, and EZD were correlated with better CRT improvement (more than 100 µm) (P < 0.05). SRF and EZD recovery can also predict better visual prognosis (P < 0.05). Conclusion: OCT biomarkers can be used to predict who may benefit the most after DEX treatment. We suggest that the DEX implant should be considered as a first line treatment in DME patients with SRF.

Study on Low-Frequency Repetitive Transcranial Magnetic Stimulation Improves Speech Function and Mechanism in Patients With Non-fluent Aphasia After Stroke.

Objective: To explore the therapeutic effect and mechanism of low-frequency repetitive transcranial magnetic stimulation on the speech function of patients with non-fluent aphasia after stroke. Methods: According to the inclusion and exclusion criteria, 60 patients with post-stroke non-fluent aphasia were included and randomly divided into treatment group (rTMS group) and sham stimulation group (S-rTMS group). Patients in rTMS group were given low-frequency rTMS + ST training. Patients in the S-rTMS group were given sham low-frequency rTMS + ST training. Once a day, 5 days a week, for a total of 4 weeks. The Western Aphasia Battery and the short-form Token test were used to evaluate the language function of the patients in the two groups before and after treatment. Part of the enrolled patients were subjected to functional magnetic resonance imaging examination, and the morning fasting venous blood of the enrolled patients was drawn before and after treatment to determine the content of BDNF and TNF-α. Results: In the comparison before and after treatment within the group, all dimensions of the WAB scale of the patients in the rTMS group increased significantly. Only two dimensions of the WAB scale of the patients in the S-rTMS group improved significantly after treatment. The results of the short-form Token test showed that patients in the rTMS group improved significantly before and after treatment. The resting state functional magnetic resonance imaging of the two groups of patients before and after treatment showed: the activation of multiple brain regions in the left hemisphere of the rTMS group increased compared with the control group. The serum BDNF content of the patients in the rTMS group was significantly higher than that of the patients in the S-rTMS group after treatment. Conclusion: Low-frequency rTMS combined with conventional speech training can significantly improve the speech function of patients with non-fluent aphasia after stroke.

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study.

Objective: The effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging (rs-fMRI). Method: A total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% resting motor threshold (rMT), and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential (MEP) amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation (ALFF) and regional homology (ReHo) at 0.01-0.08 Hz, 0.01-0.027 Hz, and 0.027-0.073 Hz. Results: After cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01-0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01-0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area. Conclusion: Repetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice.

Extraction and Matrix Cleanup Method for Analyzing Novel Per- and Polyfluoroalkyl Ether Acids and Other Per- and Polyfluoroalkyl Substances in Fruits and Vegetables.

Per- and polyfluoroalkyl ether acids (PFEAs) are a subclass of per- and polyfluoroalkyl substances (PFAS) that are detected with increasing frequency in environmental matrices. Diet can be an important route of PFEA exposure, but the presence of PFEAs in food is poorly understood. Extraction methods for food samples exist for traditionally studied PFAS, but their suitability for PFEAs and other novel PFAS remains unknown. In this study, an extraction and matrix cleanup method was developed to quantify 45 PFAS, including 13 PFEAs, 3 perfluoroalkane sulfonamides, and 6 fluorotelomer carboxylic acids in 10 types of fruits and vegetables. Homogenized samples were extracted with basic methanol, and resulting extracts were diluted with water and cleaned up using solid-phase extraction with weak anion-exchange cartridges. The method was validated by performing spike-recovery experiments at spike levels of 1 ng/g in all 10 matrices and 0.1 ng/g in 2 matrices. For PFAS without a corresponding isotopically labeled internal standard (IS), adopting an IS with a similar chromatographic retention time generated the most accurate recoveries. Dependent upon the matrix, recoveries of 38-44 PFAS (including 10-13 PFEAs) fell within 50-150% for samples spiked at 1 ng/g. Recoveries of 40 and 38 PFAS in blueberries and corn, respectively, fell within 50-150% for samples spiked at 0.1 ng/g. Method quantification limits (MQLs) of PFAS in pure solvents were determined as the lowest calibration level with an accuracy between 70 and 130%. To compensate for matrix effects, a matrix factor was applied on the basis of the analyte response in different matrices relative to the pure solvent. The MQLs of 45 PFAS (including 13 PFEAs) in 10 matrices ranged from 0.025 to 0.25 ng/g. Overall, this method is capable of sensitively quantifying 45 PFAS in many fruits and vegetables.