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Archaeal 16S rRNA gene compositions and environmental factors of four distinct solfataric acidic hot springs in Kirishima, Japan were compared. The four ponds were selected by differences of temperature and total dissolved elemental concentration as follows: (1) Pond-A: 93°C and 1679 mg L−1, (2) Pond-B: 66°C and 2248 mg L−1, (3) Pond-C: 88°C and 198 mg L−1, and (4) Pond-D: 67°C and 340 mg L−1. In total, 431 clones of 16S rRNA gene were classified into 26 phylotypes. In Pond-B, the archaeal diversity was the highest among the four, and the members of the order Sulfolobales were dominant. The Pond-D also showed relatively high diversity, and the most frequent group was uncultured thermoacidic spring clone group. In contrast to Pond-B and Pond-D, much less diverse archaeal clones were detected in Pond-A and Pond-C showing higher temperatures. However, dominant groups in these ponds were also different from each other. The members of the order Sulfolobales shared 89% of total clones in Pond-A, and the uncultured crenarchaeal groups shared 99% of total Pond-C clones. Therefore, species compositions and biodiversity were clearly different among the ponds showing different temperatures and dissolved elemental concentrations.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.

Aims and Objectives: Ethanol is widely used for the embolization treatment of vascular malformations, but it can also cause serious complications such us pulmonary hypertension, cardiopulmonary collapse and death. The complications are considered secondary to pulmonary vasospasm and ethanol-induced sludge embolism, etc., We studied the hemodynamic effects of intravenous absolute ethanol injection and ethanol sludge injection in pigs. Materials and Methods: A total of 5 pigs underwent intravenous injection of ex vivo generated ethanol-induced sludge in which residual ethanol was removed (Group S) and 4 pigs underwent intravenous injection of absolute ethanol (Group E). Hemodynamic parameters related to the pulmonary and systemic circulation were compared between the groups. Results: Transient pulmonary hypertension was observed in both groups and the hemodynamic changes were similar in both groups. Conclusions: Sludge can induce transient pulmonary hypertension or cardiopulmonary collapse, without ethanol and may be the mechanism by which ethanol induces its adverse hemodynamic effects.

Carbon dioxide (CO2) sequestration in deep aquifers is one of the options for reducing the emission of greenhouse gases to the atmosphere. It is efficient to inject super critical CO2 into an aquifer if the geomechanical stability of the aquifer -caprock system can be maintained during the injection. An axisymmetric horizontal aquifer -caprock system is modeled including hydromechanical coupling in order to study influence of various factors - such as injection rate, permeability and stiffness of the caprock and aquifer - on the stability and especially the integrity of the caprock. Here the local safety factor is considered as an index of caprock integrity. It is shown that the effective stress state of the caprock close to the injection well could become critical for shear failure quite early in the injection. A buildup of gas pressure in the aquifer causes caprock deformation, inducing an increase in deviatoric stress within the caprock. Larger injection rates and lower aquifer permeability amplify such phenomena, increasing the risk of losing caprock integrity. Increased aquifer stiffness, in contrast, restricts the caprock deformation, and lowers the risk.

Purpose To evaluate the microstructure of the inner and outer retina and the visual function after macular hole (MH) surgery using brilliant blue G (BBG) or indocyanine green (ICG) to make the internal limiting membrane (ILM) more visible. Design Comparative, retrospective, interventional case series. Participants Sixty-three eyes of 63 consecutive cases with MH were studied. Thirty-five eyes of 35 cases were treated with BBG between January and August 2011. Twenty-eight eyes of 28 MH cases were treated with ICG from April 2009 through April 2010. Methods Vitrectomy was performed with a 23-gauge system and 0.25 mg/ml BBG or with 0.125% ICG. Main Outcome Measures The best-corrected visual acuity (BCVA) and the microperimetry-determined retinal sensitivity were measured at baseline and at 3 and 6 months after surgery. The length of the defect of the photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM), the central foveal thickness (CFT), and the thickness of the ganglion cell complex (GCC) were measured in the spectral-domain optical coherence tomographic images. Results The average BCVA was significantly better in the BBG group than in the ICG group at 3 months ( P = 0.021) and 6 months ( P = 0.045) after surgery. The mean retinal sensitivity in the BBG group was improved significantly in the central 2° at 3 and 6 months ( P = 0.001 and P = 0.030, respectively), but was not significantly improved in the adjacent 10°. The length of IS/OS junction defect was significantly shorter in the BBG group at 3 months ( P = 0.048), but was not significantly different at 6 months ( P = 0.135). The length of ELM defect and the GCC thickness were not significantly different between the 2 groups at 3 and 6 months. The CFT was significantly thinner in the ICG group than in the BBG group at 3 and 6 months ( P = 0.013 and P = 0.001, respectively). Conclusions The postoperative BCVA and retinal sensitivity in the central 2° were better in eyes after BBG-assisted vitrectomy. The restoration of IS/OS junction was faster in the BBG group, and the CFT was significantly thinner in eyes after ICG. Brilliant blue G may be a better agent than ICG to make the ILM more visible. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Introduction Accelerated formation of AGE due to increasing rise in blood glucose levels leads to developments of metabolic changes, further leading to such complications as diabetic retinopathy which is a major reason of leading to blindness and affecting working population worldwide. Background The results of recent investigations have demonstrated that the death of retinal ganglion cells (RGCs) and their axons is the common pathological changes in AGE-exposed retina and the possible mechanisms that are responsible for the onset and progression of RGC death and axonal degeneration in patients with diseases associated with AGEs accumulation are represented in this review. Identifying the mechanisms of the onset and the progression of RGC neuropathy can help in discovering the pathogenetic orientated treatment. Objective This review describes recently discovered possible mechanisms of diabetic retinopathy obtained by laboratory studies with the suggestion that AGEs play an important role in the pathogenesis of diabetic retinal neuropathy triggering different mechanisms that result in neuronal dysfunction. For searching therapeutic approach the regenerative effect of different neurotrophic factors has been studied such as neurotrophin-4, hepatocyte growth factor, glial cell line-derived neurotrophic factor, and Tauroursodeoxycholic acid. Conclusion The findings for the establishment of neuroprotective and regenerative therapies for AGE-related diseases including diabetic retinopathy are represented in this review.

