Daily Meditation Practice for Managing Glaucoma Patients' Attitudes and Acceptance.

PRCIS: Overall, 63% of glaucoma patients agreed to 45-60 minutes of daily meditation. Predictors of accepting meditation included previous meditation practice, a diagnosis of glaucoma <1 year, and having a marital status of "single". PURPOSE: To explore patients' acceptance and barriers towards 45-60 minutes daily meditation for glaucoma management and to identify glaucoma patients with higher perceived stress levels who may benefit more from meditation practice. METHODS: Glaucoma patients attending the Royal Victorian Eye and Ear Hospital, Melbourne, Australia outpatient department were invited to complete a patient survey. This survey explored if patients would agree to 45-60 minutes of daily meditation and included the Determinants of Meditation Practice Inventory and Perceived Stress Scale questionnaires. Questionnaire scores were compared across participants' clinical and demographic characteristics using Student t test, ANOVA, and multiple-linear-regression analysis. RESULTS: Of the 123 eligible patients screened, 100 completed the survey (81.3%). Sixty-three (63%) patients would agree to 45-60 minutes of daily meditation if advised by their doctor. Univariate analysis showed increased acceptance of meditation (lower Determinants of Meditation Practice Inventory scores) to be associated with agreeing to meditate 45-60 minutes daily ( P =0.002), currently or previously practicing meditation ( P =0.006 and P =0.0004 respectively), and having a marital status as "single" ( P =0.02). Multivariate regression analysis showed previous meditation practice and a glaucoma diagnosis of <1 year to be predictive of accepting meditation ( P =0.01 and P =0.03 respectively). There were no predictive factors of Perceived Stress Scale scores. CONCLUSION: Given the high acceptance rate of 45-60 minutes daily meditation (63% of glaucoma patients sampled), this may be recommended for the benefit of patients. Patients who have previously meditated, have a relatively new diagnosis of glaucoma, and are single (marital status) were more accepting of meditation practice.

Receptor-ligand supplementation via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery.

Gene replacement approaches are leading to a revolution in the treatment of previously debilitating monogenic neurological conditions. However, the application of gene therapy to complex polygenic conditions has been limited. Down-regulation or dysfunction of receptor expression in the disease state or in the presence of excess ligand has been shown to compromise therapeutic efficacy. Here, we offer evidence that combined overexpression of both brain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B, is more effective in stimulating axonal transport than either receptor administration or ligand administration alone. We also show efficacy in experimental glaucoma and humanized tauopathy models. Simultaneous administration of a ligand and its receptor by a single gene therapy vector overcomes several problems relating to ligand deficiency and receptor down-regulation that may be relevant to multiple neurodegenerative diseases. This approach shows promise as a strategy to target intrinsic mechanisms to improve neuronal function and facilitate repair.

Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.

IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS: Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.

Acute Ingestion of A Novel Nitrate-Rich Dietary Supplement Significantly Increases Plasma Nitrate/Nitrite in Physically Active Men and Women.

BACKGROUND: Dietary supplements purported to increase circulating nitric oxide are very popular among consumers. We determined the acute impact of two novel dietary supplements on plasma nitrate/nitrite (NOx) and nitrite alone. METHODS: 20 men and women (age: 24 ± 5 years) ingested two different nitrate-rich supplements (Resync Recovery Blend at 7.5 g and 15 g; Resync Collagen Blend at 21 g), or placebo, on four different days. Fasting blood samples were obtained before and 75 min following ingestion and analyzed for NOx and nitrite. RESULTS: Nitrite was not differently impacted by treatment (p > 0.05). The NOx response for men and women was very similar, with no sex interactions noted (p > 0.05). Condition (p < 0.0001), time (p < 0.0001), and condition x time (p < 0.0001) effects were noted for NOx. Values increased from baseline to post-ingestion for the Resync Recovery Blend at 7.5 g (11 ± 9 to 101 ± 48 µM) and at 15 g (9 ± 5 to 176 ± 91µM), as well as for the Resync Collagen Blend (9 ± 9 to 46 ± 21µM), while values for placebo remained stable (9 ± 7 to 8 ± 5µM). CONCLUSION: While nitrite alone was not impacted by treatment, both Resync products result in an increase in plasma NOx, with the increase proportionate to the quantity of "nitric oxide blend" ingredients contained within each product. Future studies are needed to determine the physiological implications of the increased NOx, as pertaining to exercise performance and recovery, in addition to other aspects of human health.

The Capacity of Eye Care Services for Patients with Glaucoma in Botswana.

PURPOSE: To evaluate current delivery of glaucoma care in Botswana; in particular, the service infrastructure available and glaucoma-related workload. METHODS: A multi-center cross-sectional study was undertaken comprising government eye care institutions and ophthalmic personnel across Botswana. Data on human resources, equipment types and numbers, diagnostic criteria routinely used, treatments routinely provided, and new and repeat glaucoma consultations were obtained through quantitative and qualitative surveys. RESULTS: In 27 government eye care institutions there were two general ophthalmologists, neither of whom had a subspecialty interest in glaucoma, 64 ophthalmic nurses, two optometrists, one low vision therapist, one refractionist, and two equipment technicians. Only 8.5% of available ophthalmic human resources were taken up with provision of glaucoma care. About 1/3 of hospitals did not have tonometers, most primary hospitals lacked slit lamp biomicroscopes and most hospitals lacked sensitive diagnostic equipment. A diagnosis of glaucoma was made by either an ophthalmic nurse or an ophthalmologist, but only 10% of institutions could meet recommendations for follow-up assessment. Topical glaucoma medications were prescribed by almost all hospital clinics, usually by ophthalmic nurses. Drug choices were largely determined by local availability. Glaucoma surgery accounted for 0.8% of total eye operations. Glaucoma patients took up 8.5% of total clinic visits. The total number of glaucoma visits was highest in the two hospitals with ophthalmologists. New glaucoma cases took up 10.3% of total glaucoma visits. CONCLUSION: This study highlights the challenges faced in caring for glaucoma patients in Botswana; in particular, lack of professional human resources, equipment and availability of effective treatments.

Cambridge community Optometry Glaucoma Scheme.

BACKGROUND: With a higher life expectancy, there is an increased demand for hospital glaucoma services in the United Kingdom. DESIGN: The Cambridge community Optometry Glaucoma Scheme (COGS) was initiated in 2010, where new referrals for suspected glaucoma are evaluated by community optometrists with a special interest in glaucoma, with virtual electronic review and validation by a consultant ophthalmologist with special interest in glaucoma. PARTICIPANTS: 1733 patients were evaluated by this scheme between 2010 and 2013. METHODS: Clinical assessment is performed by the optometrist at a remote site. Goldmann applanation tonometry, pachymetry, monoscopic colour optic disc photographs and automated Humphrey visual field testing are performed. A clinical decision is made as to whether a patient has glaucoma or is a suspect, and referred on or discharged as a false positive referral. The clinical findings, optic disc photographs and visual field test results are transmitted electronically for virtual review by a consultant ophthalmologist. MAIN OUTCOME MEASURES: The number of false positive referrals from initial referral into the scheme. RESULTS: Of the patients, 46.6% were discharged at assessment and a further 5.7% were discharged following virtual review. Of the patients initially discharged, 2.8% were recalled following virtual review. Following assessment at the hospital, a further 10.5% were discharged after a single visit. CONCLUSIONS: The COGS community-based glaucoma screening programme is a safe and effective way of evaluating glaucoma referrals in the community and reducing false-positive referrals for glaucoma into the hospital system.

Optic nerve cupping and the neuro-ophthalmologist.

BACKGROUND: While glaucoma is the most common cause of optic disc cupping, it can also be seen in a number of congenital and acquired optic neuropathies. It behooves both glaucoma and neuro-ophthalmic specialists to be able to differentiate glaucoma from neurological conditions, which give a similar ophthalmoscopic appearance to the optic disc. EVIDENCE ACQUISITION: This review is a combination of the authors' clinical experience from tertiary glaucoma and neuro-ophthalmology referral centers, combined with a literature review using PubMed. RESULTS: Even for experienced observers, differentiation between glaucomatous and nonglaucomatous cupping can be difficult. In the majority of cases, this distinction can be made following a careful clinical examination combined with a variety of imaging techniques. Possible mechanisms, which lead to changes in optic disc morphology, are reviewed. CONCLUSIONS: Differentiating glaucomatous from nonglaucomatous optic disc cupping can be a formidable challenge for the clinician. Examination of the patient combined with imaging of the retinal nerve fiber layer and optic disc topography provides a basis to resolve this clinical conundrum.

Tart cherry juice induces differential dose-dependent effects on apoptosis, but not cellular proliferation, in MCF-7 human breast cancer cells.

Consumption of polyphenol-rich fruits, for example, tart cherries, is associated with a lower risk of cardiovascular disease and cancer. This is due, in large part, to the diverse myriad bioactive agents, that is, polyphenol anthocyanins, present in fruits. Anthocyanin-rich tart cherries purportedly modulate numerous cellular processes associated with oncogenesis such as apoptosis, cellular proliferation (CP), and cell cycle progression, although the effective concentrations eliciting these effects are unclear. We hypothesized that several dose-dependent effects over a large concentration range of 100% tart cherry juice (TCJ) would exist and affect these processes differentially with the potential for cellular protection and cellular death either by apoptosis or by necrosis. In this in vitro study, we tested the dose response of TCJ on CP and cell death in MCF-7 human breast cancer cells. TCJ was added at 0.03-30% (v/v) to cells and incubated overnight with the medium alone or with increasing TCJ. Bromodeoxyuridine incorporation was significantly reduced by 20% at ≥10% (v/v) TCJ and associated with necrosis, but was not different between the control and treatment groups at <10% TCJ. MTT reduction was also significantly reduced by 27% and 80% at 10% and 30% TCJ, respectively, and associated with necrosis. Apoptosis, but not necrosis, was increased ∼63% at 3% TCJ (∼307 nM monomeric anthocyanins), yet significantly decreased (P<.05) by 20% at 1% TCJ (920 nM) both of which were physiologically relevant concentrations of anthocyanins. The data support a biphasic effect on apoptosis and no effect on proliferation.

Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies.

PURPOSE. To validate an established adult organotypic retinal explant culture system for use as an efficient medium-throughput screening tool to investigate novel retinal ganglion cell (RGC) neuroprotective therapies. METHODS. Optimal culture conditions for detecting RGC neuroprotection in rat retinal explants were identified. Retinal explants were treated with various recognized, or purported, neuroprotective agents and cultured for either 4 or 7 days ex vivo. The number of cells surviving in the RGC layer (RGCL) was quantified using histologic and immunohistochemical techniques, and statistical analyses were applied to detect neuroprotective effects. RESULTS. The ability to replicate previously reported in vivo RGC neuroprotection in retinal explants was verified by demonstrating that caspase inhibition, brain-derived neurotrophic factor treatment, and stem cell transplantation all reduced RGCL cell loss in this model. Further screening of potential neuroprotective pharmacologic agents demonstrated that betaxolol, losartan, tafluprost, and simvastatin all alleviated RGCL cell loss in retinal explants, supporting previous reports. However, treatment with brimonidine did not protect RGCL neurons from death in retinal explant cultures. Explants cultured for 4 days ex vivo proved most sensitive for detecting neuroprotection. CONCLUSIONS. The current adult rat retinal explant culture model offers advantages over other models for screening potential neuroprotective drugs, including maintenance of neurons in situ, control of environmental conditions, and dissociation from other factors such as intraocular pressure. Verification that neuroprotection by previously identified RGC-protective therapies could be replicated in adult retinal explant cultures suggests that this model could be used for efficient medium-throughput screening of novel neuroprotective therapies for retinal neurodegenerative disease.

The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease.

