Comparative Morphology of the Penis and Clitoris in Four Species of Moles (Talpidae).

The penile and clitoral anatomy of four species of Talpid moles (broad-footed, star-nosed, hairy-tailed, and Japanese shrew moles) were investigated to define penile and clitoral anatomy and to examine the relationship of the clitoral anatomy with the presence or absence of ovotestes. The ovotestis contains ovarian tissue and glandular tissue resembling fetal testicular tissue and can produce androgens. The ovotestis is present in star-nosed and hairy-tailed moles, but not in broad-footed and Japanese shrew moles. Using histology, three-dimensional reconstruction, and morphometric analysis, sexual dimorphism was examined with regard to a nine feature masculine trait score that included perineal appendage length (prepuce), anogenital distance, and presence/absence of bone. The presence/absence of ovotestes was discordant in all four mole species for sex differentiation features. For many sex differentiation features, discordance with ovotestes was observed in at least one mole species. The degree of concordance with ovotestes was highest for hairy-tailed moles and lowest for broad-footed moles. In relationship to phylogenetic clade, sex differentiation features also did not correlate with the similarity/divergence of the features and presence/absence of ovotestes. Hairy-tailed and Japanese shrew moles reside in separated clades, but they exhibit a high degree of congruence. Broad-footed and hairy-tailed moles reside within the same clade but had one of the lowest correlations in features and presence/absence of ovotestes. Thus, phylogenetic affinity and the presence/absence of ovotestes are poor predictors for most sex differentiation features within mole external genitalia

Investigation of faecal volatile organic compounds as biomarkers for the diagnosis of necrotising enterocolitis

Necrotising enterocolitis (NEC) is the most prevalent and harmful illness in the neonatal intensive care unit. It primarily affects premature babies, with higher incidence in low birthweight patients. NEC usually occurs in the early days of life and may develop rapidly. Its diagnosis is based on medical observation because no early diagnostic tool is currently available. Over the last two decades, developments in analytical chemistry have allowed scientists to perform untargeted investigation of biological samples. Biomarkers are being sought, for a range of disorders, by investigating volatile organic compounds (VOCs) in bio-fluids. For the analysis of gas samples, solid phase micro-extraction (SPME) is a suitable technique to preconcentrate volatile compounds prior to analysis using devices such as gas chromatography – mass spectrometry (GC–MS). Recently, much attention has been directed towards the development of sensors and electronic noses to be used as diagnostic tools in hospitals, as they are generally more compact than a GC-MS and do not require specialised personnel. The work presented here is based on the hypothesis that faeces from patients suffering from necrotising enterocolitis show a specific pattern of volatile organic compounds in the days prior to diagnosis when compared with faeces from healthy patients. The objectives of this work were to develop two methods for the analysis of premature faeces using headspace–SPME–GC–MS and headspace – gas chromatography – sensor (HS–GC–Sensor), to analyse samples from healthy premature infants and premature infants affected by NEC using both instruments and to analyse the data collected. Methods were developed individually for each analytical technique. Two pipelines were applied for mass spectrometric data analysis while classification models were exclusively built using sensor data. Results obtained from HS–SPME–GC–MS data showed that the age at sampling had an influence on the number of compounds identified and on their intensities or relative abundance. Heptanal, 2-E-pentenal, hexanal and 2-methylbutanoic acid were identified as relevant compounds. Classifiers were built at days 1 to 6 prior to diagnosis. Accuracy, sensitivity and specificity of up to 74%, 62% and 79%, respectively, were obtained one day prior to diagnosis based on mass spectrometric data, while accuracy, sensitivity and specificity of 100% were obtained based on sensor data at two days prior to diagnosis. Therefore, classification of samples based on headspace analysis of faeces might have potential for the early diagnosis of necrotising enterocolitis

Admission of advanced lung cancer patients to intensive care unit: A retrospective study of 76 patients

<p>Abstract</p> <p>Background</p> <p>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.</p> <p>Methods</p> <p>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.</p> <p>Results</p> <p>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.</p> <p>Conclusions</p> <p>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.</p

Within-Subject Variability of Interferon-g Assay Results for Tuberculosis and Boosting Effect of Tuberculin Skin Testing: A Systematic Review

Background: Variability in interferon-gamma release assays (IGRAs) results for tuberculosis has implications for interpretation of results close to the cut-point, and for defining thresholds for test conversion and reversion. However, little is known about the within-subject variability (reproducibility) of IGRAs. Several national guidelines recommend a twostep testing procedure (tuberculin skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect of a preceding TST on subsequent IGRA results has been reported in studies with apparently conflicting results. Methodology/Findings: We conducted a systematic review to synthesize evidence on within-subject variability of IGRA results and the potential boosting effect of TST. We searched several databases and reviewed citations of previous reviews on IGRAs. We included studies using commercial IGRAs, in addition to non-commercial versions of the ELISPOT assay. Four studies, fulfilling our predefined criteria, examined within-subject variability and 13 studies evaluated TST effects on subsequent IGRA responses. Meta-analysis was not considered appropriate because of heterogeneity in study methods, assays, and populations. Although based on limited data, within-subject variability was present in all studies but the magnitude varied (16-80%) across studies. A TST induced ‘‘boosting’ ’ of IGRA responses was demonstrated in several studies and although more pronounced in IGRA-positive (i.e. sensitized) individuals, also occurred in a smaller but not insignificant proportion of IGRA-negative subjects. The TST appeared to affect IGRA responses only after 3 days and may apparentl

Temporal Dynamics of Interferon Gamma Responses in Children Evaluated for Tuberculosis

BACKGROUND: Development of T-cells based-Interferon gamma (IFNgamma) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube(R), QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children. METHODOLOGY/PRINCIPAL FINDINGS: 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNgamma values after 10 days of treatment (p = 0.035). In addition, IFNgamma values were significantly lower at the end of treatment compared to IFNgamma values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment. CONCLUSIONS/ SIGNIFICANCE: By following quantitative IFNgamma values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNgamma response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNgamma values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy

A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children

BACKGROUND: There are limited data comparing the performance of the two commercially available interferon gamma (IFN-gamma) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease. METHODS AND FINDINGS: The results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, kappa = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, kappa = 0.50) or T-SPOT.TB (75%, kappa = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-gamma responses was significantly influenced by TB contact history, but only the TST was influenced by age. CONCLUSIONS: Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs

Activation of EGFR/ERBB2 via Pathways Involving ERK1/2, P38 MAPK, AKT and FOXO Enhances Recovery of Diabetic Hearts from Ischemia-Reperfusion Injury

This study characterized the effects of diabetes and/or ischemia on epidermal growth factor receptor, EGFR, and/or erbB2 signaling pathways on cardiac function. Isolated heart perfusion model of global ischemia was used to study the effect of chronic inhibition or acute activation of EGFR/erbB2 signaling on cardiac function in a rat model of type-1 diabetes. Induction of diabetes with streptozotocin impaired recovery of cardiac function (cardiac contractility and hemodynamics) following 40 minutes of global ischemia in isolated hearts. Chronic treatment with AG825 or AG1478, selective inhibitors of erbB2 and EGFR respectively, did not affect hyperglycemia but led to an exacerbation whereas acute administration of the EGFR ligand, epidermal growth factor (EGF), led to an improvement in cardiac recovery in diabetic hearts. Diabetes led to attenuated dimerization and phosphorylation of cardiac erbB2 and EGFR receptors that was associated with reduced signaling via extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 mitogen activated protein (MAP) kinase and AKT (protein kinase B). Ischemia was also associated with reduced cardiac signaling via these molecules whereas EGF-treatment opposed diabetes and/or ischemia induced changes in ERK1/2, p38 MAP kinase, and AKT-FOXO signaling. Losartan treatment improved cardiac function in diabetes but also impaired EGFR phosphorylation in diabetic heart. Co-administration of EGF rescued Losartan-mediated reduction in EGFR phosphorylation and significantly improved cardiac recovery more than with either agent alone. EGFR/erbB2 signaling is an important cardiac survival pathway whose activation, particularly in diabetes, ischemia or following treatment with drugs that inhibit this cascade, significantly improves cardiac function. These findings may have clinical relevance particularly in the treatment of diabetes-induced cardiac dysfunction

Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

<p>Abstract</p> <p>Background</p> <p>Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.</p> <p>Methods</p> <p>In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON^®-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis.</p> <p>Results</p> <p>In total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years.</p> <p>Conclusions</p> <p>The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.</p