A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial.

OBJECTIVE: As a result of their complex aetiology and periodicity, dark circles are difficult to characterize and measure, with current assessment techniques relying on specialist equipment, image analysis or proprietary grading scales. There is therefore a need to develop and validate a photonumeric scale for assessing infraorbital dark circles, which can provide an objective and consumer relevant tool for evaluating this condition and the efficacy of treatment products and procedures. METHODS: A panel of expert clinical evaluators reviewed approximately three thousand facial photographs collected over a 5-year period and selected images representing a dynamic range of dark circles. A 10-point photonumeric scale was created, with corresponding descriptors and images for each grade of the scale. To rigorously validate the scale, linearity, sensitivity and precision were assessed by colorimetry and in-clinic evaluation. Reproducibility was assessed photographically with both experienced and inexperienced clinical evaluators, whereas intragrader repeatability was assessed live in-clinic. The scale was then employed in a split-face randomized clinical trial on 58 subjects to evaluate the efficacy of a cosmetic treatment product over 8 weeks. RESULTS: Colour analysis of the images showed the scale was linear, with statistically significant correlations observed when colour data (CIElab; Individual Typology Angle) were plotted against the corresponding grades (r > 0.9, P < 0.001). Colour difference (Delta E) was calculated between the infraorbital zone and the surrounding skin, and when data were plotted against the grades, a statistically significant correlation was observed (r = 0.99, P < 0.01). The magnitude of the Delta E suggested that changes in grade are visibly perceptible to the human eye, and therefore, the scale is sensitive and clinically relevant. Intergrader reproducibility showed strong correlation (0.96) and >90% agreement between experienced evaluators, whereas intragrader repeatability assessment showed >90% perfect agreement between grades. Use of this scale in a clinical trial demonstrated the efficacy of a cosmetic product, with a mean statistically significant (P < 0.001) decrease in grade of 0.74 compared to baseline, and 0.59 versus the untreated control, after 8 weeks of treatment. CONCLUSION: Our photonumeric scale for infraorbital dark circles is sensitive and robust and provides an objective and easy-to-use tool to evaluate dark circles and their treatment.

OBJECTIF: En raison de leur étiologie et de leur périodicité complexes, les cernes sont difficiles à caractériser et à mesurer, les techniques d'évaluation actuelles reposant sur des équipements spécialisés, l'analyse d'images ou des échelles de notation exclusives. Il est donc nécessaire de développer et de valider une échelle photonumérique pour évaluer les cernes infraorbitaires, laquelle peut fournir un outil objectif et pertinent pour le consommateur et tester l'efficacité des produits et des procédures de traitement. MÉTHODES: Un panel d'évaluateurs cliniques experts a examiné environ trois mille photographies du visage recueillies sur une période de 5 ans, ainsi que des images sélectionnées représentant une plage dynamique de cernes. Une échelle photonumérique à 10 points a été créée, avec des descripteurs et des images correspondants à chaque grade de l'échelle. Afin de valider rigoureusement l'échelle, la linéarité, la sensibilité et la précision ont été évaluées par colorimétrie et en clinique. La reproductibilité a été évaluée sur le plan photographique par des évaluateurs cliniques expérimentés et inexpérimentés, tandis que la répétabilité intragrade a été évaluée en direct en clinique. L'échelle a ensuite été utilisée dans un essai clinique randomisé à deux parties sur 58 sujets, afin d'évaluer l'efficacité d'un produit de traitement cosmétique sur 8 semaines. RÉSULTATS: L'analyse des couleurs des images a montré que l'échelle était linéaire, avec des corrélations statistiquement significatives observées lorsque les données de couleurs (CIElab ; angle de typologie individuel) ont été tracées par rapport aux grades correspondants (r > 0,9, P < 0,001). La différence de couleur (Delta E) a été calculée entre la zone infraorbitaire et la peau environnante, et lorsque les données ont été tracées par rapport aux grades, une corrélation statistiquement significative a été observée (r = 0,99, P < 0,01). L'ampleur du delta E a suggéré que les changements de grade sont visiblement perceptibles à l'œil humain, l'échelle étant par conséquent sensible et cliniquement pertinente. La reproductibilité intergrade a montré une forte corrélation (0,96) et une concordance > 90 % entre les évaluateurs expérimentés, tandis que l'évaluation de la répétabilité intragrade a montré une concordance parfaite > 90 % entre les grades. L'utilisation de cette échelle lors d'un essai clinique a démontré l'efficacité d'un produit cosmétique, avec une diminution moyenne statistiquement significative (P < 0,001) du grade de 0,74 par rapport à la référence, et de 0,59 par rapport au témoin non traité, après 8 semaines de traitement. CONCLUSION: Notre échelle photonumérique pour les cernes infraorbitaires est sensible et robuste, fournissant un outil objectif et facile à utiliser afin d'évaluer les cernes et leur traitement.

