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Background: Fuel filling stations workers and automobile workshops mechanics are consistently exposed to gasoline hydrocarbons during their occupation, this may cause DNA damage. Objective of this study was to evaluate the level of DNA damage in subjects occupationally exposed to these hydrocarbons., Methods: Comet assay was performed on blood lymphocytes of exposed subjects to assess the probable DNA damage. 100 cells per individual were scored and graded by comet tail length. Exposed group consisted of 98 subjects (age 25.4 ± 7.2 years), of which 68 were CNG/Petrol filling men and 30 were automobile workshop workers, selected randomly from different service stations and automobile workshops of populated and adjacent cities of Peshawar, Mardan and Nowshera of Khyber Pakhtunkhwa province, while control group included 92 subjects (age 26.7 ± 11.8 years) were also from the same areas., Results: Significantly high level of DNA damage was found in the subjects exposed to gasoline hydrocarbons as compared to control subjects (173.2 ± 50.1 and 61.0 ± 25.0, P = 0.001, respectively). Period of exposure and use of tobacco also showed considerable effects (P < 0.05) on DNA damage, while effect of age and daily working hours on total comet score (TCS) were non-significant (P > 0.05)., Conclusions: The results of our study concluded that petroleum hydrocarbons have the potential to cause DNA damage in the exposed subjects. The study also suggested that protective strategies should be implemented by the concerned authorities to minimize exposure to fuel hydrocarbons.

Objective: To study the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, compared with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX)., Methods: Patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. Patients whose swollen and tender joint counts had not improved by ≥20% were considered nonresponders at week 16 and were required to enter the protocol-defined early escape. At week 24, patients were transitioned in a blinded manner to receive apremilast 20 mg twice a day if they were initially randomized to receive placebo. Patients who were not initially randomized to receive placebo continued to receive their target apremilast dose. Patients were required to take a stable dose of MTX (7.5-25 mg/week) throughout the study. Magnetic resonance imaging (MRI) was performed in a subset of patients., Results: A total of 237 patients who were receiving MTX therapy were randomized and received ≥1 dose of study medication. At week 16, similar proportions of patients receiving placebo (35%), apremilast 20 mg twice a day (28%), and apremilast 30 mg twice a day (34%) met the American College of Rheumatology criteria for 20% improvement in disease activity (the primary efficacy end point). In the MRI substudy, mean change from baseline in total joint damage scores according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system was generally similar with either apremilast dose at week 16. At week 52, no trends were noted for clinical end points by treatment group. Both apremilast doses were generally well tolerated., Conclusion: Apremilast efficacy was not demonstrated in patients who had active RA despite stable MTX therapy., (© 2015, American College of Rheumatology.)

Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies.

Acetone and ethanol extracts of carob (Ceratonia siliqua L.) leaf and pods were evaluated for their in vitro inhibitory ability against the pectinolytic Gram negative Pectobacterium atrosepticum (Pca, CFBP-5384) bacteria, the causal agent of potato soft rot. Potato (Solanum tuberosum, var nicola) tuber rot tissues obtained after 5 day bacterial inoculation was analyzed by LC-MS and GC-MS to study Pca pathogenicity. Trans/cis N-feruloylputrescine was identified in potato tuber after 5-day inoculation with Pca in a dark moist chamber. Although glycoalkoloid (α-chaconine and α-solanine) production increased due to Pca soft rot infection, it was not a resistance-determining factor. Many secondary metabolites were identified including the phytoalexins solavetivone and fatty acids responsible for plant defence responses. Acetone extract of carob leaf (FCA) exhibited the strongest inhibitory effect (IC50 = 1.5 mg/ml) and displayed synergistic antimicrobial effect in the presence of infected potato tuber extract (Pdt-Pca extract) against Pca. This synergy could be used in an integrated control program against potato soft rot pathogens, thereby reducing chemical treatments., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A total of 956 lactation records of Holstein cows kept at Kaa Albon station, Imuran Governorate, Yemen during the period from 1991 to 2003 were used to investigate the effect of some genetic and non-genetic factors (Sire, parity, season of calving, year of calving and age at first calving as covariate) on the Total Milk Yield (TMY), Lactation Length (LL), and Dry Period (DP). Components of variance for the random effects (mixed model) were estimated by Restricted Maximum Likelihood (REML) methodology. Sires were evaluated for the TMY by three methods, Best Linear Unbiased Prediction (BLUP) using Harvey program, Transmitting Ability (TA) according to the Least Square Means of sire progeny (TALSM) and according to Means (TAM). Results showed that TMY and DP were affected significantly (P < 0.01) by all factors except season of calving and age at first calving, while LL was affected significantly (P< 0.01) only by year of calving and parity. The averages of the TMY, LL, and DP were 3919.66 kg, 298.28 days, and 114.13 days respectively. The corresponding estimates of heritability (h(2)) were 0.35, 0.06, and 0.14 respectively. The highest and lowest BLUP values of sires for the TMY were - 542.44 kg and 402.14 kg, while the corresponding estimates for TALSM and TAM were - 470.38, 380.88 kg and - 370.12, 388.50 kg respectively. The Spearman rank correlation coefficients among BLUP, TALSM and TAM ranged from 0.81 to 0.67. These results provide evidence that the selection of sires will improve the TMY in this herd because of the wide differences in genetic poetical among sires, and a moderate estimation of heritability.

