Fluopyram Suppresses Population Densities of Heterodera glycines in Field and Greenhouse Studies in Michigan.

The soybean cyst nematode (SCN), Heterodera glycines Ichinohe, causes significant damage to soybean production annually. Fluopyram is a fungicide commonly used in soybean seed treatments intended to control soilborne fungal pathogens; however, recent studies have also suggested inhibitory effects on SCN. We examined the effects of a fluopyram seed treatment, ILeVO, on SCN reproduction, sudden death syndrome (SDS) development, and yield in a 3-year field study. Overall, fluopyram had a significant effect on yield (P = 0.046) and end-of-season SCN eggs and second-stage juveniles (Pf, P = 0.033) but no significant effect on SCN reproduction (Rf) or SDS disease index (P > 0.05). Post hoc tests indicated that fluopyram increased yield and suppressed SCN quantities. However, Rf was consistently greater than 1 whether or not the seed was treated with fluopyram, indicating that SCN populations were still increasing in the presence of fluopyram. A follow-up greenhouse study indicated that fluopyram reduced SCN relative to nontreated controls, as observed in the field, but only reduced SCN DNA within roots of a susceptible cultivar. These results indicate that fluopyram can suppress SCN quantities relative to nontreated seed but may not successfully reduce nematode populations without the use of additional management strategies.

Onchocerciasis control in the Democratic Republic of Congo (DRC): challenges in a post-war environment.

OBJECTIVE: To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). METHODS: Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. RESULTS: Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. CONCLUSIONS: Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC.

The rheumatoid arthritis susceptibility polymorphism PTPN22 C1858T is not associated with leflunomide response or toxicity.

WHAT IS KNOWN AND OBJECTIVE: A common polymorphism (C1858T) in the gene that encodes the protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with altered T-cell responses and increased susceptibility to rheumatoid arthritis (RA) and other autoimmune diseases. Teriflunomide, the active metabolite of leflunomide, reduces T-cell responses through inhibition of tyrosine kinase p56LCK. We examined a potential association between PTPN22 genotype and response or toxicity to leflunomide in Caucasian RA patients taking leflunomide in combination with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients enrolled in the Royal Adelaide Hospital RA inception cohort and taking leflunomide were eligible for inclusion. Participants were followed for 12 months after leflunomide initiation or until either another DMARD was added or leflunomide was ceased. Clinical response according to change in 28-joint Disease Activity Score (DAS28) and cessation due to toxicity were assessed. RESULTS AND DISCUSSION: A total of 94 participants were included in the study, 75 of whom carried the CC genotype, 18 the CT, whereas one individual carried the TT genotype. Over the first 12 months of leflunomide treatment, there was no statistically significant relationship between carrying the T allele and change in DAS28 (-0·84 vs. -1·15, P = 0·446) nor with cessation of leflunomide treatment due to side effects (P = 0·433). These results indicate that PTPN22 C1858T genotype has no effect on response or toxicity outcomes in leflunomide-treated RA patients. WHAT IS NEW AND CONCLUSION: This is the first study to evaluate the biologically plausible hypothesis that PTPN22 genotype might be a predictor of response/toxicity to leflunomide therapy. Despite this, PTPN22 genotype was not associated with leflunomide response or toxicity in patients with RA.

Drought legacy interacts with wildfire to alter soil microbial communities in a Mediterranean climate-type forest.

Mediterranean forest ecosystems will be increasingly affected by hotter drought and more frequent and severe wildfire events in the future. However, little is known about the longer-term responses of these forests to multiple disturbances and the forests' capacity to maintain ecosystem function. This is particularly so for below-ground organisms, which have received less attention than those above-ground, despite their essential contributions to forest function. We investigated rhizosphere microbial communities in a resprouting Eucalyptus marginata forest, southwestern Australia, that had experienced a severe wildfire four years previously, and a hotter drought eight years previously. Our aim was to understand how microbial communities are affected over longer-term trajectories by hotter drought and wildfire, singularly, and in combination. Fungal and bacterial DNA was extracted from soil samples, amplified, and subjected to high throughput sequencing. Richness, diversity, composition, and putative functional groups were then examined. We found a monotonic decrease in fungal, but not bacterial, richness and diversity with increasing disturbance with the greatest changes resulting from the combination of drought and wildfire. Overall fungal and bacterial community composition reflected a stronger effect of fire than drought, but the combination of both produced the greatest number of indicator taxa for fungi, and a significant negative effect on the abundance of several fungal functional groups. Key mycorrhizal fungi, fungal saprotrophs and fungal pathogens were found at lower proportions in sites affected by drought plus wildfire. Wildfire had a positive effect on bacterial hydrogen and bacterial nitrogen recyclers. Fungal community composition was positively correlated with live tree height. These results suggest that microbial communities, in particular key fungal functional groups, are highly responsive to wildfire following drought. Thus, a legacy of past climate conditions such as hotter drought can be important for mediating the responses of soil microbial communities to subsequent disturbance like wildfire.

Effects of oligosaccharides in a soybean meal-based diet on fermentative and immune responses in broiler chicks challenged with Eimeria acervulina.

Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may modulate fermentation in the ceca, thus affecting intestinal immune responses to intestinal pathogens. We hypothesized that fermentable oligosaccharides found in SBM would positively affect cecal fermentation and intestinal immune status in chicks challenged with an acute coccidiosis (Eimeria acervulina) infection and fed either a SBM-based diet or a semi-purified soy protein isolate- (SPI) based diet. Using a completely randomized design, 1-d-old broiler chicks (n = 200; 5 replications/treatment; 5 chicks/replication) were assigned to 1 of 4 SBM- or SPI-based diets containing either dietary cellulose (4%) or a fermentable carbohydrate, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex (4%). On d 9 posthatch, an equal number of chicks on each diet were inoculated with either distilled water (sham control) or E. acervulina (1 × 10(6) oocysts) and then euthanized on d 7 postinoculation. Overall, body weight gain and feed intake were greater (P < 0.01) for SBM-fed chicks, regardless of infection status. Gain:feed ratio was greater (P ≤ 0.05) for SPI-fed chicks except during d 3-7 postinoculation. Infection status, but not fiber source, affected propionate, isobutyrate, isovalerate, and total branched-chain fatty acid concentrations (P ≤ 0.02). Soybean meal-based diets resulted in greater (P ≤ 0.04) short-chain fatty acid and branched-chain fatty acid concentrations than SPI-based diets. Messenger RNA fold changes relative to uninfected SBM-cellulose-fed chicks of all duodenal cytokines were greater (P ≤ 0.01) for infected chicks, and SBM-fed chicks had greater (P < 0.01) interferon-γ and interleukin-12ß expression compared with SPI-fed chicks. Cecal tonsil cytokine expression was also affected (P ≤ 0.02) by infection; however, protein source only affected (P < 0.01) interleukin-1ß expression in this tissue. Overall, a SBM-based diet, compared with a semi-purified SPI-based diet with a different ingredient composition, resulted in greater weight gain, feed intake, and short-chain fatty acid production regardless of infection status, and also greater duodenal cytokine expression in E. acervulina- infected chicks, which is hypothesized to be related to the nutrients and oligosaccharides found in SBM.

The effects of a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex in broiler chicks challenged with Eimeria acervulina.

