Serum Cholesterol Efflux Capacity in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Purpose: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD). Design: Case-control study. Participants: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants. Methods: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and lipoprotein subfractions measured using nuclear magnetic resonance (Nightingale, Ltd). Associations between cholesterol efflux capacity (measured in percentage) and lipid subfractions were investigated in the patients and control participants. Main Outcome Measures: Cholesterol efflux capacity and lipid subfractions in control, eAMD, and nAMD. Associations between HDL subfractions and cholesterol efflux capacity. Results: Cholesterol efflux capacity was higher in patients with eAMD (68.0 ± 11.3% [mean ± standard deviation]) and nAMD (75.9 ± 27.7%) than in the control participants (56.9 ± 16.7%) after adjusting for age, gender, and use of lipid-lowering drug (P < 0.0001). Nuclear magnetic resonance lipidomics demonstrated that the mean diameter of HDL was larger both in eAMD (9.96 ± 0.27 mm [mean ± standard deviation]) and PCV (9.97 ± 0.23 mm) compared with that of the control participants (9.84 ± 0.24 mm; P = 0.0001 for both). Among the 28 HDL subfractions, most of the small, medium, and large HDLs, but none of the 7 extra large HDLs fractions, were associated moderately with cholesterol efflux capacity in eAMD and PCV (R = 0.149-0.277). Conclusions: Serum cholesterol efflux capacity was increased in eAMD and PCV, but not tAMD, possibly reflecting differential underlying pathophysiologic features of lipid dysregulation in tAMD and PCV. Further studies should be directed toward investigating the diverse biological activities of HDL in AMD, including macular pigment transport, regulation of inflammation, and local cholesterol transport system.

The implementation of an advanced practice radiation therapy (APRT) program in Singapore.

BACKGROUND: The exploration of Advanced Practiced Radiation Therapists (APRTs) development in Singapore started in 2011. This study aims to provide an overview of the development of the APRT roles, and to discuss the approaches used to develop and implement these roles in Singapore. MATERIALS AND METHODS: A mixed methods approach was used in the development of the APRT program. A literature review was carried out to define the APRT scope of practice and core responsibilities. A competency and assessment framework were setup to assess the core competency areas. With this framework, a structured 1-year residency training program was developed. RESULTS: The scope of practice and core responsibilities of APRTs were defined with five proposed advanced practice profiles being successfully validated. A competency framework was set up to assess the core competency domains: clinical, technical and professional competencies, research, education and leadership. A 4-point scoring system was developed for the competency assessment based on two criteria; the frequency with which RTTs would demonstrate competency, and the ability of performing the task competently. A 1-year structured APRT residency program was developed and implemented. The programme consisted of structured lectures, and clinical practice-based modules where APRT residents receive structured mentoring under a mentorship program. CONCLUSION: The APRT program in Singapore employed an evidence-based implementation process that tested the feasibility of a new practice model. Multidisciplinary involvements, mentorship and clinical training were important factors for the success of the APRT program.

The Impact of Radiotherapy and Histological Risk Factors on Outcomes in Malignant Phyllodes Tumors.

