Search

Purpose: The purpose of this study is to examine 1) the degree and frequency of laterality in posterior tibial slope (PTS) with control and anterior cruciate ligament (ACL) injury groups and 2) the laterality of PTS between sides of injury and dominant legs in patients with primary ACL injuries. Methods: A total of 187 consecutive patients with clinically diagnosed noncontact ACL injuries and an age- and sex-matched 1:1 control group were identified. PTS was measured using three different methods (aPTS = anterior PTS, mPTS = middle PTS, pPTS = posterior PTS) on a lateral knee radiograph. PTS of the left and right sides were compared between the patients in the control and ACL-injured groups, and between the injured and non-injured and dominant and non-dominant legs among the patients in the ACL-injured group. The patients with a difference in PTS of ≥ 3° in mPTS were selected. The percentages were compared between left and right between and among both groups, and between the injured and non-injured, and non-dominant and dominant leg, for the ACL group. Multiple regression analysis was performed to analyze the factors influencing the degree of mPTS. Results: Both control (Right vs Left: aPTS; 9.0 ± 2.5 vs 10.5 ± 3.0, mPTS; 6.6 ± 2.3 vs 8.1 ± 2.7, pPTS; 4.0 ± 2.4 vs 5.6 ± 2.8, respectively, p < 0.01) and ACL injury groups (Right vs Left: aPTS; 10.6 ± 3.0 vs 12.6 ± 2.9, mPTS; 7.6 ± 2.6 vs 9.5 ± 2.6, pPTS; 5.9 ± 3.0 vs 8.0 ± 3.0, respectively, p < 0.01) had a significantly greater PTS on the left than on the right side, and the ACL group had a significantly greater PTS than the control group on both the left and right sides. In the ACL group, PTS was greater on the injured and the non-dominant leg than on the non-injured and the dominant leg. The percentage of patients with a PTS difference of ≥ 3° was significantly greater on the left, injured, and non-dominant leg (95.3% vs 4.7%, 73.8% vs 26.2%, 86.1% vs 13.9%, respectively, p < 0.01). Only the left leg had a significant influence on PTS in the multivariate analysis. Conclusion: There was laterality in PTS within control and ACL injury groups, and this information is of benefit for effective treatment of ACL injuries. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Objective: A pathological excitatory action of the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl− importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl− concentration ([Cl−]i) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted. Although NKCC1 is expressed in both neurons and glial cells, an involvement of glial NKCC1 in seizures has not yet been reported. Astrocytes maintain high [Cl−]i with NKCC1, and this gradient promotes Cl− efflux via the astrocytic GABAA receptor (GABAAR). This Cl− efflux buffers the synaptic cleft Cl− concentration to maintain the postsynaptic Cl− gradient during intense firing of GABAergic neurons, thereby sustaining its inhibitory action during seizure. In this study, we investigated the function of astrocytic NKCC1 in modulating the postsynaptic action of GABA in acute seizure models. Methods: We used the astrocyte‐specific conditional NKCC1 knockout (AstroNKCC1KO) mice. The seizurelike events (SLEs) in CA1 pyramidal neurons were triggered by tetanic stimulation of stratum radiatum in acute hippocampus slices. The SLE underlying GABAAR‐mediated depolarization was evaluated by applying the GABAAR antagonist bicuculline. The pilocarpine‐induced seizure in vivo was monitored in adult mice by the Racine scale. The SLE duration and tetanus stimulation intensity threshold and seizure behavior in AstroNKCC1KO mice and wild‐type (WT) mice were compared. Results: The AstroNKCC1KO mice were prone to seizures with lower threshold and longer duration of SLEs and larger GABAAR‐mediated depolarization underlying the SLEs, accompanied by higher Racine‐scored seizures. Bumetanide reduced these indicators of seizure in AstroNKCC1KO mice (which still express neuronal NKCC1), but not in the WT, both in vitro and in vivo. Significance: Astrocytic NKCC1 inhibits GABA‐mediated excitatory action during seizures, whereas neuronal NKCC1 has the converse effect, suggesting opposing actions of bumetanide on these cells. [ABSTRACT FROM AUTHOR]