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against pathogenic infection. We hypothesized that a mannose-rich, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively impact immune status and prevent weight loss resulting from acute coccidiosis (Eimeria acervulina) infection of chicks. Using a completely randomized design, 1-d-old commercial broiler chicks (n = 160; 4 replications/treatment; 5 chicks/replication) were assigned to one of 4 corn-soybean meal-based diets containing supplemental GGMO-AX (0, 1, 2, or 4%) that replaced dietary cellulose. On d 9 posthatch, an equal number of chicks on each diet were inoculated with either distilled water (sham control) or E. acervulina (1 × 10(6) oocysts). All birds were euthanized on d 7 postinoculation (PI) for collection of cecal contents and duodenal tissue. Overall, BW gain of chicks was not affected by diet PI, whereas infection decreased (P < 0.01) weight gain on d 0 to 7 PI. Feed intake was not affected by dietary treatment, but infection decreased (P < 0.01) feed intake on d 0 to 7 PI. Overall, infection, but not diet, decreased (P < 0.01) G:F on d 0 to 7 PI. Cecal propionate concentrations were independently affected by infection and diet, while butyrate concentrations were affected only by infection (P = 0.02). Cecal Bifidobacterium spp. populations were affected (P < 0.01) by diet, with the 2% GGMO-AX resulting in the highest cfu/g of cecal contents (on a DM basis). Messenger RNA expression of all duodenal cytokines evaluated was affected by infection status (P ≤ 0.02) but not by dietary treatment alone. Supplementing 4% GGMO-AX consistently resulted in the greatest fold change in proinflammatory cytokine expression, while inhibiting antiinflammatory cytokine expression, which indicates a more robust innate immune response. Despite decreasing performance, 4% dietary GGMO-AX improved select fermentation indices and the innate intestinal immune response to an acute E. acervulina infection.

Ingestion of a novel galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex affected growth performance and fermentative and immunological characteristics of broiler chicks challenged with Salmonella typhimurium.

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against a pathogenic infection. We hypothesized that a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively affect immune status and prevent colonization and shedding in Salmonella typhimurium-infected chicks. Using a completely randomized design, 1-d-old commercial broiler chicks (n = 240 chicks; 4 replications/treatment; 5 chicks/replication) were assigned to 1 of 6 dietary treatments differing in concentration of GGMO-AX (0, 1, 2, or 4%) or containing 2% Safmannan or 2% short-chain fructooligosaccharides. Cellulose was used to make diets iso-total dietary fiber. On d 10 posthatch, an equal number of chicks on each diet were inoculated with either phosphate-buffered saline (sham control) or Salmonella typhimurium (1 × 10(8) cfu). All birds were euthanized on d 10 postinoculation (PI) for collection of intestinal contents and select tissues. Body weight gain and feed intake of chicks were greater (P < 0.05) in infected chicks PI for all time periods, except for weight gain on d 0 to 3 PI. Gain:feed was affected (P < 0.05) by diet, with Safmannan-fed chicks having the highest G:F and 1% GGMO-AX-fed chicks having the lowest. The GGMO-AX substrate demonstrated effects similar to a prebiotic substrate as indicated by increased cecal short-chain fatty acid concentrations, decreased cecal pH, and increased populations of Lactobacillus spp. and Bifidobacteria spp. as dietary GGMO-AX concentration increased. Excreta Salmonella typhimurium populations on d 5 and 10 PI, and ileal and cecal Salmonella typhimurium populations, tended to be affected (P < 0.10) by the main effect of diet. Messenger RNA expression of IFN-γ in the cecal tonsils was the only cytokine independently affected by infection and diet (P < 0.01). Chicks fed 2 and 4% GGMO-AX had similar expressions of IFN-γ and IL-1ß, regardless of infection, suggesting that Salmonella typhimurium virulence was suppressed. Dietary supplementation with GGMO-AX resulted in prebiotic-like effects but did not limit Salmonella typhimurium intestinal colonization or shedding, but possibly decreased the virulence of Salmonella typhimurium within the digestive tract.

Patient-reported outcomes predict survival and adverse events following anticancer treatment initiation in advanced HER2-positive breast cancer.

BACKGROUND: The prognostic value of patient-reported outcomes (PROs) has been minimally explored in advanced breast cancer (BC), and their comparative prognostic performance against Eastern Cooperative Oncology Group performance status (ECOG PS) is largely unknown. PATIENTS AND METHODS: This study pooled individual participant data from clinical trials CLEOPATRA, EMILIA, and MARIANNE. Pre-treatment PRO associations with overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events were evaluated via Cox proportional hazards regression. Prognostic performance was assessed with the C-statistic (c). PRO values were collected via the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. All analyses were stratified by study and treatment arms. Analyses adjusted for known prognostic variables were conducted. Exploratory analysis of the prognostic performance of PROs compared to ECOG PS was undertaken. RESULTS: The study included data from 2894 patients initiated on contemporary therapies including pertuzumab (n = 765), trastuzumab (n = 1173), trastuzumab emtansine (n = 1225), taxanes (n = 1173), lapatinib (n = 496), and capecitabine (n = 496). On univariable and adjusted analysis, patient-reported physical well-being, functional well-being, and BC subscale were all identified to be associated with OS, PFS, and grade ≥3 adverse events (P < 0.05). Patient-reported physical well-being was the most prognostic PRO for all assessed outcomes. The OS prognostic performance of physical well-being (c = 0.58) was superior to ECOG PS (c = 0.56) (P < 0.05), with multivariable analysis indicating that both provide independent information (P < 0.0001). CONCLUSIONS: PROs were identified as independent prognostic factors for OS, PFS, and grade ≥3 adverse events in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced BC initiating contemporary treatment options. Further, patient-reported physical well-being was more prognostic of OS than ECOG PS and contained independent information. PROs have value as prognostic and stratification factors for clinical use and research trials of anticancer treatment in HER2-positive ABC.

Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines.

BACKGROUND: The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a key role in the signalling of stalled replication forks and DNA damage to cell cycle checkpoints and DNA repair. It has long been recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. METHODS: Cellular ATR kinase activity was determined by CHK1 phosphorylation in human fibroblasts with inducible dominant-negative ATR-kinase dead expression and human breast cancer MCF7 cells. Cell cycle effects and chemo- and radiopotentiation by NU6027 were determined in MCF7 cells and the role of mismatch repair and p53 was determined in isogenically matched ovarian cancer A2780 cells. RESULTS: NU6027 is a potent inhibitor of cellular ATR activity (IC(50)=6.7 µM) and enhanced hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. In A2780 cells sensitisation to cisplatin was greatest in cells with functional p53 and mismatch repair (MMR) and sensitisation to temozolomide was greatest in p53 mutant cells with functional MMR. Importantly, NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1. CONCLUSION: NU6027 inhibits ATR, impairing G2/M arrest and homologous recombination thus increasing sensitivity to DNA-damaging agents and PARP inhibitors. It provides proof of concept data for clinical development of ATR inhibitors.

Using qualitative research to improve tissue viability care.

This article discusses how key qualitative studies investigating patient experiences can act as an indicator of quality and guide healthcare professionals in service development and evaluation in tissue viability. There is a wealth of information available to suggest that leg ulceration affects individuals' quality of life. Commissioners are requesting that clinicians demonstrate quality-based outcomes for patients with leg ulcers to improve care and service provision.

Short-term and medium-term clinical outcomes of quinolone-resistant Campylobacter infection.

BACKGROUND: Campylobacter species is a leading cause of bacterial gastroenteritis worldwide. Quinolone resistance has emerged as an increasing problem among persons with Campylobacter infection over the past decade, but the clinical consequences are unclear. METHODS: A case-comparison study of patients infected with ciprofloxacin-resistant or ciprofloxacin-susceptible Campylobacter species was conducted in Wales during the period 2003-2004. Campylobacter isolates were classified as resistant or susceptible to ciprofloxacin on the basis of standardized disk diffusion methods. Participants were interviewed by telephone at the time of illness, 3 months later, and 6 months later to compare disease severity, duration of illness, and medium-term clinical outcomes. RESULTS: There was no difference between 145 persons with ciprofloxacin-resistant infection and 411 with ciprofloxacin-susceptible infection with regard to the severity or duration of acute illness. Mean duration of diarrhea was similar in patients with ciprofloxacin-resistant versus ciprofloxacin-susceptible infection (8.2 vs. 8.6 days; P = .57) and did not alter significantly after adjustment for potential covariates, including age, underlying disease, foreign travel, use of antidiarrheal medication, and use of antimicrobials in a multiple linear regression model. There was no difference between case patients and comparison patients in the frequency of reported symptoms or in general practitioner consultation rates at either the 3-month or the 6-month follow-up interview. CONCLUSIONS: In this study, there was no evidence of more-severe or prolonged illness in participants with quinolone-resistant Campylobacter infection, nor was there evidence of any adverse medium-term consequences. This suggests that the clinical significance of quinolone resistance in Campylobacter infection may have been overestimated.

