Global optical coherence tomography measures for detecting the progression of glaucoma have fundamental flaws

ObjectiveTo understand the problems involved in using global OCT measures for detecting progression in early glaucoma.Subjects/MethodsEyes from 76 patients and 28 healthy controls (HC) had a least two OCT scans at least 1 year apart. To determine the 95% confidence intervals (CI), 151 eyes (49 HC and 102 patients) had at least two scans within 6 months. All eyes had 24-2 mean deviation ≥-6dB. The average (global) thicknesses of the circumpapillary retinal nerve fibre layer (cRNFL), G_ONH, and of the retinal ganglion cell layer plus inner plexiform layer (RGCLP), G_mac, were calculated. Using quantile regression, the 95% CI intervals were determined. Eyes outside the CIs were classified as “progressors.” For a reference standard (RS), four experts evaluated OCT and VF information.ResultsCompared to the RS, 31 of the 76 (40.8%) patient eyes were identified as progressors (RS-P), and 45 patient, and all 28 HC, eyes as nonprogressors (RS-NP). The metrics missed (false negative, FN) 15 (48%) (G_ONH) and 9 (29%) (G_mac) of the 31 RS-P. Further, G_ONH and/or G_mac falsely identified (false positive, FP) 10 (22.2%) of 45 patient RS-NP eyes and 7 (25%) of the 28 HC eyes as progressing. Post-hoc analysis identified three reasons (segmentation, centring, and local damage) for these errors.ConclusionsGlobal metrics lead to FPs and FNs because of problems inherent in OCT scanning (segmentation and centring), and to FNs because they can miss local damage. These problems are difficult, if not impossible, to correct, and raise concerns about the advisability of using G_ONH and G_mac for detecting progression.Subject terms: Optic nerve diseases, Tomography     

Survival study of breast cancer patients treated at the hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil

This retrospective hospital-based study aimed to describe health conditions and to estimate the survival of 252 patients diagnosed with breast cancer and treated at the Mastology Outpatient Clinic at the University Hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil, from 1980 to 2000. Analysis followed the Kaplan-Meier and Cox model. Mean age was 54, and 73.4% of the patients had a histological diagnosis of invasive ductal carcinoma, 63.9% showed no lymph node involvement, and 57.6% were clinical stage II. At the end of the study, 64.7% were alive and free of breast cancer and 5.1% had died of other causes. Five-year survival was 87.7% for all women, and prognostic factors associated with survival were tumor size (HR = 12.03; > 5cm), lymph node involvement (HR = 3.08; N1) and number (HR = 4.66; None), and estrogen (HR = 0.34) and c-erbB-2 (HR = 2.51) receptors. Based on the results, intensive awareness-raising campaigns are vitally important for implementing breast cancer screening to achieve early diagnosis.     

Histopathological effects of [D-Leu]Microcystin-LR variants on liver, skeletal muscle and intestinal tract of Hypophthalmichthys molitrix (Valenciennes, 1844)

This study evaluated the effects of [D-Leu¹]Microcystin-LR variants, by the exposure of Hypophthalmichthys molitrix to Microcystis aeruginosa NPLJ4. Fish was placed in aquariums and exposed to 10⁵ cells mL⁻¹. For 15 days, 05 individuals were removed every 05 days, and tissue samples of liver, skeletal muscle and intestinal tract were collected for histopathologic analyses. Following exposure, those surviving were placed in clean water for 15 days to evaluate their recovery. A control without toxins was maintained in the same conditions and exhibited normal histology and no tissue damage. In exposed fish, samples were characterized by serious damages that similarly affected the different organs, such as dissociation of cells, necrosis and haemorrhage. Samples showed signs of recovery but severe damages were still observed. The results should be valuable to analyze the potency of microcystin toxicity and to help in the diagnosis of fish deaths.     

Use of remote sensing to study the influence of environmental changes on malaria distribution in the Brazilian Amazon

Construction of the Tucuruí hydroelectric dam in Southeast Pará State, Brazil, in 1981, caused enormous environmental changes, deforestation, and human migration to the region. This study focuses on the influence of these changes and the appearance of malaria in the municipality of Jacundá, Pará, using remote sensing and geographic information systems. The variables used to construct maps were distances from roads, farming areas, rivers, the dam, streams, and the urban area. This study confirmed the elevation of malaria to the epidemic level since the construction of the Tucuruí dam. The study suggests that a seasonal pattern of malaria incidence is associated with the flooding season and exposure of workers during harvest. Malaria cases were related to the form of land occupation, especially in more densely populated areas.     

