What triggers phenological events in plants under seasonal environments? A study with phylogenetically related plant species in sympatry / O que desencadeia eventos fenológicos em plantas em ambientes sazonais? Um estudo com espécies de plantas filogeneticamente relacionadas e em simpatria

In this study, we evaluated variation in vegetative and reproductive phenological events of four phylogenetically related plant species subjected to a seasonal environment. To this aim, we sampled 15 individuals of each plant species every fortnight for one year, between January and December of 2017. To assess when a given phenophase occurred more intensely in the population, the Fournier intensity index was used and the synchrony of individuals of the sample in a given phenological event was estimated using the activity index. The Rayleigh (Z) test was used to determine whether the phenological events have seasonal distribution. The relationship of abiotic factors (photoperiod, precipitation, relative humidity and temperature) with the intensity of phenophases was evaluated for each plant species using generalized linear models (GLMs). The phenophases of all plants showed a seasonal distribution pattern, as well as variation in synchrony of phenophases and specific sets of abiotic factors significantly influenced their phenophases. New leaves, for example, were produced throughout the seasons, with intense leaf fall in the dry season. Flowering periods, on the other hand, did not overlap. Indeed, species exhibited sequential flowering and asynchronous flowering among individuals. Our results suggest that the phenological patterns of four sympatric plant species are directly linked to climatic variables, but different abiotic factors affected different phenophases.

Neste estudo, avaliamos a variação nos eventos fenológicos vegetativos e reprodutivos de quatro espécies de plantas filogeneticamente relacionadas submetidas a um ambiente sazonal. Para isso, amostramos 15 indivíduos de cada espécie quinzenalmente, pelo período de um ano, entre janeiro e dezembro de 2017. Para avaliar quando uma determinada fenofase ocorreu de modo mais intenso na população foi utilizado o índice de intensidade de Fournier e a sincronia dos indivíduos da amostra em determinado evento fenológico foi estimada utilizando-se o índice de atividade. O teste de Rayleigh (Z) foi usado para determinar se os eventos fenológicos têm distribuição sazonal. A relação dos fatores abióticos (fotoperíodo, precipitação, temperatura e umidade relativa) com a intensidade das fenofases foi avaliada para cada espécie de planta usando modelos lineares generalizados (GLMs). As fenofases de todas as plantas apresentaram um padrão de distribuição sazonal, bem como variação na sincronia das fenofases e conjuntos específicos de fatores abióticos influenciaram significativamente suas fenofases. Folhas novas, por exemplo, foram produzidas ao longo das estações, com intensa queda de folhas na estação seca. Os períodos de floração, por outro lado, não se sobrepuseram. De fato, as espécies exibiram floração sequencial e floração assíncrona entre os indivíduos. Nossos resultados sugerem que os padrões fenológicos das quatro espécies de plantas simpátricas estão diretamente ligados às variáveis climáticas, mas diferentes fatores abióticos afetaram diferentes fenofases.

What triggers phenological events in plants under seasonal environments? A study with phylogenetically related plant species in sympatry

Abstract In this study, we evaluated variation in vegetative and reproductive phenological events of four phylogenetically related plant species subjected to a seasonal environment. To this aim, we sampled 15 individuals of each plant species every fortnight for one year, between January and December of 2017. To assess when a given phenophase occurred more intensely in the population, the Fournier intensity index was used and the synchrony of individuals of the sample in a given phenological event was estimated using the activity index. The Rayleigh (Z) test was used to determine whether the phenological events have seasonal distribution. The relationship of abiotic factors (photoperiod, precipitation, relative humidity and temperature) with the intensity of phenophases was evaluated for each plant species using generalized linear models (GLMs). The phenophases of all plants showed a seasonal distribution pattern, as well as variation in synchrony of phenophases and specific sets of abiotic factors significantly influenced their phenophases. New leaves, for example, were produced throughout the seasons, with intense leaf fall in the dry season. Flowering periods, on the other hand, did not overlap. Indeed, species exhibited sequential flowering and asynchronous flowering among individuals. Our results suggest that the phenological patterns of four sympatric plant species are directly linked to climatic variables, but different abiotic factors affected different phenophases.

Resumo Neste estudo, avaliamos a variação nos eventos fenológicos vegetativos e reprodutivos de quatro espécies de plantas filogeneticamente relacionadas submetidas a um ambiente sazonal. Para isso, amostramos 15 indivíduos de cada espécie quinzenalmente, pelo período de um ano, entre janeiro e dezembro de 2017. Para avaliar quando uma determinada fenofase ocorreu de modo mais intenso na população foi utilizado o índice de intensidade de Fournier e a sincronia dos indivíduos da amostra em determinado evento fenológico foi estimada utilizando-se o índice de atividade. O teste de Rayleigh (Z) foi usado para determinar se os eventos fenológicos têm distribuição sazonal. A relação dos fatores abióticos (fotoperíodo, precipitação, temperatura e umidade relativa) com a intensidade das fenofases foi avaliada para cada espécie de planta usando modelos lineares generalizados (GLMs). As fenofases de todas as plantas apresentaram um padrão de distribuição sazonal, bem como variação na sincronia das fenofases e conjuntos específicos de fatores abióticos influenciaram significativamente suas fenofases. Folhas novas, por exemplo, foram produzidas ao longo das estações, com intensa queda de folhas na estação seca. Os períodos de floração, por outro lado, não se sobrepuseram. De fato, as espécies exibiram floração sequencial e floração assíncrona entre os indivíduos. Nossos resultados sugerem que os padrões fenológicos das quatro espécies de plantas simpátricas estão diretamente ligados às variáveis climáticas, mas diferentes fatores abióticos afetaram diferentes fenofases.

Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC.

BACKGROUND: We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial. PATIENTS AND METHODS: This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. RESULTS: Of 793 patients, 345 (43.5%) had tTMB ≥175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB ≥175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/exome was not {OS: hazard ratio, 0.62 [95% confidence interval (CI) 0.48-0.80] and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS [hazard ratio (95% CI)] for pembrolizumab versus chemotherapy was observed regardless of STK11 [STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05)]; KEAP1 [KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99)], or KRAS [KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18)] mutation status. CONCLUSION: tTMB with a cut point of ≥175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score ≥1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status.

Omalizumab and allergen immunotherapy for respiratory allergies: A mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP)

Although currently approved to treat severe asthma and chronic spontaneous urticaria, omalizumab has also been an effective and safe add-on treatment for other allergic diseases. Namely, omalizumab has been proposed to be used as add-on therapy in patients with allergic rhinitis and asthma and undergoing specific allergen immunotherapy (AIT). AIT is the only treatment that modifies the natural history of IgE-mediated diseases. This brief review summarizes the available evidence and controversies on the efficacy and safety of omalizumab combined with specific AIT (AU)

What triggers phenological events in plants under seasonal environments? A study with phylogenetically related plant species in sympatry.

In this study, we evaluated variation in vegetative and reproductive phenological events of four phylogenetically related plant species subjected to a seasonal environment. To this aim, we sampled 15 individuals of each plant species every fortnight for one year, between January and December of 2017. To assess when a given phenophase occurred more intensely in the population, the Fournier intensity index was used and the synchrony of individuals of the sample in a given phenological event was estimated using the activity index. The Rayleigh (Z) test was used to determine whether the phenological events have seasonal distribution. The relationship of abiotic factors (photoperiod, precipitation, relative humidity and temperature) with the intensity of phenophases was evaluated for each plant species using generalized linear models (GLMs). The phenophases of all plants showed a seasonal distribution pattern, as well as variation in synchrony of phenophases and specific sets of abiotic factors significantly influenced their phenophases. New leaves, for example, were produced throughout the seasons, with intense leaf fall in the dry season. Flowering periods, on the other hand, did not overlap. Indeed, species exhibited sequential flowering and asynchronous flowering among individuals. Our results suggest that the phenological patterns of four sympatric plant species are directly linked to climatic variables, but different abiotic factors affected different phenophases.

Impactos e reflexões de uma competência profissional advinda das especializações / Impactos y reflejos de una competencia profesional a partir de las especializaciones / Impacts and reflections of a professional competence arising from specializations

A década de 1930 foi marcada pelos reflexos da Crise de 1929. A diminuição das exportações para o continente Europeu fez com que as indústrias norte-americanas acumulassem estoque de seus produtos. Diante de uma possível desvalorização, inúmeras empresas entraram em uma corrida para venda de suas ações que se encontravam na Bolsa de Valores de Nova York, o que impactou fortemente toda economia mundial [Fragmento de texto] (AU)

A DFT investigation of lithium adsorption on graphenes as a potential anode material in lithium-ion batteries.

We present a detailed study of the Li+ ion adsorption on two different hydrogenated carbon nanostructures, namely as pristine graphene (PG) and topologic Stone-Wales defective graphene (SWG) using the density functional theory (DFT). The studies are focused to analyze the structure-stability relationship with the estimated electronic and electrical properties for lithium-ion batteries (LIB) formed with an anode based on the Li/Li+#PG and Li/Li+#SWG systems. In addition, the electronic effects induced due to Li+ adsorption and the presence of SW defect on the graphene models were analyzed by the frontier molecular orbitals, ChelpG charges, Raman and UV-Vis spectra. It was verified that Li+ is more stably adsorbed on the edges on both graphene structures through an electrostatic interaction between cation and more negatively charged edges of nanostructures. TD-DFT calculations showed that the metallic nature of isolated graphene is disturbed after the adsorption of Li+, and this was demonstrated from the calculated HOMO-LUMO gap. The same Li+-Graphene geometries were optimized by introducing neutral charge in order to enable the calculation of ionization potentials. I was also found that such systems potentially contributed to the modeling of graphene-based anodes with reasonable electrical voltage responses estimated for a LIB. The simulation of Raman and UV-Vis spectra revealed significant variations in intensity and shifts the typical bands of graphene due to the presence of the Li+ ion that can contribute to point out new experiments to the spectroscopic characterization of these systems. Our results suggest that these carbon nanostructures are potential candidates for efficient applications in electrochemical systems, mainly dealing with LIB.

Vernal Keratoconjunctivitis: an update focused on clinical grading system.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of < 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region. OBJECTIVE: Aim of this review is to provide an updated overview on the disease focused on clinical grading system, searching papers published in the last decade on VKC in scientific databases. RESULTS: Currently there are no standardized criteria for diagnosis of VKC and there is no uniformity to define disease severity, which makes difficult to diagnose and treat the disease. CONCLUSIONS: Given the wide overlap of the symptoms of VKC with the allergic conjunctivitis, criteria of probable, possible or improbable diagnosis are needed, providing pediatricians with parameters useful for deciding whether to drive the patient to the ophthalmologist for diagnostic confirmation.

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial.

BACKGROUND: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01905657.

Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on sensitisation pattern to molecular allergens in children with allergic rhinoconjunctivitis

Background: The diagnostic and therapeutic approach to grass pollen allergy is now possible by detecting specific IgE (sIgE) to its allergenic components. Aim: To evaluate the correlation between the sensitisation to different molecular Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. Methods: The pilot study included 36 patients affected by allergic rhinoconjunctivitis, all treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4, 5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS) and the Average Combined Score (ACS) were evaluated before and after one year of immunotherapy. Results: Three different groups of sensitisation were defined based on the range of IgE reactivity to Phleum pratense allergens at baseline: group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5 allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79 ± 0.18 in group I; 1.81 ± 0.23 in group II; and 1.95 ± 0.34 in group III. At T1 ACS was 0.85 ± 0.55 in group I; 1.01 ± 0.31 in group II; and 1.44 ± 0.39 in group III. At T1 there was a significant improvement of ARTSS and ACS for group I (p = 0.001). Conclusions: Sublingual immunotherapy with a grass pollen is efficacious irrespective of the patients’ baseline sensitisation to either single or multiple grass pollen molecular allergens. We found that patients with few sensitisations have a greater improvement in combined symptom and medication score. SLIT improves the clinical course of allergic patients although new sensitisations may appear (AU)

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De novo transcriptome assembly of sugarcane leaves submitted to prolonged water-deficit stress.

Sugarcane production is strongly influenced by drought, which is a limiting factor for agricultural productivity in the world. In this study, the gene expression profiles obtained by de novo assembly of the leaf transcriptome of two sugarcane cultivars that differ in their physiological response to water deficit were evaluated by the RNA-Seq method: drought-tolerant cultivar (SP81-3250) and drought-sensitive cultivar (RB855453). For this purpose, plants were grown in a greenhouse for 60 days and were then submitted to three treatments: control (-0.01 to -0.015 MPa), moderate water deficit (-0.05 to -0.055 MPa), and severe water deficit (-0.075 to -0.08 MPa). The plants were evaluated 30, 60, and 90 days after the beginning of treatment. Sequencing on an Illumina platform (RNA-Seq) generated more than one billion sequences, resulting in 177,509 and 185,153 transcripts for the tolerant and sensitive cultivar, respectively. These transcripts were aligned with sequences from Saccharum spp, Sorghum bicolor, Miscanthus giganteus, and Arabidopsis thaliana available in public databases. The differentially expressed genes detected during the prolonged period of water deficit permit to increase our understanding of the molecular patterns involved in the physiological response of the two cultivars. The tolerant cultivar differentially expressed a larger number of genes at 90 days, while in the sensitive cultivar the number of differentially expressed genes was higher in 30 days. Both cultivars perceived the lack of water, but the tolerant cultivar responded more slowly than the sensitive cultivar. The latter requires rapid activation of different water-deficit stress response mechanisms for its survival. This rapid activation of metabolic pathways in response to water stress does not appear to be the key mechanism of drought tolerance in sugarcane. There is still much to clarify on the molecular and physiological pattern of plants in response to drought.

Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on sensitisation pattern to molecular allergens in children with allergic rhinoconjunctivitis.

BACKGROUND: The diagnostic and therapeutic approach to grass pollen allergy is now possible by detecting specific IgE (sIgE) to its allergenic components. AIM: To evaluate the correlation between the sensitisation to different molecular Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. METHODS: The pilot study included 36 patients affected by allergic rhinoconjunctivitis, all treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4, 5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS) and the Average Combined Score (ACS) were evaluated before and after one year of immunotherapy. RESULTS: Three different groups of sensitisation were defined based on the range of IgE reactivity to Phleum pratense allergens at baseline: group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5 allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79±0.18 in group I; 1.81±0.23 in group II; and 1.95±0.34 in group III. At T1 ACS was 0.85±0.55 in group I; 1.01±0.31 in group II; and 1.44±0.39 in group III. At T1 there was a significant improvement of ARTSS and ACS for group I (p=0.001). CONCLUSIONS: Sublingual immunotherapy with a grass pollen is efficacious irrespective of the patients' baseline sensitisation to either single or multiple grass pollen molecular allergens. We found that patients with few sensitisations have a greater improvement in combined symptom and medication score. SLIT improves the clinical course of allergic patients although new sensitisations may appear.

Clinically localized type 1 and 2 papillary renal cell carcinomas have similar survival outcomes following surgery / Los carcinomas papilares de células renales tipo 1 y 2 localizados clínicamente tienen resultados de supervivencia similares después de la cirugía

Propósito Se intentó determinar la incidencia, hallazgos patológicos, factores pronósticos y resultados clínicos para pacientes con CCR papilar clínicamente localizado. Métodos Demográfico, Se recopilaron hallazgos clínicos y patológicos en todos los pacientes con CCRP sometidos a cirugía en cuatro centros médicos académicos. El punto final primario fue la supervivencia específica del cáncer (CSS). La supervivencia sin recaída (RFS) y la supervivencia general (OS) fueron puntos finales secundarios. Kaplan- Se obtuvieron estimaciones de Meier y se usaron modelos de regresión de riesgos proporcionales de Cox para evaluar predictores de mortalidad y recaída. Resultados Identificamos 626 CCPR, de los cuales 373 (60por ciento) fueron del tipo 1 y 253 (40 por ciento) fueron del tipo 2, con tres cuartas partes de todos los tumores siendo pT1. En comparación con los pacientes con tipo 1, aquellos con tipo 2 eran mayores (edad media: 63 frente a 61; (AU)

Purpose We aimed to determine incidence, pathologic fndings, prognostic factors and clinical outcomes for patients with clinically localized papillary RCC. Methods Demographic, clinical and pathologic fndings were collected on all patients with PRCC undergoing sur-gery at four academic medical centers. The primary end-point was cancer-specifc survival (CSS). Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Kaplan­ Meier estimates were obtained, and Cox proportional hazard regression models were used to assess predictors of mortality and relapse. Results We identifed 626 PRCC, of which 373 (60 pertcent) were type 1 and 253 (40 pertcent) were type 2, with three-quar-ters of all tumors being pT1. Compared to patients with type 1, those with type 2 were older (mean age: 63 vs 61; (AU)

Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial.

BACKGROUND: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. PATIENTS AND METHODS: Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. RESULTS: Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. CONCLUSIONS: Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. CLINICAL TRIAL REGISTRATION: NCT01345682 (ClinicalTrials.gov).

The wolf in sheep's clothing: Microtomographic aspects of clinically incipient radiation-related caries.

BACKGROUND: Radiation related caries (RRC) can cause rapid progression, with a high potential for dental destruction affecting mainly cervical and incisal areas. Unlike the injuries that occur in the conventional caries, incipient RRC present in unusual surfaces have difficult diagnosis and classification stages of cavitation. MATERIAL AND METHODS: Evaluate the radiographic patterns of demineralization of RRC by using micro-CT. Ten teeth with incipient RRC and 10 teeth with incipient conventional caries (control group) matched by anatomic teeth group and caries affected surfaces were evaluated by X-ray microtomography (micro-CT) Skyscan 1174V2 (50Kv, 1.3 megapixel, Kontich, Belgium). Teeth were placed in a standard position for micro-CT (coronal, transaxial and sagittal sections) during images acquisition. Lesions were classified according to the depth of invasion and relationship with enamel, dentin and pulp. RESULTS: RRC samples presented deeper lesions with higher involvement of enamel and dentin. Control group presented focal and superficial lesions with lower involvement of enamel and dentin. CONCLUSIONS: Incipient RRC present aggressive microtomographic patterns of demineralization when compared to conventional caries, as indicated by deep lesions, regardless of its clinically incipient aspects.

Renal effects of molecular targeted therapies in oncology: a review by the Cancer and the Kidney International Network (C-KIN).

A number of cancer therapy agents are cleared by the kidney and may affect renal function, including cytotoxic chemotherapy agents, molecular targeted therapies, analgesics, antibiotics, radiopharmaceuticals and radiation therapy, and bone-targeted therapies. Many of these agents can be nephrotoxic, including targeted cancer therapies. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here, we review the renal effects associated with a selection of currenty approved targeted cancer therapies, directed to vascular endothelial growth factor or VEGF receptor(s) (VEGF/VEGFR), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor2 (HER2), BRAF, anaplastic lymphoma kinase (ALK), programmed cell death protein-1 or its ligand (PD-1/PDL-1), receptor activator of nuclear factor kappa-B ligand (RANKL), and mammalian target of rapamycin (mTOR). The early diagnosis and prompt treatment of these renal alterations are essential in the daily practice where molecular targeted therapies have a definitive role in the armamentarium used in many cancers.

Serum resistin levels in children with primary snoring.

Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS.

Anti IgE antibody as treatment of allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) occurs in 7-9% of patients with cystic fibrosis (CF) and causes a worsening of lung function and respiratory symptoms. Standard treatment of ABPA consists of oral steroids; however, higher corticosteroid therapy associated to antifungal agent (itraconazole) long-term treatments are often required to reduce respiratory exacerbations and to prevent progressive lung damage. Here we describe the case of a girl with CF who experienced clinical and functional improvement over 12-months treatment with omalizumab. At birth, our patient was diagnosed with mild-to-moderate CF and from childhood she underwent annual cycles of antibiotic and corticosteroid therapies. At 12 years, she presented with a worsening respiratory condition, asthma symptoms and reduced lung function (FEV1 of 78%). Blood tests showed an increased concentration of plasma total IgE and positive specific IgE antibodies to Aspergillus fumigatus; allergic skin tests were also positive for A. fumigatus. The patient started steroid therapy but had impaired glucose tolerance due to long-term steroid use. Subcutaneous omalizumab 300 mg every two weeks was initiated and after 14 weeks she had improved respiratory symptoms (FEV1 99%) and a marked reduction in the use of systemic antibiotic and corticosteroid therapies. No side effects were reported. Our case shows that therapy with omalizumab for a prolonged period can resolve symptoms of asthma.

Risk factors affecting quality of life in a group of Italian children with asthma.

The measure of Quality of Life (QoL) has become one of the most important criteria used to assess the impact of chronic illness, such as asthma, on the patient’s daily life, in adults and children alike. The objective of our open observational study was to measure the QoL and analyze several factors that potentially affect QoL, such as symptoms and functional respiratory parameters, in a cohort of children with asthma. One hundred and twenty-seven children with asthma, 6 to 14 years of age, living in the city of Rome, were enrolled as outpatients. They were subjected to Skin Prick Tests (SPT), underwent spirometry and filled out the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). One hundred and eleven children were diagnosed with intermittent asthma, 12 (10%) with mild asthma, and four with moderate persistent asthma. Ninety-six children had a positive SPT. The mean total score of QoL, obtained from the questionnaire, was 5.4 (∓1.2 SD). Two QoL groups were created. Children with total QoL score <5.5 were included in the “Lower QoL” score group while children with total QoL score ≥ 5.5 were included in the “Higher QoL” score group. Children in the Higher group and their mothers had a higher mean age, suffered from fewer asthma exacerbations during the year preceding the study, and showed a higher mean value of forced expiratory volume (FEV1) compared to the children in the Lower category. Using Logistic regression we identified the main factors that may affect QoL as FEV1, symptoms in the previous year and mother’s age. QoL is correlated with the frequency of asthma exacerbations and FEV1 values. Furthermore, our research shows that a significant impairment of QoL may also occur in patients with normal lung function, pointing out the importance of evaluating QoL in all children with asthma.