Videofluoroscopic Swallowing Study Features and Resting-State Functional MRI Brain Activity for Assessing Swallowing Differences in Patients with Mild Cognitive Impairment and Risk of Dysphagia.

To examine the swallowing characteristics in patients with mild cognitive impairment (MCI) and dysphagia risk and explore brain activity changes using regional homogeneity (ReHo) with resting-state functional magnetic resonance imaging (rs-fMRI). We included 28 patients with MCI and dysphagia risk and 17 age-matched older adults. All participants underwent neurological, cognitive examinations, and a videofluoroscopic swallowing study (VFSS). We quantitatively analyzed the VFSS temporal and kinetic parameters of the 5- and 10-mL swallows. The participants underwent rs-fMRI, and the ReHo values were calculated. Differences in the swallowing physiology and rs-fMRI findings between participants with MCI and controls were analyzed. Correlation analyses were also conducted. Compared to the control group, patients with MCI and dysphagia risk had lower global cognition scores, longer 10-mL oral transit times (OTTs), and lower executive function scores. ReHo in the bilateral inferior occipital lobes (IOLs) and left prefrontal lobe decreased in patients with MCI and dysphagia risk compared to participants in the control group. In patients with MCI, the 10-mL OTT was negatively correlated with the Montreal Cognitive Assessment (MoCA) score, and the ReHo values were positive correlated with quantitative temporal swallowing measurements using canonical correlation analysis. Mediation analysis revealed that the ReHo values of the left and right IOL acted as significant mediators between the MoCA score and the 10-mL OTT. We found that individuals with MCI and dysphagia risk, verified by reduced MoCA scores, demonstrated prolonged OTTs when swallowing larger boluses compared with age-matched controls. There was a negative correlation between the MoCA score and 10-mL OTT, which was partially mediated by the left and right IOL ReHo values, suggesting that functional changes in the IOLs and left prefrontal lobe associated with oral swallowing status and cognitive level in individuals with MCI and dysphagia risk.

The Effects of Midline Cerebellar rTMS on Human Pharyngeal Cortical Activity in the Intact Swallowing Motor System.

We sought to compare the effects of 10 Hz cerebellar vermis (vs. unilateral hemispheric and sham) repetitive transcranial magnetic stimulation (rTMS) on cortical neuroelectrical activity and thereafter 10 Hz cerebellar vermis (vs. sham) rTMS on swallowing behaviour. Healthy participants (n = 25) were randomly allocated to receive vermis, unilateral hemisphere or sham 10 Hz cerebellar rTMS. Recordings were made using pharyngeal electromyography and manometry catheters, obtaining motor-evoked potentials (MEPs) and pressure recordings. The amplitudes of MEPs elicited using single-pulse TMS delivered to the pharyngeal areas of the motor cortex bilaterally were measured pre- and post-cerebellar stimulation. As in previous studies, abductor policis brevis (APB) MEPs were measured to assess post-rTMS modulation specificity. Swallowing was assessed using a swallowing accuracy task. Measurements were made at baseline and 15-min intervals for an hour post-intervention. Measurements involved TMS being used to elicit 10 MEPs bilaterally over the pharyngeal areas of the motor cortex, over the APB cortical representation adjacent to the pharyngeal area with the lowest resting motor threshold and 5 MEPs bilaterally over pharyngeal areas of the cerebellar hemispheres. Swallowing accuracy was assessed by giving participants 10 attempts to swallow and hit a digital target. Cerebellar vermis rTMS caused significant suppression of cortical pharyngeal MEP amplitudes compared with unilateral rTMS and sham (P = 0.0005, 0.002). APB and cerebellar MEP amplitudes were unaffected as were pharyngeal and APB MEP latencies. Following cerebellar vermis rTMS there was a significant reduction in swallowing accuracy compared with sham (P = 0.001). Our findings demonstrate cerebellar vermis rTMS exerts a suppressive effect on pharyngeal motor cortical activity and swallowing behaviour.

