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Objective: Perihematomal edema results from disruption of the blood-brain barrier (BBB) by key mediators, such as thrombin, following intracerebral hemorrhage (ICH). Platelet-derived growth factor receptor alpha (PDGFR-α), a tyrosine kinase receptor, was found in previous studies to play a role in orchestrating BBB impairment. In the present study, we investigated the role of PDGFR-α following ICH-induced brain injury in mice, specifically investigating its effect on BBB disruption.Methods: Brain injury was induced by autologous arterial blood (30 μl) or thrombin (5 U) injection into mice brains. A PDGFR antagonist (Gleevec) or agonist (PDGF-AA) was administered following ICH. PDGF-AA was injected with a thrombin inhibitor, hirudin, in ICH mice. Thrombin-injected mice were given Gleevec or PDGF-AA neutralizing antibody. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, was delivered with PDGF-AA in naïve animals. Postassessment included neurological function tests, brain edema measurement, Evans blue extravasation, immunoprecipitation, western blot, and immunohistology assay.Results: PDGFR-α suppression prevented neurological deficits, brain edema, and Evans blue extravasation at 24 to 72 hours following ICH. PDGFR-α activation led to BBB impairment and this was reversed by SB203580 in naïve mice. Thrombin inhibition suppressed PDGFR-α activation and exogenous PDGF-AA increased PDGFR-α activation, regardless of thrombin inhibition. Animals receiving a PDGF-AA-neutralizing antibody or Gleevec showed minimized thrombin injection-induced BBB impairment.Interpretation: PDGFR-α signaling may contribute to BBB impairment via p38 MAPK-mediated matrix metalloproteinase (MMP) activation/expression following ICH, and thrombin may be the key upstream orchestrator. The therapeutic interventions targeting the PDGFR-α signaling may be a novel strategy to prevent thrombin-induced BBB impairment following ICH. [ABSTRACT FROM AUTHOR]

Cyclotides are cysteine-rich plant-derived peptides composed of 28-37 amino acids with a head-to-tail cyclic backbone and a knotted arrangement of three conserved disulfide bonds. Their beneficial biophysical properties make them promising molecules for pharmaceutical and agricultural applications. The Violaceae plant family is the major cyclotide-producing family, and to date, every examined plant from this family has been found to contain cyclotides. The presence of cyclotides in Viola communis was inferred by mass spectroscopy previously, but their sequences and properties had yet to be explored. In this study, the occurrence of cyclotides in this plant was investigated using proteomics and transcriptomics. Twenty cyclotides were identified at the peptide level, including two new members from the bracelet (Vcom1) and Möbius (Vcom2) subfamilies. Structural analysis of these newly identified peptides demonstrated a similar fold compared with cyclotides from the same respective subfamilies. Biological assays of Vcom1 and Vcom2 revealed them to be cytotoxic to Sf9 insect cell lines, with Vcom1 demonstrating higher potency than Vcom2. The results suggest that they could be further explored as insecticidal agents and confirm earlier general findings that bracelet cyclotides have more potent insecticidal activity than their Möbius relatives. Seven new cyclotide-like sequences were observed in the transcriptome of V. communis , highlighting the Violaceae as a rich source for new cyclotides with potential insecticidal activity. An analysis of sequences flanking the cyclotide domain in the various precursors from V. communis and other Violaceae plants revealed new insights into cyclotide processing and suggested the possibility of two alternative classes of N-terminal processing enzymes for cyclotide biosynthesis.

Context: Dietary diversity score (DDS) has been known as a useful and convenient indicator of overall diet quality. Previous studies have reported the association between DDS and health problems such as diabetes, metabolic syndrome and cardiovascular disease., Objectives: This systematic review and meta-analysis aimed to assess the association between dietary diversity score (DDS) and cardio-metabolic risk factors such as obesity and overweight, lipid profile, blood pressure, metabolic syndrome (MetS) and diabetes., Data Sources: We systematically searched PubMed and NLM Gateway, Scopus and Institute of Scientific Information (ISI) by up to October 2019., Data Extraction: All observational studies which assessed the association of DDS with cardio-metabolic risk factors including anthropometric measures, blood pressure, lipid profile, glycemic indices and MetS without limitation in time of publication and language were included and critically reviewed by two independent experts. Random-effects meta-analysis was used to estimate the effect sizes., Data Analysis: Among 843 documents retrieved from literature search, 23 studies met the inclusion criteria for systematic review, and 18 studies were eligible for meta-analysis. Random-effects meta-analysis showed that the association of DDS with obesity, abdominal obesity, overweight, body mass index, MetS, diabetes, blood pressure, and lipid profile (TC, LDL, HDL) was not statistically significant. On the other hand, the association of DDS and TG was statistically significant (SMD: - 0.23, 95% CI - 0.45, - 0.01)., Conclusions: Our findings revealed that there was no significant association between DDS and cardio-metabolic risk factors. Reassessment of the overall DDS tool as a criterion of diet quality and production of new and valid DDS standard tools is highly desirable. More high-quality studies are also needed to confirm the findings of this study., Study Registration: This study is registered as PROSPERO CRD42020157127., Level of Evidence: Level I, systematic reviews and meta-analyses., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Purpose: To evaluate the superficial vascular density of the optic nerve head in different stages of pseudoexfoliation disease using optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional study, 57 normal eyes, 41 eyes with pseudoexfoliation syndrome (PXS), 82 eyes with pseudoexfoliation glaucoma (PXG) and 27 non-glaucomatous fellow eyes of PXG (NL-PXG) that had OCTA were included. Circumpapillary RNFL (cpRNFL) thickness and circumpapillary capillary density (cpCD) were compared among the groups after adjusting for confounders using linear-mixed model., Results: PXG eyes had thinner global RNFL and lower cpCD (74.2±14.3 µm and 36.7±10.0%) than control (103.3±8.6 µm and 52.5±2.3%), PXS (96.8±8.8 µm and 51.5±2.3%), and NL-PXG eyes (96.3±11.1 µm and 50.1±3.9%) (p<0.001). After adjustment for age, gender and signal strength index, global cpRNFL thickness was comparable among control, PXS and NL-PXG. NL-PXG had the lowest cpCD (p=0.045) and sectoral cpCD compared to PXS and control eyes. Although cpCD was comparable between control and PXS (p=0.425) eyes, sectoral differences (p=0.009 and 0.004, for inferonasal and temporal-inferior cpCD, respectively) were detectable between the two groups. AUROC for differentiating NL-PXG eyes from normal were better for cpCD (0.78) compared to cpRNLF (0.69)., Conclusions: OCTA can detect reduced capillary density before significant changes in cpRNFL in fellow eyes of PXG patients. This can enable earlier detection of glaucomatous loss in pseudoexfoliation disease and enhance management of the disease., Competing Interests: Competing interests: Weinreb: Aerie Pharmaceuticals (C), Alcon (C), Allergan (C), Bausch & Lomb (C), Eyenovia (C), Unity (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Genentech (F), Konan (F), OptoVue (F), Topcon (F), Optos (F), Centervue (F). Rao HL: Santen (C), Carl Zeiss Meditec (C), Allergan (C). Others: none., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The increased prevalence of metabolic dyslipidemia (MD) and its association with a variety of disorders raised a lot of attention to its management. Caveolin 1 (CAV1) the key protein in the caval structure of plasma membranes is many cell types that play an important role in its function. (CAV1) is a known gene associated with obesity. Today, a novel diet recognized as the Mediterranean and Mediterranean-DASH Intervention for Neurodegenerative Delay diet (MIND) is reported to have a positive effect on overall health. Hence, we aimed to investigate the interactions between CAV1 polymorphism and MIND diet on the MD in overweight and obese patients., Results: Remarkably, there was a significant interaction between the MIND diet and CAV1 rs3807992 for dyslipidemia (β = - 0.25 ± 132, P = 0.05) in the crude model. Whereby, subjects with dominant alleles had a lower risk of dyslipidemia and risk allele carriers with higher adherence to the MIND diet may exhibit the lower dyslipidemia. This study presented the CAV1 gene as a possible genetic marker in recognizing people at higher risks for metabolic diseases. It also indicated that using the MIND diet may help in improving dyslipidemia through providing a probable interaction with CAV1 rs3807992 polymorphism., (© 2021. The Author(s).)

