Integrating human expertise & automated methods for a dynamic and multi-parametric evaluation of large language models' feasibility in clinical decision-making.

BACKGROUND: Recent enhancements in Large Language Models (LLMs) such as ChatGPT have exponentially increased user adoption. These models are accessible on mobile devices and support multimodal interactions, including conversations, code generation, and patient image uploads, broadening their utility in providing healthcare professionals with real-time support for clinical decision-making. Nevertheless, many authors have highlighted serious risks that may arise from the adoption of LLMs, principally related to safety and alignment with ethical guidelines. OBJECTIVE: To address these challenges, we introduce a novel methodological approach designed to assess the specific feasibility of adopting LLMs within a healthcare area, with a focus on clinical nursing, evaluating their performance and thereby directing their choice. Emphasizing LLMs' adherence to scientific advancements, this approach prioritizes safety and care personalization, according to the "Organization for Economic Co-operation and Development" frameworks for responsible AI. Moreover, its dynamic nature is designed to adapt to future evolutions of LLMs. METHOD: Through integrating advanced multidisciplinary knowledge, including Nursing Informatics, and aided by a prospective literature review, seven key domains and specific evaluation items were identified as follows:A Peer Review by experts in Nursing and AI was performed, ensuring scientific rigor and breadth of insights for an essential, reproducible, and coherent methodological approach. By means of a 7-point Likert scale, thresholds are defined in order to classify LLMs as "unusable", "usable with high caution", and "recommended" categories. Nine state of the art LLMs were evaluated using this methodology in clinical oncology nursing decision-making, producing preliminary results. Gemini Advanced, Anthropic Claude 3 and ChatGPT 4 achieved the minimum score of the State of the Art Alignment & Safety domain for classification as "recommended", being also endorsed across all domains. LLAMA 3 70B and ChatGPT 3.5 were classified as "usable with high caution." Others were classified as unusable in this domain. CONCLUSION: The identification of a recommended LLM for a specific healthcare area, combined with its critical, prudent, and integrative use, can support healthcare professionals in decision-making processes.

Cyclone: an accessible pipeline to analyze, evaluate, and optimize multiparametric cytometry data.

In the past decade, high-dimensional single-cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation, which are computationally intense and difficult to evaluate and optimize. Here, we present Cytometry Clustering Optimization and Evaluation (Cyclone), an analysis pipeline integrating dimensionality reduction, clustering, evaluation, and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full-spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification but also enables the unsupervised identification of lymphocytes and mononuclear phagocyte subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on a variety of cytometry datasets, which will further power immunology research and provide a scaffold for biological discovery.

Application of the Cytokinesis-Block Micronucleus Assay for High-Dose Exposures Using Imaging Flow Cytometry.

The cytokinesis-block micronucleus assay is a well-established method to assess radiation-induced genetic damage in human cells. This assay has been adapted to imaging flow cytometry (IFC), allowing automated analysis of many cells, and eliminating the need to create microscope slides. Furthermore, to improve the efficiency of assay performance, a small-volume method previously developed was employed. Irradiated human blood samples were cultured, stained, and analyzed by IFC to produce images of the cells. Samples were run using both manual and 96-well plate automated acquisition. Multiple parameter-based image features were collected for each sample, and the results were compared to confirm that these acquisition methods are functionally identical. This paper details the multi-parametric analysis developed and the resulting calibration curves up to 10 Gy. The calibration curves were created using a quadratic random coefficient model with Poisson errors, as well as a logistic discriminant function. The curves were then validated with blinded, irradiated samples, using relative bias and relative mean square error. Overall, the accuracy of the dose estimates was adequate for triage dosimetry (within 1 Gy of the true dose) over 90% of the time for lower doses and about half the time for higher doses, with the lowest success rate between 5 and 6 Gy where the calibration curve reached its peak and there was the smallest change in MN/BNC with dose. This work describes the application of a novel multi-parametric analysis that fits the calibration curves and allows dose estimates up to 10 Gy, which were previously limited to 4 Gy. Furthermore, it demonstrates that the results from samples acquired manually and with the autosampler are functionally similar.

Mapping the 3D remodeling of the extracellular matrix in human hypertrophic scar by multi-parametric multiphoton imaging using endogenous contrast.

