Development Of Non-invasive Diagnostic Methods Research Articles

Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease

BackgroundSeveral genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients’ characteristics may facilitate the development of non-invasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals, and planning of management strategies. MethodsThis study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The Rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. ResultsThe +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, p=0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had ROC AUCs of 0.529%, 0.846%, and 0.700–0.825%, respectively. We examined a diagnostic model based on these variables, and demonstrated its effectiveness. ConclusionThe Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allows for a non-invasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.

Диагностика неисправностей синхронных генераторов путем компьютерного моделирования внешнего магнитного поля

Currently, the development of non-invasive diagnostic methods for electric machines and especially generators, as the main producers of electric energy, using magnetic field fixation sensors is an urgent scientific and technical task. To solve this problem, research has been conducted to develop a method for troubleshooting a synchronous generator by analyzing an external magnetic field. The article discusses the main issues of computer modeling of an external magnetic field in the FEMM 4.2 system for troubleshooting. Mathematical expressions are given for creating a computer model of a synchronous generator in two-dimensional space, on the basis of which a numerical solution of the external magnetic field is formed using the finite element method. The modeling takes into account the design features of the synchronous generator. The main stages of work in the FEMM 4.2 system are defined. The geometric model of the synchronous generator is imported from the computer-aided design system. The physical properties of all elements of the model are determined by the structural materials of the synchronous generator and the external space. The control program, created on the basis of the algorithm presented in the article, allows you to simulate the rotation of the inductor of a synchronous generator, automate the calculations of the electromagnetic field and display the results. An example of using a computer model of a synchronous generator for troubleshooting by examining an external magnetic field is given. Based on the results of a numerical solution of the external magnetic field, a harmonic analysis of the magnetic induction of a working synchronous generator was carried out. The article shows that a diagnostic sign of static eccentricity of a synchronous generator inductor is the appearance of even harmonics in the magnetic induction spectrum of an external magnetic field Based on the results obtained, the dependence of the growth of even harmonics on the magnitude of the displacement of the inductor of the synchronous generator is determined.

Exploring the Mechanistic Interplay between Gut Microbiota and Precocious Puberty: A Narrative Review.

The gut microbiota has been implicated in the context of sexual maturation during puberty, with discernible differences in its composition before and after this critical developmental stage. Notably, there has been a global rise in the prevalence of precocious puberty in recent years, particularly among girls, where approximately 90% of central precocious puberty cases lack a clearly identifiable cause. While a link between precocious puberty and the gut microbiota has been observed, the precise causality and underlying mechanisms remain elusive. This narrative review aims to systematically elucidate the potential mechanisms that underlie the intricate relationship between the gut microbiota and precocious puberty. Potential avenues of exploration include investigating the impact of the gut microbiota on endocrine function, particularly in the regulation of hormones, such as gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Additionally, this review will delve into the intricate interplay between the gut microbiome, metabolism, and obesity, considering the known association between obesity and precocious puberty. This review will also explore how the microbiome's involvement in nutrient metabolism could impact precocious puberty. Finally, attention is given to the microbiota's ability to produce neurotransmitters and neuroactive compounds, potentially influencing the central nervous system components involved in regulating puberty. By exploring these mechanisms, this narrative review seeks to identify unexplored targets and emerging directions in understanding the role of the gut microbiome in relation to precocious puberty. The ultimate goal is to provide valuable insights for the development of non-invasive diagnostic methods and innovative therapeutic strategies for precocious puberty in the future, such as specific probiotic therapy.