HLA‐A, ‐C, ‐B, and ‐DRB1 genotypes were analyzed in 178 Japanese COVID‐19 patients to investigate the association of HLA with severe COVID‐19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA‐DRB1*09:01 and severe COVID‐19 (odds ratio [OR], 3.62; 95% CI, 1.57–8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID‐19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID‐19. [ABSTRACT FROM AUTHOR]

A 93‐year‐old woman was admitted with a 10‐day history of cough and prostration. Thoracic computed tomography revealed extensive ground‐glass opacities in both the lungs. The polymerase chain reaction test of sputum for severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) was positive. She was treated with antiviral agents and steroid pulse therapy. However, her oxygen saturation gradually declined, and she died 10 days after hospitalization. The most important autopsy finding was fuzzily segmented diffuse alveolar damage (DAD) that expanded from the subpleural to the medial area. No remarkable changes were observed in organs other than the lungs. Therefore, pneumocytes were suggested as the primary target for SARS‐CoV‐2, which might explain why coronavirus infectious disease‐19 is a serious condition. Thus, early treatment is essential to prevent viral replication from reaching a level that triggers DAD. [ABSTRACT FROM AUTHOR]

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely. [ABSTRACT FROM AUTHOR]

A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post-transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up-regulation (more than 2-fold change) and only 4 miRNAs showed down-regulation (less than 0.5-fold change) in the DRG of nerve-ligated mice. In a RT-qPCR assay, the levels of miR-21, miR-431, and miR-511-3p were significantly increased on the ipsilateral side of the DRG from 3 to 7 days after sciatic nerve ligation. These elevations were almost absent in IL-6 knockout mice. Furthermore, the expression level of miR-21, but not those of miR-431 or miR511-3p, was significantly increased in exosomes extracted from blood of nerve-ligated mice. These findings suggest that the increased expression of IL-6-regulated miR-21, miR-431, and miR-511-3p in the DRG and increased exosomal miR-21 extracted from blood after sciatic nerve ligation may play at least a partial role in neuropathic pain. Synapse 70:317-324, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Interleukin-19 suppresses microglia/macrophage antigen presentation, T helper 17 cell expansion and subsequent inflammation in the central nervous system, resulting in improvement in experimental autoimmune encephalomyelitis. Keywords: antigen presentation; macrophage; microglia; multiple sclerosis; T helper 17 cell EN antigen presentation macrophage microglia multiple sclerosis T helper 17 cell 148 149 2 09/02/21 20210801 NES 210801 Interleukin-19 serves as a negative feedback regulator to limit the pro-inflammatory response of macrophages and microglia in autocrine/paracrine manners. These data showed that IL-19 plays a pivotal role in the suppression of MS pathogenesis by inhibiting microglia/macrophage antigen presentation, Th17 cell expansion and subsequent inflammation in the CNS. [Extracted from the article]

Objectives Soluble oligomeric amyloid β ( oAβ) directly causes synaptic dysfunction and neuronal death, which are involved in the pathogenesis of Alzheimer's disease. In contrast, several lines of evidence have shown that glia-mediated excitotoxicity is also involved in the disease progression of Alzheimer's disease. However, it is still unclear how oAβ induces glia-mediated excitotoxicity. Therefore, we tried to clarify the mechanism of oAβ-induced glia-mediated excitotoxicity using mouse primary cultures. Methods Glial glutamate production was assessed using a colorimetric assay kit. Glial production of tumor necrosis factor-α ( TNF-α) was evaluated using a specific enzyme-linked immunosorbent assay kit. Microglial survival was examined using the MTS assay. mRNA and protein expression levels of excitatory amino acid transporter 2 were determined using quantitative polymerase chain reaction and western blotting, respectively. Results We showed that oAβ-stimulation induces glutamate release from astrocyte/microglia co-cultures, but not from single culture of astrocytes or microglia. oAβ increased TNF-α release from astrocytes, but not from microglia, and the astrocyte-derived TNF-α enhanced glutamate release from microglia. TNF-α elongated microglial survival and triggered sustained microglial glutamate release in a positive feedback mechanism through TNF-α receptor 1. Furthermore, treatment of oAβ decreased astrocytic expression of excitatory amino acid transporter 2, which plays a pivotal role in homeostasis of the extracellular glutamate level. Conclusions The present findings suggest that oAβ contributes to glia-mediated excitotoxicity through the two-hit mechanism by suppressing astrocytic glutamate uptake through excitatory amino acid transporter 2 and enhancing microglial glutamate release, and triggers chronic glial neuroinflammation through the TNF-α/ TNF-α receptor 1 positive feedback loop in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objectives Fingolimod ( FTY) is a new oral drug for multiple sclerosis. It acts as a functional antagonist for sphingosine 1-phosphate receptor ( S1 PR). After phosphorylateion by sphingosine kinase in vivo, FTY binds to S1 PR on lymphocytes to downregulate S1 PR, thereby preventing lymphocyte egress from lymphoid tissues to reduce infiltration of autoreactive lymphocytes into the central nervous system. FTY easily passes through the blood-brain barrier and directly affects cells in the central nervous system. Recently, we have shown that FTY exerts neuroprotective effects by suppressing pro-inflammatory functions of glial cells and by upregulating neuroprotective functions of neuronal and glial cells in vitro. In the present study, we examined whether FTY exerts neuroprotective effects in vivo in the chronic phase of experimental autoimmune encephalomyelitis ( EAE). Methods Myelin oligodendrocyte glycoprotein-induced EAE mice were orally treated with FTY (1 mg/kg/day) or vehicle (water) once a day starting at the disease peak (15 days after immunization). To evaluate gliosis and axonal damage, the lumbar spinal cords were examined immunohistochemically at 28 days after immunization. Results FTY treatment starting at disease peak improved the severity of symptoms, and reduced gliosis and axonal damage in the spinal cord, as assessed by glial staining and formation of neuritic bead/spheroid. Conclusions FTY exerts protective effects on axonal impairments during the chronic phase of EAE. The neuroprotective effect of FTY could synergistically suppress pathology of multiple sclerosis with its immunosuppressive effect. [ABSTRACT FROM AUTHOR]

Healthcare workers ( HCWs) are at increased risk of exposure to respiratory pathogens and may transmit infection to vulnerable patients. This study summarises a recent systematic review, which aimed to assess evidence that influenza or pneumococcal vaccination of HCWs provides indirect protection for those patients most at risk of severe or complicated acute respiratory infection. A number of healthcare databases and sources of grey literature were searched using a predefined strategy, and citations screened for eligibility in accordance with specified inclusion criteria. Risk of bias was assessed using validated tools and results summarised qualitatively. Twenty papers were included in the final review, all of which considered influenza vaccination of HCW. As such, planned subanalysis of pneumococcal vaccination was discarded. The majority of primary research studies included (11/14) were conducted in long-term care facilities, but there was marked heterogeneity in terms of the population, intervention/exposure and outcomes considered. Consistency in the direction of effect was observed across several different outcome measures, suggesting that influenza vaccination of HCWs is likely to offer some protection. Further evidence is, however, required from acute care settings. [ABSTRACT FROM AUTHOR]

Sleep disturbance has been reported to be one of the most frequent symptoms in patients suffered from severe pain. Benzodiazepines are effective and reduce anxiety in the hours after use, but the induced sleep tends to be less than ideal in quality, with increased Stages I-II and reduces Stages III-IV sleep. In the present study, we investigated sleep disturbance under a neuropathic pain-like state in mice using electroencephalogram (EEG)/electromyogram (EMG). In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase. Mirtazapine (MTZ) is an antidepressant, which is considered to enhance noradrenergic and serotonergic neurotransmission via antagonistic action at central α2-adrenergic autoreceptors and heteroreceptors. In the present binding study, MTZ showed higher affinity for histamine H1 and serotonin 5-HT2A/2C receptors than other receptors, including α2-adrenergic receptor, in the mouse brain tissue. The thermal hyperalgesia and sleep disturbance following nerve ligation were almost completely alleviated by MTZ. These findings suggest that MTZ may improve the quality of sleep as well as control pain in patients with neuropathic pain mainly through histamine H1- and serotonin 5-HT2-receptor antagonistic actions. Synapse, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K+ ( IA) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing IA currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Synapse, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the discriminative stimulus effects of the κ-opioid receptor agonist U-50,488H were associated with its aversive effects in rats. However, its molecular signaling mechanisms are not fully understood. The aim of this study was to investigate the intracellular signaling that plays a role in mediating the discriminative stimulus effect induced by U-50,488H. To better understand the involvement of molecular signaling mechanisms in the discriminative stimulus effects of U-50,488H, rats were subjected to a drug discrimination paradigm, and levels of immunoreactivity and mRNA expression were determined in these rats. Although U-50,488H-trained rats did not show changes in the mRNA expression of typical dopamine (DA) receptors, NMDA receptor subunits, or transcriptional activators, there were remarkable changes in the levels of immunoreactivity of several phosphorylated protein kinases. The levels of immunoreactivity of phosphorylated p38 MAPK and phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) were significantly increased in the nucleus accumbens and amygdala in lever-press, yoked and discrimination groups compared to a naive group. Furthermore, the level of phosphorylated cAMP response element-binding protein was also increased in both the discrimination and yoked groups. In contrast, the immunoreactivity of phosphorylated extracellular signaling-regulated kinase (ERK 1/2) was specifically increased in the discrimination group. These results suggest that the ERK signaling pathway in the nucleus accumbens and amygdala may be critical for the expression of the discriminative stimulus effects of U-50,488H. Synapse, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article presents the conducted study to determine the effect of gabapentin (GBP) on brain hyperactivity that are linked to pain and sleep disturbance among patients with chronic pain, including neuropathic pain. In the study conducted on mice, the functional magnetic resonance imaging (fMRI) and electroencephalogram/electromyogram (EEG/EMG) were used. Neuropathic pain is the pain due to lesions or diseases of the sensory transmission pathways in the peripheral or central nervous system.

The article discusses the study conducted to investigate the impact of mild noxious heat stimuli on the neuronal activity in the cingulate cortex (CG) of rats with sciatic nerve ligation. The mild noxious heat stimuli administered to rats seven days after sciatic nerve ligation produced flinching behaviors and resulted in an increase in glutamate release in the CG, and phosphorylated-NR1-positive cells, under a neuropathic pain.

The article discusses development of fingolimod, oral drug for treatment of multiple sclerosis that is suggested to suppresses pro-inflammatory effects and improve neuroprotective effects in astrocytes. Topics discussed include action on lymphocytes, reverse transcription polymerase chain reactions and intercellular adhesion molecule-1. IL Interleukin, histocompatibility complex and tumor necrosis factor are mentioned.

The contents of infected root canals were collected by mechanical and chemical debridement. Intracanal polyamines were identified and quantified by HPLC in all canals examined, however, no histamine was detected in any canal. The relationship between the amount of each polyamine and clinical signs of the teeth was analyzed statistically. The teeth without clinical signs tended to have limited varieties and smaller amounts of polyamines. Using X[sup2], the amounts were significantly greater in teeth with spontaneous pain, swelling and putrescent odor (p<0.01), with exudate (p<0.025) and with percussion pain p<0.1) than in teeth without. Amounts of putrescine (p<0.05) and total polyamines (p <0.01) were greater in teeth with spontaneous pain and percussion pain than in teeth without clinical sign, and those with root canal exudate also had greater amounts of total polyamines than those without (p<0.01). The amounts of cadaverine, however, from the teeth with gingival fistulae, was greater than from those without (p<0.05). No significant relationship was established between the amount of each polyamine and the presence of putrescent odor or gingival swelling. Intracanal polyamines, especially putrescine may leak out through apical foramen and may be implicated in pain production by eliciting acute inflammatory response in the periapical tissues. [ABSTRACT FROM AUTHOR]

Investigates the effects of three rapid decompression methods used to clear the mechanism of inactivation of heat tolerant spores of Bacillus stearothermophilus IFO 12550. Methods used to pressurize the spores; Details on the application of pressure sterilization methods in the food industry; Characteristics of the spores of Bacillus stearothermophilus; Features of the three decompression methods used.

The article discusses the role of astrocytic eotaxin (CCL11) on the production of microglial reactive oxygen species and in aging-related neuronal dysfunction. Topics discussed include CCL11's pathological role in allergic diseases, the study which identifies astrocytes as the primary source of CCL11 in the central nervous system (CNS), and the role of systemic inflammation to CCL11 production.