Background: Obesity is associated to dietary factors, mostly those related to nutrients and energy. The aim of the present study was to explore the interaction of dietary patterns and the age of onset of obesity on anthropometric indicators among Iranian women., Methods: A cross-sectional study was conducted on 266 obese and overweight Iranian females who were between 18 and 48 years old with BMI>25 (kg/m 2 ).Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire (FFQ) was calculated for all participants. Three dietary patterns principle component analysis (PCA) was used as a factor score for each of the three dietary patterns. Anthropometric evaluation was performed for participants., Results: A significant inverse relationship (p < 0.05) was found between DASH score and the age of onset of obesity under 18 years old, fat-free mass, and weight in women. Conversely it was observed that higher weight and body mass index (BMI) were associated with the age of onset of obesity under 18 years old compared to participants more than 18 years old (p < 0.05). Moreover, it was observed that higher adherence to DASH dietary pattern has a positive correlation with lower BMI (P = 0.07), visceral fat (P = 0.03), and body fat mass (BFM) (P = 0.07). A significant interaction between DASH pattern and onset obesity under 18 years old on weight observed in women (P = 0.001)., Conclusions: This study suggested that DASH dietary pattern is a good choice for weight management and a healthier body in general and may decrease the development of obesity-related diseases. It was suggested that higher adherence to DASH pattern may reduce the obesity markers and decrease the development of obesity-related diseases., Competing Interests: Declaration of competing interest All authors declared that they have no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background: To evaluate changes in circumpapillary vessel density (cpVD) and retinal nerve fibre layer (cpRNFL) thickness after a successfully treated episode of acute primary angle closure (APAC) and to identify factors associated with glaucoma progression in these eyes., Methods: Twenty-six patients successfully treated for a unilateral episode of APAC were included in this prospective study. Optical coherence tomography (OCT) cpRNFL thickness and OCT angiography (OCTA) cpVD were compared between 2 and 8 months after treatment. Multiple logistic regression analysis was conducted to identify factors that influenced cpRNFL outcome., Results: cpRNFL thicknesses was thinner in the affected eye (94.0 µm (95% CI: 87.3 to 100.8)) than in the unaffected fellow eye (103.1 µm (99.3 to 106.9)) at 2 months (p=0.039). The cpRNFL thickness of the affected eye decreased 8 months after remission (89.5 µm (84 to 95)), but was unchanged in the unaffected eye. Although cpVD was significantly lower (p=0.001) in APAC eyes 2 months after treatment (56.7% (53.8 to 59.7)) compared with fellow eyes (62.9% (61.4 to 64.4)), there was no significant change in cpVD of the affected eye between 2 and 8 months. In the multivariable analysis, the only factor that was associated with cpRNFL progression was lower cpVD at 2 months after APAC remission (OR=1.79, p=0.036)., Conclusion: Early reductions of the vessel density and long-term decrease in cpRNFL thickness were observed during the first 8 months after an APAC attack. A lower vessel density at 2 months was the best predictor of conversion to an abnormal cpRNFL thickness. Glaucomatous progression should be suspected in eyes with lower vessel density even after remission of an episode of APAC., Competing Interests: Competing interests: RNW: Aerie Pharmaceuticals (C), Alcon (C), Allergan (C), Bausch & Lomb (C), Eyenovia (C), Unity (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Genentech (F), Konan (F), OptoVue (F), Topcon (F), Optos (F), Centervue (F). HLR: Santen (C), Carl Zeiss Meditec (C), Allergan (C)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To examine the relationship between dietary patterns and inflammatory markers including serum high sensitivity C-reactive protein (hs-CRP) and interleukin 17A (IL-17A) in females., Methods: In the present cross-sectional study in female teachers living in Yazd, central Iran, data on anthropometric measurements and general information were gathered. A food frequency questionnaire was completed by participants and then, subjects were invited to give blood samples. Major dietary patterns were derived using principal component analysis and serum inflammatory markers were compared according to quintiles of dietary patterns scores., Results: In total, 320 subjects aged 40.38 ± 8.08 years were included. Three dietary patterns were derived: (i) 'traditional' with a high intake of poultry, salt, eggs, other vegetables and red meat; (ii) 'vegetables and fruits' with a higher intake of tomatoes, yoghurt drinks, green leafy vegetables, dried fruits, fruits, other vegetables and organ meats and (iii) 'dairy and saturated fat' with a high loading of high-fat dairy products, butter, low-fat dairy, margarine, eggs, other vegetables and green leafy vegetables. Participants in the highest quintile of the 'vegetables and fruits' dietary pattern had significantly lower serum hs-CRP levels compared to those in the lowest quintile (3.6 ± 0.4 mg/L vs 2.6 ± 0.4 mg/L, respectively; P < 0.05). None of the dietary patterns were associated with circulating IL-17 levels., Conclusions: Higher consumption of fruits and vegetables is inversely associated with serum hs-CRP but not IL-17 levels. Studies investigating the dietary patterns in association with IL-17 in other populations are recommended., (© 2018 Dietitians Association of Australia.)

Purpose: To evaluate the changes in circumpapillary vessel density (cpVD) and retinal nerve fiber layer (RNFL) thickness after an acute primary angle closure (APAC) episode., Methods: Twenty-eight patients (28 pair of eyes) with unilateral APAC and 39 normal subjects (64 eyes) were included in this prospective, observational study. cpVD as measured by optical coherence tomography angiography and RNFL thickness as measured by spectral-domain optical coherence tomography were compared at 6 weeks after an APAC episode between affected, unaffected, and normal eyes. cpVD and RNFL thickness at 1 week and 6 weeks after APAC were also compared in APAC eyes in qualified images., Results: At 6 weeks, cpVD was significantly lower in APAC eyes (57.3% ± 6.8%), compared to fellow eyes (63.1% ± 3.5%) and control eyes (63.6% ± 3.4%) (P < 0.001). There was diffuse microvascular dropout with greater vessel density loss in the superonasal sector. APAC eyes had thinner RNFL globally and in each sector (except temporal and nasal sectors) than in fellow and normal eyes at 6 weeks. cpVD in the affected eyes was significantly greater at 1 week (56.3% ± 5.3%) than values at 6 weeks (53.5% ± 7%) (P = 0.003) but less than cpVD in the fellow eyes (62.4% ± 5.0%) (P < 0.001). RNFL thickness for the APAC eyes at 1 week (120.6 ± 18.0 μm) was greater than the analogous values for affected eyes (90.1 ± 13.2 μm; P = 0.037) and fellow eyes at 6 weeks (102.5 ± 5.7 μm; P = 0.001)., Conclusions: Vessel density decreased over 6 weeks after an APAC episode compared with the contralateral unaffected eyes. In contrast, there was an initial increase in RNFL thickness that was followed by a subsequent decrease.

Background: Studies on the association between a priori dietary patterns and serum highly sensitive C-reactive protein (hs-CRP) have led to inconsistent results, and we are not aware of any study on interleukin 17A (IL-17A) as an inflammatory marker associated with autoimmune diseases., Objective: The present study aimed to investigate the association between Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean dietary patterns with circulating hs-CRP and IL-17A levels., Methods: In this cross-sectional study, female teachers (aged 20-50 years) who lived in Yazd, Iran, were randomly selected from elementary, guidance, and high schools from September 2015 to February 2016. Anthropometric data, as well as general information and dietary food intakes, were gathered, and each participant gave 1 blood sample. Participants were categorized into tertiles based on the DASH and the Mediterranean diet calculated scores. The associations between the dietary patterns and serum hs-CRP and IL-17A levels were assessed in the crude and multivariable models. In total, 320 female teachers aged 40.38 (8.08) years were included., Results: The DASH diet was associated with lower serum hs-CRP levels in the crude ( P = .05) and the fully adjusted models ( P = .02), while it was not significantly associated with IL-17A levels. The participants with the highest adherence to the Mediterranean diet had significantly lower circulating IL-17A levels ( P = .04) even controlling for all confounders ( P = .02); however, there was not a significant relationship between this diet and hs-CRP levels., Conclusions: The DASH and the Mediterranean dietary patterns might be differently associated with inflammatory markers. Further prospective studies are recommended to confirm our results.

Purpose: To compare outcomes of phacoemulsification combined with viscocanalostomy, endocyclophotocoagulation (ECP), or ab interno trabulectomy for intraocular pressure (IOP) control and safety in eyes with open-angle glaucoma and visually significant cataract., Setting: Farabi Eye Hospital, Tehran, Iran., Design: Retrospective case series., Methods: Medical records of patients who had combined surgery and were followed for at least 1 year were reviewed. Complete success, postoperative IOP, number of medications at each visit, and complications were evaluated and compared before and after adjustments for confounders., Results: Forty-six eyes had combined phacoviscocanalostomy, 35 had phaco-ECP, and 28 eyes phaco-ab interno trabulectomy. The groups were matched for baseline IOP (P = .24). At the final follow-up (mean 17.2 months ± 5.5 [SD]), the phacoviscocanalostomy group had the lowest mean IOP (13.5 ± 4.7 mm Hg, 29% decrease) (P = .01). There was no significant difference in the final IOP between phaco-ECP and phaco-ab interno trabulectomy (16.4 ± 3.9 mm Hg, 20% decrease versus 15.8 ± 4.2 mm Hg, 15% decrease) (P = .88). The reduction in the number of medications was greater with phacoviscocanalostomy (77%) than with phaco-ECP (40%) and phaco-ab interno trabulectomy (44%) (P = .01). Phacoemulsification-ab interno trabulectomy had the fewest complications. Intraocular pressure spikes were more frequent in the phaco-ECP group (20%) than in the other groups (4%) (P = .05)., Conclusions: All procedures significantly lowered IOP. Phacoemulsification-ab interno trabulectomy resulted in fewest complications and phacoviscocanalostomy led to the largest IOP drop and largest reduction of medications., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10 -14 ) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10 -8 ). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Purpose: To evaluate different mechanisms of primary angle closure (PAC) and to quantify anterior chamber (AC) parameters in different subtypes of angle closure disease using anterior segment optical coherence tomography (AS-OCT)., Methods: In this prospective study, 115 eyes of 115 patients with angle closure disease were included and categorized into three groups: 1) fellow eyes of acute angle closure (AAC; 40 eyes); 2) primary angle closure glaucoma (PACG; 39 eyes); and 3) primary angle closure suspect (PACS; 36 eyes). Complete ophthalmic examination including gonioscopy, A-scan biometry, and AS-OCT were performed. Based on the AS-OCT images, 4 mechanisms of PAC including pupillary block, plateau iris configuration, thick peripheral iris roll (PIR), and exaggerated lens vault were evaluated. Angle, AC, and lens parameter variables were also evaluated among the three subtypes., Results: There was a statistically significant difference in the mechanism of angle closure among the three groups (p = 0.03). While the majority of fellow eyes of AAC and of PACS eyes had pupillary block mechanism (77.5% and 75%, respectively), only 48.7% of PACG eyes had dominant pupillary block mechanism (p = 0.03). The percentage of exaggerated lens vault and plateau iris mechanisms was higher in PACG eyes (25.5% and 15.4%, respectively). Fellow eyes of AAC had the shallowest AC (p = 0.01), greater iris curvature (p = 0.01), and lens vault (p = 0.02) than PACS and PACG eyes. Iris thickness was not significantly different among the three groups (p = 0.45)., Conclusion: Using AS-OCT, we found that there was a statistically significant difference in the underlying PAC mechanisms and quantitative AC parameters among the three subtypes of angle closure disease.

Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models.

Aim: To assess lens thickness measurements with anterior segment-optical coherence tomography (AS-OCT) in comparison with A-scan ultrasonography (A-scan US)., Methods: There were 218 adult subjects (218 eyes) aged 59.2±9.2y enrolled in this prospective cross-sectional study. Forty-three eyes had open angles and 175 eyes had narrow angles. Routine ophthalmic exam was performed and nuclear opacity was graded using the Lens Opacities Classification System III (LOCS III). Lens thickness was measured by AS-OCT (Visante OCT, Carl Zeiss Meditec, Dublin, CA, USA). The highest quality image was selected for each eye and lens thickness was calculated using ImageJ software. Lens thickness was also measured by A-scan US., Results: Interclass correlations showed a value of 99.7% for intra-visit measurements and 95.3% for inter-visit measurements. The mean lens thickness measured by AS-OCT was not significantly different from that of A-scan US (4.861±0.404 vs 4.866±0.351 mm, P=0.74). Lens thickness values obtained from the two instruments were highly correlated overall (Pearson correlation coefficient=0.81, P<0.001), and in all LOCS III specific subgroups except in grade 5 of nuclear opacity. Bland-Altman analysis revealed a 95% limit of agreement from -0.45 to 0.46 mm. Lens thickness difference between the two instruments became smaller as the lens thickness increased and AS-OCT yielded smaller values than A-scan US in thicker lens (β=-0.29, P<0.001)., Conclusion: AS-OCT-derived lens thickness measurement is valid and comparable to the results obtained by A-scan US. It can be used as a reliable noncontact method for measuring lens thickness in adults with or without significant cataract.

