Clinical and molecular insights into BCG immunotherapy for melanoma.

The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL-BCG) immunotherapy is a highly efficient and cost-effective treatment option for inoperable stage III in-transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL-BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG-mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.

Development and quality assessment of a turbid carrot-orange juice blend processed by UV-C light assisted by mild heat and addition of Yerba Mate (Ilex paraguariensis) extract.

Carrot-orange juice processed by UV-C (10.6 kJ/m2) assisted with mild heat (H, 50 °C) and yerba mate addition (E) was obtained. UV-C/H + E treated juice was examined for native flora, polyphenol content (PC), total antioxidant activity (TAA), colour, turbidity, °Brix and pH along storage (4 °C). Consumer profiling studies were performed. UV-C/H + E provoked 2.6-5.7 native flora log reductions, preventing from recovery during 24 day-storage. The UV-C/H + E juice exhibited a significant increase in PC (720.2 µg/mL) and TAA (5.5 mg/mL) compared to untreated (PC = 205.0 µg/mL/TAA = 0.7 mg/mL) and single treated juices (PC = 302.1-408.0 µg/mL/TAA = 0.7-2.4 mg/mL), remaining constant throughout storage. UV-C/H + E juice exhibited scarce changes in colour. Nevertheless, increases in °Brix and turbidity were observed compared to single treatments. A cluster sensory analysis revealed that one group showed a marked interest in UVC/H + E beverages with herbal taste and strong aroma. CATA question revealed that some improvements should be introduced in order to satisfy the consumers' ideally beverage.

Impact of urbanization on the proteome of birch pollen and its chemotactic activity on human granulocytes.

BACKGROUND: Epidemiologic studies reveal a dramatic increase in allergies in the last decades. Air pollution is considered to be one of the factors responsible for this augmentation. The aim of this study was to analyze the impact of urbanization on birch pollen. The birch pollen proteome was investigated in order to identify differences in protein abundance between pollen from rural and urban areas. The allergenicity of birch pollen from both areas was evaluated by assessing its chemotactic potency as well as its protein and allergen contents. METHODS: Difference gel electrophoresis (DIGE) was used to analyze the pollen proteome. The chemotactic activity of aqueous pollen extracts was determined by migration assays of human neutrophils. RESULTS: DIGE revealed 26 differences in protein spot intensity between pollen from urban and rural areas. One of these proteins was identified by de novo sequencing as the 14-3-3 protein, which resembles a stress-induced factor in other plant species. Furthermore, extracts from pollen collected in urban areas had higher chemotactic activity on human neutrophils compared to pollen from rural sites. CONCLUSIONS: The present study points to an impact of air pollution on allergen carrier proteome and release of chemotactic substances. The increment in proinflammatory substances such as pollen-associated lipid mediators might contribute to the described urban-rural gradient of allergy prevalence. Furthermore, our study suggests that allergenicity is determined by more than the sole allergen content.

[Pain therapy in addicted patients]. / Schmerztherapie bei suchtmittelabhängigen Patienten.

Each individual is entitled to an adequate and sufficient pain therapy. However, only a few studies have examined the peculiarities of pain management in drug-dependent or formerly addicted patients. Any addiction is disadvantageous for a successful pain therapy, since some of the prescribed drugs may themselves cause addiction. Drug-dependent patients are often tolerant to opioids. Additionally, there is a risk of iatrogenic pain becoming chronic due to disregard for already known risk factors and comorbidities. However, a history of addiction should not prevent sufficient pain therapy, especially since there is no risk of addiction when the pain therapy employed is adequate for the pathophysiology involved. There are adequate pain therapies for addicted patients. The best results are achieved by taking into account the physiological and psychological peculiarities of drug-dependent patients. Importantly, this should be combined with a variety of different, optimized, multimodal therapeutic regimes, as well as with an interdisciplinary approach.

Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000.

The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B2, B6, and B12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B6 and methionine, may be protective against NHL.

Effectiveness of an occupational and environmental medicine curriculum as indicated by evaluation of medical student performance on an objective structured clinical examination.

Medical students must learn to recognize occupational and environmental-related illness. An occupational and environmental medicine curriculum can achieve this goal. The curriculum must be evaluated to ensure that medical students are learning to recognize exposure-related health conditions and to evaluate if this ability correlates with medical interviewing skills. A case, formatted for an Objective Structured Clinical Examination (OSCE), was developed to evaluate student performance on an exposure-related clinical problem. The OSCE results were analyzed to identify the areas that differentiated the students who recognized an exposure-related medical condition from those who did not. We conclude that an OSCE is an effective curriculum evaluation tool to assess whether a core occupational and environmental-related curriculum is contributing to student learning in exposure history-taking and associated clinical reasoning skills.

Environmental medicine content in medical school curricula.

BACKGROUND: The Institute of Medicine has recommended basic clinical competence in environmental medicine (EM) for all physicians. However, the amount and content of instruction in EM currently offered in U.S. medical schools is unknown. METHOD: This cross-sectional study was based on responses to a questionnaire regarding the EM curriculum content of U.S. medical schools, mailed in June 1994 with the Association of American Medical Colleges curriculum survey. RESULTS: Of the 126 schools, 119 (94%) responded. Of these, 29 (24%) reported no required EM content in the curriculum. Schools with EM content averaged seven hours of instruction. Eighty-one schools (68%) had faculty with environmental and occupational medicine expertise, primarily within the departments of medicine, preventive medicine, and family medicine. CONCLUSION: There is a need for increased instruction in EM in medical school curricula for students to acquire the knowledge and skills to prevent, diagnose, and treat health problems with an environmental exposure component. For those schools without EM content in the curriculum, the necessary expertise to develop EM curriculum may be available in current faculty.