The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans.

Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.

Temporal and spatial patterns in ichthyoplankton assemblages in bay and open coastal environments.

The larval fish fauna occurring in temperate bay and shelf waters off Victoria, southern Australia, was found to be diverse, comprising taxa from 52 families. The most abundant groups collected were gobiids, tripterygiids, gobiesocids and clupeids. Fish egg concentrations were highest during spring and summer (September to February). Eggs of the Australian anchovy Engraulis australis occurred mainly during spring (September to November). Total larval fish concentrations were highest during summer (December to February), and were significantly higher at 1 km than 2 and 5 km from shore in offshore samples. Larval concentrations of a number of families, mainly reef-associated taxa that attach their eggs to hard substrata, were also higher nearer to shore. These larvae are more developed upon hatching than those of pelagic spawners and more capable of avoiding passive drift. Multivariate analyses found that larval taxonomic composition did not vary significantly with distance from shore, but that seasonal and monthly groupings were evident, with different taxa dominating at different times of the year. Larvae of the families Gobiidae and Tripterygiidae occurred in all months, but were less abundant during winter. Spatial differences in the larval fish assemblage between offshore samples and samples taken in the bay were only apparent during summer. This was primarily due to a higher abundance of seagrass-associated species, such as syngnathids and hemiramphids, utilizing specific habitats in the bay.

Connectivity of a large embayment and coastal fishery: spawning aggregations in one bay source local and broad-scale fishery replenishment.

Ichthyoplankton sampling and otolith chemistry were used to determine the importance of transient spawning aggregations of snapper Chrysophrys auratus (Sparidae) in a large embayment, Port Phillip Bay (PPB), Australia, as a source of local and broad-scale fishery replenishment. Ichthyoplankton sampling across five spawning seasons within PPB, across the narrow entrance to the bay and in adjacent coastal waters, indicated that although spawning may occur in coastal waters, the spawning aggregations within the bay were the primary source of larval recruitment to the bay. Otolith chemical signatures previously characterized for 0+ year C. auratus of two cohorts (2000 and 2001) were used as the baseline signatures to quantify the contribution that fish derived from reproduction in PPB make to fishery replenishment. Sampling of these cohorts over a 5 year period at various widely dispersed fishery regions, combined with maximum likelihood analyses of the chemistry of the 0+ year otolith portions of these older fish, indicated that C. auratus of 1 to 3+ years of age displayed both local residency and broad-scale emigration from PPB to populate coastal waters and an adjacent bay (Western Port). While the PPB fishery was consistently dominated (>70%) by locally derived fish irrespective of cohort or age, the contribution of fish that had originated from PPB to distant populations increased with age. At 4 to 5+ years of age, when C. auratus mature and fully recruit to the fishery, populations of both cohorts across the entire central and western Victorian fishery, including two major embayments and c. 800 km of coastal waters, were dominated (>70%) by fish that had originated from the spawning aggregations and nursery habitat within PPB. Dependence of this broadly dispersed fishery on replenishment from heavily targeted spawning aggregations within one embayment has significant implications for management and monitoring programmes.

