Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer.

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.

Chemical restraint of coatis by the association of Detomidine, Tiletamine and Zolazepam, in allometrically scaled dosages / [Contenção farmacológica de quatis pela associação de detomidina, tiletamina e zolazepam, em doses calculadas por extrapolação alométrica]

Ten free-living adult coatis (two males and eight females) were chemically restrained with "ZAD-50", a concentrated formulation prepared with the dehydrated content of a Zoletil/50® vial diluted with 0.25mL of 1% atropine, 0.265mL of Dormiun-V®, and 2.2mL of distilled water, being exactly 3.0mL. The formula was administered to each animal previously captured and physically contained with a net. The loss of righting reflex (RR) occurred at 2.3±0.8 minutes post-injection (MPI), with anesthesia beginning at 4.4±2.7 MPI. Myorelaxant and analgesia were considered excellent at all moments of the evaluation. Conscious reactions were observed at 78.7±22.2 MPI, the return of the RR occurred at 101 ± 18 MPI, and normal ambulation was acquired at 137.0±31.0 MPI. The mean values ​​of physiological parameters measured every 10 minutes between 10 and 50 MPI were 152.2 heartbeats per minute for heart rate, 66.4 respiratory movements per minute for respiratory rate, 39.2oC for rectal temperature, 86.2% for SpO2 and 14.6 mmHg for systolic blood pressure. In the same times, the EEG registered sinus rhythm. No adverse reactions were observed, and the assessed vital parameters remained compatible with the state of chemical restraint.(AU)

Dez quatis adultos de vida livre (dois machos e oito fêmeas) foram contidos empregando-se a formulação denominada "ZAD-50". A fórmula foi preparada a partir do conteúdo desidratado de um frasco de Zoletil/50® diluído em 0,25mL de atropina a 1%, 0,265mL de Dormiun-V® e 2,2mL de água destilada, obtendo-se volume final de 3,0mL. A associação foi administrada, por via intramuscular, a cada animal capturado e contido fisicamente com puçá, em dose calculada por meio de extrapolação alométrica interespecífica. A perda da reação postural de endireitamento (RPE) ocorreu aos 2,3±0,8 minutos pós-injeção (MPI), observando-se início da anestesia aos 4,4±2,7 MPI. Miorrelaxamento e analgesia foram considerados excelentes em todos os momentos da avaliação. Reações conscientes foram observadas aos 78,7±22,2 MPI, o retorno da RPE ocorreu aos 101±18 MPI, e os animais voltaram à ambulação normal aos 137,0±31,0 MPI. Os valores médios dos parâmetros fisiológicos mensurados a cada 10 minutos entre 10 e 50 MPI foram 152,2 batimentos por minuto para frequência cardíaca, 66,4 movimentos por minuto para frequência respiratória, 39,2oC para temperatura retal, 86,2% para saturação parcial de oxigênio e 14,6mmHg para pressão arterial sistólica. Nesses tempos, observou-se ritmo sinusal no eletrocardiograma, e não foram observadas reações adversas.(AU)

Allergooncology: an expanding research area.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

Relación entre automanejo y síntomas depresivos en personas con diabetes e hipertensión / Relationship between self-management and depressive symptoms in persons with diabetes and hypertension / Relação entre automanejo e sintomas depressivos em pessoas com diabetes e hipertensão

Resumen Introducción: Las personas con diabetes e hipertensión experimentan con mayor frecuencia sintomatología depresiva, lo cual contribuye a un inadecuado automanejo de la enfermedad, que implica tareas como: la toma de la medicación, asistir a las consultas médicas, el conocimiento de signos y síntomas, además de la toma de decisiones. Objetivo: Por lo anterior, el objetivo de este trabajo es identificar la relación entre automanejo en general y sus dimensiones con síntomas depresivos en personas con diabetes e hipertensión. Método: Estudio transversal-correlacional con n=205 pacientes con diagnóstico de diabetes (100) e hipertensión (105). Muestreo no probabilístico por conveniencia. Se utilizó la estadística descriptiva y r de Pearson. Se aplicaron los instrumentos Partners in Health (PIH) y The Patient Health Questionnaire (PHQ-8). Resultados: Se encontró correlación estadísticamente significativa entre la sintomatología depresiva y el automanejo (r=-0.308 ρ<0.001). Discusión y Conclusiones: Se concluye que la sintomatología depresiva se relaciona con el automanejo de la enfermedad de la siguiente manera: a mayor automanejo menor sintomatología de depresión, o a mayor sintomatología depresiva menor automanejo; dicha relación confirma que ambas variables se afectan mutuamente y/o mantienen una relación estrecha.