About 1 in 5 patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD) in the United States are readmitted within 30 days. The U.S. Centers for Medicare and Medicaid Services has recently expanded its Hospital Readmissions Reduction Program to financially penalize hospitals with higher than expected all-cause 30-day readmission rates following a hospitalization for COPD exacerbation. In October 2013, the COPD Foundation convened a multi-stakeholder National COPD Readmissions Summit to summarize our understanding of how to reduce hospital readmissions in patients hospitalized for COPD exacerbations. Over 225 individuals participated in the Summit, including patients, clinicians, health service researchers, policy makers and representatives of academic health care centers, industry, and payers. Summit participants recommend that programs to reduce hospital readmissions: 1) Include specific recommendations about how to promote COPD self-management skills training for patients and their caregivers; 2) Adequately address co-existing disorders common to COPD in care plans during and after hospitalizations; 3) Include an evaluation of adverse events when implementing strategies to reduce hospital readmissions; and 4) Develop a strategy (e.g., a learning collaboratory) to connect groups who are engaged in developing, testing, and implementing programs to reduce hospital readmissions for COPD and other conditions.

Background: Hydration and anticoagulation are the standard of care for cerebral venous sinus thrombosis (CVST) but some patients remain refractory to medical management and warrant more aggressive therapy. Here we present the technique of endovascular transvenous manual aspiration thrombectomy (MAT) in six patients., Objective: Present an alternative technique for endovascular transvenous thrombectomy in a series of CVST patients., Methods: We reviewed the records of six patients with medically refractory CVST. Transvenous access via the femoral vein was used to advance an aspiration catheter of varying internal diameter (0.044, 0.054, 0.057, 0.070, 0.072) up to and through the thrombus. Tissue plasminogen activator was administered in select cases. Manual aspiration with a 20 ml syringe applied to the catheter hub was applied as the catheter was slowly retracted. Presentation, technique, and outcome were evaluated., Results: Clinical presentation included vomiting, dehydration, mental status changes, headaches, and acute motor deficits. On imaging, four of the six patients had hemorrhage, edema, and mass effect present before treatment, while two had edema only. All patients demonstrated continued deterioration despite early and aggressive medical anticoagulation therapy, warranting aggressive intervention. Aspiration of the superior sagittal sinus, transverse sinuses, straight sinus, sigmoid sinus, and internal jugular vein were performed in this series. There were no procedural complications. Revascularization was achieved in all instances. A modified Rankin Scale score of 1-3 was attained in 5/6 patients, while one patient died., Conclusions: In this series, transvenous MAT was a safe, simple, and effective revascularization technique to treat patients with CVST who remained refractory to medical management.