To determine the characteristics of eyes with late in-the-bag dislocation of an intraocular lens (IOL) after pars plana vitrectomy (PPV). Fourteen eyes of 14 patients with a dislocated IOL after PPV were studied retrospectively. The data collected from the medical charts included the age, sex, history of eye diseases, axial length, and interval from PPV to time of IOL dislocation. The surgical procedures used during the PPV were also recorded. Seven eyes had undergone PPV for rhegmatogenous retinal detachment; 6 eyes, for proliferative diabetic retinopathy; and 1 eye, for retinal vein occlusion. The average interval between the PPV and the diagnosis of the dislocated IOL was 6.2 years (range 2.3–10.1 years). In all eyes, the peripheral vitreous was thoroughly removed with scleral depression during the PPV. The IOL dislocation was most likely caused by damage to the zonular fibers by the peripheral vitrectomy with scleral depression.

Purpose To determine the relationship between preoperative and postoperative characteristics and visual outcomes after successful surgery for unclosed macular hole (MH). Methods The medical charts of 166 eyes of 161 patients who underwent vitrectomy for a MH were reviewed. The MH was not closed in 9 eyes of 9 patients after the initial surgery. The second vitrectomy with additional internal limiting membrane (ILM) peeling and gas tamponade was performed. The preoperative and postoperative best-corrected visual acuity (BCVA), optical coherence tomographic images, MH size, duration of MH before the first operation, and area of ILM peeling were studied. Results The MH was closed in all eyes after the second surgery. The BCVA significantly improved from 0.77 to 0.25 logMAR units (20/118 to 20/36, p = 0.002). The postoperative subfoveal ellipsoid zone (EZ) was distinct and continuous in 3 eyes with good visual recovery. The final BCVA was not significantly correlated with the baseline characteristics and area of ILM peeling but was correlated with the postoperative status of the EZ. Conclusions All MHs were closed and the mean postoperative visual acuity was significantly improved. The reason for poor visual recovery was the reduced microstructural recovery after the second surgery.

BACKGROUND/PURPOSE To determine the relationship between the alterations in the preoperative morphology of the retinal pigment epithelium (RPE) and the postoperative recovery after surgery to close an idiopathic macular hole (MH). METHODS Retrospective interventional case series. Fifty-nine eyes of 59 patients with an idiopathic MH were studied. Pars plana vitrectomy was performed with the removal of the internal limiting membrane. The best-corrected visual acuity was measured, and the retinal morphology, including the presence of small RPE protrusions at the bottom of MH, was determined by spectral domain optical coherence tomography before and at 1, 3, and 6 months postoperatively. RESULTS The mean age of the patients was 66.7 years. Forty eyes (68%) had preoperative alterations of the RPE. The minimal (P < 0.001) and the base (P < 0.001) diameters of the MH were significantly larger in eyes with preoperative RPE alterations. The best-corrected visual acuity was significantly worse at baseline (P = 0.014) and at 6 months postoperatively (P = 0.048) in the eyes with RPE alterations. The defect of the ellipsoid zone was significantly longer in eyes with baseline RPE alterations at 1, 3, and 6 months postoperatively (P < 0.001, P = 0.001, and P = 0.032). CONCLUSION The presence of RPE protrusions at baseline was significantly correlated with slower morphologic recovery and poorer visual acuity after MH closure.

Protein A chromatography (PAC) is commonly used as an efficient capture step in monoclonal antibody (mAb) separation processes. Usually dynamic binding capacity is used for choosing the right PAC. However, if aggregates can be efficiently removed during elution, it can make the following polishing steps easier. In this study a method for choosing the right PAC media in terms of mAb aggregate removal is proposed. Linear pH gradient elution experiments of two different mAbs on various PAC columns are carried out, where the elution behavior of aggregates as well as the monomer is measured. Aggregates of one mAb are more strongly retained compared with the mAb monomer. Another mAb showed different elution behavior, where the aggregates are eluted as both the weakly and strongly retained peaks. In order to remove the two types of aggregates by stepwise elution two protocols are tested. The first protocol A consisted of the sample loading, the wash with the equilibration buffer and the low pH elution. The wash stage of the second protocol B included the wash with 1.0 M arginine. No detectable peaks are observed during the wash stage of protocol A whereas significant peaks are monitored during the arginine wash of protocol B. One of the PAC columns showed a smaller peak during the arginine wash. In addition, both aggregate removal and monomer yield are higher with protocol B compared with the other PAC columns. This method is found to be useful for choosing the right PAC column.

Both neuromyelitis optica spectrum disorder (NMOsd) and multiple sclerosis (MS) patients experience optic neuritis (ON) attacks characterized by rapidly reduced best-correct visual acuity (BCVA) and slow recovery. Prognosis and effects of recurrence on recovery may differ between disorders but remain unclear.To compare ON severity, time and degree of recovery and effects of previous ON between NMOsd and MS patients.Retrospective chart review was performed. BCVA measurements acquired before ON, at nadir and during recovery were retrospectively reviewed. Records were obtained on 69 ON attacks in 36 NMOsd patients and 43 attacks in 28 MS patients, including first episodes and recurrences.NMOsd patients exhibited significantly lower BCVA values at all time points after attack (P0.05), reached nadir earlier (P=0.014) and regained a smaller fraction of baseline BCVA than MS patients (P0.001). In NMOsd, relapsed ON resulted in worse recovery and tended to reach nadir earlier than first-episode ON (P=0.030 and 0.059, respectively). In MS, relapsed ON also reached nadir earlier (P=0.042); however, there was no difference in recovery.Recovery from ON was poorer in NMOsd than in MS and was negatively affected by previous ON attacks.

Diabetic neuropathy is associated with neurotrophic ulcerations of the skin and cornea. Decreased corneal sensitivity and impaired innervation lead to weakened epithelial wound healing predisposing patients to ocular complications such as corneal infections, stromal opacification, and surface irregularity. This review presents recent findings on impaired corneal innervation in diabetic individuals, and the findings suggest that corneal neuropathy might be an early indicator of diabetic neuropathy. Additionally, the recent findings for neuroprotective and regenerative therapy for diabetic keratopathy are presented.

Reduction of thickness of ganglion cell complex after internal limiting membrane peeling during vitrectomy for idiopathic macular hole

Diabetes mellitus is a major disease worldwide, and the prevalence of diabetes has risen significantly in the past several decades. Although one of the major complications of diabetic eyes is diabetic retinopathy (DR), corneal diseases can not only develop in diabetic patients but are also difficult to manage. Diabetic neurotrophic keratopathy is a component of diabetic polyneuropathy and is recognized to be the cause of the morbidity of the cornea in diabetic patients. In addition, corneal endothelial cell damage can cause disturbances in the management of proliferative DR before and after surgeries because of endothelial decompensation with bullous keratopathy. However, there have been only a limited number of studies that have focused on the importance of corneal diseases in diabetic patients. This review describes the pathophysiological roles of different factors that have been found to be causative factors of diabetic corneal keratopathy and endothelial cell dysfunction in diabetic patients. In addition, the clinical features of the corneal changes in diabetic patients and recent studies related to the development of therapies for the management of corneal diseases are presented.

We present detailed ophthalmic findings in a case of tuberculum sellae meningioma with acute visual symptoms due to optic canal involvement. A 62-year-old Japanese woman reported a 1-week history of headaches and blurred vision in her left eye. Her visual acuity was 0.3 in the left eye with no ophthalmoscopic abnormalities. A relative afferent pupillary defect and inferior temporal field defect were found in the left eye. Pattern visual evoked potentials were undetectable in the left eye. Enhanced magnetic resonance imaging showed a 9 mm intracranial lesion around the left optic nerve anterior to the chiasm. She was diagnosed with granulomatous inflammation because of the increased cell counts and protein concentration in the cerebrospinal fluid. She was treated with steroid pulse therapy, and her visual acuity and visual field defect improved to normal in 3 weeks. However, 16 months after the onset, she suffered from headaches again and had a complete loss of vision in her left eye. There was no response to steroid pulse therapy. Enhanced magnetic resonance imaging revealed that the lesion had extended into the left optic canal, and emergency tumor removal surgery was carried out. The histopathological diagnosis was meningioma. One month after the surgery, her left visual acuity improved to 1.2, and her visual field was almost normal. Pattern visual evoked potentials were present but had a prolonged P 100 latency of 170 ms. A thinning of the ganglion cell complex was detected by optical coherence tomography. Ophthalmologists should be aware that a small tuberculum sellae meningioma can cause acute visual symptoms due to optic canal involvement. Early consultation with a neurosurgeon is necessary. Visual evoked potentials and optical coherence tomography are sensitive and helpful in following patients with optic nerve compression.

Purpose: To investigate the course of subfoveal pigment epithelial detachments (PEDs) in eyes with age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) ≥20/40. Methods: Thirty-seven eyes of 35 patients with a subfoveal PED were divided into an avascular PED group (n = 11), a vascularized PED group due to polypoidal choroidal vasculopathy (PCV, n = 14) and an occult choroidal neovascularization (CNV) group (n = 12). Intravitreal bevacizumab or ranibizumab was given as needed. The BCVA, central foveal thickness, PED thickness, and lesion size were measured at baseline and at 2 years after the initial examination. Results: The BCVA did not change significantly in the avascular group, decreased from 0.06 ± 0.11 to 0.23 ± 0.15 logMAR units in the PCV group and from 0.12 ± 0.12 to 0.71 ± 0.70 logMAR units in the CNV group. At 2 years, the central foveal and PED thicknesses were not significantly different among the 3 groups, and the lesion was significantly larger in the PCV and CNV groups than in the avascular group. Conclusions: The vascularized PED cases had a poorer visual outcome than avascular PEDs with anti-VEGF drugs at the 2-year follow-up.

Purpose To compare the effects of sub-Tenon’s capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME). Patients and methods The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments. Results The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non-SRD group than in the SRD+ group after STTA + MAPC. Conclusion Our findings indicate that MAPC has an additive effect in the non-SRD type.

The inactivation behavior of baker's yeasts during low-temperature hot air drying and freeze drying was investigated. The activity was determined by measuring the fermentative abilities. Inactivation was observed during the falling drying rate period even at low temperature (30°C). As their fermentation activities in suspensions at 30°C are maintained up to a few hours, this decrease was found to be due to dehydration inactivation. Similar dehydration inactivation was also observed during freeze drying. The dehydration inactivation became more significant when the drying rate was increased. The stability of dried yeasts increased with decreasing water content. The addition of sorbitol before drying further improved the stability of dried yeasts.

A method for designing efficient chromatography processes was proposed and verified experimentally. The model samples were polyphenols. Polystyrene divinylbenzene resins were employed for the column stationary phase. The mobile phase was an ethanol-water mixture. The distribution coefficient, K, was determined as a function of ethanol concentration, I, by linear gradient elution experiments. The HETP-mobile phase velocity (u) curves were determined as a function of I. A method for calculating the iso-resolution curve was developed with K and HETP-u as a function of I. The calculated iso-resolution curve was verified by comparison with experimental elution curves. The iso-resolution curve was found to be useful for determining suitable separation conditions.