Abstract Introduction: Persons with diabetes and hypertension frequently suffer from depression as well, a situation which contributes to an inadequate management of the condition in terms of medication, medical consultations, signs, and decision making. Objective: To identify the relationship between general self-management and depression symptoms in persons with diabetes and hypertension. Method: This is a transversal and correlational study with a sample of 205 patients, 100 with a main diagnosis of diabetes, and 105 with a main diagnosis of hypertension. The sampling process was non-probabilistic and by convenience. Descriptive statistics, including Pearson's r were calculated. The Partners in Health (PIH) and Patient Health Questionnaire (PHQ-8) instruments were administered. Results: A statistically significant correlation between depression symptoms and diabetes and hypertension self-management was found (r=-0.308 ρ<0.001). Discussion and conclusions: Depression symptoms were related to how diabetes and hypertension are self-managed in a way that, the more self-management, the less depression symptoms, or the more depression symptoms, the less self-management.

Resumo Introdução: As pessoas com diabetes e hipertensão experimentam com maior frequência a sintomatologia depressiva, o qual contribui a um inadequado automanejo da doença, que envolve tarefas como: a toma da medicação, assistir às consultas médicas, o conhecimento de signos e sintomas, além da toma de decisões. Objetivo: Pelo anterior, o objetivo deste trabalho é identificar a relação entre automanejo em geral e suas dimensões com sintomas depressivos em pessoas com diabetes e hipertensão. Método: Estudo transversal-correlacional com n=205 pacientes com diagnóstico de diabetes (100) e hipertensão (105). Amostragem não probabilística por conveniência. Utilizou-se a estatística descritiva e r de Pearson. Aplicaram-se os instrumentos Partners in Health (PIH) e The Patient Health Questionnaire (PHQ-8). Resultados: Encontrou-se correlação estatisticamente significativa entre a sintomatologia depressiva e o automanejo (r=-0.308 ρ<0.001). Discussão e Conclusões: Conclui-se que a sintomatologia depressiva relaciona-se com o automanejo da doença da seguinte maneira: a maior automanejo, menor sintomatologia de depressão, ou a maior sintomatologia depressiva, menor automanejo; esta relação confirma que ambas variáveis afetam-se mutuamente e/ou mantem uma relação estreita.

Utilidad de mediciones objetivas para la programación en implantes cocleares / Use of objective measures for cochlear implant programming

RESUMEN Introducción: La programación adecuada de los implantes cocleares permiten lograr niveles de estimulación auditivos óptimos. Se realiza de forma individualizada, siendo la detección del umbral de confort ideal un desafío. Se ha descrito la utilidad de los potenciales auditivos del tronco encefálico eléctrico (ePEATC) y el reflejo eléctrico estapedial (eREE) para este propósito. Objetivo: Determinar la posibilidad de realizar ePEATC y eREE en pacientes adultos y pediátricos con implantes cocleares, y evaluar cambios en la programación de los implantes cocleares luego de las mediciones objetivas. Material y método: Se realizó un estudio prospectivo, descriptivo, de pacientes con implante coclear marca MED-EL®, separando los pacientes en dos grupos: el grupo adulto (n =5) y el grupo pediátrico (n =5). Todos los pacientes incluidos presentaron más de 6 meses de encendido del implante. Se evaluaron variables epidemiológicas y tiempo de encendido del implante. Se realizó una otoscopía, prueba básica de funcionamiento del implante, y las mediciones objetivas eléctricas (ePEATC, eREE). Con estos resultados se ajustó el umbral de confort. Resultados: El tiempo promedio de encendido del implante en el grupo adulto fue de 27 meses, y 30 meses en el grupo pediátrico. El ePEATC requiere más tiempo y cooperación al compararlo con eREE. Luego de estas evaluaciones objetivas, fue necesario el ajuste del umbral de confort en tres pacientes adultos, y en dos pacientes pediátricos. Fue necesario realizar una audiometría de campo libre para estimar el umbral de confort en dos pacientes pediátricos que no presentaron respuesta en eREE. Conclusión: Fue posible realizar estas mediciones objetivas en pacientes adultos y pediátricos, siendo mejor tolerado y requiriendo menos tiempo, el eREE.

ABSTRACT Introduction: Mapping a cochlear implant allows for adjusting ideal electrical stimulation limits. It is an individualized process and detecting the most comfortable loudness level can be challenging. The use of electrically evoked auditory brainstem response (ePEATC) and electrically evoked stapedius reflex thresholds (eREE) have been considered for this purpose. Aim: To determine the feasibility of performing ePEATC and eREE on adult and pediatric patients with a cochlear implant, and to evaluate changes in programming following these objective measures. Material and method: A prospective, descriptive study was completed, of patients with MED-EL® cochlear implants, separating patients into two groups: adults (n=5) and children (n=5). All of the patients included had their implants activated for 6 months or longer. Epidemiological variables and duration of implant activation were evaluated. Otoscopy, a basic implant functioning evaluation, and objective measures (ePEATC, eREE) were performed. With these results, comfortable loudness levels were adjusted. Results: Average duration of implant activation was 27 months and 30 months, for adults and children respectively. Performing ePEATC required more time and cooperation as compared to eREE. Following the objective measures, adjustment of the comfortable loudness levels was required for three adult and two pediatric patients. Sound field audiometry was necessary for two pediatric patients in order to estimate the comfortable loudness levels because the eREE responses were absent. Conclusions: It is feasible to perform these objective measures for both adult and pediatric patients, with eREE requiring less time and being better tolerated by patients.

Chemically Modified Variants of Fenofibrate with Antiglioblastoma Potential.

Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have made several chemical modifications in fenofibrate structure to increase its stability, water solubility, tissue penetration, and ultimately anticancer potential. Our data show that, in comparison to fenofibrate, four new compounds designated here as PP1, PP2, PP3, and PP4 have improved anticancer activity in vitro. Like fenofibrate, the compounds block mitochondrial respiration and trigger massive glioblastoma cell death in vitro. In addition, one of the lead compounds, PP1, has improved water solubility and is significantly more stable when exposed to human blood in comparison to fenofibrate. Importantly, mice bearing large intracranial glioblastoma tumors demonstrated extensive areas of tumor cell death within the tumor mass following oral administration of PP1, and the treated mice did not show any major signs of distress, and accumulated PP1 at therapeutically relevant concentrations in several tissues, including brain and intracranial tumors.

Parâmetros comparativos de indicadores bioquímicos plasmáticos de duas populações de quatis (Nasua nasua - LINNAEUS, 1766) com e sem ação antrópica / Comparative parameters of plasma biochemical indicators of two populations of Coati (Nasuanasua - LINNAEUS, 1766) with and without human action

Os quatis são mamíferos carnívoros da família Procyonidae, são animais onívoros, encontrados nas Américas do Norte, Central e Sul, sendo amplamente distribuídos no Brasil. O objetivo deste trabalho é analisar as alterações nos parâmetros sanguíneos de duas diferentes populações de quatis (Nasua nasua), da região oeste do Paraná, e avaliar a qualidade de vida e a interferência antrópica nos hábitos alimentares desses animais. A análise sorológica foi realizada em duas diferentes populações de quatis (Nasua nasua) que habitam duas unidades de conservação em regiões distintas no município de Foz do Iguaçu. Em uma das populações, foram visualizados cerca de cinquenta indivíduos, os quais se revelam em exposição direta aos seres humanos, e outra população menor, em torno de trinta indivíduos, os quais não possuem exposição direta aos seres humanos, o que, por sua vez, revelou importantes indicativos da qualidade de vida e de saúde desses animais. Foram realizadas avaliações bioquímicas do soro sanguíneo de 10 quatis adultos; cinco animais do grupo 1, população exposta aos seres humanos, e cinco animais do grupo 2, população com menor exposição. Com os resultados obtidos, foram feitas as comparações dos valores bioquímicos entre os grupos e com os valores de referência pesquisados na literatura. Os exames bioquímicos revelaram alterações significativas nos níveis de glicose e proteínas totais e alterações no nível plasmático de triglicerídeos nos quatis capturados na população em contado direto com seres humanos. Conclui-se que a saúde dos animais que possuem exposição direta com seres humanos está sendo afetada pelo consumo de uma dieta rica em carboidratos e gorduras, oriunda de alimentos industrializados fornecidos pelos turistas.(AU)

