Dermoscopic variability of basal cell carcinoma according to clinical type and anatomic location

Background Correctly diagnosing basal cell carcinoma (BCC) clinical type is crucial for the therapeutic management. A systematic description of the variability of all reported BCC dermoscopic features according to clinical type and anatomic location is lacking. Objectives To describe the dermoscopic variability of BCC according to clinical type and anatomic location and to test the hypothesis of a clinical/dermoscopic continuum across superficial BCCs (sBCCs) with increasing palpability. Methods Clinical/dermoscopic images of nodular BCCs (nBCCs) and sBCCs with different degrees of palpability were retrospectively evaluated for the presence of dermoscopic criteria including degree of pigmentation, BCC-associated patterns, diverse vascular patterns, melanocytic patterns and polarized light patterns. Results We examined 501 histopathologically proven BCCs (66.9% sBCCs; 33.1% nBCCs), mainly located on trunk (46.7%; mostly sBCCs) and face (30.5%; mostly nBCCs). Short fine telangiectasias, leaf-like areas, spoke-wheel areas, small erosions and concentric structures were significantly associated with sBCC, whereas arborizing telangiectasias, blue-white veil-like structures, white shiny areas and rainbow pattern with nBCCs. Short fine telangiectasia, spoke-wheel areas and small erosions were independently associated with trunk location, whereas arborizing telangiectasias with facial location. Scalp BCCs had significantly more pigmentation and melanocytic criteria than BCCs located elsewhere. Multiple clinical/dermoscopic parameters displayed a significant linear trend across increasingly palpable sBCCs. Conclusions Particular dermoscopic criteria are independently associated with clinical type and anatomic location of BCC. Heavily pigmented, scalp BCCs are the most challenging to diagnose. A clinical/dermoscopic continuum across increasingly palpable sBCCs was detected and could be potentially important for the non-surgical management of the disease.

Chemical control of tomato basal rot caused by Pythiuma phanidermatum

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Chemical control of tomato basal rot caused by Pythiuma phanidermatum

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Evaluación de la involución, salud uterina y retorno de la actividad ovárica con la adición de zeolita 2% en la dieta basal de vacas lecheras

El objetivo de esta investigación fue evaluar el efecto de zeolita (Clinoptilolita) adicionado en la dieta basal de vacas lecheras durante 105 días, 60 días pre-parto (dap) y 45 días post-parto (dpp) y su influencia en la involución (IU) y salud uterina (SU), el retorno de la actividad ovárica (AO) y la condición corporal (CC). El proyecto se realizó en tres ganaderías de la comunidad de Soldados del Cantón Cuenca – Azuay, en 50 vacas secas, con una CC ≥ 3,5, entre 2 a 5 partos, clínicamente sanas y todas en las mismas condiciones sanitarias y de manejo; fueron divididas en un grupo control (n1=25), alimentadas con dieta basal y un experimental (n2=25), con dieta basal + 2% de Zeolita del consumo de materia (CMS). Se evaluó retorno de AO considerando folículos ≥ 10 mm de diámetro a los 15, 22, 35 y 45 dpp por Ultrasonografía transrectal, SU (>10 PMN) a los 35 dpp por cytobrush, IU considerando posición del útero con respecto a la pelvis (PU), simetría de los cuernos (SCU), y diámetro del cérvix (DC), a los 22 y 45 dpp por palpación rectal, y finalmente la CC a los 15 dap, parto y 45 dpp. Se usó un diseño completamente al azar (DCA) y los resultados fueron analizados con el programa estadístico SPSS versión 22.0, posteriormente fueron aplicados los estadísticos de “U de Mann Withney y Kruscall Wallis”. Se obtuvo eficacia en el GE con mayor porcentaje de vacas que retornaron su AO (respectivamente, para GC y GE fueron: 35 dpp 29,6% vs. 70,4%; 45 dpp 44,4% vs. 55,6%; p<0,05). La IU fue a los 45 dpp, los valores obtenido para GC y GE fueron: respectivamente, PU 40,0% vs. 76,0%, SCU 32,0% vs. 76,0% y DC 28,0% vs. 68,0%, (p<0,05). Y en SU también mostró eficacia en el GE obteniendo un 3,4% vs. 22,2% de PMN en comparación con el GC, (p<0,05). Finalmente, se comprobó diferencias significativas (p<0,05) en la CC al parto y 45 dpp con eficacia atribuida al GE. En conclusión, la adición de zeolita al 2% en la dieta basal mostró eficacia en la involución y salud uterina, retorno de la actividad ovárica y la condición corporal en vacas en transición, recomendando su uso en las ganaderías lecheras

