Effect of carbonation and thickening on voluntary swallow in healthy humans.

BACKGROUND: Liquid modification is a widely established strategy of treatment for patients with dysphagia. The modification of liquid particularly by thickening or carbonation is a common approach to promote safe swallowing. OBJECTIVE: This study sought to investigate how carbonated and/or thickened water modulates swallowing behaviours during swallowing in healthy young individuals. METHODS: Thirty-one healthy volunteers (9 men, 22 women; mean age ± standard deviation [SD], 25.7 ± 6.2 years) were instructed to swallow 20 mL of water, carbonated water and carbonated juice with and without added thickening agent. Electromyograms (EMGs) of the suprahyoid (S-hyo) muscles were recorded to evaluate swallowing behaviours. Obtained S-hyo EMG bursts was analysed using the following outcome parameters: onset latency, the time between swallowing que to onset of EMG burst; rising time and falling time, defined as the time between onset and peak, and between peak and offset, respectively; duration, defined as the time between onset and offset of EMG burst; and area integral value under the waveform. RESULTS: Effects of thickening demonstrated the extended onset latency, EMG burst duration including falling time and the larger area of EMG in thickened liquid compared to thin liquid, but there was not much difference between thin and thickened carbonated liquids. Carbonation significantly decreased the duration including falling time for thickened but not for thin liquids. CONCLUSION: Patients with dysphagia can benefit from use of carbonated or thickened water while the effects on swallowing physiology may differ between carbonation and thickening.

Inverted internal limiting membrane flap combined with subretinal viscoelastic injection for large or chronic macular holes.

Purpose: To report two cases with a large or chronic macular hole (MH) that was closed by combining the inverted internal limiting membrane (ILM) flap technique with the injection of ophthalmic viscoelastic device (OVD) into the subretinal space through the MH. Observations: A 76-year-old woman was referred to our clinic for surgery of a MH with a maximum diameter of 1089 µm as determined by optical coherence tomography (OCT). Her visual acuity was 20/50 in the left eye after vitrectomy was performed at a local clinic to remove vitreous opacities. For our surgery, the ILM was peeled and the ILM flap was inverted and placed over the MH. Then, cohesive OVD was injected into the subretinal space through the MH to create a retinal detachment around the MH. The MH was closed by a gas tamponade, and the vision improved to 20/40. The second patient was a 62-year-old man whose vision had been decreasing for 3 years, and he was referred to our clinic. His vision was 20/40 in the left eye and OCT detected a MH with a maximum diameter of 853 µm. After core vitrectomy, the ILM was peeled, inverted, and placed over the MH. Then, dispersive and cohesive OVD was injected through the MH. During this procedure, the MH appeared to enlarge and elevate. Then a yellowish arch-shaped lesion appeared at the temporal edge of the macular detachment. The intraoperative OCT showed that the curled-up retinal pigment epithelium (RPE) within the temporal arch-shaped lesion was adherent to the outer retinal layer. Following gas tamponade, the MH was closed but the patient noticed a paracentric scotoma on the nasal side. The fundus autofluorescence (FAF) images showed a hypo-autofluorescent lesion corresponding to the RPE defect. At postoperative 4 months, his visual acuity had improved to 20/22 and the OCT image showed that the MH was closed with a recovery of the ellipsoid zone of the photoreceptors. The subjective paracentric scotoma disappeared, however the hypo-autofluorescent lesion persisted. Conclusions and importance: A combination of the inverted ILM flap and the subretinal injection of OVD can close a large or chronic MH. An RPE detachment caused by injecting OVD into the subretinal space should be avoided.

Impact of salivary flow inhibition on masticatory behaviours in healthy individuals.

BACKGROUND: It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication. OBJECTIVES: We aimed to clarify: (1) how hyposalivation affects jaw-closing and hyoid-elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food. METHODS: Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation. RESULTS: Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p = .011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p = .013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p < .001). Suprahyoid activity/cycle was significantly greater at the middle (p = .045) and late stages (p = .002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p = .043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p < .001). CONCLUSION: Hyposalivation-induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition.

Efficacy of switching from originator etanercept to biosimilar YLB113 in real-world patients with rheumatoid arthritis: A retrospective 12 months follow-up study.

Purpose: To investigate the disease activity in real-world patients with rheumatoid arthritis (RA) who switched from originator etanercept (ETN) to biosimilar YLB113. Methods: Forty one RA patients who switched from ETN to YLB113 were divided into 2 groups based on the Disease Activity Score based on the 28-joint count (DAS28) 12 months after switching (R group: DAS28 < 2.6, N group: DAS28 ≥ 2.6), and the baseline characteristics were statistically examined. A receiver operating characteristics (ROC) analysis was performed to estimate the cut-off value of DAS28 at baseline to achieve remission 12 months after switching. Results: There was no significant difference in the DAS28 at baseline and 12 months after switching (p = .83). Sixteen out of the 20 patients in remission at baseline achieved remission after switching. A univariate analysis revealed the rheumatoid factor (p = .04) and DAS28 (p < .001) at baseline were significantly lower in the R group than in the N group. Furthermore, logistic regression analysis revealed DAS28 was an independent factor (p = .004) for achieving remission 12 months after switching. An ROC curve analysis showed the optimal cut-off value for DAS28 at baseline to achieve remission at 12 months after switching was 2.5. Conclusions: RA patients who achieved remission using originator ETN, were able to maintain remission even if they switched to YLB113.

Retinal Image Quality Through an Operating Microscope With Wavefront Shaping Extended Depth of Focus Intraocular Lens in Model Eye.

PURPOSE: To compare the quality of images of gratings placed in a model eye viewed through an extended depth of focus (EDoF) intraocular lens (IOL) to that of diffractive bifocal IOL or monofocal IOL. DESIGN: Experimental laboratory investigation. METHODS: Nondiffractive wavefront shaping EDoF (CNAET0, Alcon Laboratories), echelette-designed EDoF (ZXR00V, Johnson & Johnson Vision), diffractive bifocal IOL with low power addition (SV25T, Alcon Laboratories), or monofocal IOL (CNA0T0, Alcon Laboratories) was placed in a fluid-filled model eye. A United States Air Force Resolution Grating Target was glued to the posterior surface of the model eye and viewed through a flat or a wide-angle contact lens. The contrast of the gratings viewed through the EDoF or multifocal IOLs was compared to that through the monofocal IOL. A wavefront analyzer was used to measure the spherical power of the central 4.5 mm optics of the EDoF, multifocal, and monofocal IOLs. The distribution of the dioptric power and the dioptric power map were compared. RESULTS: The gratings observed through the flat contact lens with CNAET0, ZXR00V, or SV25T were slightly blurred when viewed through the multifocal optics. The blurred area was in the circumferential area of CNAET0, the central area of SV25T, and the peripheral area of ZXR00V. The mean contrast was 0.258 ± 0.020 for CNAET0, 0.227 ± 0.025 for ZXR00V, and 0.221 ± 0.020 for SV25T for the 16.0 cyc/mm grating. The contrast was significantly lower for ZXR00V (P = .004) and SV25T (P = .004) than 0.303 ± 0.015 for CNA0T0 but the differences were not significant for CNAET0. For the wide-angle contact lens, the contrast for CNAET0 was 0.182 ± 0.009, for ZXR00V was 0.162 ± 0.011, and for SV25T was 0.163 ± 0.007 for the 16.0 cyc/mm grating, and none was significantly different from 0.188 ± 0.012 for CNA0T0. The dioptric variations of CNAET0 indicated a ring-shaped area of higher power corresponding to the circumferential blurred zone observed through the flat contact lens. CONCLUSIONS: The wavefront shaping and echelette-designed EDoF-IOLs reduce the contrast of the grating more than the monofocal IOL when viewed through the flat contact lens. The degree of reduction depended on the design of the extended-focus optics. The difference was less through the wide-angle contact lens.

Effect of bolus property on swallowing dynamics in patients with dysphagia.