Purpose: To compare the effect of phacoemulsification (Phaco) versus combined phacoemulsification and viscogonioplasty (Phaco-VGP) on long-term intraocular pressure (IOP) in primary angle-closure glaucoma (PACG)., Methods: In this prospective randomized clinical trial, 92 eyes of 82 patients with PACG and coexisting cataract were randomized to undergo Phaco alone (46 eyes) or Phaco-VGP (45 eyes) and completed the trial. Anterior segment optical coherence tomography was performed preoperatively and at 1 year after surgery. Main outcome measures were IOP and the number of IOP-lowering medications., Results: Phaco alone reduced the mean IOP from a preoperative level of 22.3±6.3 to 14.0±3.7 mm Hg at 12 months after surgery (P<0.001). Phaco-VGP reduced the mean IOP from a preoperative level of 23.3±7.3 to 14.5±2.5 mm Hg (P<0.001). There were no statistically significant differences between the 2 groups in IOP and number of medications at all follow-up times. Trabecular-iris space-area measured by anterior segment optical coherence tomography increased significantly after Phaco alone and Phaco-VGP. The amount of the increase was higher in the Phaco-VGP. Although peripheral anterior synechiae (PAS) extent decreased significantly by Phaco alone, Phaco-VGP resulted in significantly greater reduction in PAS extent (P=0.004). The only variables that predicted change in IOP in the whole group were preoperative IOP (β=-0.891, P<0.001) and female sex (β=2.754, P=0.02)., Conclusions: Phaco alone and Phaco-VGP resulted in widening of the drainage angle, reduction of IOP, and PAS extent in PACG eyes. Phaco-VGP resulted in significantly more reduction of PAS and more opening of angle. However, it seems that additional VGP has no significant effect on long-term IOP.

This perspective commentary summarized the stroke pathophysiology evolution, especially the focus in the past on neuroprotection and neurovascular protection and highlighted the newer term for stroke pathophysiology: vascular neural network. Emphasis is on the role of venules and veins after an acute stroke and as potential treatment targets. Vein drainage may contribute to the acute phase of brain edema and the outcomes of stroke patients.

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Medical gases are pharmaceutical molecules which offer solutions to a wide array of medical needs. This can range from use in burn and stroke victims to hypoxia therapy in children. More specifically however, gases such as oxygen, helium, xenon, and hydrogen have recently come under increased exploration for their potential theraputic use with various brain disease states including hypoxia-ischemia, cerebral hemorrhages, and traumatic brain injuries. As a result, this article will review the various advances in medical gas research and discuss the potential therapeutic applications and mechanisms with regards to the field of neurobiology.

Among many proinflammatory cytokines, interleukin-1β (IL-1β) is considered a key mediator of neuronal injury. However, in order to become activated, it must be processed and cleaved by a caspase-1 enzyme. In this study, we tested the neuroprotective effect of Ac-YVAD-CMK, a known selective caspase-1 inhibitor, in a mouse model of intracerebral hemorrhage (ICH). Sixty-six adult male CD-1 mice were subjected to collagenase-induced ICH. Ac-YVAD-CMK or vehicle was administered into the left lateral ventricle 20 min before ICH modeling. Brain edema and neurological functions were assessed at 24 and 72 h after the surgery. Expression of IL-1β, phosphorylated JNK, tight junction protein zona occludens 1 (ZO-1), and matrix metalloproteinase-9 (MMP-9) were measured by Western blot along with MMP-9 activity measured by zymography at 24 h after ICH. At 24 h after ICH, Ac-YVAD-CMK treatment significantly reduced brain edema and improved neurological functions. The neuroprotection was associated with downregulation of IL-1β, JNK, MMP-9, and an inhibition of ZO-1 degradation in brain. We conclude that Ac-YVAD-CMK protects the brain against ICH-induced injury, and the neuroprotective effect may result from anti-inflammation-induced blood-brain barrier protection.