Two faba bean (Vicia faba L.) subspecies major and minor and lentil seeds grown in Algeria were separated into cotyledons and hulls. These fractions, together with their corresponding whole seeds, were extracted with two solvents, aqueous (70%) acetone and (80%) ethanol, and evaluated for antioxidant activity in relation to their phenolic contents. Acetone selectively extracted tannins from faba beans. The hulls always exhibited high antioxidant activity, measured using the reducing power (RP), antiradical activity (DPPH) or oxygen radical absorbance capacity (ORAC) assays. Aqueous ethanol (80%) extract of lentil hulls exhibited high antioxidant and anti-inflammatory activities preferentially inhibiting 15-LOX (IC(50), 55 μg/ml), with moderate COX-1 (IC(50), 66 μg/ml) and COX-2 (IC(50), 119 μg/ml) inhibitory effects on the COX pathway, whereas faba bean hull extracts exerted relatively mild LOX inhibitory activity., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

We propose and experimentally demonstrate the use of cyclic pulse coding to improve the performance of hybrid Raman/fiber Bragg grating (FBG) fiber-optic sensors, for simultaneous measurement of distributed static temperature and discrete dynamic strain over the same sensing fiber. Effective noise reduction is achieved in both Raman optical time-domain reflectometry and dynamic interrogation of time-division-multiplexed fiber FBG sensors, enhancing the sensing range resolution and providing real-time point dynamic strain measurement capabilities. The highly integrated sensor scheme employs broadband apodized low-reflectivity FBGs, a single narrowband optical source, and a shared receiver block.

We propose and experimentally demonstrate a hybrid fiber optic sensing technique that effectively combines Raman optical time domain reflectometry and in-line time-division-multiplexing for fiber Bragg grating (FBG) dynamic interrogation. The highly integrated proposed scheme employs broadband apodized low reflectivity FBGs with a single narrowband optical source and a shared receiver block, allowing for simultaneous measurements of distributed static temperature and discrete dynamic strain, over the same sensing fiber.

We propose and experimentally demonstrate the feasibility of an integrated hybrid optical fiber sensing interrogation technique that efficiently combines distributed Raman-based temperature sensing with fiber Bragg grating (FBG)-based dynamic strain measurements. The proposed sensing system is highly integrated, making use of a common optical source/receiver block and exploiting the advantages of both (distributed and point) sensing technologies simultaneously. A multimode fiber is used for distributed temperature sensing, and a pair of FBGs in each discrete sensing point, partially overlapped in the spectral domain, allows for temperature-independent discrete strain measurements. Experimental results report a dynamic strain resolution of 7.8 nε/√Hz within a full range of 1700 με and a distributed temperature resolution of 1°C at 20 km distance with 2.7 m spatial resolution.

Objective: A literature review revealed there is no outcome data for endoscopic endonasal dacryocystorhinostomy (EES-DCR) in the subgroup of patients with acquired partial nasolacrimal duct obstruction (NDO). This study aimed to compare the results of EES-DCR vs external DCR (ext-DCR) in the treatment of partial NDO., Design: This study is designed as a prospective nonrandomised comparative clinical trial., Participants: In total, 46 adult patients with acquired partial NDO participated in this study., Methods: Partial (sometimes called 'functional') NDO (epiphora in the presence of patent syringing) was confirmed by nuclear lacrimal scintigraphy or delayed drainage on dacryocystography. Patients with 'functional' epiphora from other causes were excluded. Post-operative outcome was assessed at 6 months. Overall, 21 (46%) patients had EES-DCR and 25 patients had (54%) ext-DCR., Main Outcome Measures: Subjective success was based on patient symptoms, objective success on patency with syringing and a functioning rhinostomy evaluated using the functional endoscopic dye test (FEDT)., Results: In total 18 out of 21 (86%) of EES-DCR patients had marked reduction (n=11) or complete resolution (n=7) and 25 out of 25 (100%) of ext-DCR had marked reduction (n=9) or complete resolution (n=16) of epiphora. In total 17 out of 18 (94%) of the EES-DCR patients with subjective success had a positive FEDT. All 25 out of 25 (100%) ext-DCR patients with subjective success had a positive FEDT. The three failed EES-DCR patients were all blocked on syringing. Statistically, EES-DCR does not achieve the same success rate as ext-DCR in this study (P=0.09, two-tailed Fisher's exact test, 0.045 one-tailed)., Conclusions: Both endoscopic and external DCRs provide satisfactory outcomes in acquired partial NDO. The success rate is nevertheless higher in ext-DCR compared with EES-DCR.

In Pakistan, the three days of Islamic festival of Eid ul Azha (Eid) are characterized by millions of livestock sacrifices and availability of countless breeding resources for insects of forensic importance. Thus during Eid, December, 2008, in a Pakistani village observing 70 sacrifices, we examined postmortem insect attractions on various sacrificial products (from 23 animals), i.e., blood pools, meat, hides/skins, bones, offal and real time insect succession on goats' offal at five dump sites. Thirty five insect species were collected from 14 indoor and outdoor sites. Offal at the dump sites attracted most insect species both by taxa and in numbers, followed by hides in the court yards, meat (40-70 kg/animal) in kitchens and blood pools in the court yards. Synanthropic calliphorids and muscids were found to be exclusive indoor "first and only arrivals" in comparison to a diverse array of first day insect arrivals at dump sites including calliphorids, sarcophagids, muscids, sphaerocerids, sepsids, empidids, gryllids and formicids. Though burial is usually considered as a barricade between most insect species and carrion yet dump site A with an early burial but also earliest insect colonization showed the fastest rate of decomposition. No vertebrate scavenging at any of the offal dump sites perhaps showed their private feeding inclination, thus implying that in times of mass slaughters most of the dumped winter carrion products in human vicinities are either consumed by insects and/or are buried. Here we also suggest a high rate of fly dispersal during Eid which if true has consequences for forensic investigations in Muslim populace areas especially during the Eid., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Contemporary studies in forensic entomology exhaustively evaluate gene sequences because these constitute the fastest and most accurate method of species identification. For this purpose single gene segments, cytochrome oxidase subunit I (COI) in particular, are commonly used. However, the limitation of such sequences in identification, especially of closely related species and populations, demand a multi-gene approach. But this raises the question of which group of genes can best fulfill the identification task? In this context the utility of five gene segments was explored among blowfly species from two distinct geographic regions, China and Pakistan. COI, cytochrome b (CYTB), NADH dehydrogenase 5 (ND5), nuclear internal transcribed spacers (ITS1 and ITS2), were sequenced for eight blowfly species including Chrysomya megacephala F. (Diptera: Calliphoidae), Ch. pinguis Walker, Lucilia sericata Meigen L. porphyrina Walker, L. illustris Meigen Hemipyrellia ligurriens Wiedemann, Aldrichina grahami Aldrich, and the housefly, Musca domestica L. (Muscidae), from Hangzhou, China; while COI, CYTB, and ITS2 were sequenced for four species, i.e. Ch. megacephala, Ch. rufifacies, L. cuprina, and the flesh fly, Sarcophaga albiceps Meigen (Sarcophagidae), from Dera Ismail Khan Pakistan. The results demonstrate a universal utility of these gene segments in the molecular identification of flies of forensic importance.

Pregnancy is dependent upon the endometrium acquiring a receptive phenotype that facilitates apposition, adhesion and invasion of a developmentally competent embryo. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of mid-secretory endometrial biopsies revealed a 28 kDa protein peak that discriminated highly between samples obtained from women with recurrent implantation failure and fertile controls. Subsequent tandem mass spectroscopy unambiguously identified this peak as apolipoprotein A-I (apoA-I), a potent anti-inflammatory molecule. Total endometrial apoA-I levels were, however, comparable between the study and control group. Moreover, endometrial apoA-I mRNA expression was not cycle-dependent although there was partial loss of apoA-I immunoreactivity in luminal and glandular epithelium in mid-secretory compared with proliferative endometrial samples. Because of its putative anti-implantation properties, we examined whether endometrial apoA-I expression is regulated by embryonic signals. Human chorionic gonadotrophin (hCG) strongly inhibited apoA-I expression in differentiating explant cultures but not when established from eutopic endometrium from patients with endometriosis. Pelvic endometriosis was associated with elevated apoA-I mRNA levels, increased secretion by differentiating eutopic endometrial explant cultures and lack of hCG-dependent down-regulation. To corroborate these observations, we examined endometrial apoA-I expression and its regulation by hCG in a non-human primate model of endometriosis. As in humans, hCG strongly inhibited endometrial apoA-I mRNA expression in disease-free baboons, but this response was entirely lost upon induction of pelvic endometriosis. Together, these observations indicate that perturbations in endometrial apoA-I expression, modification or regulation by paracrine embryonic signals play a major role in implantation failure and infertility.

Aims: Oculoplastic surgery has received little attention compared with other subspecialties in terms of how the internet influences patient expectations. Blepharoplasty resembles a model for oculoplastic operations. We aimed to assess the quality of information accessed by patients on blepharoplasty using the internet as a resource., Methods: After surveying doctors and lay persons, the word 'blepharoplasty' and related terms were studied using an advanced keyword search. This scanned average monthly search volume over a recent 12-month period. The three most popular search terms that were found were entered into the Google search engine. Criteria published in the Journal of the American Medical Associationfor qualifying information from the internet were used in the analysis, yielding a possible score from 0 to a maximum of 4., Results: Of the 150 websites that were studied, these criteria were fully applied to 101 websites. Only 2.5% of sites scored favourably on all four criteria; 6.5% scored three points; 10% scored two points; 41% scored one point; 40% of sites scored zero for objective quality. Superior scores were achieved by online encyclopaedias ('medipedias'), peer-reviewed journals, online abstracts, and book chapters. The websites of professional bodies scored poorly. The lowest scored were private clinics and National Health Service (NHS) hospital websites., Conclusions: Using the internet, the quality of information obtained for oculoplastic surgery seems far inferior to other subspecialties within ophthalmology as well as non-ophthalmic specialties. These findings are specifically relevant to surgeons carrying out blepharoplasty and of general relevance to ophthalmic plastic surgeons.

The forkhead transcription factor FOXO1, a downstream target of phosphatidylinositol-3-kinase/Akt signalling pathway, regulates cyclic differentiation and apoptosis in normal endometrium, but its role in endometrial carcinogenesis is unknown. Screening of endometrial cancer cell lines demonstrated that FOXO1 is expressed in HEC-1B cells, but not in Ishikawa cells, which in turn highly express the FOXO1 targeting E3-ubiquitin ligase Skp2. FOXO1 transcript levels were also lower in Ishikawa cells and treatment with the proteasomal inhibitor was insufficient to restore expression. Lack of FOXO1 expression in Ishikawa cells was not accounted for by differential promoter methylation or activity, but correlated with increased messenger RNA (mRNA) turnover. Comparative analysis demonstrated that HEC-1B cells proliferate slower, but are more resistant to paclitaxel-mediated cell death than Ishikawa cells, which were partially reversed upon silencing of FOXO1 in HEC-1B cells or its re-expression in Ishikawa cells. We further show that FOXO1 is required for the expression of the growth arrest- and DNA-damage-inducible gene GADD45alpha. Analysis of biopsy samples demonstrated a marked loss of FOXO1 and GADD45alpha mRNA and protein expression in endometrioid endometrial cancer compared to normal endometrium. Together, these observations suggest that loss of FOXO1 perturbs endometrial homeostasis, promotes uncontrolled cell proliferation and increases susceptibility to genotoxic insults.

Using cDNA microarray analysis, we identified SGK1 (serum- and glucocorticoid-regulated kinase 1) as a gene aberrantly expressed in midsecretory endometrium of women with unexplained infertility. SGK1 is a serine/threonine kinase involved primarily in epithelial ion transport and cell survival responses. Real-time quantitative PCR analysis of a larger, independent sample set timed to coincide with the period of uterine receptivity confirmed increased expression of SGK1 transcripts in infertile women compared with fertile controls. We further demonstrate that SGK1 expression is regulated by progesterone in human endometrium in vivo as well as in explant cultures. During the midsecretory phase of the cycle, SGK1 mRNA and protein were predominantly but not exclusively expressed in the luminal epithelium, and expression in this cellular compartment was higher in infertile women. In the stromal compartment, SGK1 expression was largely confined to decidualizing cells adjacent to the luminal epithelium. In primary culture, SGK1 was induced and phosphorylated upon decidualization of endometrial stromal cells in response to 8-bromo-cAMP and progestin treatment. Moreover, overexpression of SGK1 in decidualizing cells enhanced phosphorylation and cytoplasmic translocation of the forkhead transcription factor FOXO1 and inhibited the expression of PRL, a major decidual marker gene. Conversely, knockdown of endogenous SGK1 by small interfering RNA increased nuclear FOXO1 levels and enhanced PRL expression. The observation that SGK1 targets FOXO1 in differentiating human endometrium, together with its distinct temporal and spatial expression pattern and increased expression in infertile patients, suggest a major role for this kinase in early pregnancy events.

Endogenous endophthalmitis is a potentially blinding condition that occurs after the spread of organisms to the eye from a focus of infection elsewhere in the body. The holmium laser has gained increasing acceptance as being safe and effective for endoscopic lithotripsy. We report what we believe to be the first time endogenous endophthalmitis has been described as occurring after holmium laser lithotripsy, although it has been reported after extracorporeal shock wave lithotripsy. This 55-year-old woman developed infections in both eyes 2 to 3 weeks after the lithotripsy, with a good response to appropriate antibiotic treatment.

The integrity of the feto-maternal interface is critical for survival of the conceptus. This interface, consisting of the maternal decidua and the invading placental trophoblast, is exposed to profound changes in oxygen tension during pregnancy. We demonstrate that human endometrial stromal cells become extraordinarily resistant to oxidative stress-induced apoptosis upon decidualization in response to cAMP and progesterone signaling. This differentiation process is associated with the induction of the forkhead transcription factor FOXO1, which in turn increases the expression of the mitochondrial antioxidant manganese superoxide dismutase. However, silencing of FOXO1 did not increase the susceptibility of decidualized cells to oxidative cell death. Comparative analysis demonstrated that hydrogen peroxide, a source of free radicals, strongly induces FOXO3a mRNA and protein expression in undifferentiated human endometrial stromal cells but not in decidualized cells. Expression of a constitutively active FOXO3a mutant elicited apoptosis in decidualized cells. Furthermore, silencing of endogenous FOXO3a in undifferentiated cells abrogated apoptosis induced by hydrogen peroxide. These results suggest that the induction of FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage while the simultaneous repression of FOXO3a expression disables the signaling pathway responsible for oxidative cell death. The differential regulation of FOXO expression provides the decidua with a robust system capable of coping with prolonged episodes of oxidative stress during pregnancy.

Aim: To assess whether macular dysfunction caused by unilateral subretinal neovascular membranes (SRNs) is associated with pupil "evasion" (that is, increased initial rate of re-dilation following a brief light stimulus)., Methods: Comparative observational series. 20 eyes of 10 participants, all with unilateral SRNs and healthy fellow eyes. Dynamic infrared pupillography at seven stimulus intensities (duration 1100 ms, intensities over 2 log unit range). Pupil evasion ratio (PEVR; defined as the ratio of light response amplitude to amount of recovery at the mid-time point of re-dilation expressed as a percentage) was calculated for each stimulus intensity (mean of five recordings)., Results: Inter-eye PEVR is significantly reduced in eyes with SRN (that is, greater pupil evasion in SRN eyes: range p = 0.002 to p = 0.05 (paired t test)) and is most apparent at higher stimulus intensities., Conclusions: PEVR is a novel parameter that is analogous to the pupil escape ratio, but measured following a short rather than a sustained light stimulus. PEVR is significantly altered by macular disease. Clinically PEVR may be used to detect occult unilateral or asymmetric maculopathy in situations such as ocular media opacities like cataract, when pupil reactions are unaffected or augmented, while other tests of retinal function are diminished. PEVR represents altered neuronal firing in cones and macular ganglion cells.

Background/aims: Under-potent generic antibiotics sold in developing world countries may be contributing to positive selection of resistance organisms and to unpredictability in clinical outcome, leading to a loss of confidence among physicians locally. The objective of this study was to determine whether reports of unpredictable outcome for generic ciprofloxacin antibiotic eye drops in India could be the result of inadequate concentration of preparations sold by pharmacies., Methods: 130 ciprofloxacin eye drop samples sold by pharmacies were collected from seven locations in north, central, and south India; 30 were randomly selected for testing. All samples were assayed using validated methods of reverse phase chromatography and fluorescence detection at a international antibiotic reference laboratory in the United Kingdom. Results were compared with advertised concentrations within the context of internationally accepted variability ranges., Results: In total, six out of the 30 samples tested had ciprofloxacin concentrations lower than the standard advisory ranges of plus or minus 5% of stated content for 3 mg/ml pharmaceutical preparations. The ciprofloxacin content of these eye drops ranged from -36.4% to -16.1% of the stated content (median -21.73%). 24 out of 30 samples were found to be over the standard advisory ranges of plus or minus 5%, at a median of +19.42% (interquartile range (IQR) +14.28 to +25.13). Intra-batch variability of two selected samples was wide at -22.83% to +33.93% (n=11) and -17.07% to +31.20% (n=12)., Conclusions: Approximately 20% of generic ciprofloxacin eye drops, purchased without prescription in India were under-potent. In a number of preparations the antibiotic content was sufficiently low as to have a potential impact on clinical outcome and possibly lead to the selection of resistant isolates in individual patients. More widespread studies are justified to identify the extent of under-potency of widely used generic antibiotic medications in developing countries.

Purpose: Validating the current protocol of Amsler chart grid surveillance for the early detection of subretinal neovascular membrane(SRN) in age-related macular degeneration(AMD), and investigating its value in facilitating early laser therapy., Methods: A retrospective pilot study., Setting: Central London eye hospital with dedicated 24-h ophthalmic casualty serving West and West-central London., Participants: 100 consecutive AMD patients who attended casualty with vision loss fulfilling the following criteria: patients had received and been instructed in the use of Amsler charts according to the unit's dispensation protocol,fluorescein angiography which confirmed new SRN. Patients presented over 20 months. Outcome measures were detection of SRN by the Amsler chart, and laser treatment of SRN., Results: The Amsler chart surveillance protocol had detected SRN in 29 of the 100 patients. The surveillance protocol detected less than 30% of the specific patients who subsequently underwent laser treatment. A statistically significant difference was seen on comparing the ages of patients in whom the screening protocol was successful versus those in whom it was unsuccessful (student's t-test,P<3.2 x 103). Younger patients were more likely to be detected using the Amsler chart. A one-tailed Z2 test approached, but did not achieve, statistical significance (Z2 = 1.057,P <0.3) suggesting that patients who have already lost vision to SRN in one eye might not be more likely to be detected using the surveillance protocol than patients in whom SRN was affecting their first eye. In all, 38% of surveillance responders went on to receive laser therapy, compared with 37% of surveillance nonresponders., Conclusions: The current Amsler chart surveillance protocol is suboptimal for detecting SRN in AMD, and a proportion of cases suitable for early laser therapy may be missing rapid detection. The results are especially important since recent advances in laser therapy for SRN require early detection for optimal effectiveness.

Purpose: To re-assess the value of argon laser treatment for macular oedema in ischaemic branch retinal vein occlusion (I-BRVO)., Methods: Case series consisting of three patients with macular oedema following I-BRVO. Three patients were studied including two patients where ischaemia extended to include the foveal avascular zone (FAZ), with additional retinal neovascularisation in one of these. Heavy, overlapping areas of treatment were applied to the ischaemic retina up to 500 microns from the fovea., Results: All cases in the series benefited from significantly improved visual acuity. In one case laser was given several years after the initial retinal vasculopathy., Conclusions: Argon laser treatment may improve visual acuity in I-BRVO even with severe ischaemia extending into the FAZ. Treatment intensity must be sufficient to destroy ischaemic retina. Visual benefit may last for several years, and treatment can be undertaken several years after I-BRVO. The benefit to visual acuity of argon laser treatment in I-BRVO needs to be re-assessed in a prospective study.

Maltose binding protein (MBP) is widely used as a model for protein folding and export studies. We show here that macroscopic aggregates form transiently during the refolding of MBP at micromolar protein concentrations. Disaggregation occurs spontaneously without any aid, and the refolded material has structure and activity identical to those of the native, nondenatured protein. A considerable fraction of protein undergoing folding partitions into the aggregate phase and can be manually separated from the soluble phase by centrifugation. The separated MBP precipitate can be resolubilized and yields active, refolded protein. This demonstrates that both the soluble and aggregate phases contribute to the final yield of refolded protein. SecB, the cognate Escherichia coli cytosolic chaperone in vivo for MBP, reduces but does not entirely prevent aggregation, whereas GroEL and a variety of other control proteins have no effect. Kinetic studies using a variety of spectroscopic probes show that aggregation occurs through a collapsed intermediate with some secondary structure. The aggregate formed during refolding can convert directly to a near native state without going through the unfolded state. Further, optical and electron microscopic studies indicate that the MBP precipitate is not an amyloid.