BACKGROUND: Modification of foods or liquids is commonly administered as part of dysphagia treatment. However, no consensus exists on the parameters for defining texture-modified food for patients with dysphagia. OBJECTIVES: The aim of this study was to evaluate the effect of food/liquid material on swallowing physiology in patients with dysphagia and to discuss the optimal food choice for direct swallowing therapy. MATERIALS AND METHODS: A total of 140 patients underwent a videofluoroscopic swallowing study using three test foods/liquids: 3 mL of mildly thick liquid (Thick liquid), jelly made of agar and polysaccharide (Jelly) and jelly made of pectin (Reset gel). Outcome measures of videofluoroscopic images, bolus transit time and hyoid movements were compared. RESULTS: The frequency of chewing movements was highest for Jelly, followed by Reset gel and Thick liquid. While the probability of oral residue was the highest for Reset gel, pharyngeal residue after swallowing was high for Thick liquid as compared to Jelly and Reset gel. Oral transit time and pharyngeal transit time for Thick liquid were significantly smaller than that for Jelly and Reset gel. Pharyngeal delay time was significantly smaller for Thick liquid than that for Jelly and Reset gel. There was no difference in hyoid elevation time and hyoid movement time among the conditions. CONCLUSION: Mildly thick liquid material may be optimal for patients with primarily oral motor function impairment and jelly, such as Reset gel, may be more suitable for patients with primarily pharyngeal motor function impairment or oral and pharyngeal coordinative motor function decline.

Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity.

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

Chewing Well Modulates Pharyngeal Bolus Transit During Swallowing in Healthy Participants.

Mastication is controlled by central pattern generator in the brainstem and can be modulated by volition. The aim of this study was to investigate the effect of chewing well on swallowing. Twenty-six healthy participants were instructed to eat 8, 12, and/or 16 g of steamed rice with barium sulphate under the following two conditions: chewing freely task (CF; chewing naturally in their usual manner) and chewing well task (CW; chewing the food with a request to "chew well"). We evaluated bolus transport and swallowing movement using videofluoroscopy and electromyography of the masseter, suprahyoid and thyrohyoid muscles. The chewing time and pharyngeal transit time (PTT) at the first swallow showed high reproducibility in both CF and CW. PTT for CW was significantly shorter and longer than CF in 12 and 16 g, respectively. In 12 g, CW increased the pharyngeal bolus velocity and decreased thyrohyoid EMG activity during swallowing compared with CF. In 16 g, the difference between CW and CF in the estimated swallowed bolus volume was positively correlated with that in upper esophageal sphincter transit duration. We speculate that CW modulates PTT during swallowing depending on the mouthful volume.

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Continuous electrical stimulation of superior laryngeal nerve inhibits initiation of swallowing in anesthetized rats.

Pharyngeal electrical stimulation (PES) applies electrical stimulation to pharyngeal mucosa (PhM) and represents a useful approach to improve swallowing function in patients with dysphagia. To determine the optimal PES modality to treat dysphagia, the mechanism underlying the effects of PES on swallowing function must be elucidated. In this study, we evaluated how PES and electrical stimulation of the superior laryngeal nerve (SLN) modulate the initiation of swallowing in anesthetized rats. A swallow was evoked by electrical stimulation of the PhM, SLN, and nucleus of the solitary tract (nTS) and pharyngeal mechanical stimulation using a von Frey filament. A swallow was identified by electromyographic bursts in mylohyoid and thyrohyoid muscles. Bilateral SLN transection abolished the swallows evoked by PhM electrical stimulation. PhM and SLN electrical stimulation decreased swallowing frequency in a similar time-dependent manner. Intravenous administration of the GABAA receptor antagonist bicuculine did not affect the time-dependent change in swallowing frequency during SLN electrical stimulation. Continuous SLN electrical stimulation significantly inhibited pharyngeal mechanically and nTS-electrically evoked swallows compared with before and 5 min after stimulation. The present findings suggest that the SLN plays a primary role in PES-evoked swallows. Additionally, continuous SLN electrical stimulation inhibits the initiation of swallowing, and the modulation of central network associated with swallowing might be partially involved in this inhibition.

Short-term and long-term effects of unilateral external carotid artery ligation on orofacial functions in rats.