The aim of our study was to determine the relationship between vision-related quality of life (VRQOL) following the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and the macular sensitivity determined by microperimetry in patients with retinitis pigmentosa (RP). The Japanese version of the NEI VFQ-25 was used to assess the VRQOL of 30 patients with typical RP whose decimal visual acuity was ≥0.6. The mean retinal sensitivity within the central 10° was determined by fundus-related microperimetry (MP1). The correlation between the mean of the total composite NEI VFQ-25 score and MP1-determined macular sensitivity was determined. Mean NEI VFQ-25 score was 69.4 ± 14.5 (range 34.6–90.3) in RP patients. There was a significant positive correlation between mean NEI VFQ-25 score and mean retinal sensitivity within 10° (r = 0.673, P = 0.0003). The significant correlation between macular sensitivity and VRQOL measured with the NEI VFQ-25 indicates that sensitivity in the macular area is an important consideration in using VRQOL with RP patients.

Covered, self-expandable metallic stents (SEMS) have been enthusiastically adopted for the treatment of esophagotracheal fistula, but problems with stent migration have yet to be resolved. To overcome this problem, we have developed a new hanging-type esophageal stent designed to prevent migration, and we conducted an animal study to assess the efficacy of our method.A total of six female pigs were used in this study. The main characteristic of our stent was the presence of a string tied to the proximal edge of the stent for fixation under the skin of the neck. The first experiment was performed to confirm technical feasibility in three pigs with esophagotracheal fistula. The second experiment was performed to evaluate stent migration and esophagotracheal fistula in three pigs.Creation of the esophagotracheal fistula and stent placement were technically successful in all pigs. In the first experiment, esophagotracheal fistula was sealed by stent placement. In the second experiment, no stent migration was seen 11 or 12 days after stent placement. Gross findings showed no fistulas on the esophageal or tracheal wall.Our new hanging-type esophageal stent seems to offer a feasible method for preventing stent migration.

Purpose: To describe a case of choroidal osteoma with choroidal neovascularization (CNV) that was successfully treated with two intravitreal injections of bevacizumab (IVB). Design and methods: Case report on a 12-year-old Japanese girl who presented with a sudden decrease in vision in her left eye. At the first visit, 2 days after the onset of her symptoms, her visual acuity (VA) in her left eye was 0.2. Ophthalmoscopy showed a hemorrhage of 5 disc diameters under the retinal pigment epithelium and a serous retinal detachment at the posterior pole of the left eye. These findings were confirmed by optical coherence tomography. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) showed several points of leakage around the fovea, which suggested a CNV. From these findings, the patient was diagnosed with choroidal osteoma with a CNV. The submacular hemorrhage was from the CNV associated with the choroidal osteoma. We treated her with two injections of 1.25 mg/0.05 mL IVB with a 4-month interval. Results: The patient’s VA in her left eye improved to 0.7, and this vision was maintained for 4 years. The CNV disappeared in the FA and ICGA images and no recurrence was observed after 4 years. Conclusion: Our findings indicate that IVB is effective in resolving CNV in eyes with an osteoma and prevents a decrease of vision in eyes with a choroidal osteoma with a CNV.

Twelve strains of moderately thermophilic bacteria were isolated from saline hot springs (55°C, pH 8.3) located in Odaito, Hokkaido, Japan. Based on their 16S rRNA gene sequences, all the strains were closely related phylogenetically each other, indicating that the strains belong to a single species. However, maximal growth temperature and enzymatic characteristics of individual strains were slightly different each other. Some of them grew well at 55°C but others did not. The β-galactosidase activity was also different among the strains. Therefore, the representative strains BEK6 and BEK11 were chosen from individual phenotype groups, and were used for further characterization. The nucleotide sequence of full-length 16S rRNA genes of the representative strains showed 96.6% similarity with Bacillus alveayuensis indicating that the strains belong to a novel species of the genus Bacillus . The cells were Gram positive, and showed both catalase and oxidase activities. The optimal growth temperature and pH of strain BEK6 and BEK11 were around 50°C and 7-8, respectively. They were able to grow in the medium containing 10% NaCl in contrast to B. alveayuensis which can grow in the medium with up to 4% NaCl. The strain BEK11 showed relatively strong protease and amylase activities implying the potential industrial uses of these enzymes under the saline condition.

Purpose: To determine the prevalence of macular abnormalities detected by optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP), and to report the results of pars plana vitrectomy (PPV) in five patients with RP. Methods: OCT images of the macula of 622 eyes of 323 patients with RP were evaluated. All patients had a complete clinical examination, and PPV was performed on two RP patients with a macular hole (MH), two patients with vitreomacular traction (VMT) syndrome, and one patient with cystoid macular oedema (CME). Results: A macular lesion was detected by OCT in 46 eyes (7.4%) of 37 patients (11.5%). CME was detected in 34 eyes (5.5%) of 26 patients, an epiretinal membrane in four eyes of four patients, VMT in five eyes of four patients, and full-thickness MH in three eyes of three patients. PPV was performed on five of these eyes. The MH was closed with vision improvement after a single surgery in one eye, and was closed after repeated PPVs with a decrease of vision in another eye. In both patients with VMT, the visual acuity decreased after the surgery. The macular morphology and visual acuity did not improve postoperatively on the one patient with CME who underwent PPV. Conclusion: When OCT is used, macular abnormalities are present in 7.4% of patients with RP, which is lower than the prevalence reported earlier. Although vitrectomy can improve the macular morphology in some patients with RP, improvement of visual function may be limited most likely because of the long-standing retinal dysfunction.