The hypertrophic scar is an aberrant form of wound healing process, whose clinical efficacy is limited by a lack of understanding of its pathophysiology. Remodeling of collagen and elastin fibers in the extracellular matrix (ECM) is closely associated with scar progression. Herein, we perform label-free multiphoton microscopy (MPM) of both fiber components from human skin specimens and propose a multi-fiber metrics (MFM) analysis model for mapping the structural remodeling of the ECM in hypertrophic scars in a highly-sensitive, three-dimensional (3D) manner. We find that both fiber components become wavier and more disorganized in scar tissues, while content accumulation is observed from elastin fibers only. The 3D MFM analysis can effectively distinguish normal and scar tissues with better than 95% in accuracy and 0.999 in the area under the curve value of the receiver operating characteristic curve. Further, unique organizational features with orderly alignment of both fibers are observed in scar-normal adjacent regions, and an optimized combination of features from 3D MFM analysis enables successful identification of all the boundaries. This imaging and analysis system uncovers the 3D architecture of the ECM in hypertrophic scars and exhibits great translational potential for evaluating scars in vivo and identifying individualized treatment targets.

PRI: Re-Analysis of a Public Mass Cytometry Dataset Reveals Patterns of Effective Tumor Treatments.

Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm "pattern recognition of immune cells (PRI)" to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4+T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data.

All around suboptimal health - a joint position paper of the Suboptimal Health Study Consortium and European Association for Predictive, Preventive and Personalised Medicine.

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person. This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19.

Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

Mitochondriopathies as a Clue to Systemic Disorders-Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine.

The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a "vicious circle" in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.

Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy.

Immunotherapy, particularly immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, holds a great promise against cancer. These treatments have markedly improved survival in solid as well as in hematologic tumors previously considered incurable. However, durable responses occur in a fraction of patients, and existing biomarkers (e.g. PD-L1) have shown limited prediction power. This scenario highlights the need to dissect the complex interplay between immune and tumor cells to identify reliable biomarkers of response to be used for patients' selection. In this context, systems immunology represents indeed the new frontier to address important clinical challenges in biomarker discovery. Through the integration of multiple layers of data obtained with several high-throughput approaches, systems immunology may give insights on the vast range of inter-individual differences and on the influences of genes and factors that cooperatively shape the individual immune response to a given treatment. In this Mini Review, we give an overview of the current high-throughput methodologies, including genomics, epigenomics, transcriptomics, metabolomics, proteomics, and multi-parametric phenotyping suitable for systems immunology as well as on the key steps of data integration and biological interpretation. Additionally, we review recent studies in which multi-omics technologies have been used to characterize mechanisms of response and to identify powerful biomarkers of response to checkpoint inhibitors, CAR-T cell therapy, dendritic cell-based and peptide-based cancer vaccines. We also highlight the need of favoring the collaboration of researchers with complementary expertise and of integrating multi-omics data into biological networks with the final goal of developing accurate markers of therapeutic response.

Dental Adhesive Interfaces Reinforced with Magnetic Nanoparticles: Evaluation and Modeling with Micro-CT versus Optical Microscopy.

Dental adhesives are used in a wide range of applications, including to place direct composite restorations in frontal or posterior teeth. One of the most frequent causes for the failure of composite resin restorations is microleakages. The first aim of this work is to introduce a new type of self-etched dental adhesive doped with magnetic nanoparticles (MPs) synthetized in the laboratory. The scope is to produce adhesives with a minimized width/thickness to decrease the risk of microleakages. The second aim is to assess the width/thickness of the adhesive layer in all the characteristic areas of the teeth using both the less precise but most common optical microscopy and the more accurate and volumetric micro-Computed Tomography (CT) investigations. Twenty extracted teeth have been divided into four groups: Group 1 includes 'blank' samples with adhesives that are not doped with MPs; Group 2 includes samples with adhesives doped with MPs; Groups 3 and 4 include samples with adhesives doped with MPs that are subjected to an active magnetic field for 5 and 10 min, respectively. Microscopy investigations followed by micro-CT and EDAX are performed on the adhesive. While a rather good agreement is obtained between the microscopy and micro-CT results, the capability of the latter to offer a full volumetric reconstruction of the layer is exploited to analyze the adhesion of the four considered dental materials. Thus, from micro-CT results the graphs of the surface areas as functions of the adhesive layer width are modeled mathematically, as well as the volume of sealants, for each of the four groups. To our knowledge, it is the first time that such a methodology is used. Characteristic parameters are extracted and the ascertainment of the optimal parameter that should be utilized for such assessments is discussed. The study demonstrates the adhesion improvement produced for Groups 3 and 4, where MPs are used. It also concludes that the magnetic field should be applied to the adhesive material for the longest possible exposure time (with a trade-off with the clinical duration of the treatment).

Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions.

