Impact of maternal serum levels of Visfatin,AFP, PAPP-A,sFlt-1 and PlGF at 11–13 weeks gestation on small for gestational age births

Objective: Investigating potential value of maternal serum Visfatin, sFlt-1, PlGF, AFP, PAPP-A levels at first trimester for prediction of small for gestational age (SGA) at birth.

Methods: Measurements were performed in 20 SGA and 65 control cases. Logistic regression analysis adjusted for age and weeks of pregnancy at data collection was performed to estimate odds ratios (OR), 95% confidence intervals (95% CI) and p values separately for each potential predictor. A multiple regression model was used to assess the impact of all the promising predictors adjusted for each other. Receiver operating characteristic (ROC) analysis was used to indicate the ability to discriminate between SGA cases and controls.

Results: There was an association of serum PlGF levels (OR 0.53 per interquartile range [IQR] increase in PlGF; 95% CI 0.24–1.16), sFlt-1/PlGF ratio (OR 1.42 per IQR increase in sFlt-1/PlGF; 95% CI 1.03–1.96), serum Visfatin levels (OR 0.31 per IQR increase in Visfatin; 95% CI 0.10–0.95) and smoking (OR 4.24; 95% CI 1.10–16.37) with SGA at birth.

Conclusions: Associations between SGA and lower PlGF, Visfatin levels as well as increased sFlt-1/PlGF ratio and smoking status were detected which may contribute to predict SGA.     

Rag expression identifies B and T cell lymphopoietic tissues during the development of common carp (Cyprinus carpio)

The generation of lymphoid cells during carp development was studied by analyzing expression of the recombination activating genes (rag) using in situ hybridization and real time quantitative PCR. These data were combined with immunohistochemistry using the mAb's WCL9 (cortical thymocytes) and WCI12 (B cells). Carp rag-1 and rag-2 showed 90 and 89% amino acid identity, respectively, to the corresponding zebrafish sequences. Rag-1 was first expressed in the thymus at 4 days post-fertilization (dpf), while both rag-1⁺/WCL9⁺ and rag-1⁻/WCL9⁻ areas were distinguished from 1 week post-fertilization (wpf), suggesting early cortex/medulla differentiation. From 6 dpf, rag-1⁺ cells were also present cranio-lateral of the head kidney. From 1 wpf, rag-1/rag-2 was expressed in kidney (together with immunoglobulin heavy chain expression) but not in spleen, while WCI12⁺ cells appeared 1 week later in both organs, suggesting B cell recombination in kidney but not in spleen. Rag-1 expression exceeded rag-2 levels in thymus and in head- and trunk-kidney of juveniles, but this ratio was reversed in head- and trunk-kidney from approximately 16 wpf onwards. Rag-1/rag-2 expression was detected in thymi of animals over 1-year-old, but in kidney only at low levels, indicating life-long new formation of putative T cells but severely reduced formation of B cells in older fish.     

Design of Case-controls Studies with Unscreened Controls

Traditionally in genetic case‐control studies controls have been screened to exclude subjects with a personal history of illness. This control group has the advantage of optimal power to detect loci involved in illness, but requires more work and may incur substantial cost in recruitment. An alternative approach to screening is to use unscreened controls sampled from the general population. Such controls are generally plentiful and inexpensive, but in general there is a risk that some may have the same disease as the cases, which will reduce power to detect associations. We have quantified the extent of this power loss, and produced mathematical formulae for the number of unscreened controls necessary to achieve the same power as a fixed sample of screened controls. The effect of using unscreened controls will also depend on the ratio of the number of screened controls to cases specified in the original study design, and this is also investigated. We have also investigated the cost‐benefits of the screened and unscreened approaches, according to variation in the relative costs of sampling screened and unscreened controls, together with genotyping costs. We have, thus, identified the range of situations in which using unscreened controls is a cost‐effective alternative to the screened control method and could be considered when designing a study. In many of the typical, real‐world situations in complex genetics, the use of unscreened controls is potentially cost‐effective and can, in general, be considered for disorders with population prevalence K_p < 0.2. With the steady reduction in genotyping costs and the availability of common sets of “population controls” this design is likely to become increasingly cost effective.     

Timing-dependent plasticity in human primary somatosensory cortex

Animal experiments suggest that cortical sensory representations may be remodelled as a consequence of changing synaptic efficacy by timing-dependent associative neuronal activity. Here we describe a timing-based associative form of plasticity in human somatosensory cortex. Paired associative stimulation (PAS) was performed by combining repetitive median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral postcentral region. PAS increased exclusively the amplitude of the P25 component of the median nerve-evoked somatosensory-evoked potential (MN-SSEP), which is probably generated in the superficial cortical layers of area 3b. SSEP components reflecting neuronal activity in deeper cortical layers (N20 component) or subcortical regions (P14 component) remained constant. PAS-induced enhancement of P25 amplitude displayed topographical specificity both for the recording (MN-SSEP versus tibial nerve-SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse, and the sign of the modulation changed with ISIs differing by only 15 ms. The function describing the ISI dependence of PAS effects on somatosensory cortex resembled one previously observed in motor cortex, shifted by ∼7 ms. The findings suggest a simple model of modulation of excitability in human primary somatosensory cortex, possibly by mechanisms related to the spike-timing-dependent plasticity of neuronal synapses located in upper cortical layers.     

Diabetic vascular disease: it's all the RAGE

The major consequence of long-term diabetes is the increased incidence of disease of the vasculature. Of the underlying mechanisms leading to disease, the accumulation of advanced glycation end products (AGEs), resulting from the associated hyperglycemia, is the most convincing. Interaction of AGEs with their receptor, RAGE, activates numerous signaling pathways leading to activation of proinflammatory and procoagulatory genes. Studies in rodent models of macro- and microvascular disease have demonstrated that blockade of RAGE can prevent development of disease. These observations highlight RAGE as a therapeutic target for treatment of diabetic vascular disease.     

Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice

We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals.     

Breast cancer in an MSH2 gene mutation carrier

A 49-year-old woman presented with breast cancer. She is a member of a family with the hereditary nonpolyposis colorectal cancer syndrome for which a 2-base pair deletion in exon 11 of the mismatch repair gene MSH2 (c1705_1706 delGA) had been identified. Breast cancer is rare in the hereditary nonpolyposis colorectal cancer syndrome. Microsatellite analysis of the tumor showed a microsatellite instable pattern for markers Bat25, Bat26, and Bat40, and no changes for markers D2S123 and D5S346, a so-called microsatellite instability-high pattern. Immunohistochemical staining for the mismatch repair enzymes MSH2 and MSH6 was negative, whereas the tumor cells were positive for MLH1, a pattern suggestive for biallelic MSH2 gene inactivation. We tested the tumor for loss of heterozygosity of the MSH2 gene and found loss of the wild-type MSH2 allele. These data strongly suggest that the MSH2 gene was involved in the development of this breast tumor.     

NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol

Background

Most epidemiological studies on pediatric asthma rely on the report of "wheezing" in questionnaires. Our aim was to investigate the understanding of this term by parents and health professionals.

Methods

A cross-sectional survey was carried out in hospital and community settings within the south of Portugal. Parents or caregivers self-completed a written questionnaire with information on social characteristics and respiratory history. Multiple choice questions assessed their understanding of "wheezing". Health professionals (physicians, nurses and physiotherapists) were given an adapted version. We used bivariate analysis and multivariate models to study associations between definitions of "wheezing" and participants' characteristics.

Results

Questionnaires from 425 parents and 299 health professionals were included. The term "wheezing" was not recognized by 34% of parents, more frequently those who were younger (OR 0.4 per 10-year increment, 95% CI 0.3-0.7), had lower education (OR 3.3, 95% CI 1.5-7.4), and whose children had no history of respiratory disease (OR 4.6, 95% CI 2.5-8.7) (all ORs adjusted). 31% of parents familiar with "wheezing" either did not identify it as a sound, or did not locate it to the chest, while tactile (40%) and visual (34%) cues to identify "wheezing" were frequently used. Nurses reported using visual stimuli and overall assessments more often than physicians (p < 0.01). The geographical location was independently associated with how parents recognized and described "wheezing".

Conclusions

Different meanings for "wheezing" are recognized in Portuguese language and may be influenced by education, respiratory history and regional terminology. These findings are likely applicable to other non-English languages, and suggest the need for more accurate questionnaires and additional objective measurement instruments to study the epidemiology of wheezing disorders.     

Intrathoracic pressure regulation improves 24-hour survival in a pediatric porcine model of hemorrhagic shock

Hemorrhagic shock is a common cause of mortality and morbidity in the pediatric population. Intrathoracic pressure regulation (IPR) lowers intrathoracic pressure, thereby decreasing intracranial pressure and increasing venous return, cardiac output, and cerebral perfusion without the need for immediate fluid resuscitation. We hypothesized that IPR would improve hemodynamics and 24-h survival in a pediatric porcine model of hemorrhagic shock. Twenty piglets were subjected to a 50% total blood volume hemorrhage over 15 min and then randomized to treatment with either IPR or no treatment. After 60 min, survivors were autotransfused, weaned from the ventilator, and assessed and autopsied at 24 h. Mean arterial pressures (MAPs), cardiac index (CI), and arterial blood gases were recorded. MAP (mm Hg) was significantly higher in the IPR group (60.8 ± 3.7) versus controls (41.2 ± 4.6, p < 0.01). Mean CI (L/min/m2) was significantly higher with IPR (3.9 ± 0.24) versus controls (2.5 ± 0.39, p < 0.01). IPR survival rates were significantly improved with IPR [9/9 (IPR) versus 5/11 (controls); p < 0.02]. In this piglet model of hemorrhagic shock, IPR treatment safely and significantly improved MAP, CI, and 24-h survival rates.