[Endovascular stenting for idiopathic intracranial hypertension with different types of venous sinus stenosis].

Objective: To evaluate the efficacy of endovascular stenting of various types of venous sinus stenosis in idiopathic intracranial hypertension (IIH). Method: Clinical, radiological, and manometric data before and after stenting in venous sinus stenosis were retrospectively analyzed in 99 IIH patients who were refractory to medical therapy or rapidly progressed between July 2004 to July 2019. The follow-up period was between 2.3 months to 11 years. Results: Our study enrolled 21 men (21.2%)and 78 women (78.8%) with average body mass index (BMI) 19.2-40.6(27.0±4.4) kg/m2 and median age 37 years. Before stent placement, the mean transverse sinus stenosis gradient was 1-59(26±8) mmHg. Patients with extrinsic stenosis were younger than those with intrinsic and mixed stenosis. In all cases, stenting was effective for papilledema. Fifty patients complained of headaches. Pulsatile tinnitus in twenty-eight patients completely alleviated after stenting. In one patient, replacement of stent did not improve symptoms, and a subsequent CSF diversion procedure was performed and effective. Conclusion: Irrespective of the type of stenosis, stenting of venous sinus stenosis is an effective treatment for IIH. Patients with persistent papilledema post-stenting and elevated transverse pressure pre-stenting should be followed closely as high risk of stenting failure may occur and further diversion procedure is needed.

Optimized mid-long term management of ketogenic diet in children with refractory epilepsy.

This study aims to explore the mid-long term management of ketogenic diet (KD) for the treatment of refractory epilepsy in children, and carry out an efficacy assessment. The data of epileptic children who received KD in our hospital from January 2011 to August 2012 (basic management plan group, n=57) were retrospectively analyzed. On this basis, epileptic children who received KD from September 2012 to April 2014 (optimized management plan group, n=52) were managed according to the mid-long term management plan. The effective rate of KD at the first, third, sixth and ninth month was 90.4%, 73.1%, 65.4% and 38.5%, respectively, in the optimized management plan group, and 63.2%, 45.6%, 38.6% and 21.1%, respectively, in the basic management plan group, and the differences were statistically significant. The compliance rate of KD at the third, sixth and ninth month was 94.2%, 78.8% and 63.5%, respectively, in the optimized management plan group, and 82.5%, 47.4% and 28.1%, respectively, in the basic management plan group, and the differences were statistically significant. Optimized mid-long term management of KD in children can improve the control rate of epileptic seizures, and the compliance of patients.

Calcyon stimulates neuregulin 1 maturation and signaling.

Neuregulin1 (NRG1) is a single transmembrane protein that plays a critical role in neural development and synaptic plasticity. Both NRG1 and its receptor, ErbB4, are well-established risk genes of schizophrenia. The NRG1 ecto-domain (ED) binds and activates ErbB4 following proteolytic cleavage of pro-NRG1 precursor protein. Although several studies have addressed the function of NRG1 in brain, very little is known about the cleavage and shedding mechanism. Here we show that the neuronal vesicular protein calcyon is a potent activator and key determinant of NRG1 ED cleavage and shedding. Calcyon stimulates clathrin-mediated endocytosis and endosomal targeting; and its levels are elevated in postmortem brains of schizophrenics. Overexpression of calcyon stimulates NRG1 cleavage and signaling in vivo, and as a result, GABA transmission is enhanced in calcyon overexpressing mice. Conversely, NRG1 cleavage, ErbB4 activity and GABA transmission are decreased in calcyon null mice. Moreover, stimulation of NRG1 cleavage by calcyon was recapitulated in HEK 293 cells suggesting the mechanism involved is cell-autonomous. Finally, studies with site-specific mutants in calcyon and inhibitors for the major sheddases indicate that the stimulatory effects of calcyon on NRG1 cleavage and shedding depend on clathrin-mediated endocytosis, ß-secretase 1, and interaction with clathrin adaptor proteins. Together these results identify a novel mechanism for NRG1 cleavage and shedding.

Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway.

Genotoxic stress activates checkpoint signaling pathways that activate the checkpoint kinases ATM and ATR, halt cell cycle progression, and promote DNA repair. A number of proteins act in concert with ATR to phosphorylate Chk1, including RAD17, the RAD9-RAD1-HUS1 complex, ATR/ATRIP and TopBp1. However, how these proteins involved act in concert with one another to propagate and maintain the checkpoint response is not well understood. Here, we reported that upregulation of RAD9 protein increased the quantity of ATRIP, suggesting that RAD9 activation will induce more efficient accumulation of ATRIP in vivo. Furthermore, the DNA damage-induced ATRIP foci formation was faster in the mRad9-/- ES cells. Also, ATRIP interacts specifically with RAD9, but not HUS1 and RAD1. Taken together, we suggested that RAD9 could affect both the ATRIP protein levels and DNA damage-induced ATRIP foci formation. Thus, we propose a role of RAD9 in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.

Clinicopathological analysis of idiopathic membranous nephropathy in young adults.

The aim of this study was to understand the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in youth. A retrospective analysis of the clinicopathological features and prognoses of pathologically confirmed IMN in 21 patients aged 15-30 years was performed. IMN was mainly characterized as nephrotic syndrome (NS), with stage I as the main pathological stage, and associated with hyperplasia of the glomerular mesangial cells and ground substance. High-intensity immunofluorescence also showed multi-site deposition of a variety of immune complexes, and electron microscopy showed multi-site deposition of electron-condensing substances. In the present study, 4 patients received non-specific treatment. Among 17 NS patients, 12 patients exhibited a preference for glucocorticoid therapy, and of these patients, 7 were sensitive to therapy and 5 were resistant. In the 12 patients who received hormone treatment combined with immunosuppressants (including 5 patients who were treated with the combination from the initial start, 5 patients who were steroid resistant, and 2 patients who were sensitive to the initial hormone treatment but who later showed relapse), complete remission was achieved in 6 patients, partial remission was achieved in 2, the treatment was ineffective in 2, and 2 patients were lost to follow-up. In conclusion, the clinical manifestation of IMN in youth in this study was mainly NS. In most patients, the initial hormone treatment was effective, and in some patients, the combination of hormone and immunosuppressant treatment was effective. As the sample size in this study was small, further clinical validation is still required to determine the efficacy of the treatment.

Modeling disinfection of plastic poultry transport cages inoculated with Salmonella enteritids by slightly acidic electrolyzed water using response surface methodology.

In order to reduce the risk of enteric pathogens transmission in animal farms, the disinfection effectiveness of slightly acidic electrolyzed water (SAEW, pH 5.85 to 6.53) for inactivating Salmonella Enteritidis on the surface of plastic poultry transport cages was evaluated. The coupled effects of the tap water cleaning time (5 to 15 s), SAEW treatment time (20 to 40 s), and available chlorine concentrations (ACCs) of 30 to 70 mg/l on the reductions of S. Enteritidis on chick cages were investigated using a central composite design of the response surface methodology (RSM). The established RS model had a goodness of fit quantified by the parameter R2 (0.971), as well as a lack of fit test (P>0.05). The maximum reduction of 3.12 log10 CFU/cm2 for S. Enteritidis was obtained for the cage treated with tap water cleaning for 15 s followed by SAEW treatment for 40 s at an ACC of 50 mg/l. Results indicate that the established RS model has shown the potential of SAEW in disinfection of bacteria on cages.

Reduction of microbial contamination on the surfaces of layer houses using slightly acidic electrolyzed water.

The objective of this study was to evaluate the effectiveness of slightly acidic electrolyzed water (SAEW) in reducing pathogens on pure cultures and on cotton fabric surfaces in the presence of organic matter and estimate its efficacy in comparison with povidone iodine solution for reducing pathogenic microorganisms on internal surfaces of layer houses. Pure cultures of E.coli, S.enteritidis, and S.aureus and cotton fabric surfaces inoculated with these strains were treated with SAEW in the presence of bovine serum albumin (BSA). In the absence of BSA, complete inactivation of all strains in pure cultures and on cotton fabric surfaces was observed after 2.5 and 5 min treatment with SAEW at 40 mg/L of available chlorine concentration (ACC), respectively. The bactericidal efficiency of SAEW increased with increasing ACC, but decreased with increasing BSA concentration. Then, the surfaces of the layer houses were sprayed with SAEW at 60, 80, and 100 mg/L of ACC and povidone iodine using the automated disinfection system at a rate of 110 mL/m(2), respectively. Samples from the floor, wall, feed trough, and egg conveyor belt surfaces were collected with sterile cotton swabs before and after spraying disinfection. Compared to tap water, SAEW and povidone iodine significantly reduced microbial populations on each surface of the layer houses. SAEW with 80 or 100 mg/L of ACC showed significantly higher efficacy than povidone iodine for total aerobic bacteria, staphylococci, coliforms, or yeasts and moulds on the floor and feed trough surfaces (P < 0.05). SAEW was more effective than povidone iodine at reducing total aerobic bacteria, coliforms, and yeasts and moulds on the wall surface. Additionally, SAEW had similar bactericidal activity with povidone iodine on the surface of the egg conveyor belt. Results suggest that SAEW exerts a higher or equivalent bactericidal efficiency for the surfaces compared to povidone iodine, and it may be used as an effective alternative for reducing microbial contamination on surfaces in layer houses.

Spatial distribution, movement, body damage, and feather condition of laying hens in a multi-tier system.

The welfare and health of laying hens in the multitier system raise concern in public. The flock distributions during feeding time at 51 and 89 wk were studied in a multitier system. Furthermore, the ultra-high frequency radio frequency identification (UHF RFID) equipment was used to identify the transition between tiers and time spent in each tier of 48 focal hens (12 hens from each tier-group of the multitier system) at 92 wk of age. The body weight, tibia size (length and width), body damage (comb and rear part), and feather condition (neck, breast, back, tail, cloaca, and wings) of focal hens from different tier-groups were further compared. The results showed that the spatial distribution in flocks changed from top to bottom with increasing age. The hens at 51 wk of age were mainly distributed in the 4th tier (19.6 ± 5.0% in 1st tier, 9.6 ± 1.1% in 2nd tier, 23.6 ± 2.9% in 3rd tier and 47.3 ± 2.6% in 4th tier), and hens at 89 wk of age were mainly distributed in the lower tiers (33.5 ± 1.5% in 1st tier, 31.9 ± 5.1% in 2nd tier, 15.7 ± 3.4% in 3rd tier and 16.6 ± 3.1% in 4th tier). The spatial distribution of hens at 89 wk of age was more even than that at 51 wk of age. At 92 wk of age, the proportion of time spent in original tier of 4 tier-groups was 91.0 ± 5.7%, 51.9 ± 5.7%, 59.0 ± 7.0% and 63.0 ± 6.7%, respectively. Focal hens preferred to stay in the original tier and spent significantly less time in other tiers (P < 0.05). There was no significant difference in body weight, body damage score, tibia width and partial feather scores (neck, breast, tail, and cloaca) of focal hens among 4 tier-groups (P > 0.05). However, focal hens from 1st tier had worse feather scores on wings and back, and shorter tibia length compared to other tiers suggesting that there were more lower ranking birds that located in lower tier to avoid competition, but had equal access to resource, which is good for their welfare and health. In summary, the overcrowding situation was improved near the end of the laying cycle in the multitier system, thereby mitigating the potential negative effects to the lower ranking hens and maintain a satisfactory level of welfare and health for laying hens near the end of the laying cycle.

Disinfection effectiveness of slightly acidic electrolysed water in swine barns.

AIMS: To evaluate the disinfection effectiveness of slightly acidic electrolysed water (SAEW, pH 6·25-6·53), a new environmental friendly agent for inactivating micro-organisms adhered to the facility and aerosolized in the air of the swine barns and to explore the application of SAEW in livestock industries. METHODS AND RESULTS: Bacteria and fungi were isolated from the swine house air and treated by SAEW. The SAEW solution was flushed onto surfaces and sprayed within the whole swine barn. SAEW with an available chlorine concentration (ACC) of 300 mg l(-1) can inhibit isolated microbes completely. The usage of SAEW (300 mg l(-1) ) resulted in a significant (P < 0·05) reduction in microbes on the wall, rail and floor after flushing disinfection. Additionally, spraying SAEW at an ACC of 300 mg l(-1) reduced 59% of the airborne organisms in 30 min and kept the population of microbes at a reduced level for at least 8 h. SAEW treatment also reduced pathogens on surfaces (P < 0·03) after spraying disinfection except on the surface of the wall. CONCLUSIONS: SAEW may be a potential alternative disinfectant to reduce infections in swine barns. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study provide information on the antimicrobial efficiency of SAEW on the airborne bacteria and fungi in swine barns.

Application of slightly acidic electrolyzed water for inactivating microbes in a layer breeding house.

Lots of microorganisms exist in layer houses can cause bird diseases and worker health concerns. Spraying chemical disinfectants is an effective way to decontaminate pathogenic microorganisms in the air and on surfaces in poultry houses. Slightly acidic electrolyzed water (SAEW, pH 5.0-6.5) is an ideal, environmentally friendly broad-spectrum disinfectant to prevent and control bacterial or viral infection in layer farms. The purpose of this work was to investigate the cleaning effectiveness of SAEW for inactivating the microbes in layer houses. The effect of SAEW was evaluated by solid materials and surface disinfection in a hen house. Results indicate that SAEW with an available chlorine concentration of 250 mg/L, pH value of 6.19, and oxygen reduction potential of 974 mV inactivated 100% of bacteria and fungi in solid materials (dusts, feces, feather, and feed), which is more efficient than common chemical disinfectant such as benzalkonium chloride solution (1:1,000 vol/vol) and povidone-iodine solution (1:1,000 vol/vol). Also, it significantly reduced the microbes on the equipment or facility surfaces (P < 0.05), including floor, wall, feed trough, and water pipe surfaces. Moreover, SAEW effectively decreased the survival rates of Salmonella and Escherichia coli by 21 and 16 percentage points. In addition, spraying the target with tap water before disinfection plays an important role in spray disinfection.

Effects of different light-emitting diode light on hatch performance, embryo development, eye structure, and plasma melatonin in layer incubation.

Light intensity, wavelength, and photoperiod have a combined effect on chicken incubation. This study was conducted to evaluate the effect of 12-h light, 12-h dark (12L:12D) photoperiod of white light (380-780 nm, WL), blue light (455/447.5-462.5 nm, BL), and green light (525/515-535 nm, GL) in chicken perceived light intensity during layer incubation on hatching performance, embryo development, eye structure, and melatonin concentration. Three batches of eggs from Jinghong No. 1 layer breeder were used in this experiment. Light stimulation had no effect on hatchability, and no consistent effect on embryo weight and newly hatched chick weight. However, the average hatching time of white light group and green light group was 7.3 h and 5.5 h later than that of the control group. Therefore, the holding period of chicks was significantly shortened (P = 0.001) in these 2 light groups. Light stimulation had a significant effect on the thickness of retinal layers (P < 0.05), retinal layers of white light group was thicker than that of the other 3 groups. Melatonin levels of chicks hatched in the green light and blue light were significantly higher than that of chicks hatched in the white light and darkness (P < 0.05). It indicated that the monochrome green and blue light promoted the expression of melatonin in chicken embryos. No significant diurnal rhythms were found at the level of plasma melatonin in 4 groups on d 21 using cosine analysis. It was concluded that green light has a positive effect on embryo development and melatonin secretion, while white light probably has positive effect on eye development. Furthermore, both green and white light stimulation resulted in late hatch for layer egg incubation. The obtained results are important in determining the light protocol for chicken incubation.

Bionic dental pulp: its potential value following root canal therapy.