The external carotid artery (ECA) plays a major role in supplying blood to the head and neck. Although impeded blood flow in the ECA is expected to affect orofacial functions, few studies have shown how blood flow obstruction in the ECA contributes to impairment of these functions, including chewing and swallowing. This study was performed to investigate the effects of ECA ligation (ECAL) on immediate and long-term changes in masticatory and swallowing functions as well as the jaw-opening reflex evoked in the digastric muscle. The experiments were carried out using male Sprague-Dawley rats. In the acute experiment, the digastric reflex evoked by low-threshold electrical stimulation of the inferior alveolar nerve and the swallow reflex, identified by digastric and thyrohyoid electromyographic (EMG) bursts, were compared between before and 1 h after ECAL. The chronic experiment was conducted on freely moving rats. EMGs of the masseter, digastric, and thyrohyoid muscles were chronically recorded. The long-term effects of ECAL on behavior and muscle histology were compared between rats with an intact ECA and rats with ECAL. In the acute experiment, the peak amplitude of the digastric reflex on the ECAL side was significantly decreased 1 h after ECAL. In the chronic experiment, although most parameters of the masticatory and swallowing EMGs were not significantly different between the groups, the results suggest wide variation of the effect of ECAL on the muscles. Blood supply compensation from collaterals of the internal carotid artery may be permanent in some animals.NEW & NOTEWORTHY The inhibitory effect of unilateral external carotid artery ligation (ECAL) on the ipsilateral digastric reflex was small but evident. Most parameters of masticatory and swallowing muscle activity were not significantly different after ECAL. Wide variation was noted in the effect of ECAL on the ipsilateral muscle activity. Blood supply compensation from collaterals of the internal carotid artery may occur in response to the impaired blood flow.

Use of suction electrodes for measurement of intrinsic tongue muscular endurance during lingual pressure generation.

BACKGROUND: Lingual pressure (LP) generation is cooperatively controlled not only by the intrinsic tongue (I-ton) muscles but also by hyoid muscle activation. However, the measurement of endurance and fatigue properties of I-ton muscles is difficult due to the instability of electrodes. OBJECTIVE: The purpose of this study was to apply suction electrodes to measure electromyograms (EMGs) of I-ton muscle and to evaluate integrated EMG amplitude (iEMG) and mean power frequency (MPF) of EMG in the I-ton and hyoid muscles performing continuous LP. METHODS: Twenty healthy adult volunteers (10 males, 10 females, mean age 28.8 years) were instructed to perform 10-s LP generation tasks at 25%, 50%, 75% and 100% of maximum LP in randomised order with visual feedback. During each task, EMGs of the I-ton, suprahyoid (S-hyo), infrahyoid (I-hyo) and masseter (Mass) muscles were simultaneously recorded. The iEMG and MPF of EMG burst during 10-s LP tasks were compared. The recording period was divided into three substages to analyse temporal changes with the Friedman test. RESULTS: During the 10-s task, the iEMG significantly increased as the LP strength increased (p < .001). There was no time-dependent change in the I-ton iEMG; however, the MPF of the I-ton EMG burst decreased in all tasks (p < .05). The S-hyo and I-hyo iEMGs gradually increased, especially with strong LP (p < .01). CONCLUSION: While I-ton muscles may easily fatigue during 10-s LP generation, S-hyo and I-hyo muscles may help compensate for the weakened I-ton muscle activity by increasing their activity to maintain LP.

Potential role of Akt in the regulation of fibroblast growth factor 21 by berberine.