Risk factors for ciprofloxacin-resistant Campylobacter infection in Wales.

OBJECTIVES: To identify risk factors for ciprofloxacin resistance in both travel-related and domestically acquired Campylobacter infection. METHODS: Case-comparison study of patients with ciprofloxacin-resistant and ciprofloxacin-susceptible Campylobacter infection conducted in Wales during 2003 and 2004. RESULTS: Foreign travel was the major risk factor for ciprofloxacin-resistant infection [adjusted odds ratio (adjOR) 24.0, 95% confidence interval (95% CI) 12.6-45.9]. Among travellers, case patients were five times more likely to drink still bottled water (adjOR 4.7, 95% CI 1.0-21.7), whilst among non-travellers, case patients were three times more likely to drink sparkling bottled water (adjOR 3.3, 95% CI 1.5-7.4). There was no increased risk associated with eating poultry or prior quinolone use. CONCLUSIONS: Foreign travel remains the most important risk factor for ciprofloxacin-resistant Campylobacter infection. The possible association of both domestic- and travel-related ciprofloxacin-resistant Campylobacter infection with bottled water needs to be further explored.

Challenges for the integration of mass drug administrations against multiple 'neglected tropical diseases'.

Simple and safe medications for some of the common, but often neglected, diseases that afflict the poor are not only available but are often donated. Other medications indicated for neglected diseases are extremely cheap and cost-effective. These drugs can be administered together and combined, when feasible, into rapid-intervention packages based on mass drug administrations. It is therefore logical to integrate mass drug administrations when possible. Integration is, however, not always as simple as it seems, and 'integration' means different things to different people. Drugs are needed at different frequencies for different lengths of time, sometimes for the whole population, sometimes only for children. Care has to be taken that parallel systems are not created that bypass primary healthcare. Much can be achieved, however, by sensible integration, whether it be in the mapping of diseases or the setting up of treatment platforms that tackle several diseases at once. As governments and international organizations seek to create policies for integration that include not only mass drug administration but also morbidity control, and as various partnerships develop for implementation, there is the possibility to scale up health interventions, which will have a very positive impact on the poorest communities globally. Nevertheless, integration should not be forced for the sake of policy. Where things fit well they should be developed, where not, coordination within the primary-healthcare system can produce an equally long-lasting impact.

Minimal-resection arthroplasty to treat meniscal tears with associated condyle lesions: finite element analysis.

An early intervention prosthesis which minimizes the extent of resected healthy bone would be advantageous to patients for whom a total or unicompartmental replacement would sacrifice extensive healthy tissue. In this study the use of a device to treat osteoarthritis localized upon a single condyle of the femur with an associated irreparable meniscal tear is considered. The effects of implant alignment are considered from the standpoint of kinematics and potential for cartilage damage. The results suggest that alterations in implant position influence joint kinematics during stance. Anteroposterior (AP) adjustment of the medial prosthesis minimizes the capability of the knee to rotate internally, placing higher demands on the cruciate ligaments. AP adjustments of the lateral prosthesis induces greater posterior drawback, reducing internal-external rotation. Natural knee kinematics are best reproduced by the medial condyle rather than the lateral condyle. Stress exposure of the cartilage increased with the introduction of the femoral condyle prosthesis, which may progress eventually to osteoarthritis, although the results indicate that the medial condyle device is less likely to lead to cartilage damage than is lateral condyle replacement. This study demonstrates that a minimal-resection femoral condyle device may provide sufficient knee joint function to serve as an interim treatment prior to total or unicompartmental knee arthroplasty.

Primary stability in reversed-anatomy glenoid components.

Reversed-anatomy shoulder replacement is advocated for patients with poor rotator cuff condition, for whom an anatomical reconstruction would provide little or no stability. Modern generations of this concept appear to be performing well in the short-term to midterm clinical follow-up. These designs are almost always non-cemented, requiring a high degree of primary stability to encourage bone on-growth and so to establish long-term fixation. Six different inverse-anatomy glenoid implants, currently on the market and encompassing a broad range of geometrical differences, were compared on the basis of their ability to impart primary stability through the minimization of interface micromotions. Fixing screws were only included in the supero-inferior direction in appropriate implants and were always inclined at the steepest available angle possible during surgery (up to a maximum of 30 degrees). The extent of predicted bony on-growth was, of course, highly dependent on the threshold for interface micromotion. In some instances an additional 30 per cent of the interface was predicted to promote bone on-growth when the threshold was raised from 20 microm to 50 microm. With maximum thresholds of micromotion for bone on-growth set to 30 microm, the Zimmer Anatomical device was found to be the most stable of the series of the six designs tested herein, achieving an additional 3 per cent (by surface area) of bone on-growth above the closest peer product (Biomet Verso). When this threshold was raised to 50 microm, the Biomet Verso design was most stable (3 per cent above the second-most stable design, the Zimmer Anatomical). Peak micromotions were not a good indicator of the predicted area of bone on-growth and could lead to some misinterpretation of the implant's overall performance. All but one of the implants tested herein provided primary stability sufficient to resist motions in excess of 150 microm at the interface.

[Comparing specific disc findings of a European and a Bantu population]. / Vergleich papillenspezifischer Parameter einer europäischen und einer Bantu-Population.

BACKGROUND: Glaucoma is the main cause of irreversible blindness in the world. Because of the increasing mean age, glaucoma is expected to become more common in the developing countries. Besides tonometry and perimetry the appearance of the optic nerve head is a main part of glaucoma diagnosis. Ethnic differences have to be considered. This study compares the appearance of the optic nerve head between blacks and whites. STUDY DESIGN: This is a retrospective analysis of 225 whites of a Swiss population and 1027 blacks of a Congolese population. Using a matched pairs technique 207 whites and 207 blacks were chosen, regarding age, sex, intraocular pressure and examined eye (right/left). The analysis of the optic nerve head was performed by using the "Heidelberg-Retina-Tomograph II" (HRT). RESULTS: Among the 207 persons of both groups we found 116 females and 91 males. There were 103 right eyes and 104 left eyes examined. The mean age was 45.6 +/- 15.6 years. Compared with European population in the African population we found a greater disc area (2.56 vs. 1.81 mm(2)) as well as a greater cup area (0.65 vs. 0.41 mm(2)) and a greater rim area (1.91 vs. 1.40 mm(2)). Regarding the cup disc area ratio there was no significant difference between both populations found (Kinshasa: 0.24 vs. Basel: 0.21). Although there was no significant difference of the maximum cup depth of both groups we found a deeper mean cup depth in the African population. Furthermore, we found differences regarding the cup shape measure, the RNFL thickness and the height variation contour. CONCLUSION: As already described in different studies, there are significant differences in the morphology of the optic nerve head between blacks and whites. Although blacks are expected to have a greater cup disc area ratio, this fact could not be proved in this study. As a new fact we found a different mean cup depth between Africans and Europeans, which might be explained by the different cup shape of both populations.

Efficacy of Proximal Resin Infiltration on Caries Inhibition: Results from a 3-Year Randomized Controlled Clinical Trial.

This study reports 3-y outcomes of a split-mouth randomized clinical trial. Resin infiltration's capacity to arrest caries lesion progression in noncavitated proximal lesions is affirmed. Forty-two consented young adults, blinded to tooth surface allocation, were treated with resin infiltration on 1 randomly selected surface and concurrently experienced a mock infiltration procedure on another. Both treatments were provided as an adjunct to the currently accepted standard-of-care regimen (periodic prophylaxis and serial fluoride varnish applications) appropriate for the management of high caries risk. Challenging periods of low oral hygiene compliance were expected. The primary outcome measure was 3-y radiographic lesion progression. Blinded investigators evaluated each study surface for lesion progression with a series of images obtained at intervals over the 3-y course of study. Proportions of progressing lesions were compared with McNemar's test. Twenty-nine noncavitated lesion pairs in permanent posterior teeth demonstrating caries penetrating into inner enamel or outer dentin were included in the analyses. No adverse events were reported. Radiographic progression was recorded in 4 of 29 infiltrated lesions (14%) and 14 of 29 control lesions (48%, P < .003). Adjunct resin infiltration demonstrated a high 3-y efficacy of 71% (relative risk reduction). The prevented fraction was 86% for infiltration versus 52% for controls. Resin infiltration was 100% successful in arresting caries progression in inner enamel lesions (E2) and 64% in outer dentin lesions (D1). Supplementary microinvasive resin infiltration is significantly more efficacious in reducing proximal lesion progression than management by standard noninvasive therapy alone. Long-term results may shed light on whether this represents the arrest or delay of the caries disease process (ClinicalTrials.gov NCT01584024).

How compliant are we with guidelines for coronary angiography in clinical practice?

BACKGROUND: The American College of Cardiology and American Heart Association have published guidelines for coronary angiography. We evaluated the compliance rate with these guidelines in clinical practice, its correlation to results of angiography and aimed to identify problem areas of non-compliance. METHODS: We prospectively evaluated 802 consecutive referrals for coronary angiography over 5 months in 2002 in a tertiary referral hospital. These referrals were assessed by two independent reviewers blinded to the results of angiography. RESULTS: Patient age was 62 +/- 11 years (522 men, 433 inpatients, 369 day-only patients). Referrals were outside published guidelines in 34.3 and 36.2% as evaluated by the two reviewers (concordance rate 88.2%, kappa = 0.74, p < 0.001). Intraobserver agreement was 97.5%. The rate of angiography showing either normal arteries or only minor diseases (<50%) was higher for referrals outside guidelines (68.4 vs 22.6%, P < 0.001). Compliance rate was high with indications of non-ST-elevation myocardial infarction (99.2%) and ST-elevation myocardial infarction (95.8%), valvular disease (80%) and arrhythmia (80%). Compliance rate was lower with assessment of dyspnoea or heart failure (74.3%) and before non-cardiac surgery (72.7%) and was particularly low with assessment of chest pain (53.2%). Younger age (odds ratio (OR) 1.04, P < 0.001), female sex (OR 2.67, P < 0.001), day-only procedure (OR 2.27, P < 0.001) and non-invasive cardiologist referrer (OR 1.41, P = 0.046) were independent predictors of non-compliance. CONCLUSION: Referrals for coronary angiography were outside guidelines in a significant proportion of patients. Rate of negative angiography was higher when the referrals were outside guidelines. Problematic areas of non-compliance could be identified. Measures specifically targeting these areas may be more effective in improving the overall guideline compliance in clinical practice.

The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design.

BACKGROUND: HIV reverse transcriptase (RT) is a key target of anti-AIDS therapies. Structural studies of HIV-1 RT, unliganded and complexed with different non-nucleoside inhibitors (NNIs), have pointed to a common mode of binding and inactivation through distortion of the polymerase catalytic site by NNIs containing two hinged rings. The mode of binding of the TIBO family of inhibitors is of interest because these compounds do not fit the two-hinged-ring model. RESULTS: The structure of HIV-1 RT complexed with 9-chloro-TIBO (R82913) has been determined at 2.6 A resolution. As reported for the lower resolution analysis of another TIBO compound, this inhibitor binds at the same site as other NNIs, but our higher resolution study reveals the Cl-TIBO is distorted from the conformation seen in crystals of the inhibitor alone. This allows Cl-TIBO to mimic the binding of NNIs containing two hinged rings. Inhibitor-protein interactions are again predominantly hydrophobic and the protein conformation corresponds to that seen in complexes with other tight-binding NNIs. CONCLUSIONS: Although Cl-TIBO is chemically very different from other NNIs, it achieves remarkable spatial equivalence and shape complementarity with other NNIs on binding to RT. Comparison of the different RT-NNI complexes suggests modifications to the TIBO group of inhibitors which might enhance their binding and hence, potentially, their therapeutic efficacy.

Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial.

BACKGROUND: The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300µg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. METHODS: Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15µg and a randomized dose of 50, 100, or 150µg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. RESULTS: There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150µg groups than the 50µg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. CONCLUSION: The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50µg produces analgesia similar to that produced by either 100µg or 150µg.