Dental pulp can provide nutrition for teeth. The teeth after root canal therapy without pulp will turn frailer because of dehydration, and it may be easily broken. Bionic dental pulp possesses similar components of the healthy dental pulp. So we put forward a hypothesis that bionic dental pulp can be filled into root canals to provide nutrition for teeth like healthy pulp. Then the life-span of teeth after root canal therapy could increase.

Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies.

Epileptic encephalopathies are severe epilepsy disorders with strong genetic bases. We performed targeted next-generation sequencing (NGS) in 70 patients with epileptic encephalopathies. The likely pathogenicity of variants in candidate genes was evaluated by American College of Medical Genetics and Genomics (ACMG) scoring taken together with the accepted clinical presentation. Thirty-three candidate variants were detected after population filtration and computational prediction. According to ACMG, 21 candidate variants, including 18 de novo variants, were assessed to be pathogenic/likely pathogenic with clinical concordance. Twelve variants were initially assessed as uncertain significance by ACMG, among which 3 were considered causative and 3 others were considered possibly causative after analysis of clinical concordance. In total, 24 variants were identified as putatively causative, among which 19 were novel findings. SCN1A mutations were identified in 50% of patients with Dravet syndrome. TSC1/TSC2 mutations were detected in 66.7% of patients with tuberous sclerosis. STXBP1 mutations were the main findings in patients with West syndrome. Mutations in SCN2A, KCNT1, KCNQ2 and CLCN4 were identified in patients with epileptic infantile with migrating focal seizures; among them, KCNQ2 and CLCN4 were first identified as potential causative genes. Only one CHD2 mutation was detected in patients with Lennox-Gastaut syndrome. This study highlighted the utility of targeted NGS in genetic diagnoses of epileptic encephalopathies and a comprehensive evaluation of the pathogenicity of variants based on ACMG scoring and assessment of clinical concordance. Epileptic encephalopathies differ in genetic causes, and the genotype-phenotype correlations would provide insights into the underlying pathogenic mechanisms.

Cellular and subcellular distributions of beta1- and beta2-adrenoceptors in the CA1 and CA3 regions of the rat hippocampus.

Beta-adrenoceptors (ARs) in the hippocampus play an important role in regulating synaptic plasticity and memory consolidation. However, little is known about the distributions of beta-ARs in the hippocampus, especially in the cornu ammonis (CA)1 and CA3 regions of Sprague-Dawley rats. Here, we report that beta1- and beta2-ARs in the CA1 and CA3 regions have differential subcellular distributions. Using double immunofluorescence labeling and confocal laser scanning microscopy, we found that almost all of the neuronal nuclei positive cells express beta1- and beta2-ARs, while few glial fibrillary acidic protein positive cells express them. Interestingly, beta1-ARs are predominantly distributed in the cell membrane and cytoplasm, whereas beta2-ARs are predominantly distributed not only in the membrane and cytoplasm, but also in the nucleus. The differential subcellular distribution of beta1- and beta2-ARs may have functional significance.

Dorsal hippocampal administration of triiodothyronine enhances long-term memory for trace cued and delay contextual fear conditioning in rats.

Thyroid hormones play critical roles in brain maturation and cognitive functions. The present study investigated the role of thyroid hormone in emotional learning and memory using trace and delay contextual and cued fear conditioning tasks, respectively. Rats were administered triiodothyronine (T3) into the dorsal hippocampal area 10 min before training or immediately after training, and were scored for freezing behaviour in the same context and in a novel context with and without an auditory cue that had been paired previously with an aversive stimulus, a foot shock. Rats administered T3 before and after training both exhibited significantly increased long-term fear memory in the trace cued and the delay contextual fear conditioning procedures compared to their control groups. The T3-administered rats were not significantly different from their respective controls on the acquisition and short-term fear memory in the trace and delay fear conditioning tasks. No significant difference on long-term trace contextual and delay cued fear memory, respectively, was found. These results indicate that the observed T3-induced enhancement of long-term contextual and cued fear memory was specific to the hippocampus-dependent conditioning tasks. These findings are the first to demonstrate that infusion of T3 into the dorsal hippocampus can improve performance on an emotional memory task.

Adult-onset hypothyroidism impairs paired-pulse facilitation and long-term potentiation of the rat dorsal hippocampo-medial prefrontal cortex pathway in vivo.

Thyroid hormones are critical for the maturation and function of the central nervous system. Insufficiency of thyroid hormones in the adulthood causes a wide range of cognitive dysfunctions, including deficits in learning and memory. The present study investigated whether adult-onset hypothyroidism would alter synaptic functions in the dorsal hippocampo-medial prefrontal cortex (mPFC) pathway, a neural pathway important for learning and memory. Adult hypothyroidism was induced by oral administration of 1% (g/l) antithyroid acting drug 6-n-propyl-2-thiouracil (PTU) to adult male Sprague-Dawley rats for 4 weeks. Postsynaptic potentials (PSP) were recorded in the mPFC by stimulating the dorsal hippocampal CA1 region in vivo. Basal synaptic transmission was evaluated by comparing input-output relationships. Paired-pulse facilitation and long-term potentiation were recorded to examine short- and long-term synaptic plasticity. Adult-onset hypothyroidism did not change the basal synaptic transmission, but significantly reduced paired-pulse facilitation and long-term potentiation of PSP. These inhibitions can be restored by thyroid hormone replacement. The results suggest that such alterations in synaptic plasticity of the dorsal hippocampo-mPFC pathway might contribute to understanding basic mechanisms underlying learning and memory deficits associated with adult-onset hypothyroidism.

The negative cell cycle regulator, Tob (transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory.

Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory.

Local infusion of an alpha-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys.

BACKGROUND: Stimulation of alpha-2 adrenoceptors in the monkey or rat prefrontal cortex (PFC) has been known to improve spatial working memory (SWM) and stimulation of alpha-1 adrenoceptors in the rat PFC has been reported to impair SWM. The present study attempted to replicate in monkey the rat experiments on alpha-1 adrenoceptor stimulation. METHODS: The alpha-1 adrenergic agonist phenylephrine or the alpha-2 adrenergic agonist guanfacine was infused into the dorsolateral prefrontal cortex (dlPFC) of monkeys performing the delayed-response (DR) task, a task of SWM, to see how the drugs affect SWM performance. RESULTS: Phenylephrine infusion in dlPFC significantly impaired DR performance, whereas guanfacine improved performance. The effects of both drugs were delay-dependent. Infusions outside dlPFC were ineffective. CONCLUSIONS: Stimulation of prefrontal cortical alpha-1 adrenoceptors impairs SWM function in monkeys, consistent with the parallel study in rats, whereas stimulation of alpha-2 adrenoceptors improves SWM, indicating that alpha-1 and alpha-2 adrenoceptors may have opposing roles in the PFC.

Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function.

BACKGROUND: Many neuropsychiatric disorders are associated with high levels of noradrenergic turnover, and most antipsychotic medications have alpha-1 adrenoceptor blocking properties, yet little is known about alpha-1 influences on higher cortical function. METHODS: The alpha-1 adrenergic agonist, phenylephrine, was infused into the prefrontal cortex (PFC) of rats (0.1 microgram/0.5 microL) performing a spatial working memory task, delayed alternation. The phenylephrine response was challenged with coinfusion of the alpha-1 adrenergic antagonist, uripidil (0.01 microgram), or with a dose of lithium chloride (4 mEq/kg, i.p., 18 hours) known to suppress phosphotidylinositol (PI) turnover, the second messenger pathway coupled to alpha-1 adrenoceptors. RESULTS: Phenylephrine infusions in PFC markedly impaired delayed alternation performance. The phenylephrine response was reversed by coinfusion of uripidil, or by pretreatment with lithium, consistent with actions at alpha-1 adrenoceptors coupled to a PI pathway. CONCLUSIONS: These findings demonstrate that alpha-1 adrenoceptor stimulation in the PFC impairs cognitive function. Excessive stimulation of alpha-1 adrenoceptors may contribute to PFC deficits (e.g., distractibility, impulsivity) in disorders such as mania, dementia, and anxiety associated with high noradrenergic turnover.