Fibroblast growth factor 21 (FGF21) is expressed in several organs, including the liver, adipose tissue, and cardiovascular system, and plays an important role in cross-talk with other organs by binding to specific FGF receptors and their co-receptors. FGF21 represents a potential target for the treatment of obesity, type 2 diabetes mellitus, and non-alcoholic steatohepatitis (NASH). The production of FGF21 in skeletal muscle was recently suggested to be beneficial for metabolic health through its autocrine and paracrine effects. However, the regulatory mechanisms of FGF21 in skeletal muscle remain unclear. In the present study, we showed that berberine regulated FGF21 production in C2C12 myotubes in a dose-dependent manner. We also examined the effects of A-674563, a selective Akt1 inhibitor, on the berberine-mediated regulation of FGF21 expression in C2C12 myotubes. Berberine significantly increased the secretion of FGF21 in C2C12 myotubes, while A-674563 attenuated this effect. Moreover, a pre-treatment with A-674563 effectively suppressed berberine-induced increases in Bmal1 expression in C2C12 myotubes, indicating that the up-regulation of Bmal1 after the berberine treatment was dependent on Akt1. Additionally, berberine-induced increases in FGF21 secretion were significantly attenuated in C2C12 cells transfected with Bmal1 siRNA, indicating the contribution of the core clock transcription factor BMAL1 to Akt-regulated FGF21 in response to berberine. Collectively, these results indicate that berberine regulates the expression of FGF21 through the Akt1 pathway in C2C12 myotubes. Moreover, the core clock gene Bmal1 may participate in the control of the myokine FGF21. Berberine stimulated Akt1-dependent FGF21 expression in C2C12 myotubes. The up-regulation of FGF21 through the modulation of PI3K/AKT1/BMAL1 in response to berberine may be involved in the regulation of cellular function (such as Glut1 expression) by acting in an autocrine and/or paracrine manner in skeletal muscle.

Optical coherence tomographic findings of glaucomatous eyes with papillomacular retinoschisis.

OBJECTIVES: To investigate the relationship between the shape of the optic nerve head (ONH) margin detected by optical coherence tomography (OCT) and the clinical characteristics of glaucomatous eyes with papillomacular retinoschisis (PMRS). METHODS: The medical record of patients with a PMRS in a glaucomatous eye were reviewed. The eyes were placed into two groups determined by the shape of the ONH margin in the OCT images; eyes with an externally oblique ONH margin (Group 1) and eyes with an internally oblique ONH margin (Group 2). We compared the clinical characteristics of the PMRS of these two groups. RESULTS: We studied 31 eyes of 29 patients with PMRS and glaucoma with 24 eyes in Group 1 and 7 eyes in Group 2. The optic nerve fibre layer schisis on the lamina cribrosa (LC), beta zone, and gamma zone, and found that the LC defects were detected significantly more frequently in Group 1 than in Group 2 eyes (P < 0.05). A retinal nerve fibre schisis was observed around the ONH significantly more frequently in Group 2 than in Group 1 eyes (P < 0.01). CONCLUSION: The cases of glaucoma-associated PMRS could be classified into two groups according to the obliquity of the ONH. They had differences in the findings of OCT and FA. The possibility that the mechanism of PMRS development is different in both groups is suggested.

An update and frequency distribution of Y chromosome haplogroups in modern Japanese males.

Japanese males belong to the Y chromosome C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, O1b2a1a1, O2a2b1, and O2a1b haplogroups. Notably, the regional frequency of each haplogroup is homogeneous. Owing to recent developments in genome sequencing technology, the phylogenetic tree of Y chromosome haplogroups is updated annually. Therefore, in this study, we aimed to provide an update on the Y chromosome haplogroups of modern Japanese males and examine their regional distributions. Using 1,640 samples of Japanese males from seven Japanese cities (Nagasaki, Fukuoka, Tokushima, Osaka, Kanazawa, Kawasaki, and Sapporo), haplogroups C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, and O1b2a1a1 were updated based on the latest phylogenetic tree. Haplogroup C1a1 was mainly classified into C1a1a1a and C1a1a1b subgroups; C1a1a1b was more common in Tokushima and Osaka than in the other regions. Haplogroup C2 was mainly classified into C2a, C2b1a1a, C2b1a1b, C2b1a2, and C2b1b subgroups and exhibited frequency differences in Osaka. Haplogroup D1a2a was classified into D1a2a1c1 and D1a2a2 subgroups, and its frequency varied between Tokushima and Osaka. Haplogroup D1a2a-12f2b was classified into D1a2a1a2b1a1a and D1a2a1a3 subgroups; however, no significant frequency differences were observed. Haplogroup O1b2 was classified into O1b2a1a2a1a, O1b2a1a2a1b, and O1b2a1a3 subgroups, with frequency differences between Nagasaki and Kanazawa. Haplogroup O1b2a1a1 was mainly classified into O1b2a1a1a, O1b2a1a1b, and O1b2a1a1c subgroups; however, no significant frequency differences were observed. Our findings suggest that gene flow in the Kinki region is caused by human migration.

