Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic ...options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies.
To evaluate the efficacy and safety of MMF treatment in patients with NMOSD.
A 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d).
Patients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed.
Of the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5; P < .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5; P = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated.
In this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.
The intestinal microbiota affect various physiological traits of host animals such as brain development, obesity, age, and the immune system. In the swine industry, understanding the relationship ...between intestinal microbiota and growth stage is essential because growth stage is directly related to the feeding system of pigs, thus we studied the intestinal microbiota of 32 healthy pigs across five sows at 10, 21, 63, 93, and 147 d of ages. The intestinal microbiota were altered with growth of pigs and were separated into three distinct clusters. The relative abundance of several phyla and genera were significantly different between growth stages. We observed co-occurrence pattern of the intestinal microbiota at each growth stage. In addition, we predicted the functions of the intestinal microbiota and confirmed that several KEGG pathways were significantly different between growth stages. We also explored the relationship between the intestinal microbiota and innate factors such as the maternal effect and gender. When pigs were young, innate factors affected on construction of intestinal microbiota, however this tendency was disappeared with growth. Our findings broaden the understanding of microbial ecology, and the results will be used as a reference for investigating host-microbe interactions in the swine industry.
The pathogenesis of fibromyalgia (FM) has not been clearly elucidated, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main ...mechanism. The cutaneous silent period (CSP), which is a spinal reflex mediated by A-delta cutaneous afferents, is useful for the evaluation of sensorimotor integration at the spinal and supraspinal levels. To understand the pathophysiology of FM, we compared CSP patterns between patients with FM and normal healthy subjects. Twenty-four patients with FM diagnosed in accordance with the 1990 American College of Rheumatology classification system and 24 age- and sex-matched healthy volunteers were recruited. The CSP was measured from the abductor pollicis brevis muscle. Demographic data, number of tender points, and visual analog scale and FM impact questionnaire scores were collected. The measured CSP and clinical parameters of the patient and control groups were compared. In addition, possible correlations between the CSP parameters and the other clinical characteristics were analyzed. Mean CSP latencies did not differ between patients (55.50 ± 10.97 ms) and healthy controls (60.23 ± 11.87 ms; p = 0.158), although the mean CSP duration was significantly longer in patients (73.75 ± 15.67 ms) than in controls (63.50 ± 14.05 ms; p = 0.021). CSP variables did not correlate with any clinical variables. The significantly longer CSP duration in FM patients suggests central dysregulation at the spinal and supraspinal levels, rather than peripheral small fiber dysfunction.
Anecdotal studies have reported the presence of antiganglioside antibodies in acute unilateral peripheral vestibulopathy (AUPV). This study aimed to determine the prevalence, clinical ...characteristics, and neurotologic findings of AUPV associated with antiganglioside antibodies.
Serum antigangliosides were measured in consecutive patients with AUPV according to the Bárány Society criteria during the acute and recovery phases in a referral-based university hospital in South Korea from September 2019 to January 2023. Clinical characteristics and neurotologic findings were compared between those with and without antiganglioside antibodies. The results of video-oculography, video head impulse and bithermal caloric tests, and other neurotologic evaluations including ocular and cervical vestibular-evoked myogenic potentials and subjective visual vertical were compared between the 2. MRIs dedicated to the inner ear were also conducted when considered necessary.
One hundred five patients (mean age ± SD = 60 ± 13 years, 57 male) were included for analyses. During the acute phase, 12 patients (12/105, 11%) were tested positive for serum antiganglioside antibodies, including anti-GQ1b immunoglobulin (Ig) G (n = 5) or IgM (n = 4), anti-GM1 IgM (n = 3), and anti-GD1a IgG (n = 1, including 1 patient with a positive anti-GQ1b antibody). Patients with antiganglioside antibodies showed lesser intensity of spontaneous nystagmus (median interquartile range = 1.8 1.2-2.1 vs 3.4 1.5-9.5,
= 0.003) and a lesser degree of canal paresis (30 17-47 vs 58 34-79,
= 0.028) and gain asymmetry of the vestibulo-ocular reflex for the horizontal semicircular canal during head impulse tests (0.07 -0.04 to 0.61 vs 0.36 0.18-0.47,
= 0.032) than those without antibodies. Negative conversion of antibodies and vestibular recovery were observed in most patients (6/8, 75%). Among 30 patients with AUPV with 4-hour delayed 3D fluid-attenuated inversion recovery dedicated to the inner ear, gadolinium enhancement was observed in 18 (18/30, 60%), either in the vestibule (n = 9), semicircular canal (n = 6), or vestibular nerve (n = 5). The positivity rates based on specific antibodies could not be determined due to limited sample sizes.
The association between antiganglioside antibodies and AUPV suggests an immune-mediated mechanism in acute vestibular failure and extends the clinical spectrum of antiganglioside antibody syndrome.
Harvesting low‐grade waste heat, which constitutes 60% of the overall waste heat, is key to halting climate change. Electrochemical waste‐heat harvesting has recently drawn attention to practical ...low‐grade waste‐heat harvesting. In this study, a power density maximization strategy is presented in scalable and cost‐effective aqueous redox couple‐based thermo‐electrochemical cells (TECs). The n‐type feature of the water‐soluble Fe2+/3+ redox couple is essential for constructing the TEC p–n leg device; however, it has not been investigated much so far. The modulation of the chaotropicity of counteranions enhances the absolute value of the Seebeck coefficient for the Fe2+/3+ redox couple with an inner‐sphere reaction mechanism because of the greater structural disorder in the solvation shell. Moreover, the use of a cost‐effective Fe─N─C electrocatalyst shows redox kinetics and a power density comparable to those of state‐of‐the‐art Pt electrodes, economically compensating for the sluggish charge‐transfer kinetics of the inner‐sphere redox mechanism. The Fe─N─C ‐based TEC device exhibits 1.73 W m−2 of power density at 0.1 $ W−1 of cost per power, which is 1.24% with respect to the Carnot efficiency, exceeding 0.23–0.53% compared to those reported for previous Pt‐based TEC devices with the same redox chemistry.
This study focuses on scalable and cost‐effective aqueous thermo‐electrochemical cells (TECs) for low‐grade waste heat harvesting. Increasing the chaotropicity of counteranions enhances the Seebeck coefficient for n‐type Fe2+/3+ redox couple due to increased structural disorder in the solvation shell. A cost‐effective Fe─N─C‐based TEC device achieves 1.73 W m−2 power density at 0.1 $ W−1 cost, surpassing previous Pt‐based TEC devices.
Previous studies have shown that vagus nerve stimulation (VNS) can attenuate inflammatory responses in peripheral tissues and also improve some neurological disorders and cognitive function in the ...brain. However, it is not clear how VNS is involved in neuropathological processes in brain tissues. Here, we investigated the regulatory effects of VNS on the production of proinflammatory cytokines in the hippocampus of an animal model of continuous stress (CS).
CS was induced by placing rats in cages immersed with water, and acute or chronic electrical stimulation was applied to the cervical vagus nerve of CS animals. Protein levels in the gastric and hippocampal tissues were measured by western blotting and protein signals analyzed by immunofluorescence staining. von Frey test and forced swimming test were performed to assess pain sensitivity and depressive-like behavior in rats, respectively.
Levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues were significantly increased in CS animals compared to the untreated control and downregulated by acute VNS (aVNS). Iba-1-labeled microglial cells in the hippocampus of CS animals revealed morphological features of activated inflammatory cells and then changed to a normal shape by VNS. VNS elevated hippocampal expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in CS animals, and pharmacological blockade of α7 nAChR increased the production of TNF-α, IL-1β, and IL-6, thus suppressing cholinergic anti-inflammatory activity that was mediated by VNS. Chronic VNS (cVNS) down-regulated the hippocampal production of active form of caspase 3 and 5-HT1A receptors and also decreased levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues of CS animals. Pain sensitivity and depressive-like behavior, which were increased by CS, were improved by cVNS.
Our data suggest that VNS may be involved in modulating pathophysiological processes caused by CS in the brain.
The integrity of the vestibulo-ocular reflex (VOR) remains to be delineated in patients with parkinsonism. We aimed to define the findings of the VOR using head-impulse tests (HITs) and their ...differential diagnostic value in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA). From December 2019 to January 2021, 30 patients with PD and 23 patients with MSA (17 with cerebellar-type MSA and 6 with parkinsonian-type MSA) had a video-oculographic recording of HITs at two university hospitals in South Korea. Reversed (
p
= 0.034) and perverted (
p
= 0.015) catch-up saccades were more frequently observed in MSA than in PD during HITs. The gain difference between the ACs and the PCs were larger in MSA than in PD (
p
= 0.031), and positively correlated with the disease duration in patients with MSA (Spearman’s coefficient = 0.512,
p
= 0.012). Multivariate logistic regression analysis showed that reversed (
p
= 0.044) and perverted (
p
= 0.039) catch-up saccades were more frequently associated with MSA than with PD during HITs. In conclusion, HITs aid in differentiation of MSA from PD, and may serve as a surrogate marker for the clinical decline.
The study determined the effects of Lactobacillus salivarius (LS) administered early in the life of suckling piglets on their growth performance, gut morphology, and gut microbiota. Thirty litters of ...3-day-old crossbreed piglets were randomly assigned to one of the three treatments, and treatments were commenced on day 3 after birth. During the whole period of the experiment, the piglets were kept with their mothers and left to suckle ad libitum while being supplemented with a milk formula with or without the bacterial probiotic supplemented. The control group (CON) was not treated with probiotics, the HLS group was treated with LS144 (HLS) screened from feces of fast-growing pigs with high body mass index (BMI) while the NLS group was supplemented with LS160 (NLS) screened from feces obtained from pigs of normal BMI. At the weaning time, a higher abundance of Actinobacteria, Lentisphaerae, and Elusimicrobia phyla were observed in NLS piglets, whereas the abundance of Fibrobacteres phylum was significantly reduced in NLS and HLS piglets compared with the CON. A greater abundance of Lactobacillus was detected in the HLS treatment compared with the CON. The abundance of Bacteroides and Fibrobacter was higher in the CON piglets compared with the HLS and NLS piglets. Compared with the CON group, the oral administration of LS significantly increased the number of Lactobacillus and villus height in the duodenum, jejunum, and ileum. Moreover, the villus height of the duodenum was significantly improved in the HLS treatment compared with the NLS treatment. Based on the findings in the neonatal piglet model, we suggest that oral supplementation of LS, particularly LS isolated from high BMI pigs, could be beneficial by improving the intestinal villus height.
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