The effect of self-relevance of a non-critical item in the Concealed Information Test (CIT) was investigated. Respiration, skin conductance response (SCR), heart rate, and normalized pulse volume were recorded while performing the CIT using a stimulus set composed of 4 items (with one self-relevant item). Thirty participants were instructed to recognize one item as critical and the remaining items as non-critical (positive group), and 33 participants were instructed to recognize all items as non-critical (negative group). In the positive group, a differential reactivity was observed between the critical and non-critical items, despite the self-relevance of the non-critical item. In the negative group, a differential reactivity between the self-relevant and non-self-relevant items was observed for SCR only. However, when individual data were analyzed, there was a differential reactivity between self-relevant and non-self-relevant items on physiological measures other than SCR for some participants in the negative group. These results suggest that the self-relevance of a non-critical item might cause false positive results in "negative" participants, particularly when only SCR is used to assess differential reactivity.

【Purpose】To find automated diagnosis of retinopathy, the matched filters (Chaudhuri et al, 1989) were studied for retinopathy. The filters had been reported for a film-based fundus image of 2.5x105 pixels, and the image needed to be converted into a digital file with an image scanner. Now, direct digital images are available with more precise images than 107 pixels.【Methods and Subjects】Non compressed digital images were taken with a non mydriasis-type fundus camera, and images of green component were used. Fluorescein angiography was done for retinopathy, and the images were compared to the matched filters. Subjects were 11 normal volunteers and 25 patients with typical diabetic retinopathy, 7 patients with branch retinal vein occlusion, 18 patients with age-related macular degeneration, respectively.【Results】Fine retinal blood vessels, microaneurysms, neovascularization, dotted retinal bleedings and exudates were emphasized for diabetic retinopathy, but non-perfusion areas in fluorescein angiograms could not be made clear with the filters. 【Conclusion】The filters would be helpful for diagnosis of retinopathy, but the process could not alternate with fluorescein angiography. The filters were not good for the diseases of transparent part such as cataract or vitreous hemorrhage.

The purpose of this study was to determine the characteristics of primary diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac. A 77-year-old man had epiphora of the right eye for three years. After visiting five clinics and hospitals, he was referred to our hospital, and the preoperative magnetic resonance imaging findings suggested a lacrimal sac mass. Dacryocysteography showed an obstruction of the right nasolacrimal duct, so we performed dacryocystectomy. After a histopathologic examination of the specimen, the patient was diagnosed with a DLBCL. Positron emission tomography scanning excluded metastases, and the final diagnosis was made of a primary DLBCL of the right lacrimal sac. He underwent radiotherapy with 30.6 Gray in total to the right lacrimal sac. After radiotherapy, no recurrence has been observed anywhere in his body for one year. Although a malignant lymphoma of the lacrimal sac is rare, clinicians should consider a primary malignant lymphoma in the differential diagnosis in patients with chronic dacryocystitis.

The objective of this study was to investigate the effects of particle size reduction and solubilization on biogas production from food waste (FW). To clarify the effects of volatile fatty acids (VFAs) in the digestion process, the relationship between particle size and VFA accumulation was investigated in detail. For this purpose, substrates of various particle sizes were prepared by bead milling to support hydrolysis. Batch anaerobic digestion experiments were carried out using these pretreated substrates at mesophilic temperature for a period of 16 days. The results of pretreatment showed that the mean particle size (MPS) of substrates ground with a bead mill decreased from 0.843 to 0.391 mm, and solubilization accounted for approximately 40% of the total chemical oxygen demand (total COD) for grinding pretreatment by bead milling. Anaerobic digestion batch experiments revealed that MPS reduced by bead milling at 1000 rpm improved methane yield by 28% compared with disposer treatment. Moreover, this may have increased microbial degradation during the VFA production process with increasing total number of revolutions (operation time × revolutions per minute). However, excessive reduction of the particle size of the substrate resulted in VFA accumulation, decreased methane production, and decreased solubilization in the anaerobic digestion process. These results suggest that optimized reduction of the particle size of the substrate in conjunction with optimized microbial growth could improve the methane yield in anaerobic digestion processes.

The retention and binding mechanisms in electrostatic interaction-based chromatography (ion-exchange chromatography) of PEGylated proteins (covalent attachment of polyethylene glycol chains to protein) were investigated using our previously developed model. Lysozyme and bovine serum albumin were chosen as model proteins. The retention volume of PEGylated proteins shifted to lower elution volumes with increasing PEG molecular weight compared with the non-modified (native) protein retention volume. However, PEGylation did not affect the number of binding sites appreciably. The enzyme activity of PEGylated lysozyme measured with a standard insoluble substrate in suspension decreased considerably, whereas the activity with a soluble small-molecule substrate did not drop significantly. These findings indicate that when a protein is mono-PEGylated, the binding site is not affected and the elution volume reduces due to the steric hindrance between PEGylated protein and ion-exchange ligand.

Background: To determine whether a significant correlation exists among the changes in the size of the abnormal parafoveal autofluorescence ring, the length of the photoreceptor inner and outer segment (IS/OS) junction, and the visual function in patients with retinitis pigmentosa. Methods: Retrospective observational case series. A total of 50 eyes of 26 patients with typical retinitis pigmentosa and an autofluorescence ring were examined by optical coherence tomography and microperimetry. During the follow-up period of >2 years, the changes in the diameter and area of the autofluorescence ring, the length of the IS/OS line, the best-corrected visual acuity and mean retinal sensitivity in the central 10° were determined. Results: The diameter and area of the autofluorescence ring, and the length of the IS/OS line decreased significantly during the follow-up period (all, P