PURPOSE: Breast phyllodes tumors (PT) are classified into benign, borderline, and malignant grades based on histopathologic characteristics. Specific to malignant PT (MPT), surgery is the mainstay yet relapse rates are high and knowledge gaps in the literature exist regarding adjuvant radiotherapy (RT). We aimed to investigate the outcomes of patients with MPT treated in a tertiary Asian institution. METHODS AND MATERIALS: Patients with nonmetastatic MPT treated from February 1992 to June 2019 were analyzed retrospectively. RT details and relapse fields were studied. Outcomes of patients with and without RT were compared and hazard ratios were calculated using Cox proportional hazard test. Multivariable analysis was performed. RESULTS: Twenty-two of 89 patients received adjuvant RT and the median dose was 60 Gy. In the no-RT group, 4 patients received RT on relapse and had no further recurrences; a further 2 received RT for fungating relapses with good symptomatic relief. RT was only increasingly prescribed after 2004. Median follow-up in the RT group was 3.31 years, compared with 6.17 years in the no-RT group. In the RT group, 15 patients (68.2%) underwent mastectomy, versus 39 (58.2%) in the no-RT group. One patient in the RT group developed an infield local relapse, compared with 21 of 67 patients in the no-RT group. Multivariate model showed that RT decreased risk of locoregional failure (hazard ratio 0.12, 95% confidence interval [CI] 0.02-0.92, P = .04). Three-year locoregional recurrence-free survival was higher in the RT group, 92.3% (95% CI, 78.9-100) versus 73.3% (95% CI, 63.1-85.1) in the no-RT group (P = .03). There were no differences in 3-year survival. CONCLUSIONS: We recommend that adjuvant radiotherapy be discussed for malignant PT for local control, even after mastectomy.

Tailoring adjuvant radiotherapy for stage IB-IIA node negative cervical carcinoma after radical hysterectomy and pelvic lymph node dissection using the GOG score.

OBJECTIVE: The use of adjuvant radiotherapy for early stage node negative patients varies for different institutions. The recognized factors such as deep stromal invasion, lymph vascular space invasion, and size of tumor are the most common factors cited for adjuvant radiotherapy. Studies done have shown that this increases local control but may increase chronic toxicity rates. We report on our use of the GOG score to tailor our treatment decisions. METHODS: A review of all patients staged IB-IIA who underwent Type 3 Radical Hysterectomy and pelvic lymph node dissection (RH) from 1997 to 2007. The GOG score proposed by Delgado et al. was applied, and patients were stratified into 3 groups; <40: no adjuvant treatment, 40-120: Small Field RT (SmRT), and >120: Standard Field RT (StRT) RESULTS: A total of 126 patients matched these criteria. Sixty one patients underwent either SmRT or StRT. There were only 2 known relapses and one death due to inter current illness. The median follow up was 57 months and the 5 year Disease Free Survival was 98.2%. There were no documented Grade 3 or 4 chronic toxicities. There were significantly less (p=0.025) patients with lower limb lymphedema in the SmRT group compared to StRT. CONCLUSION: Our study confirms the utility of the GOG score to tailor radiotherapy for this cohort of patients. This has been proven to be high in efficacy and low in morbidity.

Activation of single-chain urokinase-type plasminogen activator by platelet-associated plasminogen: a mechanism for stimulation of fibrinolysis by platelets.

BACKGROUND AND OBJECTIVE: Platelets are essential for hemostasis, and they cause resistance to fibrinolysis by tissue-type plasminogen activator. In contrast, platelets enhance fibrinolysis mediated by single-chain urokinase-type plasminogen activator (scu-PA). This study investigated the mechanism behind this profibrinolytic role of platelets. METHODS AND RESULTS: Platelets enhanced scu-PA activity, but not urokinase-type plasminogen activator (u-PA) activity, in plasma clot lysis and chromogenic assays. We established, using the non-cleavable scu-PA mutant (Lys158-->Glu) and protease inhibitors, that platelets increased activation to u-PA by a serine protease. Activation of scu-PA was platelet-dependent, even in plasma. It occurred in platelet-rich but not in platelet-poor plasma, as assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis and zymography after addition of plasminogen activator inhibitor-1. Candidate proteases that are known to activate scu-PA and are present in platelet preparations were investigated. Factor VII activating protease was detected in platelet preparations by western blotting, but its inhibition by antibodies did not inhibit activation of scu-PA by platelets. Plasmin and plasma kallikrein both mimicked the platelet effect, but were distinguished by their responses to a range of inhibitors. Analysis of platelet-associated protease activity and the time course of scu-PA activation pointed towards plasminogen, and the data were consistent with a mechanism of reciprocal activation. The essential role of plasminogen was revealed using platelets from plasminogen-deficient mice, which could not activate scu-PA. Local plasminogen on platelet membranes was markedly more effective than solution-phase plasminogen in activation of scu-PA. CONCLUSIONS: Platelets enhance fibrinolysis by scu-PA through reciprocal activation of scu-PA and platelet-associated plasminogen, a system that is potentially important in the lysis of platelet-rich thrombi.

Identification of a resistance gene Rpi-dlc1 to Phytophthora infestans in European accessions of Solanum dulcamara.

Initial screening of 14 Solanum dulcamara accessions enabled the identification of individuals resistant and susceptible to Phytophthora infestans. Crosses between contrasting genotypes resulted in three F(2)-BC(1) populations segregating for resistance to late blight in a laboratory assay and under field conditions. Genetic profiling of one of these populations using 128 AFLP primers generated three markers linked to the resistant phenotype. Blast analysis of the sequenced markers resulted in a plausible gene position on the distal end of the long arm of chromosome 9 that could be confirmed by CAPS markers. Thus, we describe a first resistant gene, named Rpi-dlc1, from S. dulcamara, a Solanum species native to Europe. In addition, one population was tested for broadness of resistance responses using a set of seven additional P. infestans isolates, varying in virulence. This indicated the possible presence of additional Rpi genes.

Margin of manoeuvre indicators in the workplace during the rehabilitation process: a qualitative analysis.

INTRODUCTION: The task of evaluating workers' capacity to return to their pre-injury employment or other jobs continues to pose a daily challenge for clinicians. In this study, a concept frequently used in the field of ergonomics, the margin of manoeuvre (MM), was applied during the rehabilitation process. The study identified the indicators of the MM taken into account during the return to work of workers with musculoskeletal disorders. METHODS: This study used a multiple-case design. A case was defined as a dyad comprising a worker admitted to a work rehabilitation program and the clinician who was managing the return-to-work process. The results were then validated with investigators and expert ergonomists, through group interviews. Content analyses were performed using the conceptual framework for the work activity model adapted from Vézina and the procedures recommended by Miles and Huberman. RESULTS: A total of 11 workers, five clinicians, two experts and two investigators participated in this study. The interview analysis process resulted in a more detailed definition of the MM and the identification of 50 indicators. The indicators were classified according to six dimensions: (1) work context; (2) employer's requirements and expectations; (3) means and tools; (4) worker's personal parameters; (5) work activity; and (6) impacts of the work situation. CONCLUSIONS: The more specific indicators identified in this study will allow for more systematic observation of the MM. Subsequent studies will seek to link each indicator described in the model with a specific method of observation.

Workplace interventions for workers with musculoskeletal disabilities: a descriptive review of content.

BACKGROUND: Despite the convergence of scientific data to the effect that interventions in the workplace promote a healthy return to work, the interventions carried out in the real work environment appear to be very heterogeneous and ill-defined. OBJECTIVE: The goal of this review is to identify the different objectives pursued through the workplace interventions carried out in the context of a rehabilitation program, and to describe the activities involved. METHODS: A descriptive review of the literature, including various research designs, was carried out. RESULTS: This review reveals great heterogeneity in the content of interventions offered in the workplace to workers with musculoskeletal disabilities. The objectives of workplace interventions may range from gathering information in order to reproduce work demands in a clinical setting, to gradually exposing workers to the demands of the real work environment, or permanently reducing the demands of the work situation. A descriptive analysis of the literature also brings to light the diversity of actions carried out, human resources used, and workplace environments involved, while highlighting the few documented process outcome evaluations that have been done of workplace interventions. CONCLUSION: It is recommended that in future research in this area, efforts be made to better describe the components of the interventions, to develop process outcomes representing the multidimensional results obtained in the workplace, and to differentiate between temporary and permanent modifications made to the work situation.

Precision of conjunctival provocation tests in right and left eyes.

BACKGROUND: Conjunctival provocation tests (CPTs) are used for assessing the efficacy of antiallergic treatments, but their reproducibility is not well characterized. A study was carried out to assess the reproducibility of CPTs and the release of mediators during CPTs. METHODS: Both eyes of 30 grass-pollen-allergic patients were challenged with threefold increasing concentrations of a standardized orchard grass pollen extract. The positivity of the CPT was assessed by a cumulative symptom score. The release of mediators was examined by means of histamine (radioimmunoassay), prostaglandin D2 and leukotrienes C4 and D4 (enzyme immunoassay). RESULTS: There was a significant correlation between the concentrations of allergen inducing a positive CPT in both eyes (p < 0.0001, Spearman). All but one patient had a significant release of at least one mediator. After allergen CPT there was a significant release in both eyes in 13 of 20 patients for prostaglandin D2, 11 of 19 for leukotrienes C4 and D4 and 15 of 18 for histamine. The correlations between the levels of mediators released during diluent and allergen challenges in both eyes were significant for prostaglandin D2 (diluent and allergen challenges) and leukotrienes C4 and D4 (allergen challenge). CONCLUSION: Considering the whole group of patients, CPT is reproducible in both eyes, but the results are less satisfactory when patients are examined individually.

[An unknown cause of deep lymphadenopathies: polyethylene histiocytosis related to a joint prosthesis]. / Une cause méconnue d'adénopathies profondes: histiocytose ganglionnaire au polyéthylène, satellite de prothèse articulaire.

A case of deep seated lomboaortic lymph node enlargement, due to a storage hitiocytosis by fragments of polyethylene, draining the site of hip joint prosthesis is reported. These lymph node enlargement, made visible by tomodensitometry, were satellites of an ovarian adenocarcinoma. The artificial hip joint operation had taken place 17 years before and 10 years later the patient underwent a secondary operation to replace the prosthesis of the right hip. To the knowledge of the authors this is the first recorded case of lymph node enlargement due to a storage histiocytosis in response to debris shed from hip prosthesis being made visible by way of a radiological examination.

DNA polymerase B from wheat embryos: a plant delta-like DNA polymerase.

Studies in eucaryotic cells (mainly animals and yeast) indicate that at least two DNA polymerases are involved in DNA replication at the level of the replication fork: DNA polymerase alpha, which is associated with DNA primase, is involved in the replication of the lagging strand; DNA polymerase delta, associated with an exonuclease activity, synthesizes the forward continuous DNA strand. Much less information exists concerning plant systems. Previous work from this laboratory provided preliminary evidence of an association between DNA polymerase B from wheat embryo and an exonucleolytic activity. In this paper, we present additional data on the biochemical properties of DNA polymerase B. An improved purification procedure described in this article has been developed. During all the purification steps the nuclease activity was associated with DNA polymerase activity. A biochemical study of this enzyme activity shows that it is an exonuclease which hydrolyses DNA in the 3' to 5' direction. Moreover, this exonuclease confers a proofreading function to DNA polymerase B. Comparison of DNA polymerase B properties (template specificity, sensitivity to DNA replication inhibitors like aphidicolin and butyl-phenyl dGTP, copurification of DNA polymerase and exonuclease activities) with those of animal DNA polymerase delta indicates that these enzymes share many common features. To our knowledge, this is the first report of DNA polymerase delta in higher plants.

Use of collagen shields in the treatment of herpetic keratitis.

Eighteen patients with typical Herpes simplex virus dendritic keratitis confirmed by viral isolation were treated with corneal collagen shields presoaked with trifluorothymidine for 15 minutes and trifluorothymidine eye drops 5 times daily. The average healing time was 2.9 days (range 1-7 days). No allergic reactions were observed. Toxic punctate keratitis occurred in 3 eyes. The results of this open study suggest that the effect of collagen corneal shields in conjunction with trifluorothymidine shortens the average epithelial healing time compared with other studies that have used antiviral drugs alone.