Glaucoma is the leading cause for blindness affecting 60 million people worldwide. The optineurin (OPTN) E50K mutation was first identified in familial primary open-angle glaucoma (POAG), the onset ...of which is not associated with intraocular pressure (IOP) elevation, and is classified as normal-tension glaucoma (NTG). Optineurin (OPTN) is a multifunctional protein and its mutations are associated with neurodegenerative diseases such as POAG and amyotrophic lateral sclerosis (ALS). We have previously described an E50K mutation-carrying transgenic (E50K-tg) mouse that exhibited glaucomatous phenotypes of decreased retinal ganglion cells (RGCs) and surrounding cell death at normal IOP. Further phenotypic analysis of these mice revealed persistent reactive gliosis and E50K mutant protein deposits in the outer plexiform layer (OPL). Over-expression of E50K in HEK293 cells indicated accumulation of insoluble OPTN in the endoplasmic reticulum (ER). This phenomenon was consistent with the results seen in neurons derived from induced pluripotent stem cells (iPSCs) from E50K mutation-carrying NTG patients. The E50K mutant strongly interacted with TANK-binding kinase 1 (TBK1), which prohibited the proper oligomerization and solubility of OPTN, both of which are important for OPTN intracellular transition. Treatment with a TBK1 inhibitor, BX795, abrogated the aberrant insolubility of the E50K mutant. Here, we delineated the intracellular dynamics of the endogenous E50K mutant protein for the first time and demonstrated how this mutation causes OPTN insolubility, in association with TBK1, to evoke POAG.
The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential ...contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
We report a unique case of delayed brain swelling following craniectomy that improved rapidly after cranioplasty, and discuss the potential mechanism underlying this delayed and reversible ...brain swelling. A 22-year-old woman developed surgical site infection after removal of a convexity meningioma. Magnetic resonance imaging revealed an epidural abscess around the surgical site. Subsequently, the abscess was evacuated, and the bone flap was removed. Later, brain edema around the skull defect emerged and progressed gradually, despite resolution of the infection. The edematous brain developed focal swelling outward through the bone defect without ventricle dilatation. Because we suspected that the edema and swelling were caused by the state of the bone defect, we performed a cranioplasty 10 weeks after the bone flap removal, and brain edema improved rapidly. We hypothesized that the brain edema was initially caused by surgical stress and inflammation, followed by compression of cortical veins between the dural edge and brain tissue, leading to disruption of venous return and exacerbation of brain edema. When delayed focal brain edema and external swelling progress gradually after bone flap removal, after excluding other pathological conditions, cranioplasty should be considered to improve cortical venous congestion caused by postsurgical adhesion.
To evaluate the efficacy of intraparenchymal brain tumor biopsy using endoscopy and a navigation system (navigation-guided endoscopic biopsy) as a diagnostic tool, a case series of intraparenchymal ...tumor biopsies was reviewed. Navigation-guided endoscopic biopsy was applied in 9 cases, stereotactic needle biopsy in 16 cases, and open biopsy with or without navigation system in 34 cases. In all biopsy cases, 84.7% of biopsy points were sampled accurately, and 93.2% of diagnoses by biopsy were correct. Comparison of each type of biopsy showed that the resected volumes in navigation-guided endoscopic biopsy and open biopsy tended to be larger than those in stereotactic biopsy, and the mean operation time for the open biopsy procedure was the longest. To define the most applicable device or examination method to increase sampling accuracy, various factors were analyzed in 59 procedures. Navigation-guided endoscopic biopsy was the most accurate of the three types of biopsy, although the statistical difference was not significant. Older patients, histological diagnosis of high-grade glioma or malignant lymphoma, positive photodynamic diagnosis, and positive intraoperative pathology were significant factors in improving the sampling accuracy. Navigation-guided endoscopic biopsy could provide a larger sample volume within a relatively short operation time. The biopsy can be easily combined with both photodynamic diagnosis and intraoperative pathology, significantly improving the histological diagnostic yield.
Systematic review and meta-analysis.
Using a network meta-analysis (NMA), this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression.
C5 ...palsy is a well-known complication affecting the quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels.
We conducted a comprehensive search for C5 palsy and complications after 3representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (hybrid), involving 3 to 6 intervertebral levels. The incidence of C5 palsy was compared using a NMA.
We identified 1655 patients in 11 studies who met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and hybrid cases were 2.3% (16/684, 95% CI: 1.4% to 3.8%), 6.4% (39/613, 95% CI: 4.7% to 8.6%), and 3.9% (14/358, 95% CI: 2.3% to 6.5%), respectively ( P < 0.01). A NMA was performed for 15 pairwise comparisons across the 3 procedure arms: ACDF versus hybrid, 7/232 (3.0%) versus 11/234 (4.7%); hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio: 2.72, 95% CI: 1.47 to 5.01), whereas ACDF versus hybrid did not significantly differ in risk (odds ratio: 1.56, 95% CI: 0.68 to 3.60).
We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3 to 6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3 to 6 levels.
Level III.
IMPORTANCE: Ripasudil hydrochloride hydrate (K-115), a novel rho kinase inhibitor, provides statistically significant intraocular pressure (IOP)–lowering effects and has a tolerable safety profile. ...However, no studies have evaluated ripasudil combined with β-blockers and prostaglandin analogues. OBJECTIVE: To evaluate the additive IOP-lowering effects and the safety of ripasudil, 0.4%, combined with timolol, 0.5%, or latanoprost, 0.005%, in patients with primary open-angle glaucoma or ocular hypertension. DESIGN, SETTING, AND PARTICIPANTS: We conducted 2, multicenter, randomized, double-masked, parallel group comparison studies of ripasudil-timolol and ripasudil-latanoprost in 29 and 36 Japanese clinical centers, respectively. Analyses were performed on an intention-treat-treat basis. After appropriate run-in periods with timolol or latanoprost, 208 and 205 patients whose IOP levels were 18 mm Hg or higher were enrolled in the ripasudil-timolol and ripasudil-latanoprost groups, respectively. Enrollment began December 1, 2011, and follow-up was completed on September 7, 2012, in the ripasudil-timolol study. Enrollment began December 1, 2011, and follow-up was completed on September 27, 2012, in the ripasudil-latanoprost study. INTERVENTIONS: Patients were subdivided into 2 groups in each study and were treated with ripasudil or placebo twice daily for 8 weeks. MAIN OUTCOMES AND MEASURES: The IOP reductions in the ripasudil and placebo groups were analyzed with a repeated-measures analysis of variance model at weeks 4, 6, and 8, at trough (before instillation 9 am) and peak (2 hours after instillation 11 am) levels. RESULTS: In the ripasudil-timolol study, the mean IOP reductions from baseline in the ripasudil and placebo groups were −2.4 and −1.5 mm Hg at 9 am for a difference of 0.9 mm Hg (95% CI, 0.4-1.3 mm Hg; P < .001) and −2.9 and −1.3 mm Hg at 11 am for a difference of 1.6 mm Hg (95% CI, 1.1-2.1 mm Hg; P < .001), respectively. In the ripasudil-latanoprost study, those IOP reductions were −2.2 and −1.8 mm Hg at 9 am for a difference of 0.4 mm Hg (95% CI, −0.0 to 0.9 mm Hg; P = .06) and −3.2 and −1.8 mm Hg at 11 am for a difference of 1.4 mm Hg (95% CI, 0.9-1.9 mm Hg; P < .001), respectively. The most frequently reported adverse event was conjunctival hyperemia, which was mild and in most cases resolved without treatment before the next instillation. CONCLUSIONS AND RELEVANCE: These clinical trials found additive IOP-lowering effects of ripasudil from placebo at trough and peak levels in combination with timolol and at peak level in combination with latanoprost. However, a definitive difference in the addition of placebo to latanoprost was not identified in the trough level. TRIAL REGISTRATION: clinicaltrials.jp Identifiers: JAPIC111700 and JAPIC111701
To compare changes in the macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness over 5 years between surgically treated eyes (STE) and medically treated eyes (MTE) with advanced ...glaucoma.
Retrospective, comparative case series.
Eighty-six patients comprising 43 with open-angle glaucoma (OAG) with trabeculectomy and 43 with medically treated OAG. The mGCIPL thickness was measured more than 5 times during follow-up by optical coherence tomography. Main outcome measure was differences in mGCIPL thickness thinning rate between the groups.
The mean age at study initiation was 62.5 ± 9.2 years in STE and 62.7 ± 9.5 years in MTE. The mean deviations (MD), according to the Humphrey Field Analyzer central program 30-2, and the mGCIPL thickness in each sector showed no significant differences at initial measurement. The averaged intraocular pressure (IOP) throughout follow-up was 10.5 ± 2.0 mm Hg in STE and 10.8 ± 0.8 mm Hg in MTE (P = .429; Mann-Whitney U test). There was no significant difference in the MD changes over 5 years between the 2 groups (P = .405; Mann-Whitney U test). Changes in the mGCIPL thickness over 5 years in MTE were significantly greater than that in STE in all sectors (all 6 sectors P < .0001, Mann-Whitney U test). The IOP fluctuation over 5 years in STE was significantly less than that in MTE (P < .0001, Mann-Whitney U test).
The structure of the mGCIPL was better preserved in STE than in MTE, even when the IOPs during follow-up were similar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
For gigabit wireless data services, there are three important technical issues to be addressed: limited bandwidth, severe frequency-selective fading, and limited transmit power. A distributed antenna ...network (DAN) is a promising solution to the above three technical issues. In DAN, each mobile user is served by using multiple distributed antennas close to it. In this paper, recent advances in various distributed multi-input/multi-output (MIMO) techniques combined with single-carrier (SC) frequency-domain signal processing are presented for DAN. Particular attention is paid to SC frequency-domain MIMO diversity, relay, beamforming, and multiplexing jointly used with frequency-domain equalization (FDE) to significantly improve the signal transmission performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
For several decades, clinicians have predicted intraparenchymal brain pressure or brain tissue compression indirectly based on the degree of distortion of the midline structures (midline shift) and ...ventricle wall (ventriculomegaly) observed on conventional MRI. However, this method has several limitations. Diffusion tensor imaging (DTI) is a novel MRI technique that can provide information about the microstructural properties of compressed tissue. In this study, the authors evaluated whether DTI can precisely define the degree of tissue compression in patients with chronic subdural hematoma (CSDH).
The study sample consisted of 18 patients (mean age 71 years, 10 men and 8 women) with unilateral CSDH and 12 age-matched volunteers. Diffusion tensor imaging results were acquired before and after the surgical irrigation in the CSDH group. Subdural pressure during the operation was also measured. Fractional anisotropy (FA) values were evaluated at several locations, including the gray matter.
The FA values of the gray matter, especially in the caudate nucleus and putamen, were increased in the patients with CSDH compared with the control group. The change in FA data before and after surgery (ΔFA) correlated with the degree of tissue compression evaluated by measurement of the subdural pressure. Furthermore, the increased FA values in patients with CSDH decreased after surgery.
These findings indicate that FA values of the gray matter, especially in the caudate nucleus and putamen, may be important markers of tissue compression. The assessment of FA values of the gray matter will result in a new, less-invasive diagnostic technique to evaluate the degree of brain compression.
•Zinc oxide nanorods were grown by chemical bath deposition.•Three kinds of transparent conducting oxide films were used as the seed layers.•The average width of the nanorods was dominated by the ...grain size of the seed layer.•The degree of the orientation of the nanorods was related to that of the seed layer.•Spectral shapes of photoluminescence depended on the average width of the nanorods.
Zinc oxide (ZnO) nanorods (NRs) were grown directly on gallium doped ZnO (GZO), tin doped indium (III) oxide (ITO) and fluorine doped tin (IV) oxide (FTO) seed layers by chemical bath deposition using the mixed aqueous solutions of Zn(NO3)2•6H2O and C6H12N4 for the different growth times (tgs). Almost all of the NRs grown on the GZO seed layers, denoted by “NRs/GZO”, were vertically aligned to the substrate surface independently of tg. Some of the NRs grown on the ITO and FTO seed layers, denoted by “NRs/ITO” and “NRs/FTO”, respectively, were vertically aligned to the substrate surface and others were inclined. For both the NRs/ITO and NRs/FTO, moreover, the relative portion of the inclined NRs tended to increase with increasing tg. Both the average width (Wav) and average length (Lav) became larger in the order of the NRs/GZO, NRs/ITO and NRs/FTO, corresponding to the ascending order of the average diameter of the grains forming the seed layer. For the NRs/GZO, the Wav, Lav and density of NRs (nNRs) were almost unchanged at tg > 60 min. For the NRs/ITO and NRs/FTO, however, the increase in tg resulted in the increases in Wav and Lav and the decrease in nNRs. The opposite tg dependences between Wav and nNRs observed for the NRs/ITO and NRs/FTO indicated that the coalescence among the neighboring NRs contributed to the enhancement of Wav. For the NRs/GZO, the strains acting along thea- andc-axis directions were compressive and tensile strains, respectively. For both the NRs/ITO and NRs/FTO, however, both the strains along thea- andc-axis directions were compressive strains. All the photoluminescence (PL) spectra of the NRs exhibited a near-band-edge (NBE) emission at ~380 nm and an orange band (OB) emission at ~600 nm. Regardless of the kind of the seed layer, PL intensity ratio of the OB emission to the NBE emission (IOB/INBE) became smaller with the increase in Wav. The decrease inIOB/INBEwith increasingWavis probably due to the decrease in the volume ratio of the surface region with high concentration of interstitial oxygen atoms (Ois) to the bulk region with few Ois and the decrease in the band bending in the surface region.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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