Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma

PURPOSE. To assess the level of plasma glutathione in patients with untreated primary open-angle glaucoma. METHODS. Twenty-one patients with newly diagnosed primary open-angle glaucoma and 34 age- and gender-matched control subjects were subjected to a blood analysis to detect the level of circulating glutathione in its reduced and oxidized forms. The effect of age, gender, and systemic blood pressure on circulating glutathione levels was also analyzed. RESULTS. Age had a negative effect on the level of both reduced and total glutathione (P = 0.002, r = -0.52 and P = 0.002, r = -0.52, respectively) in control subjects but not in patients with glaucoma (P > 0.05, r = 0.27, and P > 0.05, r = 0.22, respectively). In the control group, men demonstrated higher levels of both reduced and total glutathione than did women (P = 0.024 and P = 0.032, respectively). After correction for age and gender influences on blood glutathione levels, patients with glaucoma exhibited significantly lower levels of reduced and total glutathione than did control subjects (P = 0.010, F = 7.24 and P = 0.006, F = 8.38, respectively). No differences between study groups were observed in either oxidized glutathione levels or redox index (P > 0.05, F = 0.50; and P > 0.05, F = 0.30, respectively). CONCLUSIONS. Patients with glaucoma exhibit low levels of circulating glutathione, suggesting a general compromise of the antioxidative defense. Copyright © Association for Research in Vision and Ophthalmology

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule for diagnosing glaucomatous optic disc damage

Purpose: To determine the accuracy with which the optic disc can be diagnosed as normal or glaucomatous according to the ISNT rule, whereby, in the normal eye, the neuroretinal rim area follows the order inferior (I) � superior (S) � nasal (N) � temporal (T). Design: Prospective, cross-sectional, observational, case series. Participants: Fifty-one normal individuals and 78 individuals with open-angle glaucoma exhibiting field loss (median mean deviation, �4.37 dB; interquartile range [IQR], �2.10 to �7.96 dB; median pattern standard deviation, 5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on the basis of the appearance of the optic disc and of the corresponding visual field. Methods: Stereoscopic optic disc photographs, acquired for each individual, were digitized at high resolution and analyzed using a digital, quad-buffered, stereoscopic viewing system in which a Z screen was used to dissociate the images to the 2 eyes of the observer. Three expert observers, trained to fellowship standard in glaucoma, independently undertook planimetry of the neuroretinal rim and of the disc margin from 1 eye of each individual, using a cursor moving in stereoscopic space to minimize parallax errors. Software automatically calculated the neuroretinal rim area in 10°, 30°, 40°, and 90° segments. For the ISNT rule to be obeyed, the 3 Boolean comparisons of the neuroretinal rim area, I�S, S�N, and N�T, had to be true. If any of the comparisons returned false, the rule was considered not to have been obeyed. Values were compared at a precision of 0.0001 mm2. Main Outcome Measures: The outcome of the ISNT rule in terms of the 3 Boolean comparisons of the neuroretinal rim area was specified in terms of the sensitivity, specificity, and hence, the positive and negative likelihood ratios. Results: Based on the ISNT rule being obeyed for 10° segments, the positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval [CI], 0.99–1.25), 1.07 (95% CI, 0.94–1.21), and 1.06 (95% CI, 0.96–1.18), respectively. It was similar for the other segment sizes. Variants of the rule were not appreciably better. Conclusions: The ISNT rule has limited utility in the diagnosis of open-angle glaucoma

Chiropractic care amongst people with multiple sclerosis: A survey of MS therapy centres in the UK

Objective: Many of the musculoskeletal symptoms associated with multiple sclerosis (MS) can be managed with physical therapy. Chiropractors are well placed to deliver this, but the extent of their involvement in the team management of multiple sclerosis in the UK is unknown. The present study investigates the level of awareness and use of chiropractic by people with MS in the UK. Methods: A retrospective cross sectional postal survey design was employed, utilising a structured, self-administered questionnaire and convenience sampling of individuals aged over 18 years with a definitive diagnosis of MS who were members of UK MS Therapy Centres. Results: Ninety-one per cent of respondents had used complementary therapy modalities of some kind, with physiotherapy being the most popular (52%), followed by massage (44%), then chiropractic (42%). Of those that had used chiropractic, 68% used it to manage their MS symptoms and most would recommend it to others with MS. Just under half had consulted their General Practitioner for approval prior to receiving the treatment, with 79% obtaining support. Of those who did not use chiropractic, 78% cited lack of knowledge about chiropractic as the main reason. All of the MS therapy centres contacted during this study offered physiotherapy and massage, but none offered chiropractic. Conclusions: There is moderate uptake of chiropractic by people with MS in the UK together with a willingness to recommend it. Further awareness of the potential benefits of chiropractic amongst stakeholders may help its integration into the team management of MS.Elizabeth A. Carsona, Gabrielle Swaita, Ian P. Johnsona and Christina Cunliffehttp://www.elsevier.com/wps/find/journaldescription.cws_home/672736/description#descriptio

Human β defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions

A rich residential microflora is harboured by the distal outer root sheath of the hair follicle and the hair canal – normally without causing skin diseases. Although the basic mechanisms involved in the development of inflammation during acne vulgaris remain unclear, microbial agents might play an important role in this process. In this study we have analyzed by in situ hybridization and immunohistochemistry the expression patterns of two antimicrobial peptides, human β defensin-1 and human β defensin-2, in healthy human hair follicles as well as in perilesional and intralesional skin of acne vulgaris lesions such as comedones, papules, and pustules. Strong defensin-1 and defensin-2 immunoreactivity was found in all suprabasal layers of the epidermis, the distal outer root sheath of the hair follicle, and the pilosebaceous duct. Marked defensin-1 and defensin-2 immunoreactivity was also found in the sebaceous gland and in the basal layer of the central outer root sheath including the bulge region. The majority of acne biopsies displayed a marked upregulation of defensin-2 immunoreactivity in the lesional and perilesional epithelium – in particular in pustules – and a less marked upregulation of defensin-1 immunoreactivity. The upregulation of β -defensin expression in acne vulgaris lesions compared to controls suggests that β -defensins may be involved in the pathogenesis of acne vulgaris