Prevalence of Dysphagia in China: An Epidemiological Survey of 5943 Participants.

OBJECTIVE: To determine the prevalence of dysphagia among an older population and patients with stroke, head and neck cancers (HNCs) or neurodegenerative diseases (NDDs) in China, to identify the factors associated with this condition, and to explore the relationship between dysphagia and nutritional status. METHODS: This study included participants 65 years and older living in the community or in nursing homes and patients who had sustained a stroke, HNC, or NDD also recruited in hospitals from 14 provinces of China. The presence of dysphagia was determined by use of a questionnaire, water swallowing test, and/or a videofluoroscopic swallowing study. Logistic regression analysis was used to assess the possible associated risk factors. Body mass index was assessed as an indicator of malnutrition. RESULTS: A total of 5943 persons met the inclusion criteria and 2341 (39.4%) were identified with dysphagia, including the following: 51.14% of patients with stroke, 34.4% in HNCs, 48.3% in NDDs, and 19.2% of otherwise healthy older adults. The elderly with comorbidity (OR = 2.90, p < 0.01) and stroke patients (OR = 2.27, p < 0.01) were significantly more likely to exhibit signs of dysphagia. Dysphagic participants were at significantly greater risk of malnutrition (OR = 1.91, p < 0.01) compared to those without dysphagia. CONCLUSION: Dysphagia is prevalent in China among older individuals and people who have suffered a stroke, HNCs, or NDDs. The prevalence of dysphagia increases steadily with increasing age and presence of comorbid disease. People with dysphagia are more likely to suffer from malnutrition.

Preconditioning human pharyngeal motor cortex enhances directional metaplasticity induced by repetitive transcranial magnetic stimulation.

KEY POINTS: Recent studies have proposed therapeutic potential for repetitive transcranial magnetic stimulation (rTMS) in swallowing rehabilitation, yet its outcomes vary across individuals and studies. Such variability may be related to the brain state before stimulation. Metaplasticity is a higher order plasticity which regulates cortical response to plasticity changes. Studies have shown that preconditioning of the hand motor cortex could increase cortical capacity for neuroplastic change and enhance rTMS outcomes. We investigated, for the first time, the directional metaplastic properties in human pharyngeal motor cortex using preconditioned rTMS. We found that preconditioned rTMS with specific time intervals between preconditioning and conditioning rTMS had stronger stimulation effects in both swallowing neurophysiology and behaviour than that without preconditioning. Our results provide evidence for enhanced directional metaplasticity in pharyngeal motor cortex and new insights into its clinical application for dysphagia. ABSTRACT: Despite growing evidence that repetitive transcranial magnetic stimulation (rTMS) can be used as a treatment for dysphagia, its efficacy varies across individuals. Such variability may relate to the pre-stimulation state of neuronal activation. Previous studies found that preconditioning the hand motor cortex before rTMS could enhance stimulation outcomes through metaplasticity. No studies have investigated such mechanisms in human pharyngeal motor cortex. Therefore, we investigated the preconditioning effects of rTMS on swallowing neurophysiology and behaviour. Healthy adults were recruited for swallowing neurophysiological (n = 14) and behavioural (n = 14) experiments. They were first given eight different preconditioned (1 and 5 Hz) rTMS interventions with varying inter-rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60 min post-rTMS. Based on the changes in pharyngeal MEPs, the optimal preconditioned 1 Hz and 5 Hz rTMS protocols were then applied as interventions while assessing swallowing performance using a reaction time task. We found that 5 Hz rTMS preconditioned with 1 Hz rTMS with 30 min inter-rTMS interval induced the greatest increase on pharyngeal cortical excitability (F1,13  = 21.244; P < 0.001). By comparison, 1 Hz rTMS preconditioned with 5 Hz rTMS with 90 min inter-rTMS interval was most optimal for suppressing pharyngeal motor cortex (F1,13  = 13.547; P = 0.003). Behaviourally, swallowing accuracy was improved after preconditioned 5 Hz rTMS (F1,13  = 10.109, P = 0.007) and reduced after preconditioned 1 Hz rTMS (F1,13  = 14.108, P = 0.009) compared to sham. Thus, two optimal protocols for inducing functional metaplasticity in human pharyngeal motor cortex have been identified. These protocols appear superior to conventional rTMS and may be relevant to future clinical application in neurogenic dysphagia.

Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms.

Herein we report that peptide dendrimers G3KL and TNS18, which were recently reported to control multidrug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, strongly inhibit biofilm formation by P. aeruginosa PA14 below their minimum inhibitory concentration (MIC) value, under which conditions they also strongly affect swarming motility. Eradication of preformed biofilms, however, required concentrations above the MIC values. Scanning electron microscopy observation and confocal laser scanning micrographs showed that peptide dendrimers can destroy the biofilm morphological structure and thickness in a dose-dependent manner, even make the biofilm dispersed completely. Membrane potential analysis indicated that planktonic cells treated with peptide dendrimers presented an increase in fluorescence intensity, suggesting that cytoplasmic membrane could be the target of G3KL and TNS18 similarly to polymyxin B. RNA-seq analysis showed that the expressions of genes in the arnBCADTEF operon-regulating lipid A modification resulting in resistance to AMPs are differentially affected between these three compounds, suggesting that each compound targets the cell membrane but in different manner. Potent activity on planktonic cells and biofilms of P. aeruginosa suggests that peptide dendrimers G3KL and TNS18 are promising candidates of clinical development for treating infections.

Natural Sweetener, Glycyrrhetinic Acid 3-O-Mono-beta-d-glucuronide, for Postprandial Hyperglycemia Management.

This study examines the inhibitory effects of a range of sweeteners on α-glucosidase. Our findings revealed that only one natural sweetener, namely, glycyrrhetinic acid 3-O-mono-beta-d-glucuronide (GAMG), derived from licorice, exhibited a mixed-type inhibition against α-glucosidase with a IC50 value of 0.73 ± 0.05 mg/mL. The fluorescence intensity of α-glucosidase was quenched by GAMG in the formation of an α-glucosidase-GAMG complex. GAMG has been shown to induce conformational changes in α-glucosidase, likely through hydrogen bonding, van der Waals force, and alkyl-alkyl interactions with amino acid residues, including Arg 281, Leu 283, Trp 376, Asp 404, Asp 443, Trp 481, Asp 518, Phe 525, Ala 555, and Asp 616. Additional animal validation experiments demonstrated that GAMG slowed starch digestion, thereby attenuating the postprandial glycemic response. Taken together, these findings provide evidence that GAMG is a natural sweetener with potent inhibitory activity that selectively targets α-glucosidase. This study supports the use of GAMG as a natural sweetener, which holds a high biological value and may be beneficial for managing postprandial hyperglycemia.

Study on the critical stable height of vertical excavation in rocky foundation pit within layered structural plane.

The structural plane characteristic was the most critical factor for determining the self-stability ability of deep foundation pit vertical-rock-wall in layered rock stratum. Multiple methods such as model testing, numerical calculation, and theoretical calculation were utilized comprehensively in this paper. The self-stabilizing control effect on the deep foundation pits vertical-rock-wall that under the different structural plane inclination angle (α) and under the different structural plane strength was systematically studied. The results indicated that the overall variation trend of "Sharp decrease ~ Slow decrease ~ Slow increase ~ Sharp increase" in the symmetrical distribution for the self-stability critical height (Hcr) varied with the gradually increasing of α was presented. Meanwhile, the variation trend of "continuously decreasing and rapidly decreasing first, and then slowly decreasing and tending to stabilize" with the structural plane strength reduction coefficient (k). The key factor to control the self-stability of the deep foundation pit vertical-rock-walls lied in fully grasping and utilizing the basic characteristics of rock structural planes. The research results of this paper provided the theoretical basis for scientifically determining the safety level and designing reasonable support structures of the deep foundation pit vertical-rock-walls in layered rock stratum.

