Cytokines are compounds that belong to a special class of signaling biomolecules that are responsible for several functions in the human body, being involved in cell growth, inflammatory, and neoplastic processes. Thus, they represent valuable biomarkers for diagnosing and drug therapy monitoring certain medical conditions. Because cytokines are secreted in the human body, they can be detected in both conventional samples, such as blood or urine, but also in samples less used in medical practice such as sweat or saliva. As the importance of cytokines was identified, various analytical methods for their determination in biological fluids were reported. The gold standard in cytokine detection is considered the enzyme-linked immunosorbent assay method and the most recent ones have been considered and compared in this study. It is known that the conventional methods are accompanied by a few disadvantages that new methods of analysis, especially electrochemical sensors, are trying to overcome. Electrochemical sensors proved to be suited for the elaboration of integrated, portable, and wearable sensing devices, which could also facilitate cytokines determination in medical practice.

There is a growing body of literature that recognizes the importance of public engagement in health technology assessment. However, there is still uncertainty regarding how the results should be recorded, analyzed, and used by decision makers.
Synthesize the contributions of the Brazilian public (women, health professionals, managers, educational institutions, and companies) about the implementation of the National Clinical Guidelines for Care in Normal Birth from the public consultation carried out in Brazil.
IRaMuTeQ software was used to organize and summarize the corpus based on three types of analysis: descriptive statistics; descending hierarchical classification; and specificities analysis. The public consultation was conducted in 2016 by the National Committee for Health Technology Incorporation (CONITEC) in the Brazilian public health system as part of the guideline development process.
The corpus consisted of 303 texts, separated into 1233 text segments, 1081 of which were used, corresponding to retention of 87.67%. Five classes emerged from our analyses: mandatory presence of an obstetrician during labor and delivery in hospital settings; barriers and facilitators for guideline implementation; use of evidence-based practices by health professionals; progression of labor and delivery and women\'s rights; and mobilization to promote the guideline For each class, the most frequent words and sentences with the highest chi-squared scores were presented. Barriers were associated with lack of financial resources, training and professional motivation, and facilitators with training to change the practices of health professionals. Obstetric nurses emerged as an alternative for supervising normal births as well as the mandatory presence of an obstetrician during childbirth in hospital settings.
Our findings summarize the contributions provided by the Brazilian public and shed some light on the barriers and facilitators of clinical guidelines for care in normal birth. These topics are not typically explored by quantitative studies. Including this information in the decision-making process would not only increase public engagement, but provide greater evidence for implementing the clinical guidelines nationwide.

BACKGROUND: Public engagement in health technology assessment (HTA) is increasing worldwide. There are several forms of public engagement and it is not always possible to determine which stakeholders participate in the HTA process and how they contribute. Our objective was to investigate which types of social representatives contributed to the public consultation on the incorporation of Trastuzumab for early-stage breast cancer treatment within the public health system in Brazil, held in 2012 by the National Committee for Health Technology Incorporation (CONITEC).
METHODS: A mixed methods approach was used to analyze social representativeness and the composition of the corpus from the public consultation, which consisted of 127 contributions. Three types of analysis were performed using IRaMuTeQ software: classic lexical analysis, descending hierarchical classification and specificities analysis. The contributions were clustered according to the main categories of discourse observed, into four social representation categories: 1) patient representation/advocacy; 2) pharmaceutical industry/advocacy; 3) healthcare professionals; and 4) individual contributions.
RESULTS: Category 1 contained words related to increased survival due to use of the drug and a low score for words pertaining to studies on Trastuzumab. The word \"safety\" obtained a positive score only in category 2, which was also the only category that exhibited a negative score for the word \"risk\". Category 3 displayed the lowest scores for \"diagnosis\" and \"safety\". The word \"efficacy\" had a negative score only in category 4.
CONCLUSIONS: Each category exhibited different results for words related to health systems and to key concepts linked to HTA. Our analysis enabled the identification of the most prominent contributions for each category. Despite the promising results obtained, further research is needed to validate this software for use in analyzing public contributions.

The rapid development of fluorescent probes for monitoring target enzymes is still a great challenge owing to the lack of efficient ways to optimize a specific fluorophore. Herein, a practical two-dimensional strategy was designed for the development of an isoform-specific probe for CYP3A4, a key cytochrome P450 isoform responsible for the oxidation of most clinical drugs. In first dimension of the design strategy, a potential two-photon fluorescent substrate (NN) for CYP3A4 was effectively selected using ensemble-based virtual screening. In the second dimension, various substituent groups were introduced into NN to optimize the isoform-selectivity and reactivity. Finally, with ideal selectivity and sensitivity, NEN was successfully applied to the real-time detection of CYP3A4 in living cells and zebrafish. These findings suggested that our strategy is practical for developing an isoform-specific probe for a target enzyme.

Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2\', 7\'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the \"gold standard\" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n = 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants.