Fire shapes fungal guild diversity and composition through direct and indirect pathways.

Fire has shaped global ecosystems for millennia by directly killing organisms and indirectly altering habitats and resources. All terrestrial ecosystems, including fire-prone ecosystems, rely on soil-inhabiting fungi, where they play vital roles in ecological processes. Yet our understanding of how fire regimes influence soil fungi remains limited and our knowledge of these interactions in semiarid landscapes is virtually absent. We collected soil samples and vegetation measurements from sites across a gradient in time-since-fire ages (0-75 years-since-fire) and fire frequency (burnt 0-5 times during the recent 29-year period) in a semiarid heathland of south-eastern Australia. We characterized fungal communities using ITS amplicon-sequencing and assigned fungi taxonomically to trophic guilds. We used structural equation models to examine direct, indirect and total effects of time-since-fire and fire frequency on total fungal, ectomycorrhizal, saprotrophic and pathogenic richness. We used multivariate analyses to investigate how total fungal, ectomycorrhizal, saprotrophic and pathogenic species composition differed between post-fire successional stages and fire frequency classes. Time-since-fire was an important driver of saprotrophic richness; directly, saprotrophic richness increased with time-since-fire, and indirectly, saprotrophic richness declined with time-since-fire (resulting in a positive total effect), mediated through the impact of fire on substrates. Frequently burnt sites had lower numbers of saprotrophic and pathogenic species. Post-fire successional stages and fire frequency classes were characterized by distinct fungal communities, with large differences in ectomycorrhizal species composition. Understanding the complex responses of fungal communities to fire can be improved by exploring how the effects of fire flow through ecosystems. Diverse fire histories may be important for maintaining the functional diversity of fungi in semiarid regions.

On-Body Piezoelectric Energy Harvesters through Innovative Designs and Conformable Structures.

Recent advancements in wearable technology have improved lifestyle and medical practices, enabling personalized care ranging from fitness tracking, to real-time health monitoring, to predictive sensing. Wearable devices serve as an interface between humans and technology; however, this integration is far from seamless. These devices face various limitations such as size, biocompatibility, and battery constraints wherein batteries are bulky, are expensive, and require regular replacement. On-body energy harvesting presents a promising alternative to battery power by utilizing the human body's continuous generation of energy. This review paper begins with an investigation of contemporary energy harvesting methods, with a deep focus on piezoelectricity. We then highlight the materials, configurations, and structures of such methods for self-powered devices. Here, we propose a novel combination of thin-film composites, kirigami patterns, and auxetic structures to lay the groundwork for an integrated piezoelectric system to monitor and sense. This approach has the potential to maximize energy output by amplifying the piezoelectric effect and manipulating the strain distribution. As a departure from bulky, rigid device design, we explore compositions and microfabrication processes for conformable energy harvesters. We conclude by discussing the limitations of these harvesters and future directions that expand upon current applications for wearable technology. Further exploration of materials, configurations, and structures introduce interdisciplinary applications for such integrated systems. Considering these factors can revolutionize the production and consumption of energy as wearable technology becomes increasingly prevalent in everyday life.

Decoding of facial strains via conformable piezoelectric interfaces.

Devices that facilitate nonverbal communication typically require high computational loads or have rigid and bulky form factors that are unsuitable for use on the face or on other curvilinear body surfaces. Here, we report the design and pilot testing of an integrated system for decoding facial strains and for predicting facial kinematics. The system consists of mass-manufacturable, conformable piezoelectric thin films for strain mapping; multiphysics modelling for analysing the nonlinear mechanical interactions between the conformable device and the epidermis; and three-dimensional digital image correlation for reconstructing soft-tissue surfaces under dynamic deformations as well as for informing device design and placement. In healthy individuals and in patients with amyotrophic lateral sclerosis, we show that the piezoelectric thin films, coupled with algorithms for the real-time detection and classification of distinct skin-deformation signatures, enable the reliable decoding of facial movements. The integrated system could be adapted for use in clinical settings as a nonverbal communication technology or for use in the monitoring of neuromuscular conditions.

Selective laser trabeculoplasty versus topical medication as initial glaucoma treatment: the glaucoma initial treatment study randomised clinical trial.

BACKGROUND/AIMS: To determine if selective laser trabeculoplasty (SLT) is superior to topical medication as a first-line treatment for glaucoma on quality of life (QoL) and clinical outcomes. METHODS: In this international, longitudinal, multisite randomised controlled trial, treatment naïve mild-to-moderate primary open angle or exfoliation glaucoma patients were randomised 1:1 to SLT or topical medication. Glaucoma-specific QoL (primary outcome) was measured using the Glaucoma Outcomes Assessment Tool (GOAT; 342 items, 12 domains). Secondary outcomes included rate of successful intraocular pressure (IOP) reduction (>25% reduction from baseline) and presence of ocular surface disease including conjunctival hyperaemia and eyelid erythema. Our intention-to-treat analysis was performed at months 12 and 24. RESULTS: Of 167 enrolled patients, 83 and 84 were randomised to SLT and topical medication, respectively; and 145 (n=75 SLT, n=70 medication) completed 24-month follow-up. While both treatment arms achieved significant within-group gains in GOAT outcomes at both endpoints, SLT patients reported a greater between-group improvement in 'social well-being' compared with medication patients (mean±SE=0.28±0.13; p=0.034) at 24 months. At month 24, the rate of successful IOP reduction was 18.6% (95% CI 3.0% to 34.3%, p=0.022) higher (absolute difference) in the medication compared with SLT group. More individuals in the medication group had conjunctival hyperaemia and eyelid erythema compared with SLT at 24 months. CONCLUSION: Overall, we did not find evidence that SLT was superior to medication in improving glaucoma-specific QoL. While we found superior IOP reduction in the medication arm, eyelid erythema and conjunctival hyperaemia were more prevalent in these patients compared with the SLT group. TRIAL REGISTRATION: ACTRN12611000720910.

Precarious manhood and muscularity: Effects of threatening men's masculinity on reported strength and muscle dissatisfaction.

The precarious manhood perspective proposes that men respond with aggression when they experience threats to their masculinity. Consistent with this view, we hypothesized that men would represent themselves as stronger and more formidable after their masculinity was threatened. A recent study, however, found that men reported less physical strength when threatened (Hunt, Gonsalkorale, & Murray, 2013). In the current two studies (Ns=193; 450), men were given false feedback about whether they were substantially less masculine (masculinity threatened) or more masculine than average (masculinity reassured). Men reported how much weight they could curl, how many push-ups they could complete, and/or measures of satisfaction with muscularity. In most analyses, threatened men reported greater strength than reassured men. Effects of masculinity threat on muscle dissatisfaction varied by outcome measure. The studies highlight the importance of replication studies, and of using experimental approaches to understand connections between precarious manhood and male body image.

Raising the issue of DNAR orders in vascular surgery patients.

The Tracey Report has recently raised the status of Do Not Attempt Cardio Pulmonary Resuscitation (DNACPR) orders in the hospital setting.[1] Guidelines are in place both nationally and locally to provide advice to clinicians on when to discuss DNACPR, and the approach to be taken. There was concern that on a busy regional vascular surgery unit, discussion of resuscitation status was not regular practice. Consequently, some patients were at risk of being inappropriately resuscitated, particularly out of hours. The North Bristol Somerset and Gloucester DNAR decision tree[2] was the tool used to decide whether a patient should have a documented discussion and/or a DNACPR form completed. We correlated the outcome of the decision tree with the presence of a DNACPR form or documented resuscitation discussion. Baseline measurements from all vascular inpatients on the vascular surgery unit demonstrated that only 27% had a DNACPR form or documented discussion in concordance with the DNACPR Decision Tree outcome. The aim of this project was to increase the proportion of patients with concordance of the DNACPR decision tree outcome with documented discussion or DNACPR form. The following three simple interventions raised concordance from 27% to 64% of patients on the vascular surgery unit. 1. Including resuscitation status of each patient as a column in the doctors daily handover. 2. Posters in staff only areas to highlight the meaning of DNACPR and raise awareness of the DNACPR decision tree. 3. Educational meeting surrounding DNACPR with the vascular surgery consultants, led by a care of the elderly consultant . This project has highlighted how raising awareness around DNACPR increases discussion amongst the clinical team surrounding resuscitation status of a patient. Consequently, this enables discussion to be had with patient and their family.