In the early twenty-first century, societies around the world are facing the paradoxal epidemic development of PCa as a non-communicable disease. PCa is the most frequently diagnosed cancer for men in several countries such as the USA. Permanently improving diagnostics and treatments in the PCa management causes an impressive divergence between, on one hand, permanently increasing numbers of diagnosed PCa cases and, on the other hand, stable or even slightly decreasing mortality rates. Still, aspects listed below are waiting for innovate solutions in the context of predictive approaches, targeted prevention and personalisation of medical care (PPPM / 3PM).A.PCa belongs to the cancer types with the highest incidence worldwide. Corresponding economic burden is enormous. Moreover, the costs of treating PCa are currently increasing more quickly than those of any other cancer. Implementing individualised patient profiles and adapted treatment algorithms would make currently too heterogeneous landscape of PCa treatment costs more transparent providing clear "road map" for the cost saving.B.PCa is a systemic multi-factorial disease. Consequently, predictive diagnostics by liquid biopsy analysis is instrumental for the disease prediction, targeted prevention and curative treatments at early stages.C.The incidence of metastasising PCa is rapidly increasing particularly in younger populations. Exemplified by trends observed in the USA, prognosis is that the annual burden will increase by over 40% in 2025. To this end, one of the evident deficits is the reactive character of medical services currently provided to populations. Innovative screening programmes might be useful to identify persons in suboptimal health conditions before the clinical onset of metastasising PCa. Strong predisposition to systemic hypoxic conditions and ischemic lesions (e.g. characteristic for individuals with Flammer syndrome phenotype) and low-grade inflammation might be indicative for specific phenotyping and genotyping in metastasising PCa screening and disease management. Predictive liquid biopsy tests for CTC enumeration and their molecular characterisation are considered to be useful for secondary prevention of metastatic disease in PCa patients.D.Particular rapidly increasing PCa incidence rates are characteristic for adolescents and young adults aged 15-40 years. Patients with early onset prostate cancer pose unique challenges; multi-factorial risks for these trends are proposed. Consequently, multi-level diagnostics including phenotyping and multi-omics are considered to be the most appropriate tool for the risk assessment, prediction and prognosis. Accumulating evidence suggests that early onset prostate cancer is a distinct phenotype from both aetiological and clinical perspectives deserving particular attention from view point of 3P medical approaches.

Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception.

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21+ IFN-γhigh PD-1low CD40Lhigh CXCR5- Bcl-6- T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-α and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.

Combinations of non-invasive indicators to detect dairy cows submitted to high-starch-diet challenge.

High-starch diets (HSDs) fed to high-producing ruminants are often responsible for rumen dysfunction and could impair animal health and production. Feeding HSDs are often characterized by transient rumen pH depression, accurate monitoring of which requires costly or invasive methods. Numerous clinical signs can be followed to monitor such diet changes but no specific indicator is able to make a statement at animal level on-farm. The aim of this pilot study was to assess a combination of non-invasive indicators in dairy cows able to monitor a HSD in experimental conditions. A longitudinal study was conducted in 11 primiparous dairy cows fed with two different diets during three successive periods: a 4-week control period (P1) with a low-starch diet (LSD; 13% starch), a 4-week period with an HSD (P2, 35% starch) and a 3-week recovery period (P3) again with the LSD. Animal behaviour was monitored throughout the experiment, and faeces, urine, saliva, milk and blood were sampled simultaneously in each animal at least once a week for analysis. A total of 136 variables were screened by successive statistical approaches including: partial least squares-discriminant analysis, multivariate analysis and mixed-effect models. Finally, 16 indicators were selected as the most representative of a HSD challenge. A generalized linear mixed model analysis was applied to highlight parsimonious combinations of indicators able to identify animals under our experimental conditions. Eighteen models were established and the combination of milk urea nitrogen, blood bicarbonate and feed intake was the best to detect the different periods of the challenge with both 100% of specificity and sensitivity. Other indicators such as the number of drinking acts, fat:protein ratio in milk, urine, and faecal pH, were the most frequently used in the proposed models. Finally, the established models highlight the necessity for animals to have more than 1 week of recovery diet to return to their initial control state after a HSD challenge. This pilot study demonstrates the interest of using combinations of non-invasive indicators to monitor feed changes from a LSD to a HSD to dairy cows in order to improve prevention of rumen dysfunction on-farm. However, the adjustment and robustness of the proposed combinations of indicators need to be challenged using a greater number of animals as well as different acidogenic conditions before being applied on-farm.

Optical Coherence Tomography Investigations and Modeling of the Sintering of Ceramic Crowns.