Background: Ocular angiogenesis is regulated by polypeptides including cytokines, which are known to affect vascular endothelial cells. We have reported that hyalocytes interact with vascular endothelial cells, and some cytokines affect these interactions. Aims: To determine the effect of various chemically active agents on the viability of endothelial cells alone and cocultured with hyalocytes. Methods: The viability of human retinal endothelial cells (HRECs) was determined after exposure to IL-1α, IL-1β, IL-6, TNFα and VEGF using the MTT assay. These results were compared to the viability when the HRECs were cocultured with porcine hyalocytes that had been exposed to different types of cytokines. The effects of bevacizumab, fenofibrate and dexamethasone on the viability of HRECs in coculture with hyalocytes were also assessed. Results: Ten micrograms/millilitre of bevacizumab decreased the percentage of living HRECs stimulated by VEGF without hyalocytes, but with the hyalocytes, 100 μg/ml of bevacizumab was required to decrease the percentage of viable HRECs stimulated by VEGF. Fenofibrate, at 5 μg/ml, decreased the viability of HRECs stimulated by IL-1β and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured with hyalocytes. Dexamethasone, at 50 μg/ml, decreased the viability of HRECs stimulated by IL-1α, IL-1β, IL-6 and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured. Conclusions: Coculturing HRECs with vitreous-derived hyalocytes depressed the effects of cytokines, bevacizumab, fenofibrate and dexamethasone. This suggests that the vitreal hyalocytes may play a role in pathogenic endothelial cell proliferation in vivo. Future studies to better understand this pathobiology should utilize coculture systems of HRECs and vitreal hyalocytes.

The total extract of resin from Callitris preissii was analyzed by gas chromatography/mass spectrometry and 34 lignans, underivatized and as trimethylsilyl ether derivatives, were identified by interpretation of the mass spectra. The lignans in the resin include 13 new lignans, i.e., four secoisolariciresinol derivatives, four lariciresinol derivatives, 3′,4′-methylenedioxy-7′-hydroxylariciresinol, 3,4-methylenedioxypinoresinol isomer, and two matairesinol derivatives. Furthermore, 17 lignans of the resin are characterized by methylenedioxy substitution on either or both guaiacylpropyl units or the syringylpropyl unit: i.e., five secoisolariciresinol derivatives, three lariciresinol derivatives, 3′,4′-methylenedioxy-7′-hydroxylariciresinol, three pinoresinol derivatives, and five matairesinol derivatives, have methylenedioxy structures. Eleven lignans, including two secoisolariciresinol derivatives, four lariciresinol derivatives, two pinoresinol derivatives, and three matairesinol derivatives, contain a syringyl moiety.

Aims: To compare the short-term therapeutic effects of intravitreal bevacizumab (IVB) to those of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). Materials and Methods: Retrospective interventional case study. Eighty-nine eyes of 89 patients with symptomatic PCV were treated by IVB or PDT. Eighteen eyes were treated with a single injection of IVB (s-IVB group), 22 eyes with three consecutive monthly IVB injections (m-IVB group), and 49 eyes with PDT alone (PDT group). The best-corrected visual acuity (BCVA) and OCT-determined central foveal thickness (CFT) were evaluated before, and one and three months after the treatment. For statistical analyses, one-factor ANOVA and Chi-square test were used. Results: The differences in the BCVA and CFT among the three groups at the baseline were not significant (P=0.992, P=0.981, respectively). Three months after the treatment, the BCVA improved by> 0.2 logMAR units in two out of 18 eyes (11%) in the s-IVB group, three out of 22 eyes (14%) in the m-IVB group, and 15 out of 49 eyes (31%) in the PDT group (P=0.124). A decrease in the CFT by> 20% was achieved in six out of 18 eyes in the s-IVB group, ten eyes (46%) in the m-IVB group, and 35 eyes (71%) in the PDT group (P=0.009). The resolution of polyps was achieved in three out of 18 eyes in the s-IVB group, one eye (5%) in the m-IVB group and 35 eyes (71%) in the PDT group (P < 0.001). Conclusion: The better short-term therapeutic outcomes in the PDT group than in the s-IVB and m-IVB groups indicate that PDT may be more effective than IVB in short term after treatment for PCV.

Temporal changes in paleoproductivity of Lake Biwa (Japan) over the past 32 kyr have been studied by analyzing bulk organic carbon and photosynthetic pigments (chlorins) in the BIW95-5 core. Primary productivity was estimated on the assumption of C/Norg values of 8 for autochthonous organic matter (OM) and 25 for allochthonous OM and using an equation developed for the marine environment. The estimate indicates that primary productivity ranges from 50 to 90 g C m−2 yr−1 in the Holocene, while it is ∼60 g C m−2 yr−1 on average in the last glacial. Pheophytin a and pheophorbide a are the major chlorins. A downcore profile of chlorin concentration normalized to autochthonous organic carbon (OC) shows a decreasing trend. Chlorin productivity was corrected by removal of the effect of post-burial chlorin degradation. The temporal profile of chlorin productivity thereby obtained resembles that from autochthonous OC. The difference in primary productivity between the Holocene and the glacial for the lake is markedly smaller than that for Lake Baikal situated in the boreal zone. This difference between the two lakes is probably caused by the difference in their climatic conditions, such as temperature and precipitation. Precipitation at Lake Biwa is relatively large during the glacial and the Holocene because of the continuous influence of the East Asian monsoon. Lake Baikal precipitation is generally small as a result of control by the continental (Siberia) climate regime. In addition, a significant difference in productivity between the glacial and the Holocene for Lake Baikal may be essentially controlled by the hydrodynamic systems in the lake. Lake Biwa terrigenous OM input events occurred at least five times over the period 11–32 kyr BP, suggesting enhanced monsoon activity. Molecular examination of the layer with a large input of terrigenous OM during the Younger Dryas indicates that concentrations of terrigenous biomarkers such as n-C27–C31 alkanes, lignin phenols, cutin acids, ω-hydroxy acids and C29 sterols are high, suggesting that soil OM with peat-like material entered the lake as a result of flooding. An enhanced sedimentation rate in the last 3000 years might have been partially caused by agricultural activity around the lake.

The retention and peak spreading in linear gradient elution of charged large biomolecules were investigated by using numerical simulations. Oligo-DNA separation by monolithic anion-exchange chromatography was chosen as a model system. The peak width and the retention were well predicted by using the parameters obtained by gradient elution experiments at different gradient slopes. As the distribution coefficient at the peak retention volume K(R) decreases with increasing molecular size, the peak became sharper for larger DNAs. This is due to very large effective charge (binding site) values of large DNAs (20-60). The peak width was well correlated with K(R) based on the model equation developed for linear gradient elution of proteins. It was shown that the monolithic disk is best suited for very large charged biomolecule separations at high flow velocities with shallow gradients slopes.

Our previous study has shown that there is a good correlation between the number of charges of DNA (from trimer to 50-mer) and the number of binding sites B in electrostatic interaction chromatography (ion-exchange chromatography, IEC). It was also found that high salt (NaCl) concentration is needed to elute large DNAs (>0.6 M). In this paper we further performed experiments with large DNAs (up to 95-mer polyT and polyA) and charged liposome particles of different sizes (ca. 30, 50 and 100 nm) with a monolithic anion-exchange disk in order to understand the binding and elution mechanism of very large charged biomolecules or particles. The peak salt (NaCl) concentration increased with increasing DNA length. However, above 50-mer DNAs the value did not increase significantly with DNA length (ca. 0.65–0.70 M). For liposome particles of different sizes the peak salt concentration (ca. 0.62 M) was similar and slightly lower than that for large DNAs (ca. 0.65–0.70 M). The binding site values (ca. 25–30) are smaller than those for large DNAs. When arginine was used as a mobile phase modulator, the elution position of polyA and polyT became very close whereas in NaCl gradient elution polyT appeared after polyA eluted. This was mainly due to suppression of hydrophobic interaction by arginine.

We characterized the compositions of organic compounds in a Cheremushka bog sediment core (deposited over the last 35 kyr), located at the eastern coast of Lake Baikal, to obtain basic information about the terrestrial organic matter (OM) which contributed to Lake Baikal sediments. The bog sediment was analyzed for the molecular composition of n -alkanes, lignin phenols and n -C 24 to C 30 alkanoic acids, as well as the carbon isotopic composition of plant wax derived n -C 27 to C 33 alkanes. Concentrations of lignin phenols [vanillyl (V) plus syringyl (S) phenols] normalized to total organic carbon (TOC) in the Holocene are twice those for the last glacial maximum (LGM), while concentrations of TOC-normalized n -C 24 to C 30 alkanoic acids do not change markedly in this period. Thus, the ratio of lignin phenols to n -C 24 to C 30 alkanoic acids increases from the LGM to the Holocene. This result is essentially consistent with pollen analysis indicating an expansion of woody plants in the Holocene and a prevailing herb-abundant environment for the LGM. The δ 13 C values of n -C 27 to C 33 alkanes (e.g. −29‰ to −33‰ for C 31 ) indicate the presence of C 3 -dominant plants throughout the core. The contribution of terrestrial OM to Lake Baikal sediments was estimated using the biomarkers, on the assumption that the OM in the bog sediments is a representative of the terrestrial OM around the lake. Hence, the estimation using lignin phenol or n -C 24 to C 30 alkanoic acid parameters indicates that 11–24% of the TOC in the Academician Ridge sediments is land-derived for both the Holocene and the LGM, which is similar to the estimates from C/N values of bulk OM. However, the estimates for terrestrial OM using the n -C 27 to C 33 alkane parameter are generally higher than those using lignin phenol or n -C 24 to C 30 alkanoic acid parameters. The difference is thought to be associated with the difference in source and behavior of these biomarkers.

Aim: To compare the results of vitrectomy with internal limiting membrane (ILM) peeling to that without ILM peeling for macular edema associated with branch retinal vein occlusion (BRVO). Methods: The medical records of 47 eyes of 47 patients with BRVO-associated macular edema were examined. To treat the macular edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA) and the optical-coherence-tomography-determined foveal thickness were obtained preoperatively and at 6 months postoperatively. Results: The mean postoperative BCVA was significantly better than the preoperative BCVA in both the ILM-removed and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The fovea was significantly thinner at 1 month after surgery in both groups (p = 0.0007 and p < 0.0001, respectively). The postoperative improvement of the mean BCVA and the foveal thickness were not significantly different for the two groups at any postoperative period. Conclusions: Because there was no significant difference in the improvement of BCVA between the two groups at 6 months postoperatively, there may be no additional benefit in removing the ILM for BRVO-associated macular edema.

Aims:To investigate the relationship between the presence of the photoreceptor inner and outer segment (IS/OS) junction and visual acuity after epiretinal membrane (ERM) surgery.Methods:Seventy eyes of 70 consecutive patients who had undergone vitrectomy for idiopathic ERM were examined by optical coherence tomography before and 3 and 6 months after surgery. The IS/OS junction was graded into three grades. The time course of recovery of the IS/OS junction, central foveal thickness (CFT) and best corrected visual acuity (BCVA) during the postoperative period was studied.Results:A normal IS/OS junction was detected in 47.1% of the eyes before surgery and in 65.7% at 3 months and 75.7% at 6 months after. There was a significant correlation between the IS/OS grade and BCVA before and at 3 and 6 months after the operation (p = 0.0001, pConclusions:The presence of a normal IS/OS junction was associated with good visual acuity after ERM surgery. A normal IS/OS junction probably indicates morphological and functional recovery of the photoreceptors.