Induction of durable remission in ocular inflammatory diseases.

PURPOSE: To describe a paradigm of care for patients with ocular inflammatory diseases aimed at induction of durable remission. METHODS: Retrospective cohort study. The records of 399 patients with ocular inflammatory diseases treated with systemic immunomodulatory therapy (IMT) at the Massachusetts Eye Research and Surgery Institution were reviewed. Durable remission was defined as control of inflammation in the absence of systemic IMT for at least 1 year. Fifty patients met the inclusion criteria. RESULTS: Mean age was 46+/-22.5 years (range 18-88). All the patients had corticosteroid therapy and failed this therapy before having IMT. Fifty-two percent of the patients had used methotrexate alone or in combination with other medications. Thirty percent of the patients required at least 2 years of therapy with systemic IMT to obtain durable remission, while 44% required 2 to 5 years of therapy to achieve the same. Twenty percent continued to stay in remission, off immunomodulatory drugs, between 2 and 5 years and 18% were in remission for more than 5 years after therapy discontinuation. CONCLUSIONS: IMT can be sight saving in patients. It can be tapered and discontinued successfully without the return of ocular inflammation. Durable drug-free remission is an achievable goal, and should be pursued by ocular inflammatory disease specialists.

Experimental data on the photoelectrochemical oxidation of phenol: Analysis of pH, potential and initial concentration.

The data collected in the present work correspond to percentages of phenol degradation by means of photoelectrochemical oxidation (PEC). Also, the information related to the energetic and kinetic performance of this advanced oxidation process (AOPs) is shown. The tests were divided into two stages: 1. Supporting electrolytes tests to determine the electrolyte that presents a better response to photocurrent and 2. Degradation of phenol to obtain the adequate conditions for the elimination of the contaminant. A central rotary composite design with uniform precision at two levels was used to analyze the influence of the initial pH, electrode potential and the initial concentration of substrate. Finally, with all the data obtained, calculation of degradation rates and the electrical energy per order EEO were made.

Enhancement of Fenton and photo-Fenton processes at initial circumneutral pH for the degradation of the ß-blocker metoprolol.

The need for acidification in the Fenton and photo-Fenton process is often outlined as one of its major drawbacks, thus in this work the acidification of the Metoprolol (MET) is avoided by the addition of resorcinol (RES), which is used to simulate model organic matter. The experiments were carried out at natural pH (6.2) with different Fe(2+) (1, 2.5, 5, and 10 mg/L) and H2O2 (25, 50, 125 and 150 mg/L) concentrations. The performance of MET and RES degradation was assessed along the reaction time. Working with the highest concentrations (5 and 10 mg/L of ferrous iron and 125 and 150 mg/L of H2O2) more than 90% of MET and RES removals were reached within 50 and 20 min of treatment, respectively, by Fenton process. However a low mineralization was achieved in both cases, likely, due to by-products accumulation. Regarding to photo-Fenton process, within 3 min with the highest iron and hydrogen peroxide concentrations, a complete MET degradation was obtained and 95% of RES conversion was achieved. Parameters such Total Organic Carbon, Chemical Oxygen Demand, and AOS were measured. Intermediates were identified and MET degradation path was proposed in the presence of resorcinol. Finally, a comparison between Fenton and photo-Fenton processes at acid pH and at initial circumneutral pH was discussed. The positive effect of RES on Fenton and photo-Fenton systems has been confirmed, allowing the work at circumneutral pH.

Conditional rescue of olfactory learning and memory defects in mutants of the 14-3-3zeta gene leonardo.

Members of the ubiquitous 14-3-3 family of proteins are abundantly expressed in metazoan neurons. The Drosophila 14-3-3zeta gene leonardo is preferentially expressed in adult mushroom bodies, centers of insect learning and memory. Mutants exhibit defects in olfactory learning and memory and physiological neuroplasticity at the neuromuscular junction. Because strong mutations in this gene are lethal, we investigated the nature of the defects that precipitate the learning and memory deficit and the role of the two protein isoforms encoded by leonardo in these processes. We find that the behavioral deficit in the mutants is not caused by aberrant development, LEONARDO protein is acutely required for learning and memory, and both protein isoforms can function equivalently in embryonic development and behavioral neuroplasticity.