Soluble HLA-G (sHLA-G) measurement might be useful as an early diagnostic biomarker and screening test for gastric cancer

Gastric cancer (GC) is the fifth most frequent malignancy worldwide and has a high mortality rate related to late diagnosis. Although the gold standard for the GC diagnosis is endoscopy with biopsy, nonetheless, it is not cost-effective and is invasive for the patient. The Human leukocyte antigen G (HLA-G) molecule is a checkpoint of the immune response. Its overexpression in cancer is associated with immune evasion, metastasis, poor prognosis, and lower overall survival. We evaluate the plasma levels of soluble HLA-G, (sHLA-G) in patients with GC and benign gastric pathologies using an ELISA test. A higher concentration of sHLA-G in patients with GC than in those with benign pathologies, higher levels of plasma sHLA-G in women with GC compared with men and significant differences in the sHLA-G levels between the benign gastric pathologies evaluated, was our main findings. As no significant differences were found between the GC assessed stages in our study population, we suggest that sHLA-G is not an adequate marker for staging GC, but it does have diagnostic potential. In addition to providing information on the potential of sHLA-G as a diagnostic marker for GC, our study demonstrate that HLA-G molecules can be found in the membrane of exosomes, which highlights the need to perform studies with a larger number of samples to explore the functional implications of HLA-G positive exosomes in the context of gastric cancer, and to determine the clinical significance and possible applications of these findings in the development of non-invasive diagnostic methods.

Combining Multi-Shell Diffusion with Conventional MRI Improves Molecular Diagnosis of Diffuse Gliomas with Deep Learning.

The WHO classification since 2016 confirms the importance of integrating molecular diagnosis for prognosis and treatment decisions of adult-type diffuse gliomas. This motivates the development of non-invasive diagnostic methods, in particular MRI, to predict molecular subtypes of gliomas before surgery. At present, this development has been focused on deep-learning (DL)-based predictive models, mainly with conventional MRI (cMRI), despite recent studies suggesting multi-shell diffusion MRI (dMRI) offers complementary information to cMRI for molecular subtyping. The aim of this work is to evaluate the potential benefit of combining cMRI and multi-shell dMRI in DL-based models. A model implemented with deep residual neural networks was chosen as an illustrative example. Using a dataset of 146 patients with gliomas (from grade 2 to 4), the model was trained and evaluated, with nested cross-validation, on pre-operative cMRI, multi-shell dMRI, and a combination of the two for the following classification tasks: (i) IDH-mutation; (ii) 1p/19q-codeletion; and (iii) three molecular subtypes according to WHO 2021. The results from a subset of 100 patients with lower grades gliomas (2 and 3 according to WHO 2016) demonstrated that combining cMRI and multi-shell dMRI enabled the best performance in predicting IDH mutation and 1p/19q codeletion, achieving an accuracy of 75 ± 9% in predicting the IDH-mutation status, higher than using cMRI and multi-shell dMRI separately (both 70 ± 7%). Similar findings were observed for predicting the 1p/19q-codeletion status, with the accuracy from combining cMRI and multi-shell dMRI (72 ± 4%) higher than from each modality used alone (cMRI: 65 ± 6%; multi-shell dMRI: 66 ± 9%). These findings remain when we considered all 146 patients for predicting the IDH status (combined: 81 ± 5% accuracy; cMRI: 74 ± 5%; multi-shell dMRI: 73 ± 6%) and for the diagnosis of the three molecular subtypes according to WHO 2021 (combined: 60 ± 5%; cMRI: 57 ± 8%; multi-shell dMRI: 56 ± 7%). Together, these findings suggest that combining cMRI and multi-shell dMRI can offer higher accuracy than using each modality alone for predicting the IDH and 1p/19q status and in diagnosing the three molecular subtypes with DL-based models.

Ten questions for the cardiologist about cardiac scintigraphy with bone tracers, amyloidosis and the heart

Although traditionally considered a rare and incurable condition, the perspective on cardiac amyloidosis (CA) has changed deeply over the last 10 years following major advances in diagnosis and treatment options. First, the development of non-invasive diagnostic methods, predominantly cardiac scintigraphy with bone tracers, has dramatically changed the epidemiology of the disease, revealing the real prevalence of the transthyretin-related form (ATTR), and has consistently reduced the need for histological amyloid confirmation by endomyocardial biopsy. Second, the availability of new specific therapies, such as tafamidis, has made CA early recognition a clinical need with major impact on patients' management and natural history. Since the demonstration of the essential role of bone tracer scintigraphy to non-invasively differentiate ATTR from immunoglobulin light-chain amyloidosis (AL), this imaging technique has become part of the vocabulary and clinical practice of physicians of many specialties, including cardiologists managing patients with cardiomyopathies.In this paper, we address the main questions regarding cardiac scintigraphy with bone tracers and CA, providing cardiologists with the knowledge to guide clinical indications, evaluation and clinical interpretation of images.

Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya

SummaryBackgroundEnvironmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder of unclear aetiology prevalent amongst children in low-income settings and associated with stunting. We aimed to characterise development of EED and its putative risk factors amongst rural Kenyan infants.MethodsIn a birth cohort study in Junju, rural coastal Kenya, between August 2015 and January 2017, 100 infants were each followed for nine months. Breastfeeding status was recorded weekly and anthropometry monthly. Acute illnesses and antibiotics were captured by active and passive surveillance. Intestinal function and small intestinal bacterial overgrowth (SIBO) were assessed by monthly urinary lactulose mannitol (LM) and breath hydrogen tests. Faecal alpha-1-antitrypsin, myeloperoxidase and neopterin were measured as EED biomarkers, and microbiota composition assessed by 16S sequencing.FindingsTwenty nine of the 88 participants (33%) that underwent length measurement at nine months of age were stunted (length-for-age Z score <-2). During the rainy season, linear growth was slower and LM ratio was higher. In multivariable models, LM ratio, myeloperoxidase and neopterin increased after cessation of continuous-since-birth exclusive breastfeeding. For LM ratio this only occurred during the rainy season. EED markers were not associated with antibiotics, acute illnesses, SIBO, or gut microbiota diversity. Microbiota diversified with age and was not strongly associated with complementary food introduction or linear growth impairment.InterpretationOur data suggest that intensified promotion of uninterrupted exclusive breastfeeding amongst infants under six months during the rainy season, where rainfall is seasonal, may help prevent EED. Our findings also suggest that therapeutic strategies directed towards SIBO are unlikely to impact on EED in this setting. However, further development of non-invasive diagnostic methods for SIBO is required.FundingThis research was funded in part by the Wellcome Trust (Research Training Fellowship to RJC (103376/Z/13/Z)). EPKP was supported by the MRC/DfID Newton Fund (MR/N006259/1). JAB was supported by the MRC/DFiD/Wellcome Trust Joint Global Health Trials scheme (MR/M007367/1) and the Bill & Melinda Gates Foundation (OPP1131320). HHU was supported by the NIHR Oxford Biomedical Research Centre (IS-BRC-1215-20008).

Spectrum of paediatric liver diseases in tertiary health care centre

Introduction: The spectrum of liver diseases is different in children and adults. Development of non-invasive diagnostic methods and advanced hepatic imaging has changed the role of liver biopsy, it is still important in evaluation of paediatric liver disease. Material and Method: This is an observational, hospital-based study of 32 liver biopsies received during period of 5 years (January 2014-October 2019), comprising cases upto 12 years of age. Results: In the 32 liver biopsies studied, male to female ratio was 0.68, extrahepatic biliary atresia was commonest histological finding followed by glycogen storage disorder and neonatal hepatitis. Common presentation was Jaundice and hepatomegaly. Clinical and biochemical investigation correlation among biliary atresia and non-biliary atresia group was done. Conclusion: Liver biopsy assisted by a good clinical examination, radiology and laboratory evaluation can succeed in diagnosis of majority of liver diseases where clinical and laboratory parameters overlap.

Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease.

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBDs have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of IBDs and dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identified a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward towards understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBDs.