Purpose: To examine the mtDNA control regions in normal and age-related macular degeneration (AMD) retinas. To identify the mtDNA variations associated with AMD., Methods: Retinas from 10 normal and 11 AMD globes were isolated and analyzed for mtDNA rearrangements by long extension-polymerase chain reaction (LX-PCR) and for the nature and frequency of single-nucleotide polymorphisms (SNPs) in the mtDNA control region by direct sequencing. Blood DNA was extracted from 99 AMD and 92 age-matched control subjects. The sequence variations that define haplogroups H, I, J, K, T, V, X, and U were characterized by PCR, restriction enzyme digestion, and/or sequencing., Results: LX-PCR of retinal mtDNAs revealed high levels of rearrangements in the patients with AMD and the control subjects, consistent with the decline in mitochondrial function with age. However, the AMD retinas had higher oxidized DNA levels and a higher number of SNPs than controls (P = 0.02). The control region SNPs T16126C and A73G, commonly found in haplogroups J and T, were more frequent in the AMD retinas than in normal retinas. The associations between AMD and haplogroups J and T were confirmed and extended by analysis of blood DNA. SNPs at position a T16126C (J; odds ratio [OR] = 3.66), T16126C+G13368A (JT; OR = 10.27), A4917G+A73G (T4; OR = 5), and T3197C+A12308G (U5; OR = infinity), were all strongly associated with AMD., Conclusions: AMD retinas exhibited increased mtDNA control region SNPs compared to normal retinas. This correlated with an increased frequency of mtDNA SNPs associated with haplogroups J, T and U in patients with AMD. These results implicate mitochondrial alterations in the etiology of AMD.

Purpose: To determine the association between complement factor H (CFH) polymorphism T1277C (tyrosine-402 --> histidine-402) and phenotypic variations of age-related macular degeneration (AMD)., Design: Cross-sectional observational study., Participants: Subjects with dry or wet AMD and a control population consisting of age-matched non-AMD subjects from 2 clinical facilities examined during the period January 1, 1999 through December 31, 2002., Methods: Total DNA isolated from the leukocytes of 66 AMD subjects and 58 age-matched control subjects was studied. The CFH gene was amplified by polymerase chain reaction and analyzed by Nla III restriction fragment length analysis., Main Outcome Measures: Incidence of CHF polymorphism with the occurrence of AMD., Results: Among the AMD patients, 15 had dry and 51 had wet AMD. For the CFH gene, the T1277C variant showed the genotype distribution as CC, TC, and TT. There was a strong association between homozygous C and AMD compared with the control population (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.32-8.74; P = 0.0053). Furthermore, dry AMD had a stronger association (OR, 8.32; 95% CI, 2.30-30.11; P = 0.001) than wet AMD (OR, 2.49; 95% CI, 0.90-6.84; P = 0.039) compared with the control population. Homozygous T was more prevalent in the control subjects compared with AMD patients (OR, 5; 95% CI, 2.18-11.43; P = 0.00005)., Conclusions: Complement factor H polymorphism T1277C (tyrosine-402 --> histidine-402) is strongly associated with both dry and wet AMD and points to a possible role for inflammation in the pathogenesis of AMD.

The double staining of S-100 beta and choline acetyltransferase (ChAT) revealed that S-100 beta immunoreactivity was localized in most, but not in all, cholinergic neurones in the somatomotor nuclei of the cranial nerves and in the ambiguus nucleus. S-100 beta was present in almost all cholinergic neurones in the brain stem reticular, red, vestibular (excluding medial), mesencephalic trigeminal and cerebellar nuclei. However, S-100 beta immunoreactivity was lacking in cholinergic neurones in the parabrachial complex, the dorsal motor nucleus of the vagal nerve and most sensory nuclei. No S-100 beta-positive neurones lacked ChAT immunoreactivity. Taken together with the fact that the vulnerability of motoneurones to axotomy is markedly reduced in the first 3 postnatal weeks, during which period neuronal S-100 beta appears and increases, a possible effect of S-100 beta on the survival of cholinergic motoneurones may be suggested.