Comparing the effectiveness of selective laser trabeculoplasty with topical medication as initial treatment (the Glaucoma Initial Treatment Study): study protocol for a randomised controlled trial.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world. Estimated to affect 60 million people worldwide, this figure is expected to rise to 80 million by 2020. Untreated, glaucoma leads to visual decay and eventually to blindness, and can significantly reduce quality of life. First-line treatment in patients with primary open-angle glaucoma and exfoliative glaucoma is topical medical therapy with ocular hypotensives as eye drops. However, eye drops have several disadvantages including cost, possible local and systemic side effects, and adherence and perseverance issues. Randomised controlled trials have demonstrated that selective laser trabeculoplasty is equally as effective in lowering intraocular pressure as eye drops. However, the impact of these two treatment modalities from the patient and economic perspectives has not been adequately determined. Thus, it remains unclear whether topical medical therapy or selective laser trabeculoplasty should be recommended as first-line treatment for glaucoma. METHODS/DESIGN: This protocol describes an international, multi-centre, randomised controlled trial to determine the optimum first-line therapy for people with primary open-angle glaucoma and exfoliative glaucoma. This study will compare the effect of selective laser trabeculoplasty and topical medication with respect to patients' generic and glaucoma-specific quality of life. The trial will also provide a detailed cost-effectiveness analysis and compare the clinical effectiveness with respect to the degree of intraocular pressure lowering and rates of treatment failure. Research coordinators in each centre will identify and recruit previously untreated patients with primary open-angle glaucoma and exfoliative glaucoma. Those who meet the eligibility criteria will be invited to enter a randomised controlled trial with either selective laser trabeculoplasty or topical ocular hypotensive therapy, according to a stepped regimen. Outcome assessment will be measured at 6 weeks and at 6, 12, and 24 months post-treatment. Regular clinic follow-ups will continue as clinically indicated between study outcome visits. DISCUSSION: The Glaucoma Initial Treatment Study is the first multi-centred RCT to determine the optimum first-line therapy for people with glaucoma. Our trial will have an unprecedented capacity to meaningfully transform the treatment and management of glaucoma in Australia and overseas. TRIAL REGISTRATION: ACTRN12611000720910; Date registered: 11 July 2011.

Hypertensive retinopathy: comparing the Keith-Wagener-Barker to a simplified classification.

PURPOSE: This study assessed the interobserver and intraobserver grading reliability of the Keith-Wagener-Barker (KWB) system to the proposed Mitchell-Wong 'simplified' three-grade classification for hypertensive retinopathy. METHODS: Digital retinal images of normal and hypertensive human fundii (n = 50 per group) were randomly graded by an optometrist and an ophthalmologist using the two systems. Interobserver agreement was compared to a 'gold standard' research grader. Intraobserver agreement was assessed through a repeat grading after 6 months. Cohen's kappa coefficients were used to assess the degree of agreement. RESULTS: Both clinicians demonstrated a good level of agreement with the KWB and simplified classification compared with a 'gold standard' grader; there was no significant difference in the level of agreement for either of the two classification methods for either observer. The simplified classification was found to be equally as efficacious as the KWB system with respect to interobserver and intraobserver agreement for both practitioners. CONCLUSION: These findings indicate that the simplified classification of hypertensive retinopathy is both reliable and repeatable. The advantage of the simplified method over the KWB system in correlating retinal microvascular signs to incident cardiovascular risk supports its adoption in clinical practice.

Inhibition of phosphodiesterases leads to prevention of the mitochondrial permeability transition pore opening and reperfusion injury in cardiac H9c2 cells.

PURPOSE: We tested if inhibition of phosphodiesterases (PDEs) with IBMX (1-methyl-3-isobutylxanthine) can modulate the mitochondrial permeability transition pore (mPTP) opening by inactivating glycogen synthase kinase 3ß (GSK-3ß). METHODS: H9c2 cells were exposed to 600 µM H(2)O(2) for 20 min to cause the mPTP opening. Mitochondrial membrane potential (ΔΨm) was assessed by imaging cells loaded with tetramethylrhodamine ethyl ester (TMRE). Cell viability was measured with propidium iodide (PI) fluorometry using a fluorescence reader. Ischemia/reperfusion injury was induced by exposing cells to ischemic solution for 90 min followed by 30 min of reperfusion. RESULTS: IBMX reduced loss of ΔΨm caused by H(2)O(2), indicating that inhibition of PDEs can prevent the mPTP opening. However, IBMX could not inhibit the pore opening in cells transfected with the constitutively active GSK-3ß (GSK-3ß-S9A) mutant, suggesting a critical role of GSK-3ß in the action of IBMX. IBMX also reduced reperfusion injury in a GSK-3ß dependent manner. In support, IBMX increased GSK-3ß phosphorylation at Ser(9), an effect that was reversed by both the PKA inhibitor H89 and the PKG inhibitor KT5823. In support, IBMX activated both PKA and PKG. IBMX failed to prevent the loss of ΔΨm in the presence of H89 or PKA siRNA. Similarly, both KT5823 and PKG siRNA reversed the protective effect of IBMX. CONCLUSION: Inhibition of PDEs prevents the mPTP opening by inactivating GSK-3ß through PKA and PKG. GSK-3ß is a common downstream target of PKA and PKG. Inhibition of PDEs may be a useful approach to prevent reperfusion injury.

Association of retinal vessel calibre with diabetic retinopathy in an urban Australian indigenous population.

PURPOSE: To assess the relationship of retinal vessel diameter and diabetic retinopathy (DR) in a subgroup of participants recruited through the Darwin Region Urban Indigenous Diabetes study. METHODS: Participants were examined as part of the Darwin Region Urban Indigenous Diabetes study. All participants with gradable fundus photographs were included in the current analysis. Assessment of retinal vascular diameter, including arteriolar diameter (central retinal arteriolar equivalent) and venular diameter (central retinal venular equivalent), was undertaken using a semi-automated retinal vascular imaging program. DR was graded according to the modified Early Treatment DR Study scale. RESULTS: A total of 110 participants, 25 men and 85 women, with a mean age of 50.8 years were included in the analysis. The odds ratio for having DR for each standard deviation increase in central retinal venular equivalent was as high as 1.62 (95% confidence intervals 0.94, 2.80); however, this did not reach statistical significance (P = 0.08). Moreover, individuals with severe non-proliferative DR and proliferative DR were found to have narrower arteriolar diameters compared with those with no DR, but this was not statistically significant (-8.1 microm, 95% confidence intervals, -39.3 microm, 23.1 microm; P = 0.612). CONCLUSION: Our data indicate a trend for narrower arteriole diameter and wider venular diameter with DR in this high-risk ethnic group, which concurs with overall trends seen in non-indigenous populations.

Natural history of central retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear. METHODS: Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO; an untreated control arm was included. RESULTS: Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. CONCLUSIONS: Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO.

Natural history of branch retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse. METHODS: English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators. RESULTS: Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels. CONCLUSIONS: Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon.

The critical role of intracellular zinc in adenosine A(2) receptor activation induced cardioprotection against reperfusion injury.

Exogenous zinc can protect cardiac cells from reperfusion injury, but the exact roles of endogenous zinc in the pathogenesis of reperfusion injury and in adenosine A(2) receptor activation-induced cardioprotection against reperfusion injury remain unknown. Adenosine A(1)/A(2) receptor agonist 5'-(N-ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size in isolated rat hearts subjected to 30min ischemia followed by 2h of reperfusion. This effect of NECA was partially but significantly blocked by the zinc chelator N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), and ZnCl(2) given at reperfusion mimicked the effect of NECA by reducing infarct size. Total tissue zinc concentrations measured with inductively coupled plasma optical emission spectroscopy (ICPOES) were decreased upon reperfusion in rat hearts and this was reversed by NECA. NECA increased intracellular free zinc during reperfusion in the heart. Confocal imaging study showed a rapid increase in intracellular free zinc in isolated rat cardiomyocytes treated with NECA. Further experiments revealed that NECA increased total zinc levels upon reperfusion in mitochondria isolated from isolated hearts. NECA attenuated mitochondrial swelling upon reperfusion in isolated hearts and this was inhibited by TPEN. Similarly, NECA prevented the loss of mitochondrial membrane potential (DeltaPsim) caused by oxidant stress in cardiomyocytes. Finally, both NECA and ZnCl(2) inhibited the mitochondrial metabolic activity. NECA-induced cardioprotection against reperfusion injury is mediated by intracellular zinc. NECA prevents reperfusion-induced zinc loss and relocates zinc to mitochondria. The inhibitory effects of zinc on both the mPTP opening and the mitochondrial metabolic activity may account for the cardioprotective effect of NECA.

The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.

OBJECTIVE: To summarize the prevalence of retinal vein occlusion (RVO) from studies in the United States, Europe, Asia, and Australia. DESIGN: Pooled analysis using individual population-based data. PARTICIPANTS: Individual participant data from population-based studies around the world that had ascertained RVO from fundus photographs. METHODS: Each study provided data on branch RVO and central RVO by age, sex, and ethnicity. Prevalence rates were directly age and sex standardized to the 2008 world population aged 30 years and older. Estimates were calculated by study and, after pooling, by ethnicity. Summary estimates included studies in which RVO was assessed from fundus photographs on >or=2 fields of both eyes. MAIN OUTCOME MEASURES: Any RVO, CRVO, or BRVO. RESULTS: The combined pooled data contained 68,751 individuals from 15 studies, with participants' ages ranging from 30 to 101 years. In analyses of 11 studies that assessed >or=2 fundus fields of both eyes (n=49,869), the age- and sex-standardized prevalence was 5.20 per 1000 (confidence interval [CI], 4.40-5.99) for any RVO, 4.42 per 1000 (CI, 3.65-5.19) for BRVO, and 0.80 per 1000 (CI, 0.61-0.99) for CRVO. Prevalence varied by race/ethnicity and increased with age, but did not differ by gender. The age- and sex-standardized prevalence of any RVO was 3.7 per 1000 (CI, 2.8-4.6) in whites (5 studies), 3.9 per 1000 (CI, 1.8-6.0) in blacks (1 study), 5.7 per 1000 (CI, 4.5-6.8) in Asians (6 studies), and 6.9 per 1000 (CI, 5.7-8.3) in Hispanics (3 studies). Prevalence for CRVO was lower than BRVO in all ethnic populations. On the basis of these data, an estimated 16.4 million (CI, 13.9-18.9) adults are affected by RVO, with 2.5 million (CI, 1.9-3.1) affected by CRVO and 13.9 million (CI, 11.5-16.4) affected by BRVO. Study limitations include non-uniform sampling frames in identifying study participants and in acquisition and grading of RVO data. CONCLUSIONS: Our study provides summary data on the prevalence of RVO and suggests that approximately 16 million people may have this condition. Research on preventive and treatment strategies for this sight-threatening eye disease is needed.

Adenosine A2A and A2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts.

We aimed to test if stimulation of both adenosine A2A and A2B receptors is required to produce an effective cardioprotection against reperfusion injury. Isolated rat hearts were subjected to 30-min regional ischemia followed by 2 h of reperfusion. The adenosine A1/A2 receptor agonist 5'-(N-ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size, an effect that was reversed by both the adenosine A2A antagonist SCH58261 and the A2B antagonist MRS1706. The A2B agonist BAY 60-6583 but not the selective A2A agonist CGS21680 reduced infarct size. Interestingly, a combination of BAY 60-6583 and CGS21680 further reduced infarct size. These results suggest that both A2A and A2B receptors are involved in NECA's anti-infarct effect at reperfusion. NECA attenuated mitochondrial swelling upon reperfusion and this was blocked by both SCH58261 and MRS1706, indicating that activation of A2 receptors with NECA can modulate reperfusion-induced mitochondrial permeability transition pore (mPTP) opening. In support, NECA also prevented oxidant-induced loss of mitochondrial membrane potential (DeltaPsi(m)) and matrix Ca2+ overload in cardiomyocytes via both the A2 receptors. In addition, NECA increased mitochondrial glycogen synthase kinase-3beta (GSK-3beta) phosphorylation upon reperfusion and this was again blocked by SCH58261 and MRS1706. In conclusion, A2A and A2B receptors work in concert to prevent reperfusion injury in rat hearts treated with NECA. NECA may protect the heart by modulating the mPTP opening through inactivating mitochondrial GSK-3beta. A simultaneous stimulation of A2A and A2B receptors at reperfusion is required to produce a strong cardioprotection against reperfusion injury.

Molecular mechanism underlying Akt activation in zinc-induced cardioprotection.

Our previous study demonstrated that zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via Akt and glycogen synthetase kinase 3beta (GSK-3beta). We aimed to address the mechanism by which zinc activates Akt. Treatment of H9c2 cells with ZnCl(2) (10 microM) in the presence of the zinc ionophore pyrithione (4 microM) for 20 min enhanced Akt phosphorylation (Ser(473)), indicating that zinc can rapidly activate Akt. Zinc did not alter either phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation and total PTEN protein levels or PTEN oxidation, implying that PTEN may not play a role in the action of zinc. However, zinc-induced Akt phosphorylation was blocked by both the nonselective receptor tyrosine kinase (RTK) inhibitor genistein and the selective insulin-like growth factor-1 RTK (IGF-1RTK) inhibitor AG1024, indicating that zinc activates Akt via IGF-1RTK. Zinc-induced phosphorylation of protein tyrosine and Ser/Thr was also abolished by AG1024. In addition, zinc markedly enhanced phosphorylation of IGF-1 receptor (IGF-1R), which was again reversed by genistein and AG1024. A confocal imaging study revealed that AG1024 abolished the preventive effect of zinc on oxidant-induced mPTP opening, confirming that IGF-1RTK plays a role in zinc-induced cardioprotection. Furthermore, zinc decreased the activity of protein phosphatase 2A (PP2A), a major protein Ser/Thr phosphatase, implying that protein Ser/Thr phosphatases may also play a role in the action of zinc on Akt activity. Taken together, these findings demonstrate that exogenous zinc activates Akt via IGF-1RTK and prevents the mPTP opening in cardiac cells. Inactivation of Ser/Thr protein phosphatases may also contribute to zinc-induced Akt activation.

Exogenous zinc protects cardiac cells from reperfusion injury by targeting mitochondrial permeability transition pore through inactivation of glycogen synthase kinase-3beta.

The purpose of this study was to determine whether exogenous zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via glycogen synthase kinase-3beta (GSK-3beta). The treatment of cardiac H9c2 cells with ZnCl2 (10 microM) in the presence of zinc ionophore pyrithione for 20 min significantly enhanced GSK-3beta phosphorylation at Ser9, indicating that exogenous zinc can inactivate GSK-3beta in H9c2 cells. The effect of zinc on GSK-3beta activity was blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 but not by the mammalian target of rapamycin (mTOR) inhibitor rapamycin or the PKC inhibitor chelerythrine, implying that PI3K but not mTOR or PKC accounts for the action of zinc. In support of this interpretation, zinc induced a significant increase in Akt but not mTOR phosphorylation. Further experiments found that zinc also increased mitochondrial GSK-3beta phosphorylation. This may indicate an involvement of the mitochondria in the action of zinc. The effect of zinc on mitochondrial GSK-3beta phosphorylation was not altered by the mitochondrial ATP-sensitive K+ channel blocker 5-hydroxydecanoic acid. Zinc applied at reperfusion reduced cell death in cells subjected to simulated ischemia/reperfusion, indicating that zinc can prevent reperfusion injury. However, zinc was not able to exert protection in cells transfected with the constitutively active GSK-3beta (GSK-3beta-S9A-HA) mutant, suggesting that zinc prevents reperfusion injury by inactivating GSK-3beta. Cells transfected with the catalytically inactive GSK-3beta (GSK-3beta-KM-HA) also revealed a significant decrease in cell death, strongly supporting the essential role of GSK-3beta inactivation in cardioprotection. Moreover, zinc prevented oxidant-induced mPTP opening through the inhibition of GSK-3beta. Taken together, these data suggest that zinc prevents reperfusion injury by modulating the mPTP opening through the inactivation of GSK-3beta. The PI3K/Akt signaling pathway is responsible for the inactivation of GSK-3beta by zinc.

Interventions for branch retinal vein occlusion: an evidence-based systematic review.

TOPIC: To assess the evidence on interventions to improve visual acuity (VA) and to treat macular edema and/or neovascularization secondary to branch retinal vein occlusion (BRVO). CLINICAL RELEVANCE: Branch retinal vein occlusion is the second most common retinal vascular disease. METHODS/LITERATURE REVIEWED: English and non-English articles were retrieved using a keyword search of Medline (1966 onwards), Embase, the Cochrane Collaboration, the National Institute of Health Clinical Trials Database, and the Association for Research in Vision and Ophthalmology Annual Meeting Abstract Database (2003-2005). This was supplemented by hand searching references of review articles. Two investigators independently identified all randomized clinical trials (RCTs) with more than 3 months' follow-up. RESULTS: From 4332 citations retrieved, 12 RCTs were identified. There were 5 RCTs on laser photocoagulation. Grid macular laser photocoagulation was effective in improving VA in 1 large multicenter RCT, the Branch Vein Occlusion Study (BVOS), but 2 smaller RCTs found no significant difference. The BVOS showed that scatter retinal laser photocoagulation was effective in preventing neovascularization and vitreous hemorrhage in patients with neovascularization, but a subsequent RCT found no significant effect. Randomized clinical trials evaluating intravitreal steroids (n = 2), hemodilution (n = 3), ticlopidine (n = 1), and troxerutin (n = 1) showed limited or no benefit. CONCLUSIONS: There is limited level I evidence for any interventions for BRVO. The BVOS showed that macular grid laser photocoagulation is an effective treatment for macular edema and improves vision in eyes with VA of 20/40 to 20/200, and that scatter laser photocoagulation can effectively treat neovascularization. The effectiveness of many new treatments is unsupported by current evidence.

Interventions for central retinal vein occlusion: an evidence-based systematic review.

TOPIC: To assess the evidence for the effectiveness of interventions to improve visual acuity (VA) and prevent or treat neovascularization secondary to central retinal vein occlusion (CRVO). CLINICAL RELEVANCE: Central retinal vein occlusion is a common cause of visual morbidity and blindness. Many different interventions have been advocated, but the evidence justifying their use remains unclear. METHODS/LITERATURE REVIEWED: English and non-English language articles were retrieved using a keyword search of Medline (1966 onwards), Embase, the Cochrane Collaboration, the National Institutes of Health Clinical Trials database, and the Association for Research in Vision and Ophthalmology (2003-2005). This was supplemented by manually searching references of review articles. Two investigators independently identified all randomized clinical trials (RCTs) on interventions in CRVO with more than 3 months' follow-up. RESULTS: Of 4133 citations retrieved, 17 RCTs comparing intervention with a control group were identified. There were 4 RCTs on laser photocoagulation. Grid macular laser photocoagulation did not improve VA in CRVO with macular edema. Prophylactic panretinal photocoagulation did not prevent angle and iris neovascularization in ischemic CRVO, but resulted in regression of angle and iris neovascularization and reduced progression to neovascular glaucoma. There were 4 RCTs that reported improvement in VA with inpatient hemodilution, 2 RCTs with no significant improvement, and 1 RCT showing deterioration in VA after outpatient hemodilution. Randomized clinical trials evaluating ticlodipine, troxerutin, and streptokinase showed a limited or no benefit. CONCLUSIONS: This review found limited level I evidence for any intervention to improve VA in patients with CRVO. Panretinal photocoagulation resulted in regression of neovascularization. Hemodilution may improve vision in some patients, but the data conflict. More robust randomized controlled trials evaluating current treatments for CRVO are needed. The results of ongoing RCTs on intravitreal triamcinolone, anti-vascular endothelial growth factor agents, and chorioretinal anastomosis are awaited with interest.

Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality.

Hypertensive retinopathy has long been regarded as a risk indicator for systemic morbidity and mortality. New population-based studies show that hypertensive retinopathy signs are strongly associated with blood pressure, but inconsistently associated with cholesterol and other risk factors of atherosclerosis. Mild hypertensive retinopathy signs, such as generalized and focal retinal arteriolar narrowing and arteriovenous nicking, are weakly associated with systemic vascular diseases. Moderate hypertensive retinopathy signs, such as isolated microaneurysms, haemorrhages and cotton-wool spots, are strongly associated with subclinical cerebrovascular disease and predict incident clinical stroke, congestive heart failure and cardiovascular mortality, independent of blood pressure and other traditional risk factors. These data support the concept that an assessment of retinal vascular changes may provide further information for vascular risk stratification in persons with hypertension.