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We aimed to investigate the diagnostic performance of new 2-D shear-wave elastography (SWE) with propagation maps and attenuation imaging (ATI) for quantification of fibrosis and steatosis in non- alcoholic fatty liver disease (NAFLD). Consecutive patients with NAFLD and healthy volunteers underwent liver stiffness measurement and steatosis quantification by means of vibration- controlled transient elastography coupled with the controlled attenuation parameter as the reference and by 2-D shear-wave elastography (2-D-SWE) with propagation maps and ATI as the investigational methods. We included 232 participants (164 in the NAFLD group and 68 in the healthy control group): 51.7%/49.3% women/men ; mean age, 54.2 +/- 15.2 y ; mean body mass index, 29.4 +/- 6.5 kg/m(2). Significant correlations were found between 2-D- SWE and vibration-controlled transient elastography (r = 0.71, p < 0.0001) and between ATI and the controlled attenuation parameter (r = 0.72, p < 0.0001). NAFLD-specific 2-D-SWE liver stiffness measurement cutoffs were as follows-F >= 2: 7.9 kPa (area under the curve [AUC] = 0.91) ; F >= 3: 10 kPa (AUC = 0.92) ; and F = 4: 11.4 kPa (AUC = 0.95). For steatosis, the best cutoffs by ATI were as follows-S1 = 0.73 dB/cm/MHz (AUC = 0.86) ; S2 = 0.76 dB/cm/MHz (AUC = 0.86) ; and S3 = 0.80 dB/cm/MHz (AUC = 0.83). According to Baveno VI criteria, the optimal 2-D-SWE liver stiffness measurement for diagnosing liver cirrhosis is 15.5 kPa (AUC = 0.94), and for ruling out compensated advanced chronic liver disease it is 9.2 kPa (AUC = 0.92). To conclude, 2-D-SWE with propagation maps and ATI is reliable for quantification of liver fibrosis and steatosis in patients with NAFLD.

Pregnancy status is usually not included in ecological studies because it is difficult to evaluate. The use of non-invasive methods to determine pregnancy, without physically restraining individuals, would enable pregnancy to be included in population studies. In this study, we evaluated sex steroid hormones in plasma and fecal samples from pregnant and non-pregnant females to develop a pregnancy predictive model for guanacos (Lama guanicoe (Müller, 1776)). Samples were obtained during live-shearing management (i.e., capture, shear, and release) of guanacos. Enzyme immunoassays were used to evaluate progesterone (P4) and estradiol (E2) concentrations in plasma and pregnanediol glucuronides (PdG) and conjugated estrogens (EC) in feces. Mean hormonal and fecal metabolite concentrations were significantly higher in pregnant females than in non-pregnant females. A linear relationship was found between each hormone and its fecal metabolite. Finally, hormonal data were combined with an independent source of pregnancy diagnosis such as abdominal ballottement to develop a logistic regression model to diagnose pregnancy in non-handled individuals. The use of predictive models and non-invasive methods might be suitable to incorporate pregnancy information in large-scale population studies on guanaco and other free-ranging ungulates. L’état de gestation n’est généralement pas inclus dans les études écologiques en raison de la difficulté que présente son évaluation. L’utilisation de méthodes non effractives pour déterminer l’état de gestation sans imposer de restriction physique aux spécimens permettrait l’intégration de l’état de gestation aux études démographiques. Nous avons évalué les hormones stéroïdiennes sexuelles dans des échantillons de plasma et de fèces de femelles gravides et non gravides afin d’élaborer un modèle pour prédire l’état de gestation chez les guanacos (Lama guanicoe (Müller, 1776)). Des échantillons ont été prélevés durant la gestion de la tonte (c.-à-d., capture, tonte et lâcher) de guanacos vivants. Des épreuves immunoenzymatiques ont été utilisées pour évaluer les concentrations de progestérone (P4) et d’estradiol (E2) dans le plasma et de glucuronides de prégnandiol (GdP) et d’estrogènes conjugués (EC) dans les fèces. Les concentrations moyennes de métabolites hormonaux et fécaux étaient significativement plus grandes chez les femelles gravides que chez les femelles non gravides. Une relation linéaire est relevée entre chaque hormone et ses métabolites fécaux. Enfin, les données hormonales ont été combinées à une épreuve diagnostique de l’état de gestation indépendante comme le ballottement abdominal afin de produire un modèle de régression logistique pour diagnostiquer la gestation chez des spécimens non manipulés. L’utilisation de modèles prédictifs et de méthodes non effractives pourrait se prêter à l’intégration d’information sur la gestation dans des études démographiques à grande échelle sur les guanacos et d’autres ongulés vivant en liberté. Fil: Marozzi, Antonela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina Fil: Cantarelli, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Gomez, Facundo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina Fil: Panebianco, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina Fil: Leggieri, Leonardo Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina Fil: Gregorio, Pablo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina Fil: Ponzio, Marina Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Carmanchahi, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina

During operational activities, military personnel face extremely demanding circumstances, which when combined lead to severe fatigue, influencing both their well-being and performance. Physical exertion is the main condition leading to fatigue, and its continuous tracking would help prevent its effects. This review aimed to investigate the up-to-date progress on non-invasive physiological monitoring to evaluate situations of physical exertion as a pre-condition to fatigue in military populations, and determine the potential associations between physiological responses and fatigue, which can later result in decision-making indicators to prevent health-related consequences. Adhering to the PRISMA Statement, four databases (Scopus, Science Direct, Web of Science and PubMed) were used for a literature search based on combinations of keywords. The eligibility criteria focused on studies monitoring physiological variables through non-invasive objective measurements, with these measurements being developed in military field, combat, or training conditions. The review process led to the inclusion of 20 studies. The findings established the importance of multivariable assessments in a real-life context to accurately characterise the effects of military practices. A tendency for examining heart rate variables, thermal responses, and actigraphy measurements was also identified. The objectives and experimental protocols were diverse, but the effectiveness of non-invasive measurements in identifying the most fatigue-inducing periods was demonstrated. Nevertheless, no assessment system for standardised application was presented. Future work may include the development of assessment methods to translate physiological recordings into actionable information in real-time and mitigate the effects of fatigue on soldiers’ performance accurately.

Altres ajuts: National Plan on Drugs, Spain, No. 2018/020, and No. 2020/024. Hepatitis C virus (HCV) infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur. Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease. Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption, which are the main therapeutic approaches for clinical management. In this review, we discuss current knowledge around the use of non-invasive methods to assess liver disease, such as abdominal ultrasound, controlled attenuation parameter, transient elastography, magnetic resonance imaging, and indices based on serum markers of liver injury.

Background Helicobacter pylori detection in asymptomatic children with suspected infection or with symptoms that suggest gastric pathology is problematic, since most of the methods depend on the endoscopic study, an invasive and expensive method. Non-invasive methods can be a feasible alternative but must be validated. The purpose of this study was to evaluate the concordance between H. pylori DNA detection in saliva and dental plaque by PCR, with antigen detection in stool by immunochromatography, among asymptomatic children in the state of Guerrero, Mexico. Methods Dental plaque, saliva, and stool samples were obtained from 171 children between 6 and 12 years old. H. pylori detection in saliva and dental plaque was performed by PCR using specific primers for the 16S rRNA gene, while the detection in stool samples was performed by immunochromatography using the CerTest kit. Results We found an overall H. pylori prevalence of 59.6% (102/171). Of the H. pylori positive children 18% (20/111) were positive in saliva samples, 28.1% (34/121) in dental plaque samples, and 50.4% (71/141) in stool samples. A higher prevalence was found in girls (64.7%, p = 0.002). Although some of the children declared some dyspeptic symptoms, these were no related to H. pylori. In conclusion, we found a high prevalence of H. pylori in asymptomatic children and the highest proportion was detected by stool antigen test, which was the most feasible method to detect H. pylori infection.

Introduction Human in vivo models of skin damage were often used in research of cutaneous disorders. The most commonly used models were tape-stripping as mechanical, sodium lauryl sulphate-induced irritation as chemical and ultraviolet radiation as physical damage model. In regard to differences between models, they were expected to have different responses to damage and recovery, with unique skin parameters' changes over time. Objective The aim was to compare skin parameters in three different skin damage models on the same anatomical location, with and without topical treatment. Methods Four test sites on each forearm were randomly assigned to three skin damage models with the fourth sites on each forearm chosen as a control, undamaged site. Skin parameters were assessed using non-invasive methods. Results Sodium lauryl sulphate irritation caused the strongest damage with delayed reaction to the irritant. Tape stripping leads to highest initial skin barrier disruption but afterwards it showed the fastest skin recovery. Ultraviolet radiation did not affect skin barrier function, but it elevated skin erythema and melanin level. Tested preparation did not lead to changes in measured parameters. Conclusion The skin of the participants had different response to three skin damage models with distinct changes of skin parameters and recovery. The trial was registered at ClinicalTrials.gov under the identifier NCT03783819.

Background & objectives: The non-invasive method of haemoglobin (Hb) estimation has unique advantages of exemption of finger prick and associated pain, over invasive methods. This study was done to compare invasive and non-invasive methods of Hb estimation in blood donors keeping haematology analyzer (HA) as a reference method. Methods: The blood donors selected or deferred on the basis of CuSO4 method (Hb ≥12.5 g/dl), were included in the study. Hb values of the donors were estimated by HemoCue and then by OrSense methods. An immediate post-donation venous sample was drawn for analysis on HA. Results: The mean Hb value was 13.98±1.27 g/dl on HA, 14.87±1.03 g/dl on OrSense and 15.03±1.31 g/dl on HemoCue. CuSO4, HemoCue and OrSense demonstrated sensitivities of 18.7, 18.7 and 13.1 per cent, positive predictive values (PPV) of 64.5, 83.3 and 60.9 per cent and specificities of 98.9, 99.6 and 99.1 per cent, respectively. The intra-class correlation coefficient for OrSense was 0.726 while that for HemoCue was 0.851. Bland-Altman plots demonstrated 2SD difference of >2.0 g/dl in Hb estimations between HA and HemoCue/OrSense. Interpretation & conclusions: The non-invasive modality may provide the near-ideal pre-donation Hb screening platform if an improvement can be done in the sensitivity and PPV of the non-invasive method keeping in view its unique advantages.