Aim: To assess the accuracy of duplex in assessment of peripheral arterial disease and determine the effect of multisegmental disease on the accuracy duplex as opposed to single lesion., Patients and Methods: One hundred and seventy-seven lower limbs were examined in 90 patients who presented with lower limb arterial disease, (59 male, 31 female, median age 68 years--81 with intermittent claudication, eight rest pain, one ulceration). Patients were examined with duplex US, and arteriography (IA DSA). Two radiologists and two technologists were involved in this double-blind study. Patients were classified into five groups; groups with single stenotic lesions, single occlusions, multiple stenotic lesions or occlusions, and multiple mixed disease. Duplex accuracy was determined in each group., Results: Duplex was able to differentiate between normal and disease arterial segment with a sensitivity of 92%, specificity 99%, PPV 91%, and NPV 100% and Kappa 0.87. Sixty-six limbs were found to have single lesions, and 68 multisegmental disease. Duplex showed accuracy with a sensitivity of 87%, and specificity of 99%, for single stenotic lesion and 95%, 96% respectively for multisegmental. For single occlusions duplex accuracy showed sensitivity 92% and specificity 100%, and for multisegmental occlusions, sensitivity 97%, and specificity 99%. For mixed multisegmental pathology (stenosis and occlusion), sensitivity 94% and specificity 97%., Conclusion: Duplex is an accurate tool in diagnosis of lower limb arterial disease and multisegmental pathology does not adversely effect this accuracy.

Rapid kinetic studies of the unfolding of the small protein barstar by urea have been used to demonstrate the presence of at least two unfolding intermediates on two competing unfolding pathways. One intermediate has native-like secondary structure but has a partially solvated hydrophobic core, while the other is devoid of considerable secondary structure but has an intact hydrophobic core. It is shown that the transition states on the two pathways are very dissimilar structurally, but very similar energetically.

A commonly occurring sequence variant in the islet-specific promoter of the glucokinase gene (-30 G to A) has been variably reported to be associated with reduced insulin secretory responses to oral glucose. The effect of this promoter variant may be subtle and only become apparent under conditions of beta-cell 'stress'. As late pregnancy is a time of increased insulin secretory demand, we have examined whether this common genetic variant was associated with impairment of insulin secretory responses to oral glucose in 92 women in the third trimester of pregnancy. The three women who were homozygous for the variant sequence had a markedly diminished 30' insulin incremental response to oral glucose (10.4, 11.4, and 17.2 pmol insulin mmol-1 glucose, respectively) compared to either heterozygous (49.3 (37.6-64.6 pmol insulin mmol-1 glucose)) (p < 0.002) or homozygous wild-type (51.4 (40.9-64.7 pmol insulin mmol-1 glucose)) (p < 0.002) Mann-Whitney U test) women. In a subset of 35 British Caucasian women with gestational diabetes, no mutations resulting in a change of amino acid sequence were detected by molecular scanning of all exons of the glucokinase gene. In summary, in a cohort of 35 British Caucasian women with gestational diabetes neither missense nor nonsense glucokinase mutations were found. However, in women in the third trimester of pregnancy, homozygosity for a common polymorphic variant in the islet-specific promoter of the glucokinase gene was associated with a highly significant reduction of early insulin secretory responsiveness to oral glucose. Under the conditions of increased secretory demand represented by late pregnancy, a promoter variant in the glucokinase gene may influence the early insulin secretory response to oral glucose.

There are approximately 1.7 million Muslims in the UK. Followers of Islam observe certain religious and cultural practices during pregnancy and childbirth which midwives need to know and understand. Husband or children should not be used as interpreters as it is culturally unacceptable for many Muslim women to talk about intimate matters in front of their families. Midwives should not make assumptions when offering pain relief - in Islam pain is accepted as a natural part of childbirth. There may be some misconceptions about breastfeeding (for example, that colostrum is 'unclean'), and Muslim mothers - like all new mothers - need education and support.