Correlación entre glucosa basal y hemoglobina glucosilada en el adulto mayor en el cantón Cuenca, 2015

INTRODUCCIÓN: Alteraciones en el metabolismo de la glucosa son causantes de Síndrome Metabólico y diabetes en adultos mayores; la determinación de hemoglobina glucosilada es un indicador exacto de la glucemia de los individuos en los últimos tres meses permitiendo comprobar el estado de salud. OBJETIVO: Establecer la correlación entre glucosa basal y hemoglobina glucosilada y su asociación con Síndrome Metabólico en adultos mayores del cantón Cuenca. METODOLOGÍA: Estudio descriptivo en 126 adultos mayores. Para la obtención de la muestra se utilizó el calculador automático EPI INFO. De los participantes un grupo con Síndrome Metabólico cumplió el criterio de la Adult Treatment Panel (APT-III). Se aplicó una encuesta para recolección de información y se tomó muestras de sangre para determinar glucosa basal y hemoglobina glucosilada. La información obtenida se procesó en el programa SPSS versión 20.0, Excel y MedLab. Se clasificaron los valores de acuerdo a frecuencia por edad, sexo y su relación con Síndrome Metabólico. RESULTADOS: Se analizaron 126 pacientes entre 65 y 96 años, siendo más frecuentes adultos mayores de sexo femenino con 65,1%. La población con Síndrome Metabólico fue 50.8%. La media de glucosa fue 87,16 y de hemoglobina glucosilada 5,65%. Luego del análisis 92% se encontraron en el rango normal de glucemia y 92,8% de HbA1; se ubicó en el rango de prediabetes 4,8% y dentro del rango de diabetes el 2,4%. Mediante coeficiente de correlación de Pearson se determinó una correlación moderada de 0.418 entre glucemia basal y hemoglobina glucosilada. Se observó una ligera relación entre alteración del metabolismo de glucosa y Síndrome Metabólico pues 12,5% de pacientes con esta enfermedad presentaron hiperglucemia y 11% HbA1 alterada

El fenotipo "basal-her2" en el cáncer de mama: caracterización clínico-molecular e implicaciones terapéuticas

Clinically HER2+ (cHER2+) breast cancer (BC), as exclusively determined by immunohistochemistry of HER2 protein overexpression and/or fluorescence in situ hybridization of HER2 gene amplification, has been largely considered a single disease entity in terms of clinical outcome and in the susceptibility to the anti-HER2 monoclonal antibody trastuzumab (Herceptin). However, although the adjuvant/neoadjuvant use of the trastuzumab has been shown to significantly reduce recurrence risk when added to standard chemotherapy in women with early-stage cHER2+ BC, not all cases derive similar benefit from trastuzumab because a significant number of cHER2+ BC patients develop disease recurrence. Unfortunately, the identification of a robust clinical predictor of trastuzumab benefit, including HER2 itself, has proven challenging in the adjuvant/neoadjuvant setting. Thus, we suggest that a new generation of research needs to refine the prognostic taxonomy of cHER2+ BC and develop easy-to-use, clinicbased prediction algorithms to distinguish between good- and poor- responders to trastuzumab-based therapy ab initio. This study offered two hypotheses: 1.) HER2 overexpression can unexpectedly take place in a molecular background owned by basal-like BC (a commonly HER2-negative BC subtype which possesses many epithelial-mesenchymal transition (EMT) characteristics and exhibits robust cancer stem cell [CSC]-like features), thus generating a so-called basal/cHER2+ BC subtype; 2.) the basal/cHER2+ phenotype confers poor prognosis and delineates a subgroup of intrinsically aggressive cHER2+ BC with primary resistance to trastuzumab...

Caracterização da estrutura demográfica e ocupação da área basal em cinco áreas de mata ciliar da região Nordeste paraense.

As matas ciliares são encontradas nas margens dos rios e mananciais e são responsáveis por proteger os cursos d'água do assoreamento, da obstrução de alguns trechos do rio pelo aumento no volume de terra e outros sedimentos carregados pela correnteza. Realizou-se o inventário florístico próxima ao leito do igarapé na região nordeste paraense, nas respectivas áreas de monitoramento: Ceará, Monte-verde, São Francisco, Ver-o-peixe e Vitório. Objetivou-se neste trabalho caracterizar a estrutura demográfica e ocupação da área basal em cinco áreas de mata ciliar da região nordeste paraense. Com base, nestes dados coletados (diâmetros, espécie) foram calculadas a abundância e área basal absoluta e relativa dos indivíduos identificados por local e tamanho de classes diamétricas e/ou altura. Foram registrados 1.213 indivíduos, sendo a maior proporção encontrada na área São Francisco que obteve 10.039 indivíduos por hectare, enquanto à área basal destacou-se Ceará com 34,2%. A distribuição da demografia apresentou alta similaridade na proporcionalidade da distribuição dos indivíduos nas classes de tamanhos (muda, vara, árvore) e averiguamos que a quantidade de indivíduos apresentados por área não necessariamente implica no acúmulo da maior área basal.

A new low temperature synthesis route of fraipontite (Zn,Al)3(Si,Al)2O5(OH)4

A low temperature synthesis method based on the decomposition of urea at 90°C in water has been developed to synthesise fraipontite. This material is characterised by a basal reflection 001 at 7.44 Å. The trioctahedral nature of the fraipontite is shown by the presence of a 06l band around 1.54 Å, while a minor band around 1.51 Å indicates some cation ordering between Zn and Al resulting in Al-rich areas with a more dioctahedral nature. TEM and IR indicate that no separate kaolinite phase is present. An increase in the Al content however, did result in the formation of some SiO2 in the form of quartz. Minor impurities of carbonate salts were observed during the synthesis caused by to the formation of CO32- during the decomposition of urea.

Prediction of highway truck conveyance configuration under over-limit prohibition and conveyance equilibrium

Aiming at the shortage of prevailing prediction methods about highway truck conveyance configuration in over-limit freight research that transferring the goods attributed to over-limit portion to another fully loaded truck of the same configuration and developing the truck traffic volume synchronously, a new way to get accumulated probability function of truck power tonnage in basal year by highway truck classified by wheel and axle type load mass spectrum investigation was presented. Logit models were used to forecast overall highway freight diversion and single cargo tonnage diversion when the weight rules and strict of enforcement intensity of overload were changed in scheme year. Assumption that the probability distribution of single truck loadage should be consistent with the probability distribution of single goods freighted, the model describes the truck conveyance configuration in the future under strict over-limit prohibition. The model was used and tested in Highway Over-limit Research Project in Anhui by World Bank.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

In vivo confocal microscopy of the palpebral conjunctiva and tarsal plate

Purpose The aim of this work is to develop a more complete understanding of the in vivo histology of the human palpebral conjunctiva and tarsal plate. Methods. The upper eyelids of 11 healthy human volunteer subjects were everted, and laser scanning confocal microscopy was used to examine the various tissue layers of the palpebral conjunctiva and tarsal plate. Results The superficial and basal epithelial layers are composed of cells with gray cytoplasm and thick, light gray borders.Nuclei can not be seen. The stroma has a varied appearance; fibrous tissue is sometimes observed, interspersed with dark,amorphous lacunae, and crevases. Numerous single white or gray cells populate this tissue, and fine blood vessels are seen traversing the field. Occasional conjunctival microcysts and Langerhans cells are observed. The tarsal plate is dark and amorphous, and meibomian gland acini with convoluted borders are clearly observed. Acini are composed of an outer lining of large cuboidal cells, and differentiated secretory cells can be seen within the acini lumen. Conclusions Laser scanning confocal microscopy is capable of studying the human palpebral conjunctiva, tarsal plate, and acini of meibomian glands in vivo. The observations presented here may provide useful supplementary anatomical information relating to the morphology of this tissue.

Groundwater flow model of the Logan river alluvial aquifer system Josephville, South East Queensland