Hepatitis C virus (HCV) infection remains an important global health problem with chronic infection affecting approximately 11 million children worldwide. The emergence of direct-acting antiviral (DAA) therapies and the development of non-invasive methods for the determination of liver fibrosis will significantly improve the management of paediatric patients with chronic HCV infection in subsequent years. For paediatric patients, a new era of highly effective DAA agents is beginning, and the first results of available clinical trials are very promising. In this era, the identification and monitoring of patients continues to be an important issue. The availability of non-invasive serological and imaging methods to measure hepatic fibrosis enables the identification of patients with significant or advanced liver fibrosis stages. This article summarizes the current data on the epidemiology and progress of research aimed to evaluate the new therapies and non-invasive methods for liver injury in paediatric patients with chronic hepatitis C.

Accepted version (after embargo period) This work presents the results of an application of optical coherence tomography (OCT) to examine a 13th century Byzantine reliquary of unparalleled artistic and historical value. The aim of this work, performed at the initial stage, before the restoration, was focused on the resolution of cleaning procedures regarding both the thick, old varnish and the gold leaf details finely applied on the painted parts of the artwork by means of an integrated approach of non-invasive and invasive analyses and diagnostics. The results allow definition of the thickness of the varnishes, their inner morphology and establishes the presence (or absence) of secondary layers of gold leaf upon the original ones. Knowledge of varnish thickness and in-depth localisation of the secondary gold leaf allowed the restoration procedure of cleaning and thinning of the altered varnish to be performed safely and effectively in order to recover the wonderful pristine sight of a precious and ancient byzantine work of art.

The study was performed at Brasov County Hospital, in the Internal Medicine, Diabetes, Gastroenterology and Cardiology Wards with the collaboration of Transylvania University of Brasov, as a study approved by the Ethical Board of the university. The study aimed at assessing the connection between the anthropometric parameters of abdominal adiposity (measured by means of an original experiment designed to determine the curvature of the thoracic-abdominal adiposity for the patients and processed by help of a mathematical model based upon Bezier curves geometry) and the fat load of the liver (assessed by ultrasound by measuring the diameters of both hepatic lobes) for the patients diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD). The existence of ten types of thoracic-abdominal curves profiles were statistically analyzed in order to evaluate in a simple manner the liver size in NAFLD. The method of diagnosis is based on an easily reproduced experiment, it is original, innovative, non-invasive, and cost-effective. Can be implemented anywhere in the world, there is no need for investment, only for determining the profile of the belly.

Background: The prevalence of morbidity and mortality associated with liver disease among HIV-infected individuals on combination antiretroviral therapy (ART) is high. Early screening of liver disease is essential, as it provides an opportunity for successful treatment. Hence, there is a need for reliable, inexpensive and non-invasive early markers of hepatic damage.Objectives: Non-invasive algorithms are available for assessing the extent of liver fibrosis as markers of ongoing inflammatory damage. This study compared the use of the FibroTest, Fibrosis-4 (FIB-4) index, APRI test and AST:ALT ratio in assessing liver fibrosis in combination ART-experienced individuals.Methods: In a comparative cross-sectional study, 79 participants between the ages of 8 and 62 years were recruited. The performance of each fibrosis algorithm was determined using established cut-off scores for clinically significant liver fibrosis.Results: The prevalence of liver fibrosis as determined by the FibroTest, FIB-4 index, APRI test and AST: ALT ratio were 19.0%, 21.5%, 12.7% and 79.7%, respectively. For individual biomarkers, A-2M concentration (p < 0.001) and AST activity (p = 0.003) remained significantly elevated in participants with fibrosis than those without as defined by FibroTest and APRI test, respectively, after adjustments for multiple comparisons.Conclusion: Our data demonstrate a high prevalence of asymptomatic liver fibrosis among combination ART-experienced individuals in Zimbabwe, and this warrants adequate monitoring of liver fibrosis in individuals on ART. Discordance of fibrosis results among the algorithms and individual biomarkers and calls for further work in identifying optimal biomarkers for detection of asymptomatic fibrosis.Keywords: Liver fibrosis; Non-invasive methods; Biomarkers; Combination anti-retroviral therapy; Zimbabwe.

Intracranial pressure (ICP) measurements are essential in evaluation and treatment of neurological disorders such as subarachnoid and intracerebral hemorrhage, ischemic stroke, hydrocephalus, meningitis/encephalitis, and traumatic brain injury (TBI). The techniques of ICP monitoring have evolved from invasive to non-invasive—with both limitations and advantages. Some limitations of the invasive methods include short-term monitoring, risk of infection, restricted mobility of the subject, etc. The invasiveness of a method limits the frequency of ICP evaluation in neurological conditions like hydrocephalus, thus hampering the long-term care of patients with compromised ICP. Thus, there has been substantial interest in developing noninvasive techniques for assessment of ICP. Several approaches were reported, although none seem to provide a complete solution due to inaccuracy. ICP measurements are fundamental for immediate care of TBI patients in the acute stages of severe TBI injury. In severe TBI, elevated ICP is associated with mortality or poor clinical outcome. ICP monitoring in conjunction with other neurological monitoring can aid in understanding the pathophysiology of brain damage. This review article presents: (a) the significance of ICP monitoring; (b) ICP monitoring methods (invasive and non-invasive); and (c) the role of ICP monitoring in the management of brain damage, especially TBI.

Background: Oral squamous cell carcinoma (OSCC) has a remarkably high incidence worldwide, and a fairly serious prognosis. This is encouraging further research into advanced technologies for non-invasive methods of making early diagnoses, ideally in primary care settings.Method:In this article, the available objective Non-imaging methods for diagnosing OSCC have been reviewed. MEDLINE, EMBASE, the Cochrane Library, and CINAHL have been searched for advanced technologies of non-invasive methods in diagnosis of OSCC, including oral brush biopsy, optical biopsy, saliva-based oral cancer diagnosis and others.Results:Toluidine blue, one of the oldest non-invasive methods for diagnosing OSCC, is unreliable because of its subjectivity, as it is dependent on the experience of the examiner. The diagnosis of Oral carcinoma by Oral brush biopsy with exfoliative cytology based on nano-bio-chip sensor platform shows 97–100% sensitivity and 86% specificity. Another promising non-invasive technique for OSCC diagnosis is saliva-based oral cancer diagnosis, which is an alternative to serum testing. Optical biopsy, which uses the technology of spectroscopy, can be used to detect changes at a sub-cellular level; thus, it provides information that may not be available with conventional histology with reliable sensitivity and specificity.Conclusion:It is clearly evident that screening and early effective detection of cancer and pre-cancerous lesions have the potential to reduce the morbidity and mortality of this disease. The imaging technologies are subjective procedures since all of them require interpretation and significantly affected by the examiner experience. These make further research for advanced objective procedures. Saliva-based oral cancer diagnosis and optical biopsy are promising objective non-invasive methods for diagnosing OSCC. They are easy to perform clinically at primary care set. They show promising pathways for future development of more effective method for the diagnosis of OSCC.

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica Mill extract (FXE) were white, homogeneous and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5–6.0), droplet size varying from 92.2 to 233.6 nm, a polydispersion index (PDI) around 0.200 and a zeta potential from −26.71 to −47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy.

Magnetic resonance spectroscopy (MRS) can give information about cellular metabolism in vivo which is difficult to obtain in other ways. In skeletal muscle, non-invasive 31P MRS measurements of the post-exercise recovery kinetics of pH, [PCr], [Pi] and [ADP] contain valuable information about muscle mitochondrial function and cellular pH homeostasis in vivo, but quantitative interpretation depends on understanding the underlying physiology. Here, by giving examples of the analysis of 31P MRS recovery data, by some simple computational simulation, and by extensively comparing data from published studies using both 31P MRS and invasive direct measurements of muscle O2 consumption in a common analytical framework, we consider what can be learnt quantitatively about mitochondrial metabolism in skeletal muscle using MRS-based methodology. We explore some technical and conceptual limitations of current methods, and point out some aspects of the physiology which are still incompletely understood.

OBJECTIVE: Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both as a single test and as a part of algorithms.MATERIALS AND METHODS: PRO-C3 was assessed in baseline samples from the NORDynamIC trial. 270 patients were stratified into groups according to baseline biopsy. Baseline APRI, FIB-4 and GUCI scores were available for comparison in 232 patients.RESULTS: PRO-C3 increased with Ishak scores (p = .001). Area under the curve (AUC) for significant fibrosis was 0.75 (95% CI 0.68-0.81) and 0.76 (95% CI 0.68-0.84) for cirrhosis. FIB-4, APRI and GUCI had similar AUCs. In a PRO-C3 algorithm including age, platelet count, body mass index (BMI) and international normalised ratio (INR), the diagnostic efficacy improved to 0.85 (CI 0.80-0.89) and 0.90 (IQR 0.84-0.96) for significant fibrosis and cirrhosis, respectively.CONCLUSIONS: In our study, PRO-C3 was an independent predictor of fibrosis stage, and may play an important role in managing CHC patients.

Given the worldwide increase in obesity and diabetes, non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is associated with increased hepatic and extrahepatic morbidity and mortality, mainly related to non-alcoholic steatohepatitis with fibrosis. An early diagnosis in the high-risk population with features of insulin resistance and a proper identification of those patients with progressive liver disease are needed. Practicing physicians dealing with NAFLD should be aware of and should carefully evaluate the extended spectrum of NAFLD-related extrahepatic diseases, which significantly affects liver- and non-liver-related prognosis. This clinical practice-oriented article reviews the diagnostic methods and staging strategies for NAFLD and proposes an investigational algorithm for a global evaluation of NAFLD patients.

The bank vole is a commonly used model species in behavioral and ecophysiological studies. Thus, presenting a validated method for noninvasive monitoring of corticosterone and testosterone secretion is of high relevance. Here, we evaluated the effect of time of day and an ACTH challenge test on measured fecal corticosterone (FCM) and testosterone (FTM) metabolites in both sexes. Furthermore, we performed radiometabolism experiments for both steroids and sexes to study metabolism and excretion of 3H-corticosterone and 3H-testosterone. FCM and FTM were analysed with a 5α-pregnane-3β,11β,21-triol-20-one enzyme immunoassay (EIA) and a testosterone (measuring 17β-hydroxyandrostanes) EIA, respectively. Males had significantly higher FCM levels than females and their main excretion route was via the feces (∼72%), whereas females excreted nearly equal portions in both feces and urine. For testosterone the main excretion route was via the feces in both sexes (∼80%). The time course of excretion was similar in both sexes, but for the first time a significant difference between injected steroids was found: Corticosterone was excreted faster than testosterone, both in urine (median of peak levels: 4 h vs 6 h) and feces (6 h vs 8 h). Several metabolites were present in the feces and the tested EIAs reacted with some of them. Time of day had a significant effect on measured fecal steroid metabolites. As expected, males had significantly higher FTM levels than females. ACTH administration significantly increased FCM values; peaks were observed 4–8 h after injection. In conclusion, both tested EIAs proved suited for a noninvasive measurement of glucocorticoids and androgens in bank voles. peerReviewed

Our research group has recently been able to demonstrate and validate the possibility of studying of 3p microsatellite alterations (MAs) in the DNA extracted from the exhaled breath condensate (EBC) of healthy smokers and of subjects with non-small cell lung cancer (NSCLC). In light of the interest that has recently been aroused in the novel molecular staging protocol of lung cancer, the evaluation of the prognostic power of the genetic alterations involved in lung cancerogenesis, including 3p microsatellite alterations could be of clinical interest. Purpose The aim of this study was to investigate the outcome predictive power of exhaled 3p microsatellite alterations in lung cancer patients. Patients and methods Seventy-one NSCLC patients were enrolled in the study. All the subjects under study had already undergone a 3p microsatellite analysis of their EBC. A total of 56 patients were either given a follow-up of at least 102 weeks, or were followed up until death. Results The number of 3p microsatellite alterations found in the exhaled breath condensate DNA exhibits a remarkable correlation with patients’ survival. D3S2338 and D3S1289 account for the microsatellites with the highest positive prognostic power; loss of heterozygosis (LOH) D3S1289 has a negative prognostic value in adenocarcinoma while microsatellite instability (MI) and LOH D3S2338 influence survival in squamous cell carcinoma; and, independently of NSCLC stage, D3S1289 is associated with poor prognosis. Conclusions In conclusion, 3p MAs in the DNA of exhaled breath condensate is strongly associated with NSCLC patients’ survival. Our results suggest that it is possible to use the study of EBC MAs as an outcome predictor for lung cancer patients.

Since the first evidence demonstrating the dramatically high incidence of H. pylori infection and the subsequent medical challenges it incurs, health management of H. pylori infection has been a high priority for health authorities worldwide. Despite a decreasing rate of infection in western countries, prevalence of H. pylori infection in developing and in some industrial countries is still very high. Whereas treatment and vaccination against H. pylori is a contemporary issue in medical communities, selective treatment and prior high-throughput screening of the subject population is a major concern of health organizations. So far, diagnostic tests are either elaborative and require relatively advanced medical care infrastructure or they do not fulfill the criteria recommended by the Maastricht IV/Florence consensus report. In this review, in light of recent scientific studies, we highlight current and possible future approaches for the diagnosis of H. pylori. We point out that novel non-invasive tests may not only cover the requirements of gold standard methods in H. pylori detection but also offer the potential for risk stratification of infection in a high throughput manner.

The use of noninvasive methods for measuring fecal glucocorticoid metabolites is a useful tool for endocrine assessment particularly in studies where animals cannot be captured, when they should be sampled without disturbing their activities, and/or when welfare needs to be maximized. However, still no complete standardization exists for the methodology, and some confounding variables may play an important role affecting measurements and interpretation of results. The present study focused on whether two different diets (laying feed or seed mixture), the time since defecation (0, 4, 24, or 48 h) and the drying method of those samples (oven-dried or naturally nonoven-dried) may affect concentrations of corticosterone metabolites (CM) measured in male Japanese quail. Half of the birds were provided with plain water (control) and the other half received a corticosterone solution. Birds fed with a seed mixture exhibited higher values of CM (nanogram/gram) in droppings than quail that received a laying feed diet suggesting that diet should be carefully considered as a potential source of variation. As expected both groups exhibited higher CM concentration after corticosterone treatment. While CM concentrations increased significantly in nonoven-dried samples over time (0 < 4 < 24 = 48 h), oven-dried samples exhibited similar high CM values. At 24 and 48 h postdefecation, nonoven-dried samples had similar CM concentrations as all oven-dried samples. Drying of samples may be considered a reliable method to reduce variations due to water loss over time, facilitating comparisons up to 48 h postdefecation. This finding would allow to enhance the range of application of this noninvasive and welfare friendly method to situations where samples cannot be collected or frozen shortly after defecation. Fil: Pellegrini, Stefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Busso, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Leche, Alvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina Fil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina

Recently the exhaled breath temperature (EBT) was seen to increase in non-small cell lung cancer and was subsequently proposed as a possible non-invasive tool for its diagnosis. The need for further studies that confirm the previous findings and support the potential scope of this method underlies the main aim of this study that seeks to explore the pathogenic mechanisms determining the EBT in lung cancer. We enrolled 44 consecutive patients with a radiological suspicion of lung cancer and ten healthy non-smoker volunteers, after which their EBT was measured. On the same day, the subjects underwent breath condensate collection for the measurement of leukotriene (LTB)-4 and of the vascular endothelial growth factor (VEGF), the former being a marker of airways inflammation and the latter of neoangiogenesis. We confirmed the presence of a higher EBT in lung cancer patients compared to the controls. The multiple linear regression model showed that the exhaled VEGF was the only predictor of elevations of EBT. In conclusion, it can be stated that for the first time in this study, we have shown that EBT is higher in subjects with lung cancer and that the airways angiogenesis drives the increase in EBT in lung cancer. Moreover, the study suggests the potential for the use of EBT in monitoring the lung cancer progression, although the implementation of more in-depth studies to verify this result is recommended.

We used a non-invasive TOBEC method (Total Body Electric Conductivity) to estimate lean body mass and fat content in mouse-eared batsMyotis myotis (Borkhausen, 1797) hibernating in Poznan Forts (W Poland) and in a semi-natural cave-mine Miedzianka (SE Poland). In December, fat content averaged 5.5 g in females (body mass = 29.4 g) and 5.3 g in males (body mass = 28.4 g). At the end of hibernation (April), fat content averaged 2.2 g in females (body mass = 25.6 g) and 1.4 g in males (body mass = 23.7 g). Fat content did not differ between the localities either in December or in April, but the pattern of changes of fat content was different. We calculated the rate of energy expenditure in hibernating bats using two methods, based on independent samples (fat content in first-time captured individuals) and based on paired observations (changes of fat content in re-captured individuals), and discussed problems associated with the two approaches. Both methods show that the bats need about 4.9 g of fat (191 kJ) to sustain a 165-day hibernation. However, the rate of fat usage varied considerably between the sites and hibernation phase. Although the average amount of fat remaining in April would be sufficient to support at least six more weeks of hibernation, the level of reserves was close to zero in some individuals.

The exhaled breath temperature (EBT) has been proven to be the expression of airways inflammation as well as of the increased vascularity. Although both these conditions characterize lung cancer pathogenesis, this is the first study where the EBT has been analysed in patients affected by non-small-cell lung cancer. The aim of this study was to verify whether and how the lung cancer being examined influences the EBT for possible future clinical implications. Eighty-two consecutive subjects with a radiological suspicion of lung cancer were enrolled and underwent standard diagnostic and staging procedures for cancer. EBT was measured in all the subjects at the enrolment with the X-Halo device. Forty patients resulted as affected by lung cancer while 42 as false-positive (controls). We found a higher EBT in NSCLC patients compared to healthy subjects. The EBT was correlated with number of packs/year and associated with the stage of lung cancer. We identified a cut-off value for the EBT that is able to screen patients with lung cancer with a high sensitivity and specificity. Our results suggest that lung cancer causes an increase in the EBT, which, whether confirmed and validated, could become a new non-invasive clinical tool in the screening and monitoring of this disease.

Background and objectives Airway remodeling is a main feature of asthma. Different biological phenotypes of severe asthma have been recently recognized by the ENFUMOSA study group and among these one is characterized by neutrophilic airway inflammation. Concentrations of MMP-9 in airways have been suggested as a marker to monitor airway remodeling in asthma. Objective The aim of the present study was to explore airway remodeling in different biological phenotypes of asthma by measuring MMP-9 in EBC and correlating these with other variables. Methods Sixty consecutive subjects with asthma and 20 healthy controls were enrolled in the study. Exhaled MMP-9, pH and NO levels and inflammatory cells in sputum were measured in all subjects enrolled. Results We observed an increase of exhaled MMP-9 in asthmatic subjects compared to controls. Higher exhaled MMP-9 concentrations were described in severe asthmatics compared to mild to moderate especially in those with neutrophilic airway inflammation. We further found a correlation between exhaled MMP-9 and percentage of neutrophils in sputum, FEV 1, exhaled NO and pH. Conclusion Our results seem to substantiate the feasibility of measuring exhaled MMP-9 in the breath of asthmatic patients. MMP-9 may be considered a proxy of the amount of the ongoing airway remodeling in asthma. MMP-9 has been shown to be differentially released in different phenotypes of asthma. The measure of exhaled MMP-9 could help to monitor the ongoing airway remodeling, recognize severe stages of asthma, and possibly help determine the appropriate choice of therapy.

Background and Aim: Liver stiffness measured by transient elastgraphy correlates with Hepatic vein pressure gradient, liver Stiffness value of 21 kpa predicts significant portal hypertension. Aim is to predict esophageal varices presence by fibroscan and possible grading by degree of liver stiffness in HCV related cirrhotic patients. Material and Methods: Thirty two HCV related cirrhotic patients were recruited, age > 18 years, BMI< 35, no history of: upper GI bleeding, hepatocellular carcinoma, abdominal collaterals, ascites. Patients underwent clinical examination, laboratory investigations, abdominal ultrasonography, upper endoscopy and fibroscan. They divided into (Group I= no varices, Group II =small varices (Grade 1 & 2), Group III = large varices (Grade 3 & 4). Results: Age is higher in Group III than I & II (55+6.6 vs 49.5+4.7 & 48.9+4.7, p-value 0.04) respectively, Groups were gender & BMI matched, fibroscan values in Group I vs II & III were 27 Vs 49.4, p value 0.01, cutoff 29.7 Kpa (sensitivity 95% & specificity 67%) while its value in Group II vs III were 38.4 vs 60.4, p value 0.002, cutoff 38.2 Kpa (sensitivity 100% & specificity77.3%). Platelet count, splenic size, platelet count/splenic size in Group I vs II & III were 107.166 vs 72.900, 13.8 vs 15.4, 803.6 vs 478, p value 0.01, 0.008, 0.005, cutoff 80.000, 14.5, 545, sensitivity & specificity (85%&75%, 75%&75%, 85%&84%) respectively. On multivariate analysis fibroscan (OR 1.113; p=0.005) & platelet count/splenic size (OR 0.995; p=0.012) were positive predictors of esophageal varices presence. Conclusion: Fibroscan is a good non-invasive method to predict esophageal varices presence & possible grading with high sensitivity.

Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either non-invasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change - even in the event of fibrosis regression. Therefore, future studies are needed to validate non-invasive methods in predicting the different phases of liver cirrhosis.

AIM To evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC). METHODS First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C. RESULTS Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3). CONCLUSION The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.

Objectives: The primary objective of this preliminary study was to test the suitability of 5-fluorouracil ointment ; interferon ointment and albothyl concentrate as alternative therapies for the treatment of cervical intraepithelial neoplasia (CIN) in the presence/absence of high risk human papilloma virus (hrHPV), as well as to compare the three treatment approaches. The secondary objective included the determination of causative factors of the genital infections and their correlation with various predictor variables. Patients and Methods: 45 patients aged 18-64 years diagnosed with CIN were included in the study. 15 patients without hrHPV were treated with albothyl. The other 30 patients were randomly divided into two subgroups and treated either by 5-fluorouracil or by interferon. The results were evaluated by canonical correlation analysis, multiple regression, general regression model and odds ratio. Results and Conclusion: Age, the presence of bacterial infection and number of births were the variables which showed the highest correlation with CIN and hrHPV. After a month-long treatment, total clearance was observed in 10 patients (22.2%) and lower grade lesions were observed in 22 of them (48.9%). Total clearance of hrHPV was found in 93.3% of the patients. There was no significant difference among the three therapeutic approaches. To the contrary, the type of contraception during the treatment had a significant influence on the outcome of the therapy. The obtained results confirmed that all the three selected approaches may be used successfully for the treatment of CIN lesions and represent a suitable alternative to surgical treatment.

Background Recent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer. Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known. The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression. Method We enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis. Results LTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum. Conclusion The high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.

Numerous paediatric liver diseases from different origins may be complicated by development of liver fibrosis and progression to cirrhosis. Although fibrogenesis, which represents a major driving force for the development of liver fibrosis, has common tracts whatever the aetiology, liver fibrosis has different histopathological patterns in paediatric liver disease. In these diseases management choices may depend upon the stage of liver fibrosis. Thus, the accurate estimation of histological pattern of liver fibrosis is important for the prevention of the subsequent complications. Liver biopsy has long been considered as a gold standard diagnostic method for assessing liver fibrosis. However, due to its several disadvantages, in the last decades alternative and accurate non-invasive means to estimate fibrosis are developed. In this review, we characterised the most frequent histological patterns of liver fibrosis in paediatric liver diseases. Furthermore, we describe use of liver biopsy in diagnosis and staging of liver fibrosis, list the alternative non-invasive techniques that have an emerging role in the assessment of liver fibrosis, and propose a management algorithm.

While the activation of the infant hypothalamic-pituitary-gonadal (HPG) axis and the existence of a postnatal gonadotrophin surge were first documented in the early 1970s, study of the longitudinal development of gonadal hormones in infancy, and the potential physiological and behavioral correlates of this development, have been hampered by reliance on infrequent serum sampling. The present study reports the validation of a noninvasive method for repeated assessment of steroid hormones in infant fecal samples. Fecal samples were collected in, and excised from cotton diaper liners, and extracted using methanol. Extracts were analyzed for estradiol using a diluted assay modification. Method validity was supported by a steroid recovery rate of at least 80%, a sensitivity of 0.35 pg/ml, and inter- and intra-assay coefficients of variations of less than 10% and 20%, respectively. Variation in estradiol concentration was assessed across (1) sample type (scraped vs. cut from diaper liner), (2) time of day (morning vs. afternoon/evening samples), (3) time interval between samples and (4) time to assay (1 day vs. 489 days after collection). Of these characteristics, only the time interval between samples within an individual was significantly associated with estradiol concentration. This is the first report of human infant fecal estradiol levels. The results support fecal recovery as a novel and powerful noninvasive tool for longitudinal studies of human infants, expanding research opportunities for investigating development of sex-specific behaviors in infancy, and the potential effects of endocrine disruptors on development.

Summary We previously investigated the androgen responsiveness of males to simulated partner and territory intrusions in five African cichlid species (Neolamprologus pulcher, Lamprologus callipterus, Tropheus moorii, Pseudosimochromis curvifrons, Oreochromis mossambicus; Hirschenhauser et al., 2004). Here we re-analysed data on 11-ketotestosterone (11-KT) levels in holding water to compare the free (presumably from the gills) and conjugated (presumably from urine and faeces) 11-KT fractions. We sampled (i) pre-test baseline control levels from individual males in social isolation and (ii) response levels released after social interactions, either with an ovulating female or a male territory intruder. In four out of five species, conjugated metabolites contributed to the observed total 11-KT responses in water during social context, which was particularly apparent in peak responsive individuals exposed to male intruders. Thus, in water from males sampled in isolation immunoreactive 11-KT seemed to derive both from gills and urine, whereas the urinary 11-KT component apparently increased in the social context, particularly when a male was challenged by a same-sex intruder. These results suggest that (i) the social context may affect urine release patterns of males and (ii) 11KT data acquired by using fish-holding water may not simply reflect the passive transmission of steroid hormones via the gills.

Introduction: insulin resistance (IR) promotes the progression of fibrosis and diminishes response to treatment in patients with hepatitis C. Recently, Sydney's index (includes IR) has been proposed as a non-invasive method for the prediction of fibrosis. Objective: to assess the usefulness of Sydney's index for the prediction of advanced fibrosis (F3-F4) or absence of significant fibrosis (F0-F1) in patients with chronic hepatitis C. Patients and methods: we included 131 patients suffering from chronic hepatitis C. Mean age was 40 ± 11, 78 men and 53 women. Fibrosis stage was (F0-F1) 69 patients, F2: 40, and advanced (F3-F4) in 22 patients. We measured baseline AST, ALT, GGT, platelet, cholesterol, alcohol, and IR (HOMA - IR) levels. Sydney, Forns' and APRI indexes were calculated. Results: the area under the curve for the diagnosis of absence of significant fibrosis in each method was: Sydney: 0.80, Forns: 0.71, APRI: 0.70; p = ns. Moreover, the diagnostic capacity of advanced fibrosis was: Sydney: 0.88, Forns: 0.83, APRI: 0.82; p = ns. The predictive negative value of significant fibrosis was 74, 72, and 67%, respectively. Due to the presence of intermediate values, the indexes were not applicable to 36, 44 and 43% of patients respectively. Conclusions: the incorporation of insulin resistance among biochemical non-invasive methods slightly improves the yield of other indexes. Nevertheless, results are suboptimal, and more than one third of patients might not be correctly classified.

The aim of the study was to test the irritancy of 6 antiseptics in an open exposure model. The following agents were tested in their normal use concentrations using open exposures, 2x daily for 4 days in 20 subjects: chlorhexidine 4% (CH), chlorhexidine 0.5% in ethanol 70% (CE), ethanol 70% (ET), iodine 1% in ethanol 70% (IE), povidone-iodine 10% (PI) and sodium hypochlorite 0.25% (SH). Responses were evaluated by visual scoring, subjective irritancy scoring, stratum corneum hydration (Corneometer), transepidermal water loss and laser Doppler flowmetry. Exposure to SH had to be discontinued after 4 applications because of severe subjective irritation. The same held true for IE (7 applications), whereas the other agents were exposed 8x. All evaluation methods showed SH to be significantly more irritating than IE, which was in turn more irritating than CH, CE, ET and PI. Thus, it can be concluded that CH, CE, ET and PI were nonirritating in this open exposure model.