Influence of perinatal inflammation on the neurodevelopmental outcome of premature infants

Objective: To evaluate the influence of perinatal inflammation on neurodevelopmental outcome of premature infants.

Study design: From a retrospective cohort study of women with preterm labor with intact membranes or preterm prelabor rupture of membranes (PPROM) with an amniocentesis to rule out intra-amniotic inflammation (IAI) and microbial invasion of the amniotic cavity (MIAC), we evaluated neurodevelopmental outcome of their infants born between 24.0 and 34.0 weeks gestation. Women with clinical chorioamnionitis at admission were excluded. Neurodevelopmental outcome was screened with the Ages & Stages Questionnaire (ASQ)-3. We analyzed the relationship between an altered ASQ-3 and antenatal, intra-partum and post-partum factors related to perinatal inflammation.

Result: Among 98 infants evaluated, 22% had an abnormal score. Amniotic fluid interleukin-6 levels and early-onset sepsis (EOS) were independent factors of an altered ASQ-3 with delivery <26.0 weeks being the strongest predictor.

Conclusions: In premature infants, the presence of IAI, delivery <26.0 weeks and EOS were found to be independent factors of an altered ASQ-3.     

Placido disk-based topography versus high-resolution rotating Scheimpflug camera for corneal power measurements in keratoconic and post-LASIK eyes: reliability and agreement

AIM: To compare the repeatability/reproducibility of measurement by high-resolution Placido disk-based topography with that of a high-resolution rotating Scheimpflug camera and assess the agreement between the two instruments in measuring corneal power in eyes with keratoconus and post-laser in situ keratomileusis (LASIK). METHODS: One eye each of 36 keratoconic patients and 20 subjects who had undergone LASIK was included in this prospective observational study. Two independent examiners worked in a random order to take three measurements of each eye with both instruments. Four parameters were measured on the anterior cornea: steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Km), and astigmatism (Ks-Kf). Intra-examiner repeatability and inter-examiner reproducibility were evaluated by calculating the within-subject standard deviation (Sw) the coefficient of repeatability (R), the coefficient of variation (CoV), and the intraclass correlation coefficient (ICC). Agreement between instruments was tested with the Bland-Altman method by calculating the 95% limits of agreement (95% LoA). RESULTS: In keratoconic eyes, the intra-examiner and inter-examiner ICC were >0.95. As compared with measurement by high-resolution Placido disk-based topography, the intra-examiner R of the high-resolution rotating Scheimpflug camera was lower for Kf (0.32 vs 0.88), Ks (0.61 vs 0.88), and Km (0.32 vs 0.84) but higher for Ks-Kf (0.70 vs 0.57). Inter-examiner R values were lower for all parameters measured using the high-resolution rotating Scheimpflug camera. The 95% LoA were -1.28 to +0.55 for Kf, -1.36 to +0.99 for Ks, -1.08 to +0.50 for Km, and -1.11 to +1.48 for Ks-Kf. In the post-LASIK eyes, the intra-examiner and inter-examiner ICC were >0.87 for all parameters. The intra-examiner and inter-examiner R were lower for all parameters measured using the high-resolution rotating Scheimpflug camera. The intra-examiner R was 0.17 vs 0.88 for Kf, 0.21 vs 0.88 for Ks, 0.17 vs 0.86 for Km, and 0.28 vs 0.33 for Ks-Kf. The inter-examiner R was 0.09 vs 0.64 for Kf, 0.15 vs 0.56 for Ks, 0.09 vs 0.59 for Km, and 0.18 vs 0.23 for Ks-Kf. The 95% LoA were -0.54 to +0.58 for Kf, -0.51 to +0.53 for Ks and Km, and -0.28 to +0.27 for Ks-Kf. CONCLUSION: As compared with Placido disk-based topography, the high-resolution rotating Scheimpflug camera provides more repeatable and reproducible measurements of Ks, Kf and Ks in keratoconic and post-LASIK eyes. Agreement between instruments is fair in keratoconus and very good in post-LASIK eyes.     

Immunophenotyping does not improve predictivity of the local lymph node assay in mice

The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry‐based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I‐A^κ and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non‐irritating sensitizers and non‐sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. Copyright © 2014 John Wiley & Sons, Ltd.     

Nanoswimmers Based on Capped Janus Nanospheres

Nanoswimmers are synthetic nanoscale objects that convert the available surrounding free energy to a directed motion. For example, bacteria with various flagella types serve as textbook examples of the minuscule swimmers found in nature. Along these lines, a plethora of artificial hybrid and non-hybrid nanoswimmers have been introduced, and they could find many uses, e.g., for targeted drug delivery systems (TDDSs) and controlled drug treatments. Here, we discuss a certain class of nanoparticles, i.e., functional, capped Janus nanospheres that can be employed as nanoswimmers, their subclasses and properties, as well as their various implementations. A brief outlook is given on different fabrication and synthesis methods, as well as on the diverse compositions used to prepare nanoswimmers, with a focus on the particle types and materials suitable for biomedical applications. Several recent studies have shown remarkable success in achieving temporally and spatially controlled drug delivery in vitro using Janus-particle-based TDDSs. We believe that this review will serve as a concise introductory synopsis for the interested readers. Therefore, we hope that it will deepen the general understanding of nanoparticle behavior in biological matrices.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.     

The natural history of clinically unrecognized anal sphincter tears over 10 years after first vaginal delivery

OBJECTIVE: To estimate the influence of clinically unrecognized anal sphincter injuries detected by endoanal ultrasonography 3 months after first vaginal delivery on symptoms of anal incontinence over the subsequent 10-year period. METHODS: One-hundred fifty-six consecutive primigravid women were recruited, anal endosonography performed, and bowel habit predelivery characterized by means of a validated 24-point questionnaire. After excluding four women with a clinically recognized sphincter tear after delivery and 18 who delivered by cesarean, these procedures were repeated 3 months postpartum. The questionnaire was repeated at 5 and 10 years to estimate continence change over the decade after delivery. Logistic regression was used to examine the effect of clinically unrecognized sphincter tears on continence. RESULTS: After delivery, continence deteriorated from baseline in 37 (28%) women, eight of whom had anal sphincter tears. Continence did not deteriorate in 97 women, six of whom had anal sphincter tears. At 10 years, 59 (55%) of 107 contactable women had continence scores greater than zero, 23 of whom had deteriorated from baseline. There was a significant relationship between a sphincter tear that was symptomatic after delivery and continence deterioration sustained at 5 and 10 years (odds ratio 2.8 for change in continence score). However, no relationship was found over 10 years for those women who sustained a sphincter tear but whose continence did not deteriorate postpartum. CONCLUSION: Ultrasonographic anal sphincter defects without postpartum incontinence are not associated with deterioration in continence over the following decade. LEVEL OF EVIDENCE: II.     

Prepregnancy body mass index and adverse pregnancy outcomes

OBJECTIVE: The aim of this study was to evaluate the association between prepregnancy BMI, and adverse maternal and neonatal outcomes. METHOD: In this retrospective cohort study 916 consecutive singleton gestations were included who gave birth between 1 January 2006 and 31 August 2006 at the Department of Obstetrics and Gynecology, University of Udine, Italy. Statistical analysis was performed using univaried logistic regression and measured by odds ratio. RESULTS: The obese patients had a statistically, significantly increased incidence of Caesarean section (OR = 2.17, p = 0.009). Women with overweight (OR = 2.43, p = 0.002) and obese weight (OR = 4.86, p < 0.0001) were at increased risk for preterm deliveries. The pre-eclampsia and the fetal macrosomia (> or =4,000 g) were increased in obese women (OR = 5.68, p < 0.0001; OR = 2.58, p = 0.033, respectively). CONCLUSION: Maternal prepregnancy obesity is significantly associated with increased risk of Caesarean section, preterm delivery, pre-eclampsia and macrosomia.     

Hyperspectral evaluation of vasculature in induced peritonitis mouse models

Imaging of blood vessel structure in combination with functional information about blood oxygenation can be important in characterizing many different health conditions in which the growth of new vessels contributes to the overall condition. In this paper, we present a method for extracting comprehensive maps of the vasculature from hyperspectral images that include tissue and vascular oxygenation. We also show results from a preclinical study of peritonitis in mice. First, we analyze hyperspectral images using Beer-Lambert exponential attenuation law to obtain maps of hemoglobin species throughout the sample. We then use an automatic segmentation algorithm to extract blood vessels from the hemoglobin map and combine them into a vascular structure-oxygenation map. We apply this methodology to a series of hyperspectral images of the abdominal wall of mice with and without induced peritonitis. Peritonitis is an inflammation of peritoneum that leads, if untreated, to complications such as peritoneal sclerosis and even death. Characteristic inflammatory response can also be accompanied by changes in vasculature, such as neoangiogenesis. We demonstrate a potential application of the proposed segmentation and processing method by introducing an abnormal tissue fraction metric that quantifies the amount of tissue that deviates from the average values of healthy controls. It is shown that the proposed metric successfully discriminates between healthy control subjects and model subjects with induced peritonitis and has a high statistical significance.