The study focuses on an alluvial plain situated within a large meander of the Logan River at Josephville near Beaudesert which supports a factory that processes gelatine. The plant draws water from on site bores, as well as the Logan River, for its production processes and produces approximately 1.5 ML per day (Douglas Partners, 2004) of waste water containing high levels of dissolved ions. At present a series of treatment ponds are used to aerate the waste water reducing the level of organic matter; the water is then used to irrigate grazing land around the site. Within the study the hydrogeology is investigated, a conceptual groundwater model is produced and a numerical groundwater flow model is developed from this. On the site are several bores that access groundwater, plus a network of monitoring bores. Assessment of drilling logs shows the area is formed from a mixture of poorly sorted Quaternary alluvial sediments with a laterally continuous aquifer comprised of coarse sands and fine gravels that is in contact with the river. This aquifer occurs at a depth of between 11 and 15 metres and is overlain by a heterogeneous mixture of silts, sands and clays. The study investigates the degree of interaction between the river and the groundwater within the fluvially derived sediments for reasons of both environmental monitoring and sustainability of the potential local groundwater resource. A conceptual hydrogeological model of the site proposes two hydrostratigraphic units, a basal aquifer of coarse-grained materials overlain by a thick semi-confining unit of finer materials. From this, a two-layer groundwater flow model and hydraulic conductivity distribution was developed based on bore monitoring and rainfall data using MODFLOW (McDonald and Harbaugh, 1988) and PEST (Doherty, 2004) based on GMS 6.5 software (EMSI, 2008). A second model was also considered with the alluvium represented as a single hydrogeological unit. Both models were calibrated to steady state conditions and sensitivity analyses of the parameters has demonstrated that both models are very stable for changes in the range of ± 10% for all parameters and still reasonably stable for changes up to ± 20% with RMS errors in the model always less that 10%. The preferred two-layer model was found to give the more realistic representation of the site, where water level variations and the numerical modeling showed that the basal layer of coarse sands and fine gravels is hydraulically connected to the river and the upper layer comprising a poorly sorted mixture of silt-rich clays and sands of very low permeability limits infiltration from the surface to the lower layer. The paucity of historical data has limited the numerical modelling to a steady state one based on groundwater levels during a drought period and forecasts for varying hydrological conditions (e.g. short term as well as prolonged dry and wet conditions) cannot reasonably be made from such a model. If future modelling is to be undertaken it is necessary to establish a regular program of groundwater monitoring and maintain a long term database of water levels to enable a transient model to be developed at a later stage. This will require a valid monitoring network to be designed with additional bores required for adequate coverage of the hydrogeological conditions at the Josephville site. Further investigations would also be enhanced by undertaking pump testing to investigate hydrogeological properties in the aquifer.

(-)-CGP12177 increases contractile force through beta1l-adrenoceptors but not through beta3-adrenoceptors in human right atrial myocardium

(-)-CGP12177 is a non-conventional partial agonist that causes modest and transient increases of contractile force in human atrial trabeculae (Kaumann and Molenaar, 2008). These effects are markedly increased and maintained by inhibition of phosphodiesterase PDE3. As verified with recombinant receptors, the cardiostimulant effect of (-)-CGP12177 is mediated through a site at the beta1-adrenoceptor with lower affinity (beta1LAR) compared to the site through which (-)-CGP12177 antagonizes the effects of catecholamines (beta1HAR). However, in a recent report it was proposed that the positive inotropic effects of CGP12177 are mediated through beta3-adrenoceptors (Skeberdis et al 2008). We therefore investigated whether the effects of (-)-CGP12177 on human atrial trabeculae are antagonized by the beta3-adrenoceptor-selective antagonist L-748,337 (1 microM). (-)-CGP12177 (200 nM) caused a stable increase in force which was significantly reduced by the addition of (-)-bupranolol (1 microM), P = 0.002, (basal 4.45 ± 0.78 mN, IBMX (PDE inhibitor) 5.47 ± 1.01 mN, (-)-CGP12177 9.34 ± 1.33 mN, (-)-bupranolol 5.79 ± 1.08 mN, n = 6) but not affected by the addition of L-748,337 (1 microM), P = 0.12, (basal 4.48 ± 1.32 mN, IBMX 7.15 ± 2.28 mN, (-)-CGP12177 12.51 ± 3.71 mN, L-748,337 10.90 ± 3.49 mN, n = 6). Cumulative concentration-effect curves for (-)-CGP12177 were not shifted to the right by L-748,337 (1 microM). The –logEC50M values of (-)-CGP12177 in the absence and presence of L-748,337 were 7.21±0.09 and 7.41±0.13, respectively (data from 25 trabeculae from 8 patients, P=0.2) The positive inotropic effects of (-)-CGP12177 (IBMX present) were not antagonized by L-748,337 but were blunted by (-)-bupranolol (1 microM). The results rule out an involvement of beta3-adrenoceptors in the positive inotropic effects (-)-CGP12177 in human right atrial myocardium and are consistent with mediation through beta1LAR. Kaumann A and Molenaar P (2008) Pharmacol Ther 118, 303-336 Skeberdis VA et al (2008) J Clin Invest, 118, 3219-3227