Biphenotypic acute leukemia with t(15;17).

Biphenotypic acute leukemias (BAL) represent 5% of all acute leukemias. The most frequent cytogenetic abnormalities described are Philadelphia chromosome and 11q23 involvement. Here we report a BAL case, with blasts showing lymphoblast morphology and positivity for myeloperoxidase (in 6% of the blast cells). Immunophenotype revealed the compromise of myeloid and B-lymphoid lineages. Cytogenetic analysis showed the t(15;17) and 8 trisomy. PML/RARa rearrangement was detected by fluorescent in situ hybridization (FISH) on interphase nuclei while PML/RARa fusion transcript was detected in the bone marrow and peripheral blood by molecular biology studies (RT-PCR). This report describes a BAL case with an unfrequent cytogenetic abnormality, and highlights the importance of correlating the results of multiple diagnostic methods in order to establish a correct diagnosis and treatment in BAL patients.

Polymorphic variants of GSTM1, GSTT1, and GSTP1 genes in childhood acute leukemias: A preliminary study in Argentina.

BACKGROUND AND AIM: Despite recent major advances in leukemia research, the etiopathogenesis of childhood leukemias remains far elusive. Individual predisposing factors, including polymorphisms in detoxification enzymes, have been implicated in the molecular pathogenesis and heterogeneity of the disease. Genetic polymorphisms of glutathione S-transferases (GSTs) that alter enzyme activity could be an additional factor that increases the risk of acute leukemia, but data are lacking in Argentina. We assessed the association of GST polymorphisms and the susceptibility to childhood leukemia in Argentina by conducting an exploratory case-control study and correlated patients' genotype to clinical and biological features. METHODS: Deletion polymorphisms in GSTM1 and GSTT1 genes and the single nucleotide polymorphism in GSTP1 c.313A>G (rs1695; p.105Ile>Val) were genotyped by PCR-RFLP in 36 patients and 133 healthy individuals. RESULTS: GSTM1-null genotype was associated with a lower risk of developing acute leukemia (P = 0.013; OR: 0.31; CI: 0.12-0.80), while GSTP1-GG variants displayed an increased risk (P = 0.01; OR: 3.9; CI: 1.85-8.2). However, no differences were found for GSTT1 gene. Conclusion These preliminary results, to be validated in a larger population from Argentina, suggest that the development of pediatric leukemia may be differentially influenced by polymorphic variants in GST genes.

Interleukin-1beta and its type 1 receptor are expressed in developing neural circuits in the frog, Xenopus laevis.

The cytokine interleukin-1 beta (IL-1beta) is an evolutionarily conserved molecule that was originally identified in the immune system. In addition to regulating peripheral immune responses, IL-1beta plays an important role in mediating neural-immune interactions and regulating glial activities during healing and repair in the damaged nervous system. Active IL-1beta is produced by interleukin-converting enzyme (ICE), a caspase thought to be involved in the induction of apoptosis. We report that, in the developing frog, Xenopus laevis, IL-1beta and the IL-1 type 1 receptor proteins are coexpressed in specific neurons that comprise early sensory-motor circuits. IL-1beta and IL-1 type 1 receptor proteins are colocalized in specific midbrain and hindbrain reticular cells, including Mauthner's neuron; specific cells in the trigeminal (fifth), lateral line (seventh), and vestibular (eighth) cranial ganglia; oculomotor neurons; and the primordial Purkinje cells of the lateral cerebellar auricle. In the spinal cord, Rohon-Beard sensory neurons, dorsal root ganglion cells, and primary motoneurons are immunopositive. Anteriorly, the olfactory pits, olfactory nerves, and olfactory bulbs are labeled, as are retinal cells, especially photoreceptor inner segments. With regard to the function of IL-1beta during neural development, IL-1beta and its type 1 receptor are present throughout the course of neural development in identifiable, long-lived neurons, such as Mauthner's neuron. These and other data suggest that IL-1beta and its type 1 receptor may be involved in the maintenance of cell survival rather than induction of neuronal death.

Promyelocytic blast crisis of chronic myelogenous leukaemia with translocations (9;22) and (15;17).

The promyelocytic blast crisis is a rare form of transformation during the evolution of chronic myeloid leukaemia (CML). We report a case of promyelocytic blast crisis with t(15;17) in addition to t(9;22). The morphology and immunophenotype of the blasts were similar to those seen in acute promyelocytic leukaemia (APL). The t(15;17) was confirmed by FISH. The patient had evidence of coagulopathy with clinical and laboratory findings of disseminated intravascular coagulation (DIC). This report highlights the importance of correlating the results of multiple diagnostic methods in order to establish a correct diagnosis of the promyelocytic blast crisis of CML.

Prenatal care, infant birthweight and infant mortality in Puerto Rico.

This study purports to analyze selected demographic and socio-economic correlated of prenatal care in Puerto Rico. Also, the relationship between prenatal care and infant birthweight and mortality is examined. The data was obtained from the 1986 live birth and death certificates. Three indicators of adequacy of prenatal care were utilized in the analysis: number of prenatal care visits, trimester in which this care began and the "Kessner Index". The findings of the study revealed that prenatal care in Puerto Rico has improved both in terms of early care and in continuity, since 1980. Great geographical differences in adequacy of prenatal care were observed throughout the Island. Prenatal care varies considerably among different population subgroups. Inadequate prenatal care was more frequent among adolescent, unwed and high parity mothers as well as among those of the lowest socio-economic strata. Furthermore, these groups had the highest proportion of low birthweight babies and their offsprings, the highest mortality rates. The statistical evidence obtained from this study suggests that this is in part due to the inadequate prenatal care received by these mothers.

[Cytogenetic and in situ hybridization (FISH) follow-up in minimal residual disease]. / Seguimiento citogenético e hibridización in situ (FISH) en la enfermedad mínima residual.

Cytogenetic studies are an important tool for diagnosis, prognosis and minimal residual disease (MRD) follow up specially in oncohematology. Conventional cytogenetics, also known as G banding technique, brings complete information for the spectrum of aneuploidies and structural changes present in malignant cells with a sensitivity of 1-5% depending on the number of metaphases analyzed. FISH technique with a higher sensitivity, 10(-2)-10(-4), attempts to make up for one of the principal limitations of G banding which is the absence of metaphases, thus employing different probes and allowing the study of interphase nucleus. Our patients were monitored with both methodologies during the course of the disease looking for MRD. FISH is the best methodology for quantifying the abnormal clone until we can apply quantitative PCR routinely. It will also be important for the follow up of rearrangements for which we do not yet have molecular determinations available. Our findings are coincident with those of other research groups in the need of evaluating higher series of patients with different pathologies in order to arrive at conclusions allowing us to predict relapse with any certainty.

Cirugía extracassular de Cataratas con lente intraocular en un canino: reporte de csoo / Extracapslar Cattaract surgery with intraocular lens in a dog: a case report

El presente artículo expone el caso de Muñeco, un perro macho de 12 años de edad de raza poodle que presenta cataratas bilaterales desde hace cinco meses, perdiendo de manera progresiva su visión, hasta el punto que presentó ceguera total. Durante el examen clínico se encontró un paciente con soplo 3/6 de la válvula mitral, al que se le diagnosticó insuficiencia valvular mitral por endocardiosis valvular. En el examen oftalmológico se encontraron ambos ojos con epífora leve y cataratas seniles hipermaduras. Por tanto, el paciente fue intervenido quirúrgicamente para extraer la catarata y colocar en su lugar un lente intraocular, utilizando la técnica conocida como cirugía extracapsular de cataratas. Luego de esto, el paciente recuperó su capacidad visual después de llevar varios años con ceguera bilateral.

This article presents the case of Muñeco, a poodle, male; 12 years of age, which presents opaqueness in both eyes for five months, losing his vision progressively until reaching total blindness. During the clinical examination we found a patient with heart murmur 3/6 in mitral valve, diagnosed with mild mitral regurgitation secondary to valvular endocardiosis. In the ophthalmological examination we found mild bilateral epiphora, opacity of the crystalline lens and hyper mature senile Cataracts. The patient underwent surgery to remove the cataract and an intraocular lens was placed using a technique known as extracapsular cataract surgery. The patient recovered visual capacity after several years of being blind in both eyes.

Cytogenetic study of 50 de novo cases of ANLL from Argentina.

BACKGROUND AND METHODS: Consistent and specific chromosomal aberrations have been observed in an increasing number of neoplasias. In the present report, we describe the cytogenetic findings from 50 cases of de novo ANLL in Argentina, South America, studied at diagnosis. In addition, their relation with the FAB classification is analyzed. Children with Down's syndrome and secondary ANLL were excluded from this analysis. RESULTS AND CONCLUSIONS: Out of 50 banded cases studied, 11 (22%) had normal karyotype, while the remaining 39 (78%) presented abnormal metaphases with structural alterations in the majority of them. Chromosomes 7 and 22 were most frequently involved in numerical alterations in children, while chromosomes 6, 8, 14 and 16 were the ones most often involved in adults. Consistent chromosome rearrangements were observed and they were linked to specific cytomorphologic subsets. The translocations t(8;21) and t(15;17) were seen only in M2 and M3, respectively. The inversion of chromosome 16, inv(16), was a typical finding in M4, but was not restricted to this subtype. Translocation t(2;3) was observed in three cases, all M4, each with a variable chromosome pattern. These results are in accordance with cytogenetic findings in Western Europe and the USA.

Leukemic transformation in patients with 5Q- and additional abnormalities.

BACKGROUND AND METHODS: We analyze myelodysplastic patients with the 5q- marker as sole abnormality, or with additional anomalies, and their relationship to clinical evolution. The study was performed on 12 patients (6 females and 6 males): 3 with refractory anemia (RA), 5 with RA with ring sideroblasts (RA-S), 3 RA with excess of blasts (RAEB) and 1 with RAEB in transformation (RAEB-T). The cytogenetic study was carried out on bone marrow cells at the time of diagnosis. The G- banding technique was used for chromosome identification. The follow-up was for 50 months. RESULTS AND CONCLUSIONS: Five patients (3 with RA and 2 with RA-S) showed a single 5q- marker. They had a long survival without evolution to leukemia. All cases with 5q- plus additional abnormalities: del(12p), del(7q), del(14q), i(11q) and i(17q), showed a neoplastic evolution in a short period of time. We can conclude that the presence of the 5q- marker with complex karyotypes or additional abnormalities is associated with a high risk of neoplastic evolution, indicating the prognostic value of cytogenetic study in myelodysplasia.

Comparative genomic hybridization study of de novo myeloid neoplasia.

Comparative genomic hybridization (CGH) was used to detect chromosomal imbalances in 20 patients with a diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). The results obtained were compared with G-banding analysis. This last methodology showed 50% of cases with clonal abnormalities whereas CGH detected 70% of cases with copy number changes. Gains were more frequent than losses and constituted 66% of total changes detected. The most common gains included chromosomes 21 and chromosome region 18p for AML and chromosome 17 and region 1p33p35 for MDS. Losses represent 34% of changes and the regions involved were 5q31q32, 7q22, 7p12 and 13q21q22. CGH revealed additional chromosome imbalances in 12 of 20 cases (60%) which were not detected by traditional cytogenetic studies, demonstrating complex karyotype in 50% (6/12). Combination of CGH and G-banding provides an efficient method to identify critical regions present in the malignant clone, which is of great value in the prognosis and outcome of myeloid neoplasias.