The coatis, carnivorous mammals of the Procyonidae family, are omnivorous animals, found in North, Central and South America and are widely distributed in Brazil. The objective of this study was to analyze changes in blood parameters in two different populations of coatis (Nasua nasua), of the western region of Paraná, and to evaluate the quality of life and the human interference in eating habits of these animals. Serologic analysis was performed in two different populations of coatis (Nasua nasua) inhabiting two conservation units in different areas in the city of Foz do Iguaçu. In one population, approximately fifty individuals were visualized, revealing themselves in direct exposure to humans as well as another minor population of about thirty individuals, which have no direct exposure to humans, which revealed important indicatives of the quality of life and health of these animals. Biochemical assessments of ten adults coatis serum were perfomred, five animals in group 1, population exposed to humans and five animals of the group 2, population less exposed. With the obtained results, comparisons were made between the groups' biochemical values and the reference values found in the literature. Biochemical tests revealed significant changes in glucose levels and total protein and changes in plasma levels of triglycerides in coatis captured in the population in direct contact with humans. It follows that the health of animals that have direct exposure to humans is being affected by the consumption of a diet high in carbohydrates and fats, coming from processed foods provided by tourists.(AU)

Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

BACKGROUND: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. OBJECTIVE: We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models were used in this study. RESULTS: Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re-purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.

A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.

Low-cysteine alpha-keratins and corneous beta-proteins are initially formed in the regenerating tail epidermis of lizard.

During tail regeneration in lizards, the stratified regenerating epidermis progressively gives rise to neogenic scales that form a new epidermal generation. Initially, a soft, un-scaled, pliable, and extensible epidermis is formed that is progressively replaced by a resistant but non-extensible scaled epidermis. This suggests that the initial corneous proteins are later replaced with harder corneous proteins. Using PCR and immunocytochemistry, the present study shows an upregulation in the synthesis of low-cysteine type I and II alpha-keratins and of corneous beta-proteins with a medium cysteine content and a low content in glycine (formerly termed beta-keratins) produced at the beginning of epidermal regeneration. Quantitative PCR indicates upregulation in the production of alpha-keratin mRNAs, particularly of type I, between normal and the thicker regenerating epidermis. PCR-data also indicate a higher upregulation for cysteine-rich corneous beta-proteins and a high but less intense upregulation of low glycine corneous protein mRNAs at the beginning of scale regeneration. Immunolabeling confirms the localization of these proteins, and in particular of beta-proteins with a medium content in cysteine initially formed in the wound epidermis and later in the differentiating corneous layers of regenerating scales. It is concluded that the wound epidermis initially contains alpha-keratins and corneous beta-proteins with a lower cysteine content than more specialized beta-proteins later formed in the mature scales. These initial corneous proteins are likely related to the pliability of the wound epidermis while more specialized alpha-keratins and beta-proteins richer in glycine and cysteine are synthesized later in the mature and inflexible scales. J. Morphol. 278:119-130, 2017. ©© 2016 Wiley Periodicals,Inc.

Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype.

Neuroendocrine tumors (NETs), which can have survival rates as low as 4%, currently have limited therapeutic interventions available highlighting the dire need for the identification of novel biological targets for use as new potential drug targets. One such potential target is retinoblastoma-binding protein 2 (RBP2), an H3K4 demethylase whose overexpression has been linked to cancer formation and metastasis in non-endocrine tumor types. We measured RBP2 mRNA and protein levels in enteropancreatic NETs by measuring RBP2 in matched human normal and NET tissue samples. Further, proliferation, migration, invasion and colony formation assays were performed in the physiologically relevant NET cell lines ßlox5, H727 and QGP-1 to understand the role of RBP2 and its demethylase activity on end points of tumorigenesis. Our data indicate a strong correlation between RBP2 mRNA and protein expression in NET specimens. RBP2 was overexpressed relative to tissue-matched normal controls in 80% of the human tumors measured. In vitro studies showed RBP2 overexpression significantly increased proliferation, migration, invasion and colony formation, whereas knockdown significantly decreases the same parameters in a demethylase-independent manner. The cell cycle inhibitors p21 and p57 decreased with RBP2 overexpression and increased upon its depletion, suggesting a regulatory role for RBP2 in cellular proliferation. Taken together, our results support the hypothesis that the aberrant overexpression of RBP2 is a frequent contributing factor to tumor formation and metastasis in enteropancreatic NETs.

Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol.

Scaffolds constituted by electrospun microfibers of poly(ethylene glycol) (PEG) and poly(butylene succinate) (PBS) were studied. Specifically, coaxial microfibers having different core-shell distributions and compositions were considered as well as uniaxial micro/nanofibers prepared from mixtures of both polymers. Processing conditions were optimized for all geometries and compositions and resulting morphologies (i.e. diameter and surface texture) characterized by scanning electron microscopy. Chemical composition, molecular interactions and thermal properties were evaluated by FTIR, NMR, XPS and differential scanning calorimetry. The PEG component of electrospun fibers could be solubilized by immersion of scaffolds in aqueous medium, giving rise to high porosity and hydrophobic samples. Nevertheless, a small amount of PEG was retained in the PBS matrix, suggesting some degree of mixing. Solubilization was slightly dependent on fiber structure; specifically, the distribution of PEG in the core or shell of coaxial fibers led to higher or lower retention levels, respectively. Scaffolds could be effectively loaded with hydrophobic drugs having antibacterial and anticarcinogenic activities like triclosan and curcumin, respectively. Their release was highly dependent on their chemical structure and medium composition. Thus, low and high release rates were observed in phosphate buffer saline (SS) and SS/ethanol (30:70 v/v), respectively. Slight differences in the release of triclosan were found depending on fiber distribution and composition. Antibacterial activity and biocompatibility were evaluated for both loaded and unloaded scaffolds.

Relative performance of the two hands in simple and choice reaction time tasks

There is evidence that the left hemisphere is more competent for motor control than the right hemisphere. This study investigated whether this hemispheric asymmetry is expressed in the latency/duration of sequential responses performed by the left and/or right hands. Thirty-two right-handed young adults (16 males, 16 females; 18-25 years old) were tested in a simple or choice reaction time task. They responded to a left and/or right visual target by moving their left and/or right middle fingers between two keys on each side of the midline. Right hand reaction time did not differ from left hand reaction time. Submovement times were longer for the right hand than the left hand when the response was bilateral. Pause times were shorter for the right hand than the left hand, both when the responses were unilateral or bilateral. Reaction time results indicate that the putatively more efficient response preparation by the left hemisphere motor mechanisms is not expressed behaviorally. Submovement time and pause time results indicate that the putatively more efficient response execution by the left hemisphere motor mechanisms is expressed behaviorally. In the case of the submovements, the less efficient motor control of the left hand would be compensated by a more intense attention to this hand.

Temporal and geographic clustering of polyomavirus-associated olfactory tumors in 10 free-ranging raccoons (Procyon lotor).

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

Biomolecular identification of beta-defensin-like peptides from the skin of the soft-shelled turtle Apalone spinifera.

Numerous bacteria are frequently observed in the superficial corneocytes forming the corneous layer of the soft-shelled turtle Apalona spinifera. The resistance to bacterial penetration through the living epidermis in this turtle suggests the presence of an antimicrobial barrier, possibly derived from the presence of anti-microbial peptides in the epidermis. Four beta-defensin-like peptides, named As-BD-1 to 4, have been characterized from skin tissues using molecular and bioinformatics methods. The precursor peptides contain the beta-defensin motif with the typical cysteine localization pattern. The analysis of the expression for the four different beta-defensin-like proteins show that these molecules are expressed in the skin (epidermis and dermis) of the carapace, neck, digit, and tail but are apparently not expressed in the liver or intestine under normal conditions. These data suggest that in the skin of the soft-shelled turtle there are potential effective anti-microbial peptides against epidermal bacteria.

Anti-leukemic mechanisms of pegylated arginase I in acute lymphoblastic T-cell leukemia.

New treatments for adults with acute lymphoblastic T-cell leukemia (T-ALL) are urgently needed, as the current rate of overall remission in these patients is only about 40 percent. We recently showed the potential therapeutic benefit of the pegylated-human-arginase I (peg-Arg I) in T-ALL. However, the mechanisms by which peg-Arg I induces an anti-T-ALL effect remained unknown. Our results show the induction of T-ALL cell apoptosis by peg-Arg I, which associated with a global arrest in protein synthesis and with the phosphorylation of the eukaryotic-translation-initiation factor 2 alpha (eIF2α). Inhibition of eIF2α phosphorylation in T-ALL cells prevented the apoptosis induced by peg-Arg I, whereas the expression of a phosphomimetic eIF2α form increased the sensibility of T-ALL cells to peg-Arg I. Phosphorylation of eIF2α by peg-Arg I was mediated through kinases PERK and GCN2 and down-regulation of phosphatase GADD34. GCN2 and decreased GADD34 promoted T-ALL cell apoptosis after treatment with peg-Arg I, whereas PERK had an unexpected anti-apoptotic role. Additional results showed that phospho-eIF2α signaling further increased the anti-leukemic effects induced by peg-Arg I in T-ALL-bearing mice. These results suggest the central role of phospho-eIF2α in the anti-T-ALL effects induced by peg-Arg I and support its study as a therapeutic target.

Facilitatory effects of an auditory warning stimulus in a visual location identification task and a visual shape identification task

The occurrence of a weak auditory warning stimulus increases the speed of the response to a subsequent visual target stimulus that must be identified. This facilitatory effect has been attributed to the temporal expectancy automatically induced by the warning stimulus. It has not been determined whether this results from a modulation of the stimulus identification process, the response selection process or both. The present study examined these possibilities. A group of 12 young adults performed a reaction time location identification task and another group of 12 young adults performed a reaction time shape identification task. A visual target stimulus was presented 1850 to 2350 ms plus a fixed interval (50, 100, 200, 400, 800, or 1600 ms, depending on the block) after the appearance of a fixation point, on its left or right side, above or below a virtual horizontal line passing through it. In half of the trials, a weak auditory warning stimulus (S1) appeared 50, 100, 200, 400, 800, or 1600 ms (according to the block) before the target stimulus (S2). Twelve trials were run for each condition. The S1 produced a facilitatory effect for the 200, 400, 800, and 1600 ms stimulus onset asynchronies (SOA) in the case of the side stimulus-response (S-R) corresponding condition, and for the 100 and 400 ms SOA in the case of the side S-R non-corresponding condition. Since these two conditions differ mainly by their response selection requirements, it is reasonable to conclude that automatic temporal expectancy influences the response selection process.

Distribution of specific keratin-associated beta-proteins (beta-keratins) in the epidermis of the lizard Anolis carolinensis helps to clarify the process of cornification in lepidosaurians.

The epidermis of different scales in the lizard Anolis carolinensis expresses specific keratin-associated beta-proteins (beta-keratins). In order to localize the sites of accumulation of different beta-proteins, we have utilized antibodies directed against representative members of the main families of beta-proteins, the glycine-rich (HgG5), glycine-cysteine rich (HgGC3), glycine-cysteine medium-rich (HgGC10), and cysteine-rich (HgC1) beta-proteins. Immunoblotting and immunocytochemical controls confirm the specificity of the antibodies made against these proteins. Light and ultrastructural immunocytochemistry shows that the glycine-rich protein HgG5 is present in beta-layers of different body scales but is scarce in the oberhautchen and claws, and is absent in alpha-layers and adhesive setae. The cysteine-glycine-rich protein HgGC3 is low to absent in the oberhautchen, beta-layer, and mesos-layer but increases in alpha-layers. This beta-protein is low in claws where it is likely associated with the hard alpha-keratins previously studied in this lizard. The glycine-cysteine medium-rich HgGC10 protein is low in the beta-layer, higher in alpha-layers, and in the oberhautchen. This protein forms a major component of setal proteins including those of the adhesive spatula that allow this lizard to stick on vertical surfaces. HgC1 is poorly localized in most epidermis analyzed including adhesive setae and claws and appears as a minor component of the alpha-layers. In conclusion, the present study suggests that beta- and alpha-layers of lizard epidermis represent regions with different accumulation of glycine-rich proteins (mainly for mechanical resistance and hydrophobicity in the beta-layer) or cysteine-glycine-rich proteins (for both resistance and elasticity in both alpha- and beta-layers).