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect.

Breynia spp. are a key source of sulfur-containing spiroketal glycosides with potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals - breynin J (1), epibreynin J (2), and probreynogenin (3) - along with four known compounds - probreynin I (4), phyllaemblic acid (5), breynin B (6), and epibreynin B (7) - were isolated from the roots of Breynia disticha. The structures of compounds 1-7 were elucidated by extensive 1D and 2D NMR spectroscopic analyses, including 1D total correlation spectroscopy (TOCSY), HSQC, HMBC, double quantum-filtered (DQF)-COSY, heteronuclear two-bond correlation (H2BC), and HSQC-TOCSY experiments, as well as high-resolution electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory effects of the isolated compounds were evaluated based on the mRNA levels of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Compounds 1, 2, 6, and 7 inhibited the increase in interleukin (IL)-1ß and IL-6 mRNA levels stimulated by LPS. Moreover, the most potent compound 7 was found to significantly inhibit the production of IL-1ß and IL-6 proteins, as revealed by the analysis of culture supernatants.

Identification of Plasma Proteins as Biomarkers for Mild Cognitive Impairment and Alzheimer's Disease Using Liquid Chromatography-Tandem Mass Spectrometry.

Blood proteins can be used for biomarkers to monitor the progression of cognitive decline, even in the early stages of disease. In this study, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based blood test to identify plasma proteins that can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). Using this system, we quantified plasma proteins using isotope-labeled synthetic peptides. A total of 192 patients, including 63 with AD, 71 with MCI, and 58 non-demented controls (NDCs), were analyzed. Multinomial regression and receiver operating characteristic (ROC) analyses were performed to identify specific combinations of plasma protein panels that could differentiate among NDCs, those with MCI, and those with AD. We identified eight plasma protein biomarker candidates that can be used to distinguish between MCI and AD. These biomarkers were associated with coagulation pathways, innate immunity, lipid metabolism, and nutrition. The clinical potential to differentiate cognitive impairment from NDC was assessed using area under the curve values from ROC analysis, which yielded values of 0.83 for males and 0.71 for females. This LC-MS-based plasma protein panel allows the pathophysiology of AD to be followed through detection of cognitive decline and disease progression markers.

Modulation of reflex responses of the anterior and posterior bellies of the digastric muscle in freely moving rats.

BACKGROUND: Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. OBJECTIVE: This study explored the modulation of reflex responses in the anterior and posterior bellies (ant-Dig and post-Dig, respectively) of the digastric muscle evoked by low-intensity trigeminal stimulation in conscious rats. METHODS: The ant-Dig and post-Dig reflexes were evoked by using low-intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak-to-peak amplitudes and onset latencies were measured. RESULTS: No difference was observed between threshold and onset latency for evoking ant-Dig and post-Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak-to-peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw-closing phase of chewing and licking. Onset latency was significantly largest during the jaw-closing phase. Inhibitory level was similar between the ant-Dig and post-Dig reflex responses and between the ipsilateral and contralateral sides. CONCLUSION: These results suggest that both the ant-Dig and post-Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics.

T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS.

Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is a condition frequently occurring in immunocompromised patients receiving antiretroviral therapy. C-IRIS patients exhibit many critical symptoms, including pulmonary distress, potentially complicating the progression and recovery from this condition. Here, utilizing our previously established mouse model of unmasking C-IRIS (CnH99 preinfection and adoptive transfer of CD4+ T cells), we demonstrated that pulmonary dysfunction associated with the C-IRIS condition in mice could be attributed to the infiltration of CD4+ T cells into the brain via the CCL8-CCR5 axis, which triggers the nucleus tractus solitarius (NTS) neuronal damage and neuronal disconnection via upregulated ephrin B3 and semaphorin 6B in CD4+ T cells. Our findings provide unique insight into the mechanism behind pulmonary dysfunction in C-IRIS and nominate potential therapeutic targets for treatment.