Background: Neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. However, the mechanisms for neuronal cell death in diabetic retinopathy remain unclear. Aim: To determine whether altered expression of Bax, caspase-9 and -3 is associated with degenerative neurons in diabetic retinopathy. Methods: Immunohistochemistry was performed on cryosections obtained from five pairs of normal and five pairs of age-matched diabetic human retinas. Diabetic eyes had no proliferative diabetic retinopathy and no histories of photocoagulation or ocular surgery. In this study, Fluoro-Jade B (FJB) was used as a marker for identification of degenerative neurons. Results: In diabetic retinas, Bax overexpression coexisted with FJB positive signals in the ganglion cell layer (GCL) compared with very low FJB levels in the normal retina. Increased level of the active forms of caspase-9 and -3 expressions coexisted with FJB positive cells in the GCL of diabetic retinas compared with those in normal retinas. Conclusions: Upregulation of Bax, caspase-9 and -3 expression was associated with neuronal degeneration in diabetic retinopathy. The mitochondria- and caspase-dependent cell-death pathway may be, in part, associated with neuronal degeneration in diabetic retinas.

To determine the relationship between the postoperative visual acuity (VA) and the presence of a photoreceptor inner segment (IS) and outer segment (OS) junction (IS/OS) in optical coherence tomographic (OCT) images after macular hole (MH) surgery.Twenty-three eyes of 23 cases of idiopathic MH treated by vitrectomy were studied. The postoperative VA and OCT3 images of the fovea at 1, 3, and 6 months were examined. The relationship between the presence of the IS/OS junction and the visual acuity was studied.All MHs were successfully closed. The IS/OS junction appeared as a distinct, highly reflective line just vitread to the retinal pigment epithelial layer in the postoperative OCT3 images. A normal IS/OS junction was detected postoperatively in one eye at 1 month, three eyes at 3 months, and seven eyes at 6 months. The VA was significantly better in eyes in which a normal IS/OS junction was detected than in those not detected at 3 and 6 months postoperatively (P = 0.046 and P = 0.040, respectively).The normal IS/OS junction observed in OCT3 images is associated with good visual recovery after MH closure. The presence of normal IS/OS junction may be important for visual recovery after MH repair.

Protein aggregation is a ubiquitous phenomenon significant to all aspects of science. Notably, the formation of protein aggregates is frequently encountered in biochemical research and biopharmaceutical industry. Formation of protein aggregates is generally regarded to be associated with partially folded intermediate species that are susceptible to self-association due to the exposure of hydrophobic core. Evidence supports the concept that the formation of aggregates in vitro is a generic property of proteins. In human etiology, more than 20 different devastating human diseases have been reported to be associated with protein aggregation. Although protein aggregation diseases have been the center of intense research, much remains to be learned regarding the underlying molecular mechanisms. In this review, the general background information on protein aggregation is first provided. Next, we summarize the properties, characteristics and causes of protein aggregates. Finally, from the perspectives of epidemiology, pathogenesis, existing mechanisms, relevant hypotheses, and current as well as potential therapeutic approaches, two examples of protein aggregation diseases, Alzheimer's disease and cataract, are briefly discussed. Importantly, while a variety of molecules have been suggested, the effective therapeutic drugs for curing the diseases involving protein aggregation have yet to be identified. We believe that a better understanding of the mechanisms of protein aggregation process and an extensive investigation into the drug penetration, efficacy, and side effects will certainly aid in developing the successful pharmacological agents for these diseases.

PURPOSE To report a case of age-related macular degeneration (AMD) with massive subretinal hemorrhage easily removed through a retinal break. CASE REPORT A 57-year-old Japanese man with a massive subretinal hemorrhage in an eye with AMD developed a rhegmatogenous retinal detachment after intraocular gas injection. The subretinal hemorrhage was easily removed using perfluorocarbon liquid during vitrectomy, and the retinal degeneration was minimal. CONCLUSION Rhegmatogenous retinal detachment is an unfavorable complication after intraocular gas injection for the treatment of AMD. In our case, the subretinal hemorrhage was easily removed, and visual recovery was possible to some degree.

Purpose To evaluate the efficacy of radial optic neurotomy (RON) on retinal function in patients with central retinal vein occlusion (CRVO). Methods Ten eyes of 10 patients with CRVO underwent pars plana vitrectomy and RON. Standardized combined electroretinograms (ERGs) to full-field bright-flash stimuli were recorded preoperatively and, 3 months postoperatively. The best-corrected visual acuity and foveal thickness were also determined, before and 3 months postoperatively. Results The mean best-corrected visual acuity and mean foveal thickness were both significantly improved after vitrectomy and RON. The mean amplitudes of a- and b-waves did not change significantly, but the mean b/a wave ratio was increased significantly after vitrectomy and RON. An improvement of the b/a ratio was observed in six eyes, however, an improvement of retinal circulation was confirmed on postoperative fluorescein angiograms in two of these six eyes. Conclusions Significant improvements were observed in the b/a wave ratio of the standard combined ERGs after surgery in eyes with CRVO. The improvement of retinal function was most likely due to improved oxygenation of retina caused by vitrectomy and not by RON.

As a method for surveying efficient separation conditions for the mobile phase, a 96-well micro-plate based monolithic ion-exchange chromatography system was developed. Discontinuous flow was accomplished by a vacuum manifold. Linear salt gradient elution experiments were carried out with this system and the elution curves were compared with those for monolithic disk column IEC. The normalized gradient slope–the peak salt concentration data for the micro-plate system agreed with those for the monolithic disk column IEC. This system is useful as the liquid volume needed for the experiment is highly reduced, and large amounts of data are obtained quickly.

As it is important to understand how protein conformational changes affect the separation performance in ion exchange chromatography (IEC), we investigated two model systems, unfolded proteins (lysozyme and bovine serum albumin) with urea and dithiothreitol, and PEGylated proteins (lysozyme attached with polyethyleneglycol molecular weight 5000). Linear gradient elution IEC experiments were carried out and the data were analysed by our model previously presented in order to obtain the binding site value B and the peak salt concentration IR. Unfolded proteins (bovine serum albumin and lysozyme) with urea and dithiothreitol showed weaker retention and larger binding site values compared with the values for native proteins. Multiple PEGylated lysozyme peaks were separated, and eluted earlier than the native peak appeared. There is a good correlation between B and IR for PEGylated lysozymes.