Regular consumption of fruits and vegetables is strongly associated with a reduced risk of cardiovascular disease (CVD). This effect occurs, in part, because of the plethora of bioactive agents in foods and their subsequent function as antioxidants. Ergothioneine (ERT), a novel antioxidant, is present in edible mushrooms and is not synthesized, but is accumulated, by humans through diet. In this study, we tested whether ERT, a bioactive agent, could interrupt pro-inflammatory induction of adhesion molecule expression associated with atherogenesis. Human aortic endothelial cells (HAECs) were incubated with increasing concentrations of ERT (0.01-10.0 mM) overnight (16 hours) followed by incubation with medium alone or with the pro-inflammatory cytokine interleukin (IL)-1ß (5 ng/mL) for 6 hours to induce expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial-leukocyte adhesion molecule (ELAM-1 or E-selectin). ERT at 0.1-0.3 mM significantly (P < .05) reduced VCAM-1, ICAM-1, and E-selectin expression up to 41%. VCAM-1 was suppressed to the greatest extent followed by E-selectin and then ICAM-1. We next tested if binding of preloaded U937 human monocytes to HAECs would be inhibited. U937 binding to HAECs was significantly reduced in IL-1ß-stimulated HAECs preincubated with 1 and 3 mM ERT. Unstimulated monolayers demonstrated marginal, but significant, reductions. ERT was not toxic to HAECs at any concentration used. These data provide evidence that ERT found in commonly consumed dietary mushrooms can protect against events observed in atherogenesis, suggesting increased dietary intake of edible mushrooms would be a prudent medicinal means of reducing CVD risk.

Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women.

Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers and lipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2 diets low in saturated fat and cholesterol, and high in PUFA varying in ALA (ALA Diet) and linoleic acid (LA Diet) compared with an average American diet (AAD). The ALA Diet provided 17% energy from PUFA (10.5% LA; 6.5% ALA); the LA Diet provided 16.4% energy from PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA; 0.8% ALA). The ALA Diet decreased C-reactive protein (CRP, P < 0.01), whereas the LA Diet tended to decrease CRP (P = 0.08). Although the 2 high-PUFA diets similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the ALA Diet, P < 0.01; -11.0% by the LA Diet, P < 0.01), the ALA Diet decreased vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E-selectin (-14.6% vs. -8.1%, P < 0.01) more than the LA Diet. Changes in CRP and VCAM-1 were inversely associated with changes in serum eicosapentaenoic acid (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after subjects consumed the ALA Diet. The 2 high-PUFA diets decreased serum total cholesterol, LDL cholesterol and triglycerides similarly (P < 0.05); the ALA Diet decreased HDL cholesterol and apolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond its lipid-lowering effects.

Timing of supplementation with the antioxidant N-acetyl-L-cysteine reduces tumor multiplicity in novel, cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) transgenic mice but has no impact on malignant progression.

Epidemiological studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence suggests that antioxidant supplements may actually exacerbate carcinogenesis. We explored this paradox in a model containing two common genotypic characteristics of human cancers. We selected p53 haploinsufficient Tg.AC (v-Ha-ras) mice as a model, because it contains an activated, carcinogen-inducible ras oncogene and an inactivated p53 tumor suppressor gene. These mice develop chemically induced benign and malignant skin tumors rapidly. Mice were fed basal diet with or without 3% N-acetyl-L-cysteine (NAC) before and after topical application of the carcinogen benzo[a]pyrene (64 micrograms twice per week for 7 wk) until 50% of mice within a group displayed at least one lesion. Half each of mice fed the basal and the NAC-supplemented diet were then switched to the alternate diet. Mice fed the NAC-supplemented diet or switched from the NAC-supplemented to the basal diet displayed 38% and 26% reductions, respectively, in tumor multiplicity and a 15% reduction if switched from the basal to the NAC-supplemented diet. Although latency was unaffected, NAC induced a lag in tumor incidence, which exceeded 90% at 10 wk for all groups. The timing of NAC supplementation did not affect malignant progression. Thus dietary NAC was chemoprotective by slowing tumorigenesis but did not affect malignant conversion.