Lipofuscin-Type Pigment as a Marker of Colorectal Cancer

The study of the optical properties of biological tissues for a wide spectral range is necessary for the development and planning of noninvasive optical methods to be used in clinical practice. In this study, we propose a new method to calculate almost all optical properties of tissues as a function of wavelength directly from spectral measurements. Using this method, and with the exception of the reduced scattering coefficient, which was obtained by traditional simulation methods, all the other optical properties were calculated in a simple and fast manner for human and pathological colorectal tissues. The obtained results are in good agreement with previous published data, both in magnitude and in wavelength dependence. Since this method is based on spectral measurements and not on discrete-wavelength experimental data, the calculated optical properties contain spectral signatures that correspond to major tissue chromophores such as DNA and hemoglobin. Analysis of the absorption bands of hemoglobin in the wavelength dependence of the absorption spectra of normal and pathological colorectal mucosa allowed to identify differentiated accumulation of a pigment in these tissues. The increased content of this pigment in the pathological mucosa may be used for the future development of noninvasive diagnostic methods for colorectal cancer detection.

Noninvasive Self-monitoring of Blood Glucose at Your Fingertips, Literally!: Smartphone-Based Photoplethysmography

AbstractDiabetes is a chronic disease and one of the major public health problems worldwide. It is a multifactorial disease, caused by genetic factors and lifestyle habits. Brazil had ∼ 16.8 million individuals living with diabetes in 2019 and is expected to reach 26 million people by 2045. There are global increasing needs for the development of noninvasive diagnostic methods and use of mobile health, mainly in face of the pandemic caused by the coronavirus disease 2019 (COVID-19). For daily glycemic control, diabetic patients use a portable glucometer for glycemic self-monitoring and need to prick their fingertips three or more times a day, generating a huge discomfort throughout their lives. Our goal here is to present a review with very recent emerging studies in the field of noninvasive diagnosis and to emphasize that smartphone-based photoplethysmography (spPPG), powered by artificial intelligence, might be a trend to self-monitor blood glucose levels. In photoplethysmography, a light source travels through the tissue, interacts with the interstitium and with cells and molecules present in the blood. Reflection of light occurs as it passes through the biological tissues and a photodetector can capture these interactions. When using a smartphone, the built-in flashlight is a white light-emitting LED and the camera works as a photodetector. The higher the concentration of circulating glucose, the greater the absorbance and, consequently, the lesser the reflected light intensity will be. Due to these optical phenomena, the signal intensity captured will be inversely proportional to the blood glucose level. Furthermore, we highlight the microvascular changes in the progression of diabetes that can interfere in the signals captured by the photodetector using spPPG, due to the decrease of peripheral blood perfusion, which can be confused with high blood glucose levels. It is necessary to create strategies to filter or reduce the impact of these vascular changes in the blood glucose level analysis. Deep learning strategies can help the machine to solve these challenges, allowing an accurate blood glucose level and interstitial glucose prediction.

A novel sensitive detection method for DNA methylation in circulating free DNA of pancreatic cancer.

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cell-free (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD–ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD–ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-sequencing analysis in cancer tissues and corresponding cfDNA revealed that more than 80% of methylated regions were overlapping; DNA methylation profiles of cancerous tissues and cfDNA significantly correlated with each other (R = 0.97). Our data indicate that newly developed MBD–ddPCR is a sensitive method to detect cfDNA methylation and that using five marker genes plus KRAS mutations may be useful for the detection of pancreatic cancers.

The analytical capabilities of the systems of artificial sense of smell and taste. Part 1. “Electronic nose”

The first part of the analytical review presents the main directions of application of modern Multisensor systems such as "electronic nose". The review is based on the results of the umbrella search for information on the given words and phrases. Umbrella search has shown its effectiveness in organizing publications in the selected area, reducing the number of repetitive links and unrelated to the topic of the search. The search was carried out on the electronic catalogs of Russian and international search engines. The tendency of growth of interest to the chosen subject for the last 10 years is traced. Traditional research directions for artificial smell systems are noted. After a slight decline in 2005-2010, the share of work to address the challenges of improving quality and safety in all sectors of human activity, including the food industry, agriculture and the environment, is growing. Some solutions in the field of analysis of food products, raw materials, finished products are systematized. A new direction of research using "electronic nose" systems based on sensors of different types of action is discussed. This direction is medicine, while there is a significant breakthrough in the intensity of the use of EN in medical practice for the development of non-invasive diagnostic methods. The positive properties of such devices and approaches are a short study time, minimal sample preparation and recovery of the system after measurement, as well as a small mass/volume of the sample, the possibility of non-invasive diagnosis. The most frequently published research on the results of the use of such systems in the analysis of bioassays, especially interesting non-invasive diagnosis. Among the diagnosed lead direction oncological, gynecological, psychiatric. However, there are single publications and to solve problems in Pediatrics, dentistry, endocrinology and others.

Role of Noncoding RNA in Development of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence globally, but little is known about its specific molecular mechanisms. During the past decade, noncoding RNAs (ncRNAs) have been linked to NAFLD initiation and progression. They are a class of RNAs that play an important role in regulating gene expression despite not encoding proteins. This review summarizes recent research on the relationship between ncRNAs and NAFLD. We discussed the potential applicability of ncRNAs as a biomarker for early NAFLD diagnosis and assessment of disease severity. With further study, ncRNAs should prove to be valuable new targets for NAFLD treatment and benefit the development of noninvasive diagnostic methods.

Fingerprinting breast cancer vs. normal mammary cells by mass spectrometric analysis of volatiles.

There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyzed the volatile metabolic signature of human breast cancer cell lines versus normal human mammary cells. Volatile compounds in the headspace of conditioned culture medium were directly fingerprinted by secondary electrospray ionization-mass spectrometry. The mass spectra were subsequently treated statistically to identify discriminating features between normal vs. cancerous cell types. We were able to classify different samples by using feature selection followed by principal component analysis (PCA). Additionally, high-resolution mass spectrometry allowed us to propose their chemical structures for some of the most discriminating molecules. We conclude that cancerous cells can release a characteristic odor whose constituents may be used as disease markers.

Discovery of Tumor Markers for Gastric Cancer by Proteomics

Gastric cancer (GC) has a high rate of morbidity and mortality among various cancers worldwide. The development of noninvasive diagnostic methods or technologies for tracking the occurrence of GC is urgent, and searching reliable biomarkers is considered.This study intended to directly discover differential biomarkers from GC tissues by two-dimension-differential gel electrophoresis (2D-DIGE), and further validate protein expression by western blotting (WB) and immunohistochemistry (IHC).Pairs of GC tissues (gastric cancer tissues and the adjacent normal tissues) obtained from surgery was investigated for 2D-DIEG.Five proteins wereconfirmed by WB and IHC, including glucose-regulated protein 78 (GRP78), glutathione s-transferase pi (GSTpi), apolipoprotein AI (ApoAI), alpha-1 antitrypsin (A1AT) and gastrokine-1 (GKN-1). Among the results, GRP78, GSTpi and A1ATwere significantlyup-regulated and down-regulated respectively in gastric cancer patients. Moreover, GRP78 and ApoAI were correlated with A1AT for protein expressions.This study presumes these proteins could be candidates of reliable biomarkers for gastric cancer.

Nonalcoholic fatty liver disease: updates in noninvasive diagnosis and correlation with cardiovascular disease.

Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat (mainly triglycerides) within hepatocytes. Approximately 20%-30% of adults in the general population in developed countries have NAFLD; this trend is increasing because of the pandemicity of obesity and diabetes, and is becoming a serious public health burden. Twenty percent of individuals with NAFLD develop chronic hepatic inflammation [nonalcoholic steatohepatitis (NASH)], which can be associated with the development of cirrhosis, portal hypertension, and hepatocellular carcinoma in a minority of patients. And thus, the detection and diagnosis of NAFLD is important for general practitioners. Liver biopsy is the gold standard for diagnosing NAFLD and confirming the presence of NASH. However, the invasiveness of this procedure limits its application to screening the general population or patients with contraindications for liver biopsy. The development of noninvasive diagnostic methods for NAFLD is of paramount importance. This review focuses on the updates of noninvasive diagnosis of NAFLD. Besides, we review clinical evidence supporting a strong association between NAFLD and the risk of cardiovascular disease because of the cross link between these two disorders.

Endometrial fluid is a specific and non-invasive biological sample for protein biomarker identification in endometriosis

The development of non-invasive diagnostic methods for endometriosis requires sensitive and disease specific biomarkers. Here, we describe the use of aspirated endometrial fluid from women with and without endometriosis as a novel biological sample for biomarker discovery. Differential protein expression profiling of aspirates from women with early endometriosis (n = 14), advanced endometriosis (n = 32) and without evidence of the disease (n = 32) was assessed by two-dimensional gel electrophoresis (2-DE). A biomarker validation study was performed in an independent cohort (early endometriosis n = 6 and advanced endometriosis n = 14, controls n = 15). The analysis resulted in the identification of 31 proteins showing statistically significant differences in expression. The proteins identified are related to cell signalling, cell death and cell movement, processes that may be involved in the onset and/or progression of endometriosis. The differences in expression observed for 14-3-3 (signal transduction) and moesin (cytoskeletal structure) were confirmed in an independent group of endometriosis patients. Endometrial fluid represents a novel sample for proteomic analysis offering reliable, disease specific information on protein expression, facilitating the discovery of biomarkers for endometriosis. The results described here complement previous proteomic studies, providing new endometriosis-related proteins to be validated as diagnostic markers.

Spatial Localization of Biosensor Fluorescence Signals in Human Skin under the Effect of Eequalization of the Refractive Index of the Surrounding Medium

A priority line of biomedical applications of optics is the development of noninvasive diagnostic methods based on the scanning of fluorescence radiation of biosensors embedded in biological tissue. Their main advantage is a high sensitivity and selectivity with respect to given parameters of tissues and their variations. In this study, we present a method for and results of modeling of excitation and propagation of fluorescence radiation in a multilayer randomly inhomogeneous highly scattering and absorbing medium imitating human skin. The model takes into account the spatially inhomogeneous distribution of skin fluorophores and their photophysical characteristics. Both the spatial distribution of fluorescence of skin tissues and the possibility of localization of a detected fluorescence signal are studied. The spatial distribution of fluorescence centers (fluorophores) in the medium is assumed to closely follow the spatial distribution of collagen fibers of the skin. The equalization of the refractive indices at the air-skin interface is shown to lead to a higher degree of localization of the fluorescence signal detected from a biosensor located in a near-surface skin layer.

Clinical Validity of the MoSeSS RARE-Sequence at CSF Flow Disturbances

The development of non-invasive diagnostic methods is a matter of great importance. This paper describes Motion Sensitized Single Shot RARE Sequences (MoSeSS) as a new, non-invasive diagnostic method in CSF-flow disturbances. The range of applications and clinical validity are examined. The strongly T2-weighted RARE-sequence displays selectively unbound water. The addition of flowencoding gradients shows moving spins flow-dependently as a signal reduction. ECG-triggering enablesthe registration of present flow phases, and the CSF-flow can be observed as cine-mode in quasi real-time. Thirty healthy subjects and 137 patients from subcollectives with diverse CSF-flow disturbances were investigated. The MoSeSS RARE-sequence provides reliable information in occlusion or stenoses of the inner CSF-spaces and in ventriculocisternostomies. Indirect signs of shunt dysfunction are CSF turbulences which correlate in degree with the increase in CSF pressure. Determination of localization and degree of dural impairment in traumatic or postoperative pseudomeningoceles is dependent on the activity of the CSF-flow at the leak. Depending on the stage of NPH, a variably marked active flow oscillation in the aqueduct and in the third ventricle is shown. Liquorrhoea has no definable flow detectable with the MoSeSS RARE-sequence. Vascular pulsation can make differentiation of the CSF-flow from artefacts difficult near larger vessels. The MoSeSS-RARE-Sequence is a fast, non-invasive and radiation-free method, which yields valid clinical information on circulation disturbances in the inner CSF-spaces. With the cine-mode technique, CSF movements can be observed in quasi real-time. Positive enhancement of the CSF is necessary in assessing processes with an undefined, non-detectable flow.