Children staying in hospital: a research on psychological stress of caregivers.
Having a child hospitalized is a stressful event for parents. Previous studies have found increased stress in families with children affected by different kinds of pathologies, and analyzed disease related objective variables producing stress. However, most of these studies recruited caregivers of children with chronic or serious illnesses, and focused on evaluation of objective environmental stressors and did not consider subjective "perception" of stress. The aim of this study was to investigate perception of acute stress in caregivers taking care of children without serious physical damage that were hospitalized for short periods. Moreover, some variables, such as recreational and school services offered to children, influencing perception of cognitive, physiological and behavioral state relating to the sensation of "being stressed" were analyzed. This study was realized with a sample of caregivers of children hospitalized for mild acute diseases. Research was conducted using two standardized tests, PSM (Psychological Stress Measure) and STAI (State Trait Anxiety Inventory), whose characteristics of reliability and validity had been successfully established. Present data showed that caregivers of hospitalized children perceived high levels of stress and anxiety. Perception of stress was influenced by the degree of kindred with patients, length of hospitalization, and, notably, participation in some of the activities offered to children, mainly school services. Findings showed that child hospitalization is a stressful event for caregivers, even if hospitalization is for middle and transient pathologies. Perception of stress was influenced by length of hospitalization, and by degree of kindred. Findings even suggest that some services offered to children can modulate caregivers' perception of stress and impact of hospitalization. Caregivers whose children used school services describe themselves as less irritable and with higher emotional control compared to other caregivers. Considering the importance of education in a child's life, the possibility to continue school activities helped caregivers to feel less under pressure. In the light of this finding, amelioration of scholastic activities in pediatric departments may represent a critical point in order to provide a more agreeable hospital stay for children and their caregivers and, as a consequence, improve family involvement in care management.


Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination.
This work reports a novel approach to the assessment of the surface properties of compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining intrinsic dissolution rate (IDR), an important parameter in early stage drug development. Surface topography, post-compaction and post-SDI run, have been measured using a non-contact, optical, three-dimensional microscope based on focus variation, the Alicona Infinite Focus Microscope, with the aim of correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic changes that may have occurred post-compaction and post-SDI run. IBUs IDR decreased from 0.033mg/min/cm2 to 0.022mg/min/cm2 from 10 to 20min, respectively, during the experiment. XRD and DSC showed no form changes during the SDI run. The surface topography images showed that a distinct imprint was embossed on the surfaces of some compacts which could affect IDRs. Surface parameter values were associated with the SDI experiments which showed strong correlations with the IDR values. The variable-focus microscope can be used as a complimentary tool in the determination of IDR values from the SDI.


Serum and tissue levels of insulin-like growth factor-I in women with dysplasia and HPV-positive cervical cancer.
The ectocervical epithelium is the target of the oncogenic human papillomavirus (HPV), which acts as an etiological agent in the development of cervical carcinoma. However, the HPV-mediated transformation of human epithelial cells is a multi-step process dependant on unknown factors additional to the virus, which is a necessary but, in and of itself, insufficient catalyst. In the present study, we characterized the role of insulin-like growth factor-I (IGF-I) in this process. IGF-I is an endocrine hormone with an autocrine and paracrine role in many tissues. Our data demonstrated that autocrine secretion of IGF-I can contribute to HPV-induced carcinogenesis of the epithelium. An immunohistochemical study showed that IGF-I was present in the nuclei of the reproductive layer of the paraepidermal epithelium in 89% of cases of intraepithelial neoplasia (CIN I-III) and 60% of cases of invasive cervical cancer. The presence of IGF-I at a nuclear localization in the cells studied suggests that it may also have intranuclear actions.


At what wavelengths should we search for signals from extraterrestrial intelligence?
It has often been concluded that searches for extraterrestrial intelligence (SETI) should concentrate on attempts to receive signals in the microwave region, the argument being given that communication can occur there at minimum broadcasted power. Such a conclusion is shown to result only under a restricted set of assumptions. If generalized types of detection are considered-in particular, photon detection rather than linear detection alone-and if advantage is taken of the directivity of telescopes at short wavelengths, then somewhat less power is required for communication at infrared wavelengths than in the microwave region. Furthermore, a variety of parameters other than power alone may be chosen for optimization by an extraterrestrial civilization. Hence, while partially satisfying arguments may be given about optimal wavelengths for a search for signals from extraterrestrial intelligence, considerable uncertainty must remain.


Electron microscopic localization of specific carbohydrate groups in thin sections of tissues embedded in a hydrophilic resin: concanavalin A receptors in mouse spleen.
An improved postembedding method for electron microscopic localization of concanavalin A (Con A) receptors in ultrathin sections is reported. Materials are embedded in a hydrophilic resin, glycol methacrylate copolymerized with glutaraldehyde and urea, using a precisely controlled polymerization schedule that preserves ultrastructural integrity. Ferritin-Con A binds specifically in ultrathin sections of mouse spleen tissue and of Sephadex beads embedded in this resin. Quantitative investigations of procedures for decreasing nonspecific labeling demonstrate that preincubation of sections with bovine serum albumin reduces background to a very low level. This high-resolution method allows macromolecular affinity probes access to receptors in all cellular locations, while maintaining good morphological preservation.


Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system.
Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.


Optimising the follow-up of adult coeliac disease with a clinical-based score to identify patients in need of a histological reassessment: a retrospective single centre study.
Follow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999-November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12-24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data.


Spirituality and Physical Activity and Sedentary Behavior among Latino Men and Women in Massachusetts.
To examine the relationships between spirituality and physical activity and sedentary behavior in a sample of Latino adults in Massachusetts. This is a cross-sectional analysis of the Lawrence Health and Well Being Study; a study that was conducted among patients at the Greater Lawrence Family Health Center (GLFHC) in Lawrence, Massachusetts. 602 Latino or Hispanic adults aged 21 to 85 years completed the study. There was a significant negative relationship between spirituality and sedentary behavior (β= -.12, p = .004). Although not statistically significant, higher spirituality was associated with increased odds of engaging in physical activity. There were no significant associations between spirituality and physical activity among men or women. Men with greater spirituality were significantly less sedentary (β = -.17, P = .005). There was no relationship between sedentary behavior and spirituality among women. This study found that individuals who are more spiritual are also less sedentary, and this association was stronger in men than women. Findings provide insight for developing future interventions to promote activity in this high-risk population, which has been greatly understudied. Future research endeavors should consider investigating the impact of spirituality-based messages to reduce sedentary behavior among Latinos.


Twist1 transcriptional targets in the developing atrio-ventricular canal of the mouse.
Malformations of the cardiovascular system are the most common type of birth defect in humans, frequently affecting the formation of valves and septa. During heart valve and septa formation, cells from the atrio-ventricular canal (AVC) and outflow tract (OFT) regions of the heart undergo an epithelial-to-mesenchymal transformation (EMT) and invade the underlying extracellular matrix to give rise to endocardial cushions. Subsequent maturation of newly formed mesenchyme cells leads to thin stress-resistant leaflets. TWIST1 is a basic helix-loop-helix transcription factor expressed in newly formed mesenchyme cells of the AVC and OFT that has been shown to play roles in cell survival, cell proliferation and differentiation. However, the downstream targets of TWIST1 during heart valve formation remain unclear. To identify genes important for heart valve development downstream of TWIST1, we performed global gene expression profiling of AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq). Using this resource we identified a novel set of 939 genes, including 123 regulators of transcription, enriched in the valve forming regions of the heart. We compared these genes to a Tag-seq library from the Twist1 null developing valves revealing significant gene expression changes. These changes were consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. To study the role of TWIST1 at the DNA level we performed chromatin immunoprecipitation and identified novel direct targets of TWIST1 in the developing heart valves. Our findings support a role for TWIST1 in the differentiation of AVC mesenchyme post-EMT in the mouse, and suggest that TWIST1 can exert its function by direct DNA binding to activate valve specific gene expression.


Strain- and serotype-dependent affinity of Shiga toxin-producing Escherichia coli for bovine milk fat globules.
Shiga toxin-producing Escherichia coli (STEC) are widely detected in raw milk products intended for human consumption. Although STEC are a worldwide public health problem, the pathogenicity of STEC in cheese remains unclear. In fact, bacterial association with compounds in raw milk cheeses could reduce their pathogenicity. A previous study showed the association of 2 STEC strains with raw milk cream in a natural creaming assay. Different concentrations of each strain were required to saturate the cream. In this study, we hypothesized that all STEC strains could be associated with milk fat globules (MFG) in raw milk and that the bacterial load required for saturation of the cream is serotype dependent. We evaluated the affinity of STEC strains belonging to the O157:H7, O26:H11, and O103:H2 serotypes for bovine raw milk cream and analyzed saturation of the cream layer by natural creaming assay. We used 12 STEC strains and 3 strains belonging to another pathotype to assess the effects of serotypes on this phenomenon. We performed sucrose density gradient centrifugation assays with 2 STEC model strains to confirm the results obtained by natural creaming. The localization of STEC within MFG-enriched creams was observed by confocal and electron microscopy. We recovered approximately 10 times more STEC from the cream layer after natural creaming than from raw bovine milk. The concentration of STEC required to saturate the cream layer (the saturation concentration) was estimated for each strain by nonlinear regression, highlighting a strain and serotype effect. Moreover, the concentration of STEC in the cream was milk fat level dependent. However, even in nonsaturating conditions, a high level of STEC was still present in the aqueous phase, after fat separation. Thus, natural creaming should not be used as the sole preventive measure to remove STEC from naturally contaminated raw milk. The results of our study suggest that cream saturation is a complex mechanism, most likely involving specific interactions between STEC and raw MFG.


The influence of brood comb cell size on the reproductive behavior of the ectoparasitic mite Varroa destructor in Africanized honey bee colonies.
Africanized honey bees (Apis mellifera, Hymenoptera: Apidae) in Brazil are tolerant of infestations with the exotic ectoparasitic mite, Varroa destructor (Mesostigmata: Varroidae), while the European honey bees used in apiculture throughout most of the world are severely affected. Africanized honey bees are normally kept in hives with both naturally built small width brood cells and with brood cells made from European-sized foundation, yet we know that comb cell size has an effect on varroa reproductive behavior. Three types (sizes) of brood combs were placed in each of six Africanized honey bee colonies: new (self-built) Africanized comb, new Italian comb (that the bees made from Italian-sized commercial foundation), and new Carniolan comb (built naturally by Carniolan bees). About 100 cells of each type were analyzed in each colony. The Africanized comb cells were significantly smaller in (inner) width (4.84 mm) than the European-sized comb cells (5.16 and 5.27 mm for Italian and Carniolan cells, respectively). The brood cell infestation rates (percentage cells infested) were significantly higher in the Carniolan-sized comb cells (19.3%) than in the Italian and Africanized cells (13.9 and 10.3%, respectively). The Carniolan-sized cells also had a significantly larger number of invading adult female mites per 100 brood cells (24.4) than did the Italian-sized cells (17.7) and the natural-sized Africanized worker brood cells (15.6). European-sized worker brood cells were always more infested than the Africanized worker brood cells in the same colony. There was a highly significant correlation (P<0.01) between cell width and the rate of infestation with varroa in four of the six colonies. The small width comb cells produced by Africanized honey bees may have a role in the ability of these bees to tolerate infestations by Varroa destructor, furthermore it appears that natural-sized comb cells are superior to over-sized comb cells for disease resistance.


[Effect of angiotensin ii on Na+/H+ exchangers of the renal tubule].
Angiotensin II is a key element in regulating the volume of extracellular liquid. It acts indirectly through aldosterone secretion by adrenals and directly on the renal tubule too: It regulates luminal Na+/H+ antiporters (NHE3 and possibly NHE2) after binding to membrane AT1 receptors located both on the basolateral and on the apical side of the cells. The main site of Ang II action is proximal tubule, mainly the S1 segment which has a high level of AT1 receptors. Circulating Ang II concentrations (10(-12) to 10(-10) M), increased NaCl, water and NaHCO3 reabsorption via NHE3 in the proximal tubule. There is also a synthesis of Ang II within the cells of proximal tubule, which is secreted within the lumen where the physiological concentration is stable 10(-8) M, i.e. 100 to 1000 times higher than the circulating concentration. Luminal ANG II originating from kidney has a physiological autocrine function on NaCl, water and probably NaHCO3 reabsorption, since inhibiting Ang II synthesis, by conversion enzyme inhibition, or effect, by AT1 receptor antagonists, induces a reduction of proximal tubule reabsorption. The stimulatory effects of circulating and intrarenal Ang II seem to be explained by protein kinase C stimulation and possibly by a reduction of cAMP production or by a stimulation of a non-receptor tyrosine kinase. When pharmacological doses of Ang II (> 10(-8) M) are applied in the peritubular or the luminal medium of isolated microperfused proximal tubule in vitro, a paradoxical inhibition of NHE3 was observed. These effects appear to involve arachidonic acid metabolites through the cytochrome P450 pathway and possibly a rise in cytosolic free Ca++. The physiological significance of these supraphysiological effects are unknown.


Long-term placement of silastic nasolacrimal tubes.
We retrospectively reviewed the complication rate associated with silastic tube intubation in the treatment of congenital and acquired obstructions of the lacrimal system in 82 patients with a follow-up of 3 to 66 months. Complications included tube prolapse, extrusion or breakage, punctal erosion, conjunctival irritation, intranasal discomfort, and tube inspissation with mucoid debris ("dirty tubes"). The rate was highest in the first 3 months (41%); it decreased to less than 10% after 6 months. Based on these findings, we recommend that silastic nasolacrimal tubes be regarded as semi-permanent devices which may safely be left in place for years.


Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia.
By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals-"copies" of motor signals sent to sensory areas-permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD-FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD-FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD-FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients.SIGNIFICANCE STATEMENT People with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.


[Epidemiological survey of wrist fractures in children].
The incidence of wrist fractures is increasing in children. We undertook an epidemiological survey in western France to determine characteristic features. A prospective multicentric study was conducted over one year in five university hospital centers in western France. The survey included 839 wrist fractures in children aged 6 to 16 years. The following criteria were recorded: age and gender, date and energy of the trauma, side and description of the fracture. Displacement was measured on the AP and lateral radiographs. The boys were older than the girls at the time of the wrist fractures, generally during the summer season (May to October). The left wrist was involved in 55% of the fractures; 83% were metaphyseal fractures. Fractures with epiphyseal detachment were more frequent in adolescents and occurred after high-energy trauma. Metaphyseal fractures were more common in girls than in boys. Displacement was greater in older children, particularly in case of epiphyseal detachment. We did not observe the male predominance often reported in our country. The girls probably practice sports as much as boys.


Neural Affective Mechanisms Predict Market-Level Microlending.
Humans sometimes share with others whom they may never meet or know, in violation of the dictates of pure self-interest. Research has not established which neuropsychological mechanisms support lending decisions, nor whether their influence extends to markets involving significant financial incentives. In two studies, we found that neural affective mechanisms influence the success of requests for microloans. In a large Internet database of microloan requests (N = 13,500), we found that positive affective features of photographs promoted the success of those requests. We then established that neural activity (i.e., in the nucleus accumbens) and self-reported positive arousal in a neuroimaging sample (N = 28) predicted the success of loan requests on the Internet, above and beyond the effects of the neuroimaging sample's own choices (i.e., to lend or not). These findings suggest that elicitation of positive arousal can promote the success of loan requests, both in the laboratory and on the Internet. They also highlight affective neuroscience's potential to probe neuropsychological mechanisms that drive microlending, enhance the effectiveness of loan requests, and forecast market-level behavior.


Antidepressant effects of sleep deprivation and phototherapy.
In contrast to drugs, sleep deprivation and phototherapy rapidly induce depressive remissions, which are rapidly reversible. These characteristics make them useful tools for prospective, longitudinal studies of the psychobiology of depression. It seems likely that discovery of the mechanism of action of these two antidepressant procedures would increase our understanding of the pathogenesis of depression and lead to novel, rapidly acting pharmacological treatments. Further progress in this direction depends on careful delineation of which conditions of the procedures are necessary for their antidepressant efficacy and identification and pharmacological manipulation of biological correlates of the procedures that may be relevant to their mechanism of action. Analogies between the two procedures suggest that similar mechanisms may be involved in both.


Clinical applications of gene therapy for primary immunodeficiencies.
Primary immunodeficiencies (PIDs) have represented a paradigmatic model for successes and pitfalls of hematopoietic stem cells gene therapy. First clinical trials performed with gamma retroviral vectors (γ-RV) for adenosine deaminase severe combined immunodeficiency (ADA-SCID), X-linked SCID (SCID-X1), and Wiskott-Aldrich syndrome (WAS) showed that gene therapy is a valid therapeutic option in patients lacking an HLA-identical donor. No insertional mutagenesis events have been observed in more than 40 ADA-SCID patients treated so far in the context of different clinical trials worldwide, suggesting a favorable risk-benefit ratio for this disease. On the other hand, the occurrence of insertional oncogenesis in SCID-X1, WAS, and chronic granulomatous disease (CGD) RV clinical trials prompted the development of safer vector construct based on self-inactivating (SIN) retroviral or lentiviral vectors (LVs). Here we present the recent results of LV-mediated gene therapy for WAS showing stable multilineage engraftment leading to hematological and immunological improvement, and discuss the differences with respect to the WAS RV trial. We also describe recent clinical results of SCID-X1 gene therapy with SIN γ-RV and the perspectives of targeted genome editing techniques, following early preclinical studies showing promising results in terms of specificity of gene correction. Finally, we provide an overview of the gene therapy approaches for other PIDs and discuss its prospects in relation to the evolving arena of allogeneic transplant.


Detection of one-lung intubation incidents.
Lung sounds are very common source for monitoring and diagnosis of pulmonary function. This approach can be used for detecting one lung intubation (OLI) during anesthesia or intensive care. In this paper, an algorithm for detecting OLI from lung sounds is presented. The algorithm assumes a multiple-input-multiple-output system, in which a multi-dimensional auto-regressive model relates the input (lungs) and the output (recorded sounds). An OLI detector is developed based on the generalized likelihood ratio test (GLRT), assuming coherent distributed sources for each lung. This method exhibited reliable results also when the lungs were modeled by incoherent distributed sources, which is a more accurate model for lung sources. The algorithm was tested using real breathing sounds recorded in an operating room, and it achieved an OLI detection rate of more than 95%, for each breathing cycle.


In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals.
Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.


Ferulic acid attenuates diabetes-induced cognitive impairment in rats via regulation of PTP1B and insulin signaling pathway.
Cognitive impairment has been recognized as a typical characteristic of neurodegenerative disease in diabetes mellitus (DM) and this cognitive dysfunction may be a risk factor for Alzheimer's disease (AD). Ferulic acid, a phenolic compound commonly found in a range of plants, has emerged various properties including anti-inflammatory and neuroprotective effects. In the present study, the protective activities and relevant mechanisms of ferulic acid were evaluated in diabetic rats with cognitive deficits, which were induced by a high-glucose-fat (HGF) diet and low dose of streptozotocin (STZ). It was observed that ferulic acid significantly increased body weight and decreased blood glucose levels. Meanwhile, ferulic acid could markedly ameliorate spatial memory of diabetic rats in Morris water maze (MWM) and decrease AD-like pathologic changes (Aβ deposition and Tau phosphorylation) in the hippocampus, which might be correlated with the inhibition of inflammatory cytokines release and reduction of protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, the levels of brain insulin signal molecules p-IRS, p-Akt and p-GSK3β were also investigated. We found that ferulic acid administration restored the alterations in insulin signaling. In conclusion, ferulic acid exhibited beneficial effects on diabetes-induced cognition lesions, which was involved in the regulation of PTP1B and insulin signaling pathway. We suppose that PTP1B inhibition may represent a promising approach to correct abnormal signaling linked to diabetes-induced cognitive impairment.


Antioxidant defense system parameters in isolated fish hepatocytes exposed to bisphenol A - Effect of vitamin C.
In this study, isolated hepatocytes of pearl mullet (Alburnus tarichi) were exposed to bisphenol A (BPA) at concentrations of 25, 50, 100, and 200 μM for 24 h. Moreover, an in vitro antioxidant concentration of vitamin C (50 μM) was administrated to the culture medium along with the BPA exposures. Next, the antioxidant defense system parameters were analyzed. According to the results, the highest concentration of BPA (200 μM) proved to be severely toxic for the cells. The increased activities of superoxide dismutase (SOD) and glutathione-S-transferase (GST), the fluctuated activities of glutathione peroxidase (GPx), and the decreased content of reduced glutathione (GSH) were compared to the control group after the BPA exposures. Vitamin C co-administration was found to cause further increases in the SOD, GPx, and GST activities in some of the experimental groups and vitamin C could not restore the GSH content. Malondialdehyde (MDA) levels were observed to be unaffected in all exposure groups. These results show that BPA causes alterations in the antioxidant defenses of the isolated fish hepatocytes. In addition, vitamin C co-administration along with BPA was found to be non-protective against BPA-induced oxidative stress, consequently, aggravated a negative BPA impact.


[Effectiveness of using Maliutka and Malysh adapted propionic-acidophilus mixtures in the combined treatment of congenital hypotrophy].
The physical and psychomotor development, immune responsiveness, and intestinal microflora were studied in 82 infants with congenital hypotrophy depending on the nutrition pattern. It was shown that children who received the propionic-acidophilic mixtures Malyutka and Malush manifested the highest daily weight gain, the most rapid disappearance on the manifestations of food allergy, an increase in immune responsiveness. A decrease in the cultivation rate of Proteus vulgaris and pathogenic staphylococcus, as well as an increase in the cultivation of bifidobacteria. The data obtained permit recommending the use of the propionic-acidophilic mixtures Malyutka and Malysh in combined treatment of children with congenital hypotrophy.


Subtle neurological abnormalities as risk factors for cognitive and functional decline, cerebrovascular events, and mortality in older community-dwelling adults.
Subtle, but clinically detectable, neurological abnormalities (SNAs) are associated with impaired physical performance in elderly persons without overt neurological diseases. We investigated whether SNAs were prospectively associated with cognitive and functional status, death, and cerebrovascular events (CVEs) in older community-dwelling individuals. In participants without history of stroke, parkinsonism and dementia, or cognitive impairment, a score (N(SNA)) was obtained by summing SNAs detected with a simple neurological examination. Cognitive status and disability were reassessed 4 years later, and deaths and CVEs were documented over 8 years. Of 506 participants free of neurological diseases (mean [SEM] age, 71.9 [0.3] years; 42% were men), 59% had an N(SNA) of 1 or more (mean [SEM], 1.1 [0.06]; range, 0-8). At baseline, the N(SNA) increased with age and with declining cognitive and physical performance, depressive symptoms, and disability, after adjusting for several covariates, but did not increase with falls and urinary incontinence. The N(SNA) prospectively predicted worsening cognitive status and disability, adjusting for demographics and for baseline comorbidity and cognitive and physical performance. The mortality rates were 22.6, 23.3, 23.9, 58.6, and 91.9 per 1000 person-years in participants with an N(SNA) of 0, 1, 2, 3, and 4 or higher, respectively. Compared with an N(SNA) of less than 3, having an N(SNA) of 3 or higher was associated with an increased adjusted risk of death (hazard ratio, 1.77; 95% confidence interval [CI], 1.25-2.74) and of CVE (hazard ratio, 1.94; 95% CI, 1.07-3.54) over 8 years. In this sample of older community-dwelling persons without overt neurological diseases, multiple SNAs were associated with cognitive and functional decline and independently predicted mortality and CVEs.


Assessment of articular displacement of distal radius fractures.
Intraarticular step and gap displacements represent the most common indication for surgical treatment of distal radius fractures. Most often, treatment decision making relies only on good-quality plain radiographs taken before and after reduction with measurement accuracy maximized by using the longitudinal axis method. When plain radiographs alone prove insufficient, CT scans or tomograms will significantly improve interobserver and intraobserver reliability of measurements, especially when evaluated using the arc method. Tomography is an effective method for postoperative evaluation of fractures immobilized in splints or casts. The role of MRI in assessing intraarticular distal radius fractures is limited to confirming injuries to carpal ligaments or the triangular fibrocartilage complex. Intraoperatively, we use fluoroscopy to obtain 30 degrees cephalad posteroanterior views and as 22 degrees lateral views to best observe articular surface reduction. Our current operative indications include fractures with radiocarpal or distal radioulnar joint step or gap deformities greater than 1-2 mm, gross distal radioulnar joint instability, or those with extensive metaphyseal comminution rendering them particularly unstable after closed reduction. In general, we tend to lean toward operative fixation in younger, more active patients.


Histochemistry in biology and medicine: a message from the citing journals.
Especially in recent years, biomedical research has taken advantage of the progress in several disciplines, among which microscopy and histochemistry. To assess the influence of histochemistry in the biomedical field, the articles published during the period 2011-2015 have been selected from different databases and grouped by subject categories: as expected, biological and biomedical studies where histochemistry has been used as a major experimental approach include a wide of basic and applied researches on both humans and other animal or plant organisms. To better understand the impact of histochemical publications onto the different biological and medical disciplines, it was useful to look at the journals where the articles published in a multidisciplinary journal of histochemistry have been cited: it was observed that, in the five-years period considered, 20% only of the citations were in histochemical periodicals, the remaining ones being in journals of Cell & Tissue biology, general and experimental Medicine, Oncology, Biochemistry & Molecular biology, Neurobiology, Anatomy & Morphology, Pharmacology & Toxicology, Reproductive biology, Veterinary sciences, Physiology, Endocrinology, Tissue engineering & Biomaterials, as well as in multidisciplinary journals.It is easy to foresee that also in the future the histochemical journals will be an attended forum for basic and applied scientists in the biomedical field. It will be crucial that these journals be open to an audience as varied as possible, publishing articles on the application of refined techniques to very different experimental models: this will stimulate non-histochemist scientists to approach histochemistry whose application horizon could expand to novel and possibly exclusive subjects.


Antitumor effect of cell therapy with mesenchymal stem cells on murine melanoma B16-F10.
In this study, the antitumor and immunomodulatory effects of mesenchymal stem cells (MSC) obtained from bone marrow in the treatment of dorsal melanoma B16-F10. The MSC cells were obtained from the bone marrow of isogenic C57BL/6J mice, characterized and inoculated by two routes, intratumor (it) and intravenous (iv). The hematological profile, expression markers and receptors, phases of the cell cycle and mitochondrial electrical potential were evaluated by flow cytometry. The dorsal tumor mass showed a significant reduction after treatment by the two routes of administration with a significant effect by the intravenous route. MSC showed immunomodulatory potential and did not induce an increase in the markers involved in tumor control and progression. The number of cells in the sub-G1 phase increased significantly after treatments compared to the control group. The percentage of cells in phases G0/G1, S and G2/M decreased, with only the group (it) showing a significant reduction. The intratumor group showed a significant decrease in the G2/M phase. Treatment with MSC provided a significant decrease in the percentage of metabolically active tumor cells, demonstrating its intrinsic effect in the control of cell proliferation. Regarding the mechanism of cell death, MSCs modulated the expression of proteins involved in the regulation of the cell cycle, angiogenesis receptors and pro-apoptotic proteins by intrinsic and extrinsic routes. Therefore, the use of undifferentiated MSC, administered intratumor and intravenous is possibly a promising treatment for melanoma.


Measuring efficacy and safety of different inhaled corticosteroid preparations.
Inhaled corticosteroids are the mainstay of treatment for persistent asthma because of their proven efficacy, which is better than any other class of antiasthma therapy. Concerns about unwanted systemic effects with long-term use has, however, limited their use. Efforts have been made to develop inhaled corticosteroids with less systemic activity for a given clinical effect, thereby improving their therapeutic index. Many different study designs and outcome variables have been used to compare different inhaled corticosteroids. Differences in pharmacologic properties between drugs are most easily and accurately measured and quantified by measures of systemic effects. However, these differences should always be related to differences in clinical effects. It is difficult to draw firm conclusions with respect to the therapeutic index of different inhaled corticosteroids because no direct placebo-controlled, dose-response comparisons of clinical effects have been made. Despite this caveat, the available studies suggest that microgram for microgram, when delivered by a pressurized metered-dose inhaler (pMDI), fluticasone propionate (FP) is more effective than beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), or budesonide; however, the efficacy of budesonide delivered by Turbuhaler is equipotent to that of FP delivered by pMDI or Diskhaler and more effective than that of BDP. When comparative safety is considered, budesonide or TAA delivered by pMDI have less systemic activity than FP delivered by pMDI, whereas BDP and FP delivered by pMDI appear to be equivalent. Also, budesonide delivered by Turbuhaler has less systemic activity than FP delivered by Diskhaler.


Guillain-Barré syndrome: a prospective, population-based incidence and outcome survey.
The authors evaluated the incidence and long-term prognostic factors of Guillain-Barré syndrome (GBS) in a prospective, population-based study. Patients with GBS diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke criteria in the 2-year period 1995 to 1996 in two Italian regions were prospectively followed up for 2 years after onset of GBS. A total of 120 patients were found, corresponding to a crude annual incidence rate of 1.36/100,000 population (95% CI, 1.13 to 1.63). A total of 7 (5.8%) patients, all but one with axonal or mixed EMG pattern, died acutely within 30 days from the onset of the disease. Acute mortality was due to respiratory involvement and intensive care unit complications. In multivariate analysis, a worse 2-year outcome (Hughes score >or=2) was related to a higher Hughes grade at nadir, axonal or mixed EMG, age >or=50 years, and absence of respiratory infections preceding GBS. The persistence of disability 2 years after the acute phase was related to axonal involvement and a worse status at nadir. After adjustment to US population, the incidence rates for GBS from different countries showed no significant differences. Both acute mortality and long-term disability in GBS seem to be related to an axonal involvement and a Hughes grade >or=2 at nadir.


Paradoxical Role of High Mobility Group Box 1 in Glioma: A Suppressor or a Promoter?
Gliomas represent 60% of primary intracranial brain tumors and 80% of all malignant types, with highest morbidity and mortality worldwide. Although glioma has been extensively studied, the molecular mechanisms underlying its pathology remain poorly understood. Clarification of the molecular mechanisms involved in their development and/or treatment resistance is highly required. High mobility group box 1 protein (HMGB1) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, through receptor for advanced glycation end products and toll like receptors in a number of cancers including gliomas. It is known that excessive release of HMGB1 in cancer leads to unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. In this review we explore the mechanisms by which HMGB1 regulates apoptosis and autophagy in glioma. We also looked at how HMGB1 mediates glioma regression and promotes angiogenesis as well as possible signaling pathways with an attempt to provide potential therapeutic targets for the treatment of glioma.


Control of repetitive lip and finger movements in Parkinson's disease: influence of external timing signals and simultaneous execution on motor performance.
This study addresses the question of whether external timing signals and/or simultaneous rhythmic movements of other limbs can alleviate sequencing motor deficits associated with Parkinson's disease (PD). Subjects performed rhythmic lip and finger movements simultaneously or in isolation. In addition, they had to self-pace their movements or match them to an external signal. Our results are summarized as follows: (1) Seven of 12 patients had adequate mean repetition rates; that is, they fulfilled the task requirements on a global scale. The remaining five patients had various degrees of hastened responses and were not fully able to synchronize their movements to an external pacing signal. (b) PD patients exhibited hypometria in their finger tapping, but not in their lip movements. Their movements were not abnormally slowed, but peak velocity was appropriately scaled, even to reduced movement amplitudes. (c) Mean repetition rates, stability of frequency response, and kinematics did not differ between conditions of external and internal stimulation within the PD group, but were different form the control group performance. (d) Kinematic measures were not improved during dual-task execution. PD patients were not able to maintain a 1:1 rhythm between effectors. The incidence of hastening increased during simultaneous motor execution. We conclude that the use of external pacing signals might aid movement initiation of PD patients, but does not improve their temporal or spatial coordination when generating repetitive movements. Simultaneous execution does not necessarily enhance motor performance, but might actually have detrimental effects in patients prone to hastening.


A self-consistent model to link surface electronic band structure to the voltage dependence of hot electron induced molecular nanoprobe experiments.
Understanding the ultra-fast transport properties of hot charge carriers is of significant importance both fundamentally and technically in applications like solar cells and transistors. However, direct measurement of charge transport at the relevant nanometre length scales is challenging with only a few experimental methods demonstrated to date. Here we report on molecular nanoprobe experiments on the Si(111)-7 × 7 at room temperature where charge injected from the tip of a scanning tunnelling microscope (STM) travels laterally across a surface and induces single adsorbate toluene molecules to react over length scales of tens of nanometres. A simple model is developed for the fraction of the tunnelling current captured into each of the surface electronic bands with input from only high-resolution scanning tunnelling spectroscopy (STS) of the clean Si(111)-7 × 7 surface. This model is quantitatively linked to the voltage dependence of the molecular nanoprobe experiments through a single manipulation probability (i.e. fitting parameter) per state. This model fits the measured data and gives explanation to the measured voltage onsets, exponential increase in the measured manipulation probabilities and plateau at higher voltages. It also confirms an ultrafast relaxation to the bottom of a surface band for the injected charge after injection, but before the nonlocal spread across the surface.


Urease-positive bacteria in the stomach induce a false-positive reaction in a urea breath test for diagnosis of Helicobacter pylori infection.
This study investigated the influence of urease-positive non-Helicobacter pylori bacteria on the results of a urea breath test (UBT) to evaluate the diagnostic utility of a UBT using film-coated [(13)C]urea tablets. The UBT was performed in 102 patients treated with a proton pump inhibitor and antibiotics for the eradication of H. pylori. Urease-producing bacteria other than H. pylori were isolated and identified from the oral cavity and stomach. In 4/102 patients, the UBT gave false-positive results. These false-positive results were found to be caused by the presence of urease-positive bacteria in the oral cavity and stomach. Five bacterial species with urease activity (Proteus mirabilis, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae and Staphylococcus aureus) were subsequently isolated from the oral cavity and/or stomach. As there was no correlation between the in vitro urease activity of urease-positive non-H. pylori bacteria and the UBT value, and all of the patients with a false-positive UBT result were suffering from atrophic gastritis, it is possible that the false-positive results in the UBT were a result of colonization of urease-positive bacteria and gastric hypochlorhydric conditions. Thus, for the diagnosis of H. pylori infection using a UBT, the influence of stomach bacteria must be considered when interpreting the results.


Visualizing phosphatidylcholine via mass spectrometry imaging: relevance to human health.
Mass spectrometry imaging (MSI) techniques are nowadays widely used to obtain spatially resolved metabolite information from biological tissues. Since (phospho)lipids occur in all animal tissues and are very sensitively detectable, they are often in the focus of such studies. This particularly applies for phosphatidylcholines (PC) which are very sensitively detectable as positive ions due to the permanent positive charge of their choline headgroup. Areas covered: After a short introduction of lipid species occurring in biological systems and approaches normally used to obtain spatially resolved mass spectra (with the focus on matrix-assisted laser desorption/ionization coupled to time-of-flight (MALDI-TOF) MSI) a survey will be given which diseases have so far been characterized by changes of the PC composition. Expert commentary: Since PC species are very sensitively detectable by MS, sensitivity is not a major issue. However, spatial resolution is still limited and cellular dimensions can be hardly resolved by MALDI-TOF MSI, which is a critical point of the available approaches. Due to lacks of reproducibility and standardization further development is required.


Flexible Seaweed-Like Triboelectric Nanogenerator as a Wave Energy Harvester Powering Marine Internet of Things.
The marine internet of things (MIoT), an increasingly important foundation for ocean development and protection, consists of a variety of marine distributed sensors under water. These sensors of the MIoT have always been highly dependent on batteries. To realize in situ power supply, a flexible seaweed-like triboelectric nanogenerator (S-TENG) capable of harvesting wave energy is proposed in this study. The flexible structure, designed with inspiration from the seaweed structure, processes extensive marine application scenarios. The bending and recovering of the S-TENG structure under wave excitations are converted to electricity. As the output performance increases with the number of parallel connected S-TENG units, an S-TENG system with multiple units could serve for floating buoys, coastal power stations, and even submerged devices. Through the demonstration experiments performed in this study, the flexible, low-cost S-TENG could become an effective approach to achieve a battery independent MIoT.


Current dangers and problems in the topical use of steroids.
The hazards of the topical use of steroids, especially the fluorinated steroids, are reviewed. Attention is drawn, especially to the site of application, the face and flexures. The masking of bacterial and fungal infection by topical corticosteroid preparations is mentioned, as are the possible dangers of using them in skin malignancy. The query is raised as to the value of topical use of antibiotics.


Pharmacological strategies for targeting platelet activation in asthma.
The activation of platelets during host defence and inflammatory disorders has become increasingly documented. Clinical studies of patients with asthma reveal heightened platelet activation and accumulation into lung tissue. Accompanying studies in animal models of allergic lung inflammation, using protocols of experimentally induced thrombocytopenia proclaim an important role for platelets during the leukocyte recruitment cascade, tissue integrity, and lung function. The functions of platelets during these inflammatory events are clearly distinct to platelet functions during haemostasis and clot formation, and have led to the concept that a dichotomy (or polytomy, depending on what else platelets do) in platelet activation exists. The platelet, therefore, presents us with novel opportunities for modulating these inflammatory responses. This review discusses the rationale and effectiveness of current anti-platelet drugs in their use to supress inflammation with regard to asthma, and the need to consider novel possibilities for pharmacological modulation of platelet function associated with inflammation that are pharmacologically distinct to current anti-platelet therapies.


Organic matter composition in the sediment of three Brazilian coastal lagoons: district of Macaé, Rio de Janeiro (Brazil).
Freshwater lagoons comprise important coastal ecosystems and natural buffers between urbanized land areas and open ocean in the Rio de Janeiro State, Brazil. Studies of sediment and water chemistry, zooplankton and bacterial communities to assess the extent of anthropogenic disturbance are available. Here we contribute with an organic-geochemical approach supplemented by some microbiological aspects to complete the characterization of these lagoonal ecosystems. Bulk organic matter and extractable lipids (aliphatic hydrocarbons, alcohols and fatty acids, sterols) were investigated from two locations per lagoon: at the seaward site and landward ends - and at two depth intervals (0-3 and 3-6 cm) per site. Urbanized Imboacica Lagoon received increased anthropogenic input over the most recent years represented by the topmost 3 cm of sediment, whereas deeper sediment layers are less affected by human influence. Eutrophication or nutrient availability favored enhanced algal/cyanobacterial growth. In remote Cabiúnas and Comprida Lagoons pristine conditions are preserved. Organic matter from vascular plants dominates (chain length of free lipids up to C36), which is exceptionally well preserved by acidic lagoonal waters. Differentiation between landward and seaward sites in these two lagoons is less well established due to much smaller surface/volume to catchment ratios. No anthropogenic influences are yet detectable in sediments of Cabiúnas and Comprida Lagoons.


The effects of KT3-671, a new angiotensin II (AT 1) receptor blocker in mild to moderate hypertension.
To compare the antihypertensive effect, and tolerability and safety of once daily doses of KT3-671 with that of placebo in patients with mild to moderate uncomplicated essential hypertension. A randomised, multicentre, double blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single blind, run-in phase. Patients eligible for the double-blind phase were randomised to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The primary end-point was trough mean sitting office DBP. The study had 90% power to detect a 5 mmHg change between treatments and placebo at the 5% level of significance. The secondary end-points were 24 hour, daytime and night time mean ABPM. Office DBP was significantly lower with KT3-671 40 mg but not the other 2 dosage groups (-3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80 mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with treatment related adverse events were comparable to placebo (38.8% KT3-671 vs 32.8% placebo). There was some evidence of a dose-response relationship with fall in nocturnal ABPM. Oral KT3-671 was well tolerated. KT3-671 reduced office systolic BP at all doses and diastolic BP at some of the doses. Due to greater precision and power, the falls in mean ambulatory systolic and diastolic pressure were all significantly lower than placebo.


Two-stent techniques for coronary bifurcation lesions (main vessel first versus side branch first): results from the COBIS (COronary BIfurcation Stenting) II registry.
It has not been known which two-stent technique is best for treating bifurcation lesions. We aimed to compare the outcomes from main vessel (MV) first and side branch (SB) first techniques for patients with bifurcation lesions requiring a two-stent approach. A total of 673 patients with bifurcation lesions were treated with two-stent techniques: MV first (n=250) or SB first (n=423). The rate of a composite of cardiac death, myocardial infarction, or target lesion revascularisation (TLR) was similar in the two groups (SB first versus MV first, 15.1% versus 15.6% in the total population [p=0.90]; 14.3% versus 17.4% in a propensity score-matched population [p=0.80]). There were significant interactions associated with TLR risk between MV and SB first techniques according to angiographic factors. Patients in the MV first group had a lower risk of TLR when they had a lesion with MV diameter stenosis ≥70% (p for interaction=0.04), more severe stenosis of the MV than of the SB (p for interaction=0.008), or MV lesion length ≥18 mm (p for interaction=0.01). Clinical outcomes were similar for patients treated with MV or SB first two-stent techniques. Using "more severe lesion first" two-stent techniques might offer a favourable prognosis.


Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma.
Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours. Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols. Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively. The 3-year overall survival (OS) rate for patients with an activated PI3K/Akt signalling pathway was significantly higher than that for those with inactive pathway (91 vs 40%, hazard ratio 0.24 (95% confidence interval (CI) 0.10-0.56), P=0.0010). Similarly, the OS was significantly higher in patients with the activated RTK/Ras signalling pathway than in those with the inactive pathway (91 vs 53%, hazard ratio 0.35 (95% CI 0.13-0.94), P=0.0373). Multivariable analysis revealed that activation of the PI3K/Akt and RTK/Ras signalling pathways was an independent prognostic factor for patients with OCCC. The PI3K/Akt and RTK/Ras signalling pathways may be potential prognostic biomarkers for OCCC patients. Furthermore, our whole-genome sequencing data highlight important pathways for molecular and biological characterisations and potential therapeutic targeting in OCCC.


Impact of biopersistent fibrous dusts on glycolysis, glutaminolysis and serine metabolism in A549 cells.
The conversion rates of different metabolic pathways summarized as a metabolic signature mirror the physiological functions and the general physiological status of a cell. The present study compared the impact of crocidolite and chrysotile asbestos, glass fibers and multi‑walled carbon nanotubes (MWCN) of two different lengths (1‑2 µm and 5‑15 µm) on the conversion rates in glycolysis, glutaminolysis and serine metabolism of A549 cells. The concentration tested was 1 µg/cm2 for all fibers. A concentration of 5 µg/cm2 was additionally used for chrysotile and crocidolite, and 25 µg/cm2 for glass fibers and MWCN. With respect to the inhibitory effect on cell proliferation and the extent of metabolic alterations, the present study revealed the following ranking among the fibers tested: Chrysotile>crocidolite>glass fibers>MWCN 5‑15 µm>MWCN 1‑2 µm. For the asbestos and glass fibers this ranking correlated best with the number of fibers. It appeared that the results observed for MWCN did not match this correlation. However, electron microscopy revealed an agglomeration of MWCN. The agglomeration decreased the toxicologically relevant number of fibers by forming larger particle‑like shapes and explained the smaller effects of MWCN 5‑15 µm and 1‑2 µm on cell proliferation and metabolism.


Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta.
Radiation exposure is associated with the development of various cardiovascular diseases. Although irradiation is known to cause elevated oxidant stress and chronic inflammation, both of which are detrimental to vascular function, the molecular mechanisms remain incompletely understood. We previously demonstrated that radiation causes endothelial dysfunction and increased vascular stiffness by xanthine oxidase (XO) activation. In this study, we investigated whether dietary inhibition of XO protects against radiation-induced vascular injury. We exposed 4-mo-old rats to a single dose of 0 or 5 Gy gamma radiation. These rats received normal drinking water or water containing 1 mM oxypurinol, an XO inhibitor. We measured XO activity and superoxide production in rat aorta and demonstrated that both were significantly elevated 2 wk after radiation exposure. However, oxypurinol treatment in irradiated rats prevented aortic XO activation and superoxide elevation. We next investigated endothelial function through fluorescent measurement of nitric oxide (NO) and vascular tension dose responses. Radiation reduced endothelium-dependent NO production in rat aorta. Similarly, endothelium-dependent vasorelaxation in the aorta of irradiated rats was significantly attenuated compared with the control group. Dietary XO inhibition maintained NO production at control levels and prevented the development of endothelial dysfunction. Furthermore, pulse wave velocity, a measure of vascular stiffness, increased by 1 day postirradiation and remained elevated 2 wk after irradiation, despite unchanged blood pressures. In oxypurinol-treated rats, pulse wave velocities remained unchanged from baseline throughout the experiment, signifying preserved vascular health. These findings demonstrate that XO inhibition can offer protection from radiation-induced endothelial dysfunction and cardiovascular complications.


Adenosine production inside rat polymorphonuclear leucocytes.
Adenosine synthesis was studied during 2-deoxyglucose-induced ATP catabolism in intact rat polymorphonuclear leucocytes. When both adenosine kinase (EC 220.127.116.11) and adenosine deaminase (EC 184.108.40.206) were selectively inhibited, adenosine accumulated. Adenosine formation took place inside the intact cells by a metabolic pathway independent of the ecto-5'-nucleotidase (EC 126.96.36.199). Distinct metabolic pathways are proposed for adenosine production from intracellular or extracellular nucleotides.


Efficient proximal gradient algorithm for inference of differential gene networks.
Gene networks in living cells can change depending on various conditions such as caused by different environments, tissue types, disease states, and development stages. Identifying the differential changes in gene networks is very important to understand molecular basis of various biological process. While existing algorithms can be used to infer two gene networks separately from gene expression data under two different conditions, and then to identify network changes, such an approach does not exploit the similarity between two gene networks, and it is thus suboptimal. A desirable approach would be clearly to infer two gene networks jointly, which can yield improved estimates of network changes. In this paper, we developed a proximal gradient algorithm for differential network (ProGAdNet) inference, that jointly infers two gene networks under different conditions and then identifies changes in the network structure. Computer simulations demonstrated that our ProGAdNet outperformed existing algorithms in terms of inference accuracy, and was much faster than a similar approach for joint inference of gene networks. Gene expression data of breast tumors and normal tissues in the TCGA database were analyzed with our ProGAdNet, and revealed that 268 genes were involved in the changed network edges. Gene set enrichment analysis identified a significant number of gene sets related to breast cancer or other types of cancer that are enriched in this set of 268 genes. Network analysis of the kidney cancer data in the TCGA database with ProGAdNet also identified a set of genes involved in network changes, and the majority of the top genes identified have been reported in the literature to be implicated in kidney cancer. These results corroborated that the gene sets identified by ProGAdNet were very informative about the cancer disease status. A software package implementing the ProGAdNet, computer simulations, and real data analysis is available as Additional file 1. With its superior performance over existing algorithms, ProGAdNet provides a valuable tool for finding changes in gene networks, which may aid the discovery of gene-gene interactions changed under different conditions.


Autonomously shaping natural climbing plants: a bio-hybrid approach.
Plant growth is a self-organized process incorporating distributed sensing, internal communication and morphology dynamics. We develop a distributed mechatronic system that autonomously interacts with natural climbing plants, steering their behaviours to grow user-defined shapes and patterns. Investigating this bio-hybrid system paves the way towards the development of living adaptive structures and grown building components. In this new application domain, challenges include sensing, actuation and the combination of engineering methods and natural plants in the experimental set-up. By triggering behavioural responses in the plants through light spectra stimuli, we use static mechatronic nodes to grow climbing plants in a user-defined pattern at a two-dimensional plane. The experiments show successful growth over periods up to eight weeks. Results of the stimuli-guided experiments are substantially different from the control experiments. Key limitations are the number of repetitions performed and the scale of the systems tested. Recommended future research would investigate the use of similar bio-hybrids to connect construction elements and grow shapes of larger size.


Targeting the cell cycle inhibitor p57Kip2 promotes adult human β cell replication.
Children with focal hyperinsulinism of infancy display a dramatic, non-neoplastic clonal expansion of β cells that have undergone mitotic recombination, resulting in paternal disomy of part of chromosome 11. This disomic region contains imprinted genes, including the gene encoding the cell cycle inhibitor p57Kip2 (CDKN1C), which is silenced as a consequence of the recombination event. We hypothesized that targeting p57Kip2 could stimulate adult human β cell replication. Indeed, when we suppressed CDKN1C expression in human islets obtained from deceased adult organ donors and transplanted them into hyperglycemic, immunodeficient mice, β cell replication increased more than 3-fold. The newly replicated cells retained properties of mature β cells, including the expression of β cell markers such as insulin, PDX1, and NKX6.1. Importantly, these newly replicated cells demonstrated normal glucose-induced calcium influx, further indicating β cell functionality. These findings provide a molecular explanation for the massive β cell replication that occurs in children with focal hyperinsulinism. These data also provided evidence that β cells from older humans, in which baseline replication is negligible, can be coaxed to re-enter and complete the cell cycle while maintaining mature β cell properties. Thus, controlled manipulation of this pathway holds promise for the expansion of β cells in patients with type 2 diabetes.


[Biological models of IgE-dependent bronchial asthma: methodology and prospects for application].
The present work was aimed to review modern approaches to simulation of bronchial asthma using laboratory animals. Various modes of immunization and challenge for the induction of typical pathological features in mice are described along with the methods for detection of these markers (including ones for studying murine lung function). Advantages and drawbacks of the models, difficulties and prospects of their application for the study of pathogenesis and preliminary estimation of the safety and efficacy of antiasthmatic therapy (especially antigen-specific immunotherapy) are analyzed. Moreover, the paper presents concise characteristic of short-term adjuvant-free murine models of timothy pollen extract- and ovalbumin-induced bronchial asthma developed in this country.


The structures of alpha 2u-globulin and its complex with a hyaline droplet inducer.
Alpha 2u-globulin (A2U) is the major urinary protein excreted by adult male rats. The structure of a monoclinic crystal form of A2U was reported in 1992 [Böcskei et al. (1992). Nature (London), 360, 186-188]. The structures of an orthorhombic crystal form of A2U at 2. 5 A resolution (refined to an R factor of 0.248; Rfree = 0.264) and of a complex between A2U and d-limonene 1,2-epoxide (DLO) at 2.9 A resolution (R factor = 0.248; Rfree = 0.260) are presented here. DLO is one of a diverse group of chemicals which cause a male rat-specific renal carcinogenesis called hyaline-droplet nephropathy. The rate-determining step in the development of this disorder is the binding of the toxin to A2U. Comparison of the cavities in A2U and in the corresponding mouse urinary protein (MUP) reveal that the former is tailor-made for small oval hydrophobic ligands such as DLO. The cavity in MUP is more shallow and elongated and cannot easily accommodate such ligands.


[Chronic inflammatory demyelinating neuropathies and their variants]
The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.


Fabrication of arrayed metallic nano-particles on a flexible substrate for inducing localized surface plasmon resonance.
This paper presents a new method for fabricating periodic arrays of metallic nano-particles on flexible substrates. This method is based on metallic film contact transfer method and high-power pulsed laser annealing. Experiments have been carried out to produce arrayed metallic nano-particles oriented in a hexagonal pattern. The nano-particle size is 70 nm in diameter and the center-to-center pitch of the hexagonal array is 400 nm. Large-area patterning and fabrication of these arrayed nano-particles can be easily achieved up to an area size of few cm(2). Besides, composite or compounded metallic nano-particle arrays can also be produced using different metal materials. The localized surface plasmon resonance (LSPR) effects induced by the fabricated arrays of nano-particles are experimentally observed and quantitatively measured. Numerical simulation on these LPSR effects is performed and the simulation results are in good agreement with experimental data.


A case-comparison study of executive functions in alcohol-dependent adults with maternal history of alcoholism.
As executive dysfunctions frequently accompany alcohol dependence, we suggest that reports of executive dysfunction in alcoholics are actually due, in some case to a maternal history of alcohol misuse (MHA+). A history of maternal alcohol dependence increases the risk for prenatal alcohol exposure to unborn children. These exposures likely contribute to executive dysfunction in adult alcoholics. To assess this problem, we propose a case-comparison study of alcohol-dependent subjects with and without a MHA. Ten alcohol-dependent subjects, with a maternal history of alcoholism (MHA) and paternal history of alcoholism (PHA), were matched with 10 alcohol-dependent people with only a paternal history of alcoholism (PHA). Executive functions (cancellation, Stroop, and trail-making A and B tests) and the presence of a history of three mental disorders (attention deficit hyperactivity disorder, violent behavior while intoxicated, and suicidal behavior) were evaluated in both populations. Alcohol-dependent subjects with MHA showed a significant alteration in executive functions and significantly more disorders related to these functions than PHA subjects. The major measures of executive functioning deficit are duration on task accomplishment in all tests. Rates of ADHD and suicidality were found to be higher in MHA patients compared to the controls. A history of MHA, because of the high risk of PAE (in spite of the potential confounding factors such as environment) must be scrupulously documented when evaluating mental and cognitive disorders in a general population of alcoholics to ensure a better identification of these disorders. It would be helpful to replicate the study with more subjects.


Long non-coding RNA H19 protects acute myocardial infarction through activating autophagy in mice.
We investigate the effect of long non-coding RNA H19 in acute myocardial infarction (AMI) and the underlying mechanism. C57BL/6 mice were subjected to AMI and injected with lentivirus pcDNA-H19. After AMI procedures for 3 weeks, cardiac function was detected by echocardiography. The infarct size was stained by triphenyltetrazolium chloride. H19 expression in mice was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Protein expressions of LC3, Beclin-1, and ATG-7 in mice were measured by Western blot. Our results indicated that H19 expression was significantly downregulated in the infarcted myocardium. Overexpression of H19 after injection with pcDNA-H19 in mice could reduce infarct size and improve cardiac function through upregulating the ratio of LC3-II/I and expressions of Beclin-1 and ATG-7. Overexpression of H19 could protect AMI in mice via activating autophagy.


Late-Onset Mirror Syndrome.
Mirror syndrome is a rare clinical condition in pregnancy associated with significant fetal mortality and maternal morbidity. It is characterized by a triad of complications: fetal hydrops, placenta oedema, and maternal oedema. We are reporting one case of late-onset Mirror syndrome in which the patient presented later in the gestation of 36 weeks due to excessive weight gain and clinical sign mimicking preeclampsia. Awareness of this disease is essential, as a failure of recognition will delay the treatment and cause higher maternal and perinatal morbidity and mortality.


Metal ions affecting the kidney.
This chapter provides a succinct summary of the nephrotoxic effects of a number of metals/metalloids on an individual or mixture basis. There is a discussion of routes of exposure, mechanisms of uptake by renal cells and the potential impact of nanomaterials on these processes. An emphasis is placed on the toxicity of these metals/ metalloids to individual cell types in the kidney and the application of biomarkers for the early detection of kidney cell injury prior to the onset of an overt clinical state such as end-stage renal disease. The issue of interactions between nephrotoxic metals in mixture exposures is discussed in relation to the application of molecular biomarkers for early detection of renal cell injury.


Dementia and Nutrition. Intervention study in institutionalized patients with Alzheimer disease.
To know nutritional status of a group of institutionalized patients with moderate Alzheimer's Disease (AD), and to ascertain the effects of an intervention with nutritional supplements on morbidity and mortality after one year follow-up. 99 patients (mean age: 86.5 years), 80 women, with a diagnosis of AD according with NINCDS/ADRDA criteria, were recruited from 8 nursing-homes. 25 were included in an intervention group and received a nutritional supplements along 12 months. Evolution was evaluated according to the Functional Assessment Staging Test (FAST). Patients with FAST levels 5-6 were included. General clinical variables as well as variables reflecting cognitive state and nutritional status: anthropometric, biochemical data and Mini Nutritional Assessment (MNA) were analysed. Statistical analysis was carry out with the SPSS 10.0 package. Mean time since diagnosis was 49 months, with a 20.2 months duration of institutionalization. Mean value of MNA was 20.1 3.5. 16.5% of patients had a BMI equal o lower than 21. After one year the intervention group showed higher levels of albumin (P=05), pre-albumin (P=05), iron (P=01), zinc (P=05), and beta-carotene (P=05) than the control group. The same response in BMI (P=05), MNA (P=05), and triceps skinfold (P=01). Mortality was lower (16% vs. 22.7%), without statistical significance, in the intervention group, as it was the number of infectious events (47% vs. 66% P=05), and the days in bed (7.5 2.1 vs. 17.3 5.6 P=05). Nutritional supplements applied to a group of patients with AD living in nursing-homes can reduce morbidity and mortality after one year follow-up.


A binary wavelet decomposition of binary images.
We construct a theory of binary wavelet decompositions of finite binary images. The new binary wavelet transform uses simple module-2 operations. It shares many of the important characteristics of the real wavelet transform. In particular, it yields an output similar to the thresholded output of a real wavelet transform operating on the underlying binary image. We begin by introducing a new binary field transform to use as an alternative to the discrete Fourier transform over GF(2). The corresponding concept of sequence spectra over GF(2) is defined. Using this transform, a theory of binary wavelets is developed in terms of two-band perfect reconstruction filter banks in GF(2). By generalizing the corresponding real field constraints of bandwidth, vanishing moments, and spectral content in the filters, we construct a perfect reconstruction wavelet decomposition. We also demonstrate the potential use of the binary wavelet decomposition in lossless image coding.


Lower eyelid fornix deepening: A new indication for the facial artery myomucosal flap.
Eye socket contracture is a well-known late complication of enucleation surgery, and the additional insult of radiotherapy at an early age causes even further fibrosis and scarring of the socket. Management of the contracted socket is challenging, and several methods have been proposed. We report a case of eye socket contracture after enucleation and radiotherapy in which multiple reconstructive procedures failed. The recurrent contracture caused difficulty in housing and retaining the eye prosthesis. We reconstructed the lower eyelid with a facial artery myomucosal flap and nasolabial flap, and the upper eyelid with a Fricke flap following reconstruction of the orbital rims (supraorbital and infraorbital rims with a calvarial bone graft, and further augmentation of the infraorbital rim with a rib bone graft). Cosmesis post-reconstruction was acceptable and the prosthesis was retained very well.


Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format.
Ribonucleotide reductase (RNR) catalyzes reduction of the four different ribonucleotides to their corresponding deoxyribonucleotides and is the rate-limiting enzyme in DNA synthesis. RNR is a well-established target for the antiproliferative drugs Gemzar and Hydrea, for antisense therapy, and in combination chemotherapies. Surprisingly, few novel drugs that target RNR have emerged, partly because RNR activity assays are laboratory-intense and exclude high-throughput methodologies. Here, we present a previously undescribed PCR-based assay for RNR activity measurements in microplate format. We validated the approach by screening a diverse library of 1,364 compounds for inhibitors of class I RNR from the opportunistic pathogen Pseudomonas aeruginosa, and we identified 27 inhibitors with IC(50) values from ∼200 nM to 30 μM. Interestingly, a majority of the identified inhibitors have been found inactive in human cell lines as well as in anticancer and in vivo tumor tests as reported by the PubChem BioAssay database. Four of the RNR inhibitors inhibited growth of P. aeruginosa, and two were also found to affect the transcription of RNR genes and to decrease the cellular deoxyribonucleotide pools. This unique PCR-based assay works with any RNR enzyme and any substrate nucleotide, and thus opens the door to high-throughput screening for RNR inhibitors in drug discovery.


[The role of the short-wave therapy in rehabilitation of elderly patents with chronic obstructive pulmonary disease].
The positive clinical effects of using the short-wave therapy in rehabilitation of patients with chronic obstructive pulmonary disease are presented in this article. 49 patients were included in this investigation. The criteria of successful rehabilitation were more expressive in the cases when the short-wave therapy was included in rehabilitative program.


Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: angiographic and histologic characterization.
To develop a model of verteporfin photodynamic therapy (PDT) for experimental choroidal neovascularization CNV in the rat. A laser injury model was used to induce experimental CNV in rats. The transit and accumulation of the photosensitizer verteporfin was assessed angiographically in CNV lesions, to determine the optimal time for delivery of light energy. The CNV lesions were then treated with verteporfin PDT, with two doses of verteporfin (3.0 and 6.0 mg/m(2)) and four activating doses of light energy (10, 25, 50, and 100 J/cm(2)). Closure of the CNV was assessed both angiographically and histologically. Verteporfin PDT was also performed on areas of normal choroid and retina at the two verteporfin doses and four light energy doses. The effect of these treatments on these structures was also assessed angiographically and histologically. Peak verteporfin intensities in the CNV were detected at 15 to 20 minutes after intravenous injection. Rates of closure of the CNV varied as a function of the dose of verteporfin and of the activating light energy. Angiographic closure of the CNV correlated with damage to the neovascular complex, as seen with light and electron microscopy. Damage to areas of normal choroid and retina treated with verteporfin PDT also varied as a function of the verteporfin and light energy doses. Verteporfin PDT for experimental CNV in the rat is a feasible, effective, and reproducible model that can be used for testing the efficacy of adjunctive therapy to verteporfin PDT.


Dynamic hydrogen bond cross-linking binder with self-healing chemistry enables high-performance silicon anode in lithium-ion batteries.
The structure instability and cycling decay of silicon (Si) anode triggered by stress buildup hinder its practical application to next-generation high-energy-density lithium-ion batteries (LIBs). Herein, a cross-linking polymeric network as a self-healing binder for Si anode is developed by in situ polymerization of tannic acid (TA) and polyacrylic acid (PAA) binder labelled as TA-c-PAA. The branched TA as a physical cross-linker complexes with PAA main chains through abundant dynamic hydrogen bonds, endowing the cross-linking TA-c-PAA binder with unique self-healing property and strong adhesion for Si anode. Benefiting from the mechanical robust and hard adhesion, the Si@TA-c-PAA electrode exhibits high reversible specific capacities (3250 mAh/g at 0.05C (1C = 4000 mA g-1)), excellent rate capability (1599 mAh/g at 2C), and impressive cycling stability (1742 mAh/g at 0.25C after 450 cycles). After Ex situ morphology characterization, in situ swelling analysis, and finite element simulation, it is found that the TA-c-PAA binder allows the Si anode to dissipate stress and prevent pulverization during lithiation and delithiation, thus the hydrogen bonds among interpenetrating network may be adaptable to the stress intensity. Our work paves a new avenue for the design of efficient and cost-effective binders for next-generation Si anode in LIBs.


Molecular and histopathologic predictors of distant failure in endometrial cancer.
A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction > or =9%, proliferative index > or =14%, and DNA index > or =1.5 significantly (P<0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR=43.73; P<0.005), lymphovascular invasion (OR=11.59; P<0.001), and cervical stromal invasion (OR=11.29; P=0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P<0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.


North America Wound, Ostomy, and Continence and Enterostomal Therapy Nurses Current Ostomy Care Practice Related to Peristomal Skin Issues.
The purpose of this study was to describe the practice of 796 ostomy nurses in North America in 2014 related to peristomal skin issues. Descriptive study. Participants were 796 wound, ostomy, and continence (WOC) and enterostomal therapy (ET) nurses currently practicing in the United States or Canada and caring for patients with ostomies. The collection of data occurred in conjunction with an educational program on peristomal skin complications and practice issues and solicited the participant's perception on the incidence and frequency of peristomal skin issues as well as on practice patterns. Participants attended an educational program. They were also asked to anonymously respond to multiple-choice questions on ostomy care management via an audience response system followed by discussion of each item and their responses. This descriptive study reports on the answers to the questions as well as the pertinent discussion points. Participants estimated that approximately 77.70% of their patients developed peristomal skin issues. The most commonly encountered problem was irritant contact dermatitis (peristomal moisture-associated skin damage). Contributing factors were inappropriate use of a pouching system owing to lack of follow-up after hospital discharge. Reported interventions for the prevention and management of peristomal skin issues included preoperative stoma site marking, use of a convex pouching system, and barrier rings. However, subsequent discussion revealed that the frequency of use of these products varied considerably. Participants identified shortened hospital stays, absence of preoperative stoma marking, and limited outpatient follow-up as contributing to development of peristomal skin problems. WOC and ET nurses estimate that more than three-quarters of persons living with an ostomy develop peristomal skin problems. Multiple interventions for managing these problems were identified, but some variability in management approaches emerged.


Consequences of gestational and pregestational diabetes on placental function and birth weight.
Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimental models, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proinflammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.


Comparison of liquid nitrogen-free slow freezing protocols toward enabling a practical option for centralized cryobanking of ovarian tissue.
Geographically distributed ovarian tissue cryobanks remain limited due to the high facility and staff costs, and cold transportation to centers is associated with ischemia-induced tissue damage that increases with transport distance. It is ideal to perform the cryopreservation procedure at a tissue removal site or local hospital before shipment to cost-effective centralized cryobanks. However, conventional liquid nitrogen-based freezers are not portable and require expensive infrastructure. To study the possibility of an ovarian tissue cryopreservation network not dependent on liquid nitrogen, we cryopreserved bovine ovarian tissue using three cooling techniques: a controlled rate freezer using liquid nitrogen, a liquid nitrogen-free controlled rate freezer, and liquid nitrogen-free passive cooling. Upon thawing, we evaluated a panel of viability metrics in frozen and fresh groups to examine the potency of the portable liquid nitrogen-free controlled and uncontrolled rate freezers in preserving the ovarian tissue compared to the non-portable conventional controlled rate freezer. We found similar outcomes for reactive oxygen species (ROS), total antioxidant capacity (TAC), follicular morphology, tissue viability, and fibrosis in the controlled rate freezer groups. However, passive slow cooling was associated with the lowest tissue viability, follicle morphology, and TAC, and the highest tissue fibrosis and ROS levels compared to all other groups. A stronger correlation was found between follicle morphology, ovarian tissue viability, and fibrosis with the TAC/ROS ratio compared to ROS and TAC alone. The current study undergirds the possibility of centralized cryobanks using a controlled rate liquid nitrogen-free freezer to prevent ischemia-induced damage during ovarian tissue shipment.


Development of the organisational health literacy responsiveness (Org-HLR) framework in collaboration with health and social services professionals.
The health literacy skills required by individuals to interact effectively with health services depends on the complexity of those services, and the demands they place on people. Public health and social service organisations have a responsibility to provide services and information in ways that promote equitable access and engagement, that are responsive to diverse needs and preferences, and support people to participate in decisions regarding their health and wellbeing. The aim of this study was to develop a conceptual framework describing the characteristics of health literacy responsive organisations. Concept mapping (CM) workshops with six groups of professionals (total N = 42) from across health and social services sectors were undertaken. An online concept mapping consultation with 153 professionals was also conducted. In these CM activities, participants responded to the seeding statement "Thinking broadly from your experiences of working in the health system, what does an organisation need to have or do in order to enable communities and community members to fully engage with information and services to promote and maintain health and wellbeing". The CM data were analysed using multidimensional scaling and hierarchical cluster analyses to derive concept maps and cluster tree diagrams. Clusters from the CM processes were then integrated by identifying themes and subthemes across tree diagrams. Across the workshops, 373 statements were generated in response to the seeding statement. An additional 1206 statements were generated in the online consultation. 84 clusters were derived within the workshops and 20 from the online consultation. Seven domains of health literacy responsiveness were identified; i) External policy and funding environment; ii) Leadership and culture; iii) Systems, processes and policies; iv) Access to services and programs; v) Community engagement and partnerships; vi) Communication practices and standards; and vii) Workforce. Each domain included 1 to 5 sub-domains (24 sub-domains in total). Using participatory research processes, a conceptual framework describing the characteristics, values, practices and capabilities of organisational health literacy responsiveness was derived. The framework may guide the planning and monitoring of health service and health system improvements, and has the potential to guide effective public health policy and health system reforms.