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Abstract Objectives The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. Methods A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. Results The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035). Conclusions sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions. Level of evidence 3.

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OBJECTIVES: The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. METHODS: A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. RESULTS: The range of sPD-L1 in the study group was 0.16-1.63ng/mL, mean 0.64±0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p= 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p= 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC=0.664, 95% CI 0.529‒0.8, p-value=0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value=0.035). CONCLUSIONS: sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions.

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Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response.

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During the Gorgonzola-type cheese preparation there are proteolysis and lipolysis which may be influenced by the type of starter culture chosen. Six manufacturing steps were selected to identify which of them is most suitable for biogenic amines (BA) formation (1- milk, 2- lactic acid bacterial culture and fungus addition, 3- curd, 4- dry salting, 5- maturation at 30 days and maturation at 60 days); perform research on enterobacteria; accomplish the research of BA-producing bacteria (BAPB); detect and quantify the most abundant BA (putrescine, cadaverine, tyramine, histamine, spermidine and spermine) in the six steps of Gorgonzola cheese production and in bacterial isolates using high performance liquid chromatography and UV-Vis SPD/10AV detector and define if the presence of enterobacteria and BAPB would be correlated with BA production in this cheese. The bacterial culture used increased its log population by 7 log cycles and reached its highest level in batch 2 during cheese maturation. There was a decrease in the enterobacterial population in 2 log cycles after 60 days of maturation in batch 1. Tyramine was the BA with the highest concentration 306.32 mg.Kg-1 quantified in step 6 (60 days maturation) in batch 1. Criterion is requiered in bacterial starter culture selection because it is a quality determinant factor in relation to BA production and more rigor in raw material selection.

Durante a elaboração do queijo tipo Gorgonzola ocorre proteólise a partir das bactérias e dos fungos adicionados ao leite que podem levar a formação de aminas biogênicas (AB) neste tipo de queijo. Portanto, no presente estudo foi feito o acompanhamento com coleta de amostras em seis etapas na fabricação deste queijo paraidentificar em qual delas haveria maior formação de aminas biogênicas (AB). As amostras coletadas em três diferentes lotes foram o leite cru (1), leite pasteurizado adicionado de cultura de bactérias ácido-láticas (2), massa coalhada (3), queijo após a etapa de salga seca (4), queijo após 30 dias de maturação (5) e queijo após 60 dias de maturação (6). Também foram realizadas a pesquisa de enterobactérias e bactérias ácido-láticas com característica capacidade de descarboxilação de aminoácidos e produção de aminas biogênicas (BPAB); detecção e quantificação da AB mais abundante (putrescina, cadaverina, tiramina, histamina, espermidina e espermina) nas seis etapas de fabricação do queijo tipo Gorgonzola e nos isolados bacterianos utilizando cromatografia líquida de alta eficiência e detector UV-Vis SPD/10AV e a verificação se a presença de enterobactérias e BPAB estariam correlacionadas com a produção de AB nesse queijo. A cultura bacteriana utilizada cresceu aumentando em sete ciclos logarítmicos sua população e alcançou seu maior nível no lote 2 na etapa de maturação do queijo. Houve diminuição da população enterobactérias em 2 ciclos logarítmicos após 60 dias de maturação no lote 1. A tiramina foi a AB com concentração mais elevada 306,32 mg.Kg-1 quantificada na etapa 6 (60 dias de maturação) no lote 1. É necessário dar mais atenção em duas etapas na elaboração dos queijos: mais critério na seleção da cultura bacteriana iniciadora por ser um fator determinante na qualidade em relação à produção de AB e mais rigor na seleção da matéria-prima.Palavras chaves: cromatografia, cultura iniciadora, detector SPD/10AV UV­Vis, maturação, tiramina.

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During the Gorgonzola-type cheese preparation there are proteolysis and lipolysis which may be influenced by the type of starter culture chosen. Six manufacturing steps were selected to identify which of them is most suitable for biogenic amines (BA) formation (1- milk, 2- lactic acid bacterial culture and fungus addition, 3- curd, 4- dry salting, 5- maturation at 30 days and maturation at 60 days); perform research on enterobacteria; accomplish the research of BA-producing bacteria (BAPB); detect and quantify the most abundant BA (putrescine, cadaverine, tyramine, histamine, spermidine and spermine) in the six steps of Gorgonzola cheese production and in bacterial isolates using high performance liquid chromatography and UV-Vis SPD/10AV detector and define if the presence of enterobacteria and BAPB would be correlated with BA production in this cheese. The bacterial culture used increased its log population by 7 log cycles and reached its highest level in batch 2 during cheese maturation. There was a decrease in the enterobacterial population in 2 log cycles after 60 days of maturation in batch 1. Tyramine was the BA with the highest concentration 306.32 mg.Kg-1 quantified in step 6 (60 days maturation) in batch 1. Criterion is requiered in bacterial starter culture selection because it is a quality determinant factor in relation to BA production and more rigor in raw material

Durante a elaboração do queijo tipo Gorgonzola ocorre proteólise a partir das bactérias e dos fungos adicionados ao leite que podem levar a formação de aminas biogênicas (AB) neste tipo de queijo. Portanto, no presente estudo foi feito o acompanhamento com coleta de amostras em seis etapas na fabricação deste queijo paraidentificar em qual delas haveria maior formação de aminas biogênicas (AB). As amostras coletadas em três diferentes lotes foram o leite cru (1), leite pasteurizado adicionado de cultura de bactérias ácido-láticas (2), massa coalhada (3), queijo após a etapa de salga seca (4), queijo após 30 dias de maturação (5) e queijo após 60 dias de maturação (6). Também foram realizadas a pesquisa de enterobactérias e bactérias ácido-láticas com característica capacidade de descarboxilação de aminoácidos e produção de aminas biogênicas (BPAB); detecção e quantificação da AB mais abundante (putrescina, cadaverina, tiramina, histamina, espermidina e espermina) nas seis etapas de fabricação do queijo tipo Gorgonzola e nos isolados bacterianos utilizando cromatografia líquida de alta eficiência e detector UV-Vis SPD/10AV e a verificação se a presença de enterobactérias e BPAB estariam correlacionadas com a produção de AB nesse queijo. A cultura bacteriana utilizada cresceu aumentando em sete ciclos logarítmicos sua população e alcançou seu maior nível no lote 2 na etapa de maturação do queijo. Houve diminuição da população enterobactérias em 2 ciclos logarítmicos após 60 dias de maturação no lote 1. A tiramina foi a AB com concentração mais elevada 306,32 mg.Kg-1 quantificada na etapa 6 (60 dias de maturação) no lote 1. É necessário dar mais atenção em duas etapas na elaboração dos queijos: mais critério na seleção da cultura bacteriana iniciadora por ser um fator determinante na qualidade em relação à produção de AB e mais rigor na seleção da matéria-prima.

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During the Gorgonzola-type cheese preparation there are proteolysis and lipolysis which may be influenced by the type of starter culture chosen. Six manufacturing steps were selected to identify which of them is most suitable for biogenic amines (BA) formation (1- milk, 2- lactic acid bacterial culture and fungus addition, 3- curd, 4- dry salting, 5- maturation at 30 days and maturation at 60 days); perform research on enterobacteria; accomplish the research of BA-producing bacteria (BAPB); detect and quantify the most abundant BA (putrescine, cadaverine, tyramine, histamine, spermidine and spermine) in the six steps of Gorgonzola cheese production and in bacterial isolates using high performance liquid chromatography and UV-Vis SPD/10AV detector and define if the presence of enterobacteria and BAPB would be correlated with BA production in this cheese. The bacterial culture used increased its log population by 7 log cycles and reached its highest level in batch 2 during cheese maturation. There was a decrease in the enterobacterial population in 2 log cycles after 60 days of maturation in batch 1. Tyramine was the BA with the highest concentration 306.32 mg.Kg-1 quantified in step 6 (60 days maturation) in batch 1. Criterion is requiered in bacterial starter culture selection because it is a quality determinant factor in relation to BA production and more rigor in raw material

Durante a elaboração do queijo tipo Gorgonzola ocorre proteólise a partir das bactérias e dos fungos adicionados ao leite que podem levar a formação de aminas biogênicas (AB) neste tipo de queijo. Portanto, no presente estudo foi feito o acompanhamento com coleta de amostras em seis etapas na fabricação deste queijo paraidentificar em qual delas haveria maior formação de aminas biogênicas (AB). As amostras coletadas em três diferentes lotes foram o leite cru (1), leite pasteurizado adicionado de cultura de bactérias ácido-láticas (2), massa coalhada (3), queijo após a etapa de salga seca (4), queijo após 30 dias de maturação (5) e queijo após 60 dias de maturação (6). Também foram realizadas a pesquisa de enterobactérias e bactérias ácido-láticas com característica capacidade de descarboxilação de aminoácidos e produção de aminas biogênicas (BPAB); detecção e quantificação da AB mais abundante (putrescina, cadaverina, tiramina, histamina, espermidina e espermina) nas seis etapas de fabricação do queijo tipo Gorgonzola e nos isolados bacterianos utilizando cromatografia líquida de alta eficiência e detector UV-Vis SPD/10AV e a verificação se a presença de enterobactérias e BPAB estariam correlacionadas com a produção de AB nesse queijo. A cultura bacteriana utilizada cresceu aumentando em sete ciclos logarítmicos sua população e alcançou seu maior nível no lote 2 na etapa de maturação do queijo. Houve diminuição da população enterobactérias em 2 ciclos logarítmicos após 60 dias de maturação no lote 1. A tiramina foi a AB com concentração mais elevada 306,32 mg.Kg-1 quantificada na etapa 6 (60 dias de maturação) no lote 1. É necessário dar mais atenção em duas etapas na elaboração dos queijos: mais critério na seleção da cultura bacteriana iniciadora por ser um fator determinante na qualidade em relação à produção de AB e mais rigor na seleção da matéria-prima.(AU)

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Recent evidence has revealed that PD-L1 is expressed in two functional forms, namely, a membrane-bound form (mPD-L1) and a soluble form (sPD-L1). The identification of the soluble form of PD-L1 represents the discovery of a new potential mechanism for the activation of the PD-1 pathway that may mediate a physiological apoptotic mechanism through a cell-cell signalling-independent pathway and may also favour T cell dysfunction during HIV infection. Since the presence of sPD-L1 has not been well established in the scenario of chronic viral infection, we investigated the presence of sPD-L1 in the plasma of viraemic HIV+ individuals and the potential mechanism that promotes its production. We report the following: 1) the level of the soluble form of PD-L1 is increased in the plasma of viraemic HIV+ individuals, 2) the level of the soluble form of PD-L1 in viraemic HIV+ individuals correlates with markers of microbial product translocation and inflammation, 3) the expression of the membrane-bound form of PD-L1 on conventional dendritic cells from viraemic HIV+ individuals correlates with the levels of soluble PD-L1 and MMP-2, and 4) monocyte-derived dendritic cells not only increase their expression of mPD-L1 and MMP-2 but also produce sPD-L1 after LPS and TNF-α stimulation, as demonstrated by functional in vitro experiments, which provides insight into the potential source of sPD-L1 production.

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OBJECTIVES: To target pediatric dermatologists directly in order to evaluate their current demographics and the most important motivating factors that influenced their career choice. Pediatric dermatology is one of the pediatric subspecialties with an inadequate supply to meet current patient needs. STUDY DESIGN: A survey was designed to evaluate the training pathway, employment status, participation in teaching, and clinical practice characteristics of pediatric dermatologists. The survey was administered to attendants of the 2010 Society for Pediatric Dermatology annual meeting. Any remaining board certified pediatric dermatologists who had not previously responded were queried via Survey Monkey. RESULTS: There was a 71% response rate. The majority chose a career in pediatric dermatology early, often prior to starting a dermatology residency. The vast majority of respondents noted mentorship as the most important influence on their decision to pursue a career in pediatric dermatology. The most common obstacles cited by respondents were financial hardship and resistance of some dermatology programs to accept applicants previously trained in pediatrics. CONCLUSIONS: Our survey provides evidence to support the importance of early exposure to the field and, most importantly, to committed pediatric dermatologists who can serve as mentors. This information may be helpful in approaching solutions to the workforce shortage in the field of pediatric dermatology.

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