Suppression of NLRP3 inflammasome activation by astragaloside IV via promotion of mitophagy to ameliorate radiation-induced renal injury in mice.

Background: Irradiation (IR) promotes inflammation and apoptosis by inducing oxidative stress and/or mitochondrial dysfunction (MD). The kidneys are rich in mitochondria, and mitophagy maintains normal renal function by eliminating damaged mitochondria and minimizing oxidative stress. However, whether astragaloside IV (AS-IV) can play a protective role through the mitophagy pathway is not known. Methods: We constructed a radiation injury model using hematoxylin and eosin (HE) staining, blood biochemical analysis, immunohistochemistry, TdT-mediated dUTP nick end labeling (TUNEL) staining, ultrastructural observation, and Western blot analysis to elucidate the AS-IV resistance mechanism for IR-induced renal injury. Results: IR induced mitochondrial damage; the increase of creatinine (SCr), blood urea nitrogen (BUN) and uric acid (UA); and the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and apoptosis in renal tissue. AS-IV administration attenuated the IR-induced MD and reactive oxygen species (ROS) levels in the kidney; enhanced the levels of mitophagy-associated protein [PTEN-induced putative kinase 1 (PINK1)], parkin proteins, and microtubule-associated protein 1 light 3 (LC3) II/I ratio in renal tissues; diminished NLRP3 inflammasome activation-mediated proteins [cleaved cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1ß (IL-1ß)] and apoptosis-related proteins [cleaved caspase-9, cleaved caspase-3, BCL2-associated X (Bax)]; reduced SCr, BUN, and UA levels; and attenuated the histopathological alterations in renal tissue. Conversely, mitophagy inhibitor cyclosporin A (CsA) suppressed the AS-IV-mediated protection of renal tissue. Conclusions: AS-IV can strongly diminish the activation and apoptosis of NLRP3 inflammasome, thus attenuating the renal injury induced by radiation by promoting the PINK1/parkin-mediated mitophagy. These findings suggest that AS-IV is a promising drug for treating IR-induced kidney injury.

Dapagliflozin treatment and cardiovascular outcome in RBP4/TTRVal30Met (transthyretin cardiac amyloidosis) mice.

AIMS: Whether sodium-glucose co-transporter 2 inhibitors are effective for heart failure caused by ATTR-CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR-CA mice model with dapagliflozin treatment. METHODS AND RESULTS: Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1 mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor-beta (TGF-ß), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFß1, TNFα, IL-1ß, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo-treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72 ± 0.46, RBP4[KI/KI], TTRVal50Met [KI/KI]: 1.44 ± 0.60, P = 0.043), indicating more significant heart failure progression in ATTR-CA mice than normal mice. In ATTR-CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFß1, TNFα, and IL-1ß), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. CONCLUSIONS: Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR-CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR-CA. More pre-clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Effect of starch-protein interaction on regulating the digestibility of waxy rice starch under radio frequency treatment with added CaCl2.

This study investigated the effect of starch-protein interaction on regulating the digestibility of waxy rice starch under radio frequency (RF) treatment with added salts. The results showed that starch-protein interactions could significantly reduce the digestibility of waxy rice starch (WRS) under synergetic Ca2+-RF treatment. With the increase of Ca2+ content (0-2 %), the resistant starch content of WRS-WPI, WRS-SPI and WRS-PPI increased from 35.53 %, 36.12 % and 38.78 % to 51.05 %, 52.82 % and 55.93 %, respectively. The addition of appropriate Ca2+ content could increase the short-range ordered structure and lamella structure and form a more compact and uniform microstructure. In addition, the interaction between WRS and protein was mainly through hydrogen bonding and hydrophobic interactions during RF treatment. Furthermore, the presence of Ca2+ could improve the distribution and mobility of water molecules and regulate the rheological properties of WRS-protein complexes. This study offers theoretical guidance for the design and production of rice starch-based products with lower digestibility.

Unveiling the mechanisms of nephrotoxicity caused by nephrotoxic compounds using toxicological network analysis.

Billions of people worldwide have experienced irreversible kidney injuries, which is mainly attributed to the complexity of drug-induced nephrotoxicity. Consequently, there is an urgent need for uncovering the mechanisms of nephrotoxicity caused by compounds. In the present study, a network-based methodology was applied to explore the mechanisms of nephrotoxicity induced by specific compounds. Initially, a total of 42 nephrotoxic compounds and 60 kinds of syndromes associated with nephrotoxicity were collected from public resources. Afterward, network localization and separation algorithms were used to map the targets of compounds and diseases into the human interactome. By doing so, 199 statistically significant nephrotoxic networks displaying the interaction between compound targets and disease genes were obtained, which played pivotal roles in compounds-induced nephrotoxicity. Subsequently, enrichment analysis pinpointed core Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways that highlight commonalities in nephrotoxicity induced by nephrotoxic compounds. It was found that nephrotoxic compounds primarily induce nephrotoxicity by mediating the advanced glycosylation end products-receptor for advanced glycosylation end products signaling pathway in diabetic complications, human cytomegalovirus infection, lipid and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and the phosphatidylinositol 3-kinase-Akt pathways. These results provide valuable insights for preventing drug-induced nephrotoxicity. Furthermore, the approaches we used are also helpful in conducting research on other kinds of toxicities.

Data-mining-based of ancient traditional Chinese medicine records from 475 BC to 1949 to potentially treat COVID-19.

Traditional Chinese Medicine (TCM) plays a role in preventing and treating COVID-19 in China. Based on the manifestations and symptoms of COVID-19, our study used the data mining method to summarize related therapeutic experience left by predecessors who used TCM to treat epidemics in their eras. Initially, we collected abundant medical records with similar manifestations of COVID-19 in Chinese ancient times. The key words including wen (), yi (), li (), and zhang () were searched in ZhongyiZhiku (https://www.zk120.com/) from Warring States Period (475 BC-221 BC) to the Republic of China era (1912-1949) to locate ancient medical records according to inclusion criteria and exclusion criteria. Moreover, COVID-19-related manifestations and corresponding medications in those records were categorized. Eventually, Traditional Chinese Medicine Inheritance Support System version 2.5 was used to build a medical record database of TCM treating COVID-19. Our study collected 263 epidemic medical records comprising COVID-19 related manifestations and found that Chinese Materia Medica (CMM) combinations excavated from ancient medical records included Ren Shen Bai Du San, Wu Ling San, Xiao Chai Hu Tang, Da Cheng Qi Tang, Da Chai Hu Tang, Ling Gui Zhu Gan Tang, and Qing Wen Bai Du Yin. The recurrent CMMs with a high frequency for treating COVID-19 manifestations were Scutellariae Radix (Huang Qin), Paeoniae Alba Radix (Bai Shao), Poria (Fu Ling), and Bupleuri Radix (Chai Hu). Our study suggests that TCM might offer new therapeutic strategies for COVID-19.

Total Synthesis of the Phenolic Steroid Myrmenaphthol A.

Myrmenaphthol A is a structurally unique phenolic steroid with a naphthyl AB-ring system and an unusual C2 hydroxy group. Herein, we report the first total synthesis of this natural product in 10 steps from inexpensive, commercially available sitolactone. Key features of the synthesis include a Baran decarboxylative coupling and a Friedel-Crafts cyclization/olefin isomerization/aromatization cascade that rapidly assembled the tetracyclic core framework. This synthetic strategy is expected to be readily amenable to the synthesis of other phenolic steroids.

Synthesis of 9,11-Secosteroids Pinnisterol E, Glaciasterol B, and 6-Keto-aplidiasterol B.

A 10-step gram-scale synthesis of 9,11-secosteroid pinnisterol E from the inexpensive ergosterol is reported. This synthesis features a series of highly selective redox transformations such as regioselective olefin hydrogenation (PtO2), acid-sensitive endoperoxide reduction (Al-Ni alloy, Zn), and regio- and diastereoselective dienone oxidation. The robustness of this strategy is clearly demonstrated through the formal synthesis of 11(9 → 7)abeo-steroid pleurocin B and the divergent synthesis of 9,11-secosteroids glaciasterol B and 6-keto-aplidiasterol B from the inexpensive cholesterol.

A feasibility pilot study of the effects of neurostimulation on swallowing function in Parkinson's Disease [version 2; peer review: 1 approved, 3 approved with reservations, 1 not approved].

Introduction: Dysphagia often occurs during Parkinson's disease (PD) and can have severe consequences. Recently, neuromodulatory techniques have been used to treat neurogenic dysphagia. Here we aimed to compare the neurophysiological and swallowing effects of three different types of neurostimulation, 5 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS and pharyngeal electrical stimulation (PES) in patients with PD. Method: 12 PD patients with dysphagia were randomised to receive either 5 Hz rTMS, 1 Hz rTMS, or PES. In a cross-over design, patients were assigned to one intervention and received both real and sham stimulation. Patients received a baseline videofluoroscopic (VFS) assessment of their swallowing, enabling penetration aspiration scores (PAS) to be calculated for: thin fluids, paste, solids and cup drinking. Swallowing timing measurements were also performed on thin fluid swallows only. They then had baseline recordings of motor evoked potentials (MEPs) from both pharyngeal and (as a control) abductor pollicis brevis (APB) cortical areas using single-pulse TMS. Subsequently, the intervention was administered and post interventional TMS recordings were taken at 0 and 30 minutes followed by a repeat VFS within 60 minutes of intervention. Results: All interventions were well tolerated. Due to lower than expected recruitment, statistical analysis of the data was not undertaken. However, with respect to PAS swallowing timings and MEP amplitudes, there was small but visible difference in the outcomes between active and sham. Conclusion: PES, 5 Hz rTMS and 1 Hz rTMS are tolerable interventions in PD related dysphagia. Due to small patient numbers no definitive conclusions could be drawn from the data with respect to individual interventions improving swallowing function and comparative effectiveness between interventions. Larger future studies are needed to further explore the efficacy of these neuromodulatory treatments in Parkinson's Disease associated dysphagia.

The asymptotic stability of numerical analysis for stochastic age-dependent cooperative Lotka-Volterra system.

In this study, we explore a stochastic age-dependent cooperative Lotka-Volterra (LV) system with an environmental noise. By applying the theory of M-matrix, we prove the existence and uniqueness of the global solution for the system. Since the stochastic age-dependent cooperative LV system cannot be solved explicitly, we then construct an Euler-Maruyama (EM) numerical solution to approach the exact solution of the system. The convergence rate and the pth-moment boundedness of the scheme have also been obtained. Additionally, numerical experiments have been conducted to verify our theoretical results.

Exploring parameters of gamma transcranial alternating current stimulation (tACS) and full-spectrum transcranial random noise stimulation (tRNS) on human pharyngeal cortical excitability.

BACKGROUND: Transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have been shown to have physiological and functional effects on brain excitability and motor behavior. Yet, little is known about their effects in the swallowing system. AIM: To examine the effects and optimal stimulation parameters of tACS and tRNS for modulating excitability of human pharyngeal motor cortex. METHODS: 10 Hz (alpha), 20 Hz (beta), 70 Hz (gamma) tACS, 0.1-640 Hz (full-spectrum) tRNS, and sham were applied over pharyngeal motor cortices at 1.5 mA current intensity for 10 min in 15 healthy participants. Pharyngeal motor-evoked and thenar motor-evoked potentials (PMEPs and TMEPs) were assessed before and up to 2 h after stimulation with single-pulse transcranial magnetic stimulation. Averaged MEP amplitude and latency changes were analyzed using repeated measures ANOVA (rmANOVA). KEY RESULTS: Two-way rmANOVA across all active interventions demonstrated a significant MEP interaction both in the stimulated pharyngeal cortex (F (4, 56) = 1.731, p = 0.038) and in the ipsilateral thenar cortex (F (4, 56) = 1.506, p = 0.048). Compared to sham, subsequent post hoc tests showed site-specific and sustained (60-120 min) increases in PMEPs with gamma tACS and tRNS (p = 0.005, p = 0.027, respectively) and for TMEPs with beta tACS (p = 0.006). CONCLUSIONS AND INFERENCES: Our findings suggest that the effects of tACS and tRNS are frequency-dependent and cortical (representation) site-specific with both gamma tACS and full-spectrum tRNS enhancing human pharyngeal cortical excitability. These techniques hold promise as potential treatments for neurological dysphagia.

Natural edible materials made of protein-functionalized aerogel particles for postprandial hyperglycemia management.

α-Amylase inhibitors (α-AIs) delay digestion of dietary starch by inhibiting α-amylase in the gut, thereby reducing the postprandial glycemia, which is beneficial to the patients with obesity and diabetes. The proteinaceous α-AIs from wheat can effectively control starch digestion and regulate postprandial hyperglycemia. However, their gastric intolerance remains a challenge, which limits its commercial production and industrial application. In this study, sodium alginate/chitosan aerogels loaded with wheat protein α-AIs were prepared and evaluated as potential transportation and protection matrices for important components in food or pharmaceutical applications. Specifically, the biodegradable aerogel cross-linked with sodium alginate-chitosan-calcium chloride, has a large surface area and open porous structure, which can adsorb staple wheat proteins as an integrated edible material to block around 88,660 U/g of α-amylase activity. The aerogel particles were able to protect the activity of wheat α-AIs in the stomach, leading to the slow passage of the wheat α-AIs through the small intestine to inhibit starch digestion more effectively. Animal experiments further showed that the postprandial blood glucose levels in rats were effectively controlled through delayed increase, after administration of wheat protein-functionalized aerogel particles loaded with wheat α-AIs, which are natural biological macromolecules. This is a novel, safe, and economical method for the prevention and pretreatment of diabetes.

Advances in the Use of Neuromodulation for Neurogenic Dysphagia: Mechanisms and Therapeutic Application of Pharyngeal Electrical Stimulation, Transcranial Magnetic Stimulation, and Transcranial Direct Current Stimulation.

Purpose The swallowing motor system and, specifically, its cortical substrates appear to have certain unique properties that make it highly susceptible to brain plasticity, both driven and following injury. Furthermore, neurogenic dysphagia is a common complication of brain disease, associated with poor outcomes, and yet treatment options remain limited. Therefore, translating the physiology of neurostimulation into clinical populations becomes imperative. In this review, we describe therapeutic application of neuroplasticity in the human swallowing motor system by initially examining the role of pharyngeal electrical stimulation from a mechanistic perspective and then reporting on clinical studies using this approach. Thereafter, we explore the application of noninvasive brain stimulation, which has previously been used to treat nervous system disorders such as depression, pain modulation, and cognitive impairment. Transcranial brain stimulations, in particular, transcranial magnetic stimulation and transcranial direct current stimulation, have been utilized by a number of investigators for rehabilitation in early-stage clinical trials, including dysphagia after neurological disease. In this review, we assess its usefulness in neurogenic dysphagia. Conclusion Early studies indicate these emerging neurostimulatory techniques hold future therapeutic promise. However, both a greater number of and larger clinical trials are required to provide evidence delineating their efficacy and scope of application.