Validation of the accuracy of the sentinel lymph node procedure in patients with vulvar cancer: results of a multicenter study in Germany

ObjectiveTo investigate the diagnostic accuracy of the sentinel node procedure in patients with vulvar cancer, a multicenter study was launched in Germany in 2003 involving 7 oncology centers.Patients and methodsBetween 2003 and 2006, 127 women with primary T1–T3 vulvar cancer were entered in the study and treated with sentinel node removal after application of ^99mTechnetium labeled nanocolloid and/or blue dye. Subsequently, in all women a complete inguinofemoral lymphadenectomy and the adequate vulvar operation were performed. Sentinel lymph nodes were examined by routine pathologic examination (H&;E), followed by step-sectioning and immunhistochemistry if negative.ResultsThe sentinel node procedure was successful in 125 out of 127 cases, in 2 cases no sentinel nodes were detected. 21 patients received unilateral lymphadenectomy, 103 women were operated on both groins. In 39 women out of 127, positive lymph nodes in one or both groins were identified (30.7%). In 36 women, the sentinel nodes were also positive (sensitivity 92.3%). We had three cases with a false negative sentinel node (false negative rate: 7.7%), all of these women presenting with tumors in midline position. One tumor was a T1 tumor (10 mm), 2 tumors being classified as T2 (40 and 56 mm, respectively). In one additional case (18 mm T1 tumor, midline position), the sentinel was positive in the right groin, but false negative on the left side.ConclusionsThis study shows that identification of SLN in squamous cell cancer of the vulva is feasible, however not highly accurate depending on tumor localization and size. The false negative rate seems to be acceptable if the procedure is restricted to stage 1 tumors with clinically negative lymph node status. Tumors situated in or close to the midline seem to be less suitable for this procedure. Implementation of SLNB into clinical practice should be performed with care and only by experienced teams as to avoid preventable groin relapses.     

Pathogenesis and genetics of neural tube defects

After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC).     

Isolated left-sided congenital diaphragmatic hernia: cardiac axis and displacement before fetal viability has no role in predicting postnatal outcome

OBJECTIVES: The purpose of this retrospective study was to determine whether objective assessment of cardiac shifting on two-dimensional ultrasonography can predict postnatal outcome in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: Still images at the level of the four-chamber view were obtained in 23 fetuses with left-sided CDH. A group of 12 fetuses (3 non-survivors and 9 survivors) were examined at two periods, between 20 and 30 weeks and between 31 and 40 weeks. A further 11 fetuses (2 non-survivors and 9 survivors) were examined between 31 and 40 weeks. Fetal heart axis and position were determined manually and associated with postnatal outcome. RESULTS: The cardiac axis remained constant in the 9 survivors (15.5 +/- 3.2 versus 17.2 +/- 3.3, p = 0.71) and 3 non-survivors (19.0 +/- 11.5 versus 18.5 +/- 11.8, p = 0.97). There was no statistical difference between the 9 survivors and 3 non-survivors at the two periods. Cardiac displacement remained constant in the 9 survivors (0.2 +/- 0.02 versus 0.2 +/- 0.02, p = 0.32) but increased significantly in the 3 non-survivors (0.2 +/- 0.04 versus 0.4 +/- 0.02, p = 0.015). The difference between survivors and non-survivors was statistically significant between the18 survivors and 5 non-survivors examined between 31 and 40 weeks of gestation (0.2 +/- 0.02 versus 0.4 +/- 0.02, p = 0.037). CONCLUSION: This study does not support the hypothesis that objective assessment of mediastinal shift in fetuses with left-sided CDH has a role in predicting postnatal outcome before fetal viability, which is when it would be more useful for counseling patients regarding whether to continue with the pregnancy or to opt for termination.     

Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers

The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.     

Potentially Bio-Accessible Metabolites from an Extract of Cornus mas Fruit after Gastrointestinal Digestion In Vitro and Gut Microbiota Ex Vivo Treatment

Targeting pancreatic lipase and α-amylase by digestion-derived fractions of ethanolic-aqueous (60%, v/v) extract from Cornus mas fruit (CM) in relation to the control and prevention of metabolic disorders, including diabetes, was the first purpose of the present study. Taking into consideration the significance of bio-accessibility of compounds, we attempted to identify metabolites of CM after gastrointestinal digestion in vitro, as well as their kinetic changes upon gut microbiota treatment. The digestion of extract was simulated with digestive enzymes in vitro and human gut microbiota ex vivo (1 h, 3 h, 6 h, 24 h), followed by chromatographic analysis using the UHPLC-DAD-MSⁿ method. The effect of fractions from gastrointestinal digestion in vitro on the activity of pancreatic lipase and α-amylase was studied with fluorescence-based assays. The gastric and intestinal fractions obtained after in vitro digestion of CM inhibited pancreatic lipase and α-amylase. Loganic acid as the main constituent of the extract was digested in the experimental conditions in contrast to cornuside. It was found in most analytes such as salivary, gastric, intestinal, and even colon (fecal slurry, FS) fractions. In all fractions, kaempferol hexoside and reduced forms of kaempferol, such as aromadendrin, and benzoic acid were assigned. The signals of tannins were detected in all fractions. Cornusiin A was tentatively assigned in the gastric fraction. The metabolites originating from kinetic analytes have been classified mainly as phenolic acids, hydrolyzable tannins, and flavonoids. Phenolic acids (protocatechuic acid, gallic acid), tannins (digalloylglucose, tri-O-galloyl-β-D-glucose), and flavonoids (aromadendrin, dihydroquercetin) were detected in the late phases of digestion in fecal slurry suspension. Cornuside was found in FS analyte after 3 h incubation. It was not detected in the samples after 6 and 24 h incubation with FS. In conclusion, cornuside, aromadendrin, and phenolic acids may be potentially bio-accessible compounds of CM. The presence of plants’ secondary metabolites in the intestinal fractions allows us to indicate them as responsible for decreasing glucose and lipid absorption.     

Early Feeding Factors and Eating Behaviors among Children Aged 1–3: A Cross-Sectional Study

Early nutrition plays a crucial role not only in providing essential nutrients for proper child development, but may also be an important step in creating desirable eating behaviors, which can be transmitted into adulthood. The aim of this study was to assess possible links between early feeding factors, such as breastfeeding, complementary feeding (timing and method) as well as types of complementary foods and mealtime environment during the first three months of complementary feeding and eating behaviors in children aged 1–3 years old. This cross-sectional, online survey involved 467 mothers of toddlers aged 1–3 years old from the whole of Poland. The questionnaire consisted of questions about early feeding and the Children’s Eating Behavior Questionnaire (CEBQ). The adjusted linear regression model revealed that longer duration of any breastfeeding was negatively related to enjoyment of food (EF), desire to drink (DD) and positively related to satiety responsiveness (SR) and slowness in eating (SE) subscales. Moreover, offering homemade complementary foods more often than commercial may be related to higher SR. Eating meals during distraction seems to be negatively associated with EF, and positively with DD and SE subscales. Our study highlights possible links between early feeding factors and toddlers’ eating behaviors, so further investigation, also including dietary factors, is needed.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Using measures of reading time regularity (RTR) to quantify eye movement dynamics,and how they are shaped by linguistic information

In this article, we present the concept of reading time regularity (RTR) as a measure to capture reading process dynamics. The first study is concerned with examining one of the assumptions of RTR, namely, that process measures of reading, such as eye movement fluctuations and fixation durations, exhibit higher regularity when contingent on sequentially structured information, such as texts. To test this, eye movements of 26 German native speakers were recorded during reading-unrelated and reading-related tasks. To analyze the data, we used recurrence quantification analysis and sample entropy analysis to quantify the degree of temporal structure in time series of gaze steps and fixation durations. The results showed that eye movements become more regular in reading compared to nonreading conditions. These effects were most prominent when calculated on the basis of gaze step data. In a second study, eye movements of 27 native speakers of German were recorded for five conditions with increasing linguistic information. The results replicate the findings of the first study, verifying that these effects are not due to mere differences in task instructions between conditions. Implications for the concept of RTR and for future studies using these metrics in reading research are discussed.