Evaluation of the cytotoxic and antimutagenic effects of biflorin, an antitumor 1,4 o-naphthoquinone isolated from Capraria biflora L

Biflorin is a natural quinone isolated from Capraria biflora L. Previous studies demonstrated that biflorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective effects of biflorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using different approaches. In the Salmonella/microsome assay, biflorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biflorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biflorin did not induce significant mutagenic and recombinogenic effects at the employed concentration range. In addition, the pre-treatment with biflorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H₂O₂) in S. cerevisiae. In V79 mammalian cells, biflorin was cytotoxic at higher concentrations. Moreover, at low concentrations biflorin pre-treatment protected against H₂O₂-induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modified comet assay using DNA glycosylases. Our results suggest that biflorin cellular effects are concentration dependent. At lower concentrations, biflorin has significant antioxidant and protective effects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H₂O₂ in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biflorin is cytotoxic and genotoxic.     

Induction of apoptosis and cell cycle arrest in L‐1210 murine lymphoblastic leukaemia cells by (2E)‐3‐(2‐naphthyl)‐1‐(3′‐methoxy‐4′‐hydroxy‐phenyl)‐2‐propen‐1‐one

Objectives New compounds with biological targets and less cytotoxicity to normal cells are necessary for cancer therapy. In this work ten synthetic chalcones derived from 2‐naphtaldehyde were evaluated for their cytotoxic effect in murine acute lymphoblastic leukemia cells L‐1210. Methods A series of ten chalcones derived from 2‐naphtaldehyde and corresponding acetophenones were prepared by aldolic condensation, using methanol as solvent under basic conditions, at room temperature for 24 h. The cell viability was determined by MTT colorimeter method. The cell cycle phase analysis was carried out by flow cytometry after propidium iodide staining. The apoptosis induction was assessed by exposure to phosphatidylserine (ANNEXIN V‐FITC). Cytometric analysis was performed to evaluate the expression of p53, Bcl‐2 and Bax protein. The caspase‐3 expression was studied by immunoblotting analysis. Key findings A preliminary screening of a series of ten chalcones derived from 2‐naphtaldehyde showed that chalcone 8 , (2E)‐3‐(2‐naphtyl)‐1‐(3′‐methoxy‐4′‐hydroxy‐phenyl)‐2‐propen‐1‐one, had the highest cytotoxic effect (IC50 of 54 µm ), but not in normal human lymphocytes. To better understand the cytotoxic mechanism of chalcone 8 , its effect on cell cycle and apoptosis was assessed. Our results showed that chalcone 8 caused cell cycle arrest in the G2/M phase and a significant increase in the proportion of cells in the subG0/G1 phase. Our results also demonstrated that chalcone 8 promoted a modification in Bax : Bcl‐2 ratio and increased p53 expression and caspase‐3 activation. Conclusions The studied chalcone 8 has cytotoxic effect against L‐1210 lymphoblastic leukaemic cells, and this effect is associated with increase of p‐53 and Bax expression.     

Esthetic perception of facial profile changes in Class II patients treated with Herbst or Forsus appliances

ObjectiveTo evaluate the esthetic perceptions of orthodontists and laypersons for facial profile changes after orthodontic treatment using Herbst or Forsus appliances.Materials and MethodsPre- and posttreatment facial profile contour images of 20 Class II patients treated with Herbst (group H; n = 10) and Forsus (group F; n = 10) appliances were analyzed by 30 orthodontists and 30 laypersons, who graded them from 1 (unattractive) to 10 (very attractive) using a visual analog scale. Two assessments were carried out with a 15 day-interval. In the first evaluation, 40 images were presented in a random sequence. In the second evaluation, initial and final facial profile images of each patient were randomly presented side by side. To compare groups in relation to treatment method, Mann-Whitney tests were used. To evaluate differences between time points, Wilcoxon tests were used.ResultsIn the first evaluation, there was a significant difference between initial and final images only for group H, for both laypersons (P = .017) and orthodontists (P = .037). There was also a significant difference between laypersons and orthodontists in their ratings of posttreatment Herbst appliance profiles (P = .028). There was no significant difference between initial and final facial profile images for group F and no significant differences between or within evaluator groups in their ratings of initial or final Forsus appliance profiles. In the second evaluation, there was a significant difference between appliance groups only for laypersons, who considered cases treated with the Herbst appliance more attractive than those treated with the Forsus (P = .031). Laypersons also considered Herbst profiles more attractive than did orthodontists (P = .047).ConclusionsClass II malocclusion treatment using the Herbst appliance may produce a more esthetically improved facial profile silhouette compared with Forsus appliances. The magnitude of perceived changes may not be considered clinically relevant.