Dental prostheses are sintered in ovens that sometimes suffer from a loss of calibration. This can lead to variations of the sintering temperature outside the range recommended by the manufacturer. Stress and even fractures in dental ceramics may occur, and this leads to the necessity to rebuild the dental construct. The aim of this work is to monitor the quality of sintering processes using an established biomedical imaging technique-optical coherence tomography (OCT). Conventional current procedures imply the fabrication of supplemental samples that add to the expenses and are only evaluated visually. To our knowledge, we were the first to propose the use of OCT, a non-destructive method that brings objectivity for such assessments, focusing, in a previous study, on metal ceramic dental prostheses. Here, a different material, pressed ceramics, is considered, while we propose a quantitative assessment of the results-using reflectivity profiles of en-face (i.e., constant-depth) OCT images of sintered samples. The results for both the pressed ceramics and metal ceramics prostheses are discussed by obtaining the analytic functions of their reflectivity profiles. A multi-parametric analysis demonstrates the best parameter to characterize the loss of calibration of dental ovens. Rules-of-thumb are extracted; producing dental prostheses with defects can thus be avoided.

Multi-Parametric Screening in Arabidopsis thaliana Seedlings.

Phenotypic screening and subsequent target identification approaches are very valuable to identify chemical probes that can be used to explore the connection between phenotypes and biological pathways. However, assessing a phenotypic effect in plants in a high-throughput fashion is a challenging task and often requires expensive readout devices. In this chapter, we describe a cost-effective multi-parametric screening procedure that is compatible with liquid-handling systems and that enables the assessment of phenotypes in Arabidopsis thaliana seedlings in an automated way.

Advanced Cell Classifier: User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data.

High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org.

Lateral flow based immunobiosensors for detection of food contaminants.

Safety of food is of great concern these days due to various contaminations including toxins, infectious agents and chemical contaminants. Therefore, there is a need to develop promising and user's friendly method to monitor food safety. Lateral flow tests are new, simple and rapid alternative for detection of food-borne pathogens compared with traditional methods. In this review article, we surveyed application of lateral flow biosensors in detection of different food contaminants and labels used to enhance the efficiency of the system. Finally, the unique feature of multi-parametric analysis of analytes by lateral flow device has been reported, proving a lateral flow system is able to be designed in a way to detect multiple targets, simultaneously.

Multi-parametric analysis of phagocyte antimicrobial responses using imaging flow cytometry.

We feature a multi-parametric approach based on an imaging flow cytometry platform for examining phagocyte antimicrobial responses against the gram-negative bacterium Aeromonas veronii. This pathogen is known to induce strong inflammatory responses across a broad range of animal species, including humans. We examined the contribution of A. veronii to the induction of early phagocyte inflammatory processes in RAW 264.7 murine macrophages in vitro. We found that A. veronii, both in live or heat-killed forms, induced similar levels of macrophage activation based on NF-κB translocation. Although these macrophages maintained high levels of viability following heat-killed or live challenges with A. veronii, we identified inhibition of macrophage proliferation as early as 1h post in vitro challenge. The characterization of phagocytic responses showed a time-dependent increase in phagocytosis upon A. veronii challenge, which was paired with a robust induction of intracellular respiratory burst responses. Interestingly, despite the overall increase in the production of reactive oxygen species (ROS) among RAW 264.7 macrophages, we found a significant reduction in the production of ROS among the macrophage subset that had bound A. veronii. Phagocytic uptake of the pathogen further decreased ROS production levels, even beyond those of unstimulated controls. Overall, this multi-parametric imaging flow cytometry-based approach allowed for segregation of unique phagocyte sub-populations and examination of their downstream antimicrobial responses, and should contribute to improved understanding of phagocyte responses against Aeromonas and other pathogens.

Multi parametric voice assessment: sri ramachandra university protocol.

Emergence of "Voice specialty clinics" in ENT and Speech Language Pathologist (SLP) practice in India necessitates development of standard protocols for assessment and management of voice disorders. Based on recommendations from European Laryngological Society in Dejonckere (Eur Arch Otorhinolaryngol 258:77-82, 2001), a comprehensive voice assessment protocol was adapted for Indian population. This study aimed at verifying the face validity and feasibility of using the developed voice assessment protocol in a multi specialty tertiary care hospital. It included: history, clinical examination, visual analysis, perceptual analysis, aerodynamic measures, acoustic analysis and patients' self assessment of voice. The developed protocol was administered on 200 patients with voice concerns and problems. Correlation of self assessment with the assessment by the professionals was done using Kendaul tau_b correlation test. The scores of self assessment did not correlate significantly with acoustic measures. Differences in lab findings and self percept of voice indicated that these two were complementary measures in the protocol. Further, diagnosis and management decisions were arrived through a consensus discussion involving the ENT surgeon, SLP and the patient. Vocal hygiene and voice conservation were advised to all patients. Recommendations for voice therapy and/or surgery were provided based on findings from the protocol. The study demonstrated feasibility of using a comprehensive protocol for effective documentation, comparisons, review, training and treatment planning.

Multi-parametric profiling network based on gene expression and phenotype data: a novel approach to developmental neurotoxicity testing.

The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children's environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds.