Nucleation Selectivity and Lateral Coalescence of GaAs over Graphene on Ge(111).
We use epitaxial lateral overgrowth (ELO) to produce semimetallic graphene nanostructures embedded in a semiconducting GaAs matrix for potential applications in plasmonics, THz generation and detection, and tunnel junctions in multijunction solar cells. We show that (1) the combination of low sticking coefficient and fast surface diffusion on graphene enhances nucleation selectivity at exposed regions of the substrate and (2) high growth temperatures favor efficient lateral overgrowth, coalescence, and planarization of epitaxial GaAs films over the graphene nanostructures. Our work provides a more complete understanding of ELO using graphene masks, as opposed to more conventional dielectric masks, and enables new types of metal/semiconductor nanocomposites.


A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator.
The post-transcriptional regulation of gene expression by RNA-binding proteins is an important element in controlling both normal cell functions and animal development. The diverse roles are demonstrated by the Elav family of RNA-binding proteins, where various members have been shown to regulate several processes involving mRNA. We have identified another family of RNA-binding proteins distantly related to the Elav family but closely related to Bruno, a translational regulator in Drosophila melanogaster. In humans, six Bruno-like genes have been identified, whereas other species such as Drosophila, Xenopus laevis, and Caenorhabditis elegans have at least two members of this family, and related genes have also been detected in plants and ascidians. The human BRUNOL2 and BRUNOL3 are 92% identical in the RNA-binding domains, although the BRUNOL2 gene is expressed ubiquitously whereas BRUNOL3 is expressed predominantly in the heart, muscle, and nervous system. Both of these proteins bind the same target RNA, the Bruno response element. The RNA-binding domain that recognizes the Bruno response element is composed of two consecutive RNA recognition motifs at the amino terminus of vertebrate Bruno protein. The possible involvement of the Bruno family of proteins in the CUG repeat expansion disease myotonic dystrophy is discussed.


The xid mutation diminishes memory B cell generation but does not affect somatic hypermutation and selection.
In this study, we examine the relationship between primary and secondary T cell-dependent immune responses using the response of xid mice to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) as an experimental model. The reduced serologic primary immune response of xid mice was demonstrated to be caused by a substantially decreased Ab-forming cell (AFC) generation. Furthermore, the germinal center reaction in the primary xid immune response was diminished and the frequency of NP-specific memory B cells prior to secondary immunization was reduced 10-fold. Despite the poor primary response of xid mice, secondary exposure to Ag generated a response that was qualitatively and quantitatively equal to that of wt mice. The number of IgG1 AFCs in spleen and bone marrow increased equally in both groups, as did the proportion of AFCs secreting high affinity Ab in both locations. The extent and distribution of somatic mutations in the V(H) genes of xid secondary response B cells was also found to be normal, indicating that the xid gene product is not critical for the processes that result in affinity maturation. Thus, although xid mice generate memory B cells of normal phenotype but at a substantially lower frequency, this does not limit the magnitude of the secondary response. Therefore, our results imply that the reduced memory B cell frequency in xid mice is still above some threshold value necessary for a normal secondary immune response.


Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.
To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.


Tenascin interferes with fibronectin action.
Primary chick embryo fibroblasts attach to a tenascin substrate, but remain rounded and do not spread out. The proportion between tenascin and fibronectin in mixtures used to coat the substrate determines the shape of the cells. Tenascin inhibits integrin-mediated chick fibroblast attachment to fibronectin, laminin, and the GRGDS peptide. Rat fibroblast attachment to fibronectin, but not to laminin, is inhibited by tenascin. A monoclonal antibody against tenascin, as well as its Fab fragments, is able to neutralize the inhibitory activity on cell attachment and is therefore assumed to mask the cell-binding site of tenascin. On electron micrographs showing this monoclonal antibody bound to tenascin, its epitope can be localized to the terminal knob at the distal ends of the tenascin arms.


On the mechanism of basal and agonist-induced activation of the G protein-gated muscarinic K+ channel in atrial myocytes of guinea pig heart.
Using the patch clamp technique, we examined the agonist-free, basal interaction between the muscarinic acetylcholine (m-ACh) receptor and the G protein (GK)-gated muscarinic K+ channel (IK.ACh), and the modification of this interaction by ACh binding to the receptor in single atrial myocytes of guinea pig heart. In the whole cell clamp mode, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S) gradually increased the IK.ACh current in the absence of agonists (e.g., acetylcholine). This increase was inhibited in cells that were pretreated with islet-activating protein (IAP, pertussis toxin) or N-ethylmaleimide (NEM). In inside-out patches, even in the absence of agonists, intracellular GTP caused openings of IK.ACh in a concentration-dependent manner in approximately 80% of the patches. Channel activation by GTP in the absence of agonist was much less than that caused by GTP-gamma S. The agonist-independent, GTP-induced activation of IK.ACh was inhibited by the A promoter of IAP (with nicotinamide adenine dinucleotide) or NEM. As the ACh concentration was increased, the GTP-induced maximal open probability of IK.ACh was increased and the GTP concentration for the half-maximal activation of IK.ACh was decreased. Intracellular GDP inhibited the GTP-induced openings of IK.ACh in a concentration-dependent fashion. The half-inhibition of IK.ACh openings occurred at a much lower concentration of GDP in the absence of agonists than in the presence of ACh. From these results, we concluded (a) that the interaction between the m-ACh receptor and GK is essential for basal stimulation of IK.ACh, and (b) that ACh binding to the receptor accelerates the turnover of GK and increases GK's affinity to GTP analogues over GDP.


The Influence of a Juvenile's Abuse History on Support for Sex Offender Registration.
We investigated whether and how a juvenile's history of experiencing sexual abuse affects public perceptions of juvenile sex offenders in a series of 5 studies. When asked about juvenile sex offenders in an abstract manner (Studies 1 and 2), the more participants (community members and undergraduates) believed that a history of being sexually abused as a child causes later sexually abusive behavior, the less likely they were to support sex offender registration for juveniles. Yet when participants considered specific sexual offenses, a juvenile's history of sexual abuse was not considered to be a mitigating factor. This was true when participants considered a severe sexual offense (forced rape; Study 3 and Study 4) and a case involving less severe sexual offenses (i.e., statutory rape), when a juvenile's history of sexual abuse backfired and was used as an aggravating factor, increasing support for registering the offender (Study 3 and Study 5). Theoretical and practical implications of these results are discussed.


[Verrucous carcinoma of the larynx. An analysis of 20 years of experience].
Retrospective study about 10 verrucous carcinomas of the larynx surgically treated in a 20-year-term. This variety accounted por the 1.9 percent of the cancers seen in that period of time. Tabagism and alcoholism predominated in 8 and 6 patients respectively. Glottis was the localization and dysphony the paramount symptom. In the paper are emphasized the most important histologic features. Koilocytosis was present in 6 cases. Four patients developed a second tumor of epidermoid carcinoma type. No one exitus due to the verrucous growth. Only in 3 the death was attributed to the second malignancy.


Early Autonomy May Contribute to an Increase in the General Surgical Workforce.
Nationally, 85% of general surgery graduates pursue fellowships reducing the incoming general surgical workforce with a predicted shortage of 41,000 general surgeons by 2025. In recent studies, the lack of confidence appears to be a major factor contributing to resident decision to pursue fellowship. The aim of the study was to determine if a hybrid academic/community program contributes to early autonomy and the decision to pursue fellowship in general surgery graduates. We evaluated the level of confidence, level of autonomy, and decision to pursue fellowship at a hybrid academic/community program that historically graduates 70% of their residents into general surgery practice through an anonymous survey. Participants responded using Likert scales along with simple polar questions. Most current residents (90%) reported, upon graduation, that they feel very confident (45%) or fairly confident (45%) performing major cases independently. Most attendings (64%) reported that during their third year of residency, they began performing the majority (more than 75%) of their major cases as surgeon junior while current residents (55%) reported they were performing the majority as a second-year resident. Fifty-five percent of residents felt that confidence played a role in the decision to pursue fellowship. Thirty-three percent of our current chief residents and only 34% of the total general surgery residents plan to pursue fellowships. Conclusions: Our study showed that our residents appear to have earlier levels of autonomy than that experienced by our practicing surgeons when they were residents. Confidence continues to play a role in the decision to pursue fellowship and overall our residents are confident in technical skills at graduation. Our unique program continues to graduate the majority of our surgical residents into successful general surgery practice.


Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary.
Somatomedin-C stimulates somatostatin release to a maximum of 390 percent of basal release during short-term (20-minute) incubation of rat hypothalamus. It has no effect on basal or stimulated growth hormone release from primary cultures of rat adenohypophyseal cells during a 4-hour incubation, but inhibits stimulated release by more that 90 percent after 24 hours. These findings suggest that somatomedin-C participates in the growth hormone negative feedback loop with an immediate effect on hypothalamic somatostatin and a delayed effect on the anterior pituitary.


Glycosyl-phosphatidylinositol anchor attachment in a yeast in vitro system.
The yeast mating pheromone precursor prepro-alpha factor was fused to C-terminal signals for glycosyl-phosphatidylinositol (GPI) anchor attachment, based on the sequence of the Saccharomyces cerevisiae protein Gas1p. Maturation of fusion proteins expressed in vivo required the presence of both a functional GPI attachment site and the synthesis of GPI precursors. Constructs were translated in vitro for use in cell-free studies of glycolipid attachment. The radiolabelled polypeptides were post-translationally translocated into yeast microsomes, where at least one third of the molecules received a GPI anchor. This approach offers distinct advantages over anchor attachment reactions that require co-translational translocation of secretory peptide substrates.


Emerging Clinical Benefits of New-Generation Fat Emulsions in Preterm Neonates.
Soybean oil-based intravenous fat emulsions (IVFEs) have been the predominant parenteral nutrition IVFE used in the United States for neonates over the past 45 years. Even though this emulsion has proven useful in supplying infants with energy for growth and essential fatty acids, there have been concerns over its composition in the development of several morbidities, ranging from sepsis to liver disease, bronchopulmonary dysplasia, and impaired neurodevelopment and growth. The exact mechanisms that drive these morbidities in preterm infants are multifactorial, but potential contributors include high ω-6 (n-6) fatty acid composition, low docosahexaenoic acid and antioxidant supplementation, and the presence of potentially harmful nonnutritive components (eg, phytosterols). To address these issues, new-generation IVFEs with various types and amounts of fat have been developed containing greater amounts of the medium-chain fatty acids, long-chain polyunsaturated fatty acid, docosahexaenoic acid, lower concentrations of ω-6 polyunsaturated fatty acids, supplemental vitamin E, and low or negligible amounts of phytosterols. This review examines the clinical outcomes associated with different morbidities of parenteral nutrition in neonates who have received either soybean oil-based or new-generation IVFEs and addresses whether the proposed benefits of new-generation IVFEs have improved outcomes in the neonatal population.


Topical lidocaine enhanced by laser pretreatment: a safe and effective method of analgesia for facial rejuvenation.
Injectable forms of anesthesia for nonsurgical facial rejuvenation, although efficacious, are uncomfortable for the patient. Preclinical studies have demonstrated that laser pretreatment at low energies enhances absorption of topical lidocaine. The authors assess the safety and efficacy of laser-assisted transdermal delivery of topical anesthetic. Ten patients were split into 2 groups (A and B). All patients received 15 g of BLT (20% benzocaine, 6% lidocaine, and 4% tetracaine triple anesthetic cream) for 20 minutes with no occlusion. Then the cream was removed and the first blood draw taken. Group A patients were pretreated with the full ablative laser and group B patients with a fractional ablative laser to the full face. A further 15 g BLT was applied for another 20 minutes. Group A patients then underwent full ablative laser treatment, and group B received fractionated ablative laser treatment. Blood draws were taken at 60, 90, 120, 180, and 240 minutes after the initial topical anesthetic application, and the serum was analyzed for lidocaine and monoethylglycinexylidide (MEGX) levels. Patients were asked to rate the pain felt at intervals during the procedure. No patient required supplemental nerve blocks. Pain scores were equivalent at the end of the first pass for both groups (P = .436). Group A patients had significantly lower pain scores at the start of the second laser treatment (P = .045), but pain scores became equivalent by the end (P = .323). Combined serum lidocaine and MEGX levels were significantly higher in group A patients up to 90 minutes (peak average of 0.61 µg/mL for group A and 0.533 µg/mL for group B; P = .0253), which corresponded to greater initial analgesic effect. Data from this study demonstrate that topical anesthetic for facial rejuvenation can be enhanced with laser pretreatment while maintaining safe blood serum levels. Further studies should examine optimal application amount and time to allow safe multipass facial rejuvenation without the need for invasive nerve blocks.


Extracellular signal-regulated kinase mediates phosphorylation of tropomyosin-1 to promote cytoskeleton remodeling in response to oxidative stress: impact on membrane blebbing.
Oxidative stress induces in endothelial cells a quick and transient coactivation of both stress-activated protein kinase-2/p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases. We found that inhibiting the ERK pathway resulted, within 5 min of oxidative stress, in a misassembly of focal adhesions characterized by mislocalization of key proteins such as paxillin. The focal adhesion misassembly that followed ERK inhibition with the mitogen-activated protein kinase kinase (MEK) inhibitor PD098059 (2'-amino-3'-methoxyflavone) or with a kinase negative mutant of ERK in the presence of H(2)O(2) resulted in a quick and intense membrane blebbing that was associated with important damage to the endothelium. We isolated by two-dimensional gel electrophoresis a PD098059-sensitive phosphoprotein of 38 kDa that we identified, by mass spectrometry, as tropomyosin-1. In fact, H(2)O(2) induced a time-dependent phosphorylation of tropomyosin that was sensitive to inhibition by PD098059 and UO126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butanediane). Tropomyosin phosphorylation was also induced by expression of a constitutively activated form of MEK1 (MEK(CA)), which confirms that its phosphorylation resulted from the activation of ERK. In unstimulated cells, tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation of ERK by H(2)O(2) or by expression of MEK(CA). We propose that phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions. Incidentally, ML-7 (1-[5iodonaphthalene-1-sulfonyl]homopiperazine, HCl), an inhibitor of cell contractility, inhibited phosphorylation of tropomyosin and blocked the formation of stress fibers and focal adhesions, which also led to membrane blebbing in the presence of oxidative stress. Our finding that tropomyosin-1 is phosphorylated downstream of ERK, an event that modulates its interaction with actin, may lead to further understanding of the role of this protein in regulating cellular functions associated with cytoskeletal remodeling.


MiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models.
Phosphatidylinositol 3-kinase/protein kinase B ((PI3K/AKT) signaling pathway plays a role in regulating cell survival and apoptosis. Phosphatase and tensin homologue deleted on chromosome ten (PTEN) can negatively regulate PI3K/AKT signaling pathway, while DJ-1 (Parkinson gene 7) can negatively regulate expression and function of PTEN. DJ-1-PTEN/PI3K/AKT signaling pathway plays a role in the regulation of ischemic reperfusion (IR) injury. Bioinformatics analysis showed that there was a targeted complementary binding site between microRNA-122 (miR-122) and 3'-UTR of DJ-1 mRNA. This study aimed to investigate the effects of miR-122 in regulating DJ-1-PTEN/PI3K/AKT signaling pathway and acute renal I-R injury. Rat renal artery was clamped and restored after 30 min to establish renal IR injury model. Renal tissue samples were collected at 10 h and 20 h after operation. miR-122 and DJ-1 mRNA were detected with quantitative Real-time PCR (qRT-PCR). DJ-1 protein was tested by using Western blot. Blood urea nitrogen (BUN) and serum creatinine (SCr) were measured. Rat tubular epithelial cells, RRTEC, were cultured in vitro and divided into transfection (miR-NC group) and treatment group (miR-122 inhibitor group). IR treatment was performed after 72 h of transfection. DJ-1, PTEN, AKT, and phosphorylated AKT (p-AKT) were detected using Western blot. Cell apoptosis and reactive oxygen species (ROS) were measured with flow cytometry. Compared with Sham group, blood BUN and SCr contents significantly increased (p < 0.05), miR-122 level significantly elevated (p < 0.05), while DJ-1 mRNA and protein markedly declined (p < 0.05) in IR model rats. Compared with control group, I-R treatment significantly up-regulated miR-122 and PTEN expressions (p < 0.05), decreased DJ-1 and p-AKT levels (p < 0.05), and induced apoptosis and ROS production (p < 0.05) in RRTEC cells. Transfection with miR-122 inhibitor markedly up-regulated DJ-1 expression (p < 0.05), enhanced PTEN/PI3K/AKT pathway activity (p < 0.05), and reduced apoptosis and ROS production (p < 0.05). MiR-122 increased significantly, while DJ-1 declined significantly during renal I-R injury. Down-regulation of miR-122 markedly elevated DJ-1, enhanced PTEN/PI3K/AKT pathway activity, and inhibited apoptosis and ROS generation in rat renal tubular epithelial cells to alleviate IR injury.


Design and synthesis of "dumb-bell" and "triangular" inorganic-organic hybrid nanopolyoxometalate clusters and their characterisation through ESI-MS analyses.
A series of tris(hydroxymethyl)aminomethane (TRIS)-based linear (bis(TRIS)) and triangular (tris(TRIS)) ligands has been synthesised and were covalently attached to the Wells-Dawson type cluster [P(2)V(3)W(15)O(62)](9-) to generate a series of nanometer-sized inorganic-organic hybrid polyoxometalate clusters. These huge hybrids, with a molecular mass similar to that of small proteins in the range of ≈10-16 kDa, were unambiguously characterised by using high-resolution ESI-MS. The ESI-MS spectra of these compounds revealed, in negative ion mode, a characteristic pattern showing distinct groups of peaks corresponding to different anionic charge states ranging from 3(-) to 8(-) for the hybrids. Each peak in these individual groups could be unambiguously assigned to the corresponding hybrid cluster anion with varying combinations of tetrabutylammonium (TBA) and other cations. This study therefore highlights the prowess of the high-resolution ESI-MS for the unambiguous characterisation of large, nanoscale, inorganic-organic hybrid clusters that have huge mass, of the order of 10-16 kDa. Also, the designed synthesis of these compounds points to the fact that we were able to achieve a great deal of structural pre-design in the synthesis of these inorganic-organic hybrid polyoxometalates (POMs) by means of a ligand design route, which is often not possible in traditional "one-pot" POM synthesis.


Gastrointestinal stromal tumor of the anal wall in a Nigerian.
Documented reports of gastrointestinal stromal tumors (GIST) are relatively few in the sub-Saharan continent. The body of evidence points towards anal wall involvement being a rarity indeed. In this article we document a 61 year old Nigerian man who presented with bleeding per rectum and in whom the histological features (including immunohistochemistry) of the biopsied anal lesion was GIST.


Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation.
The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO) and/or prostacyclin (PGI2), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium-dependent vasodilation induced by BK is unlikely to involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.


Robot-Supported Collaborative Learning (RSCL): Social Robots as Teaching Assistants for Higher Education Small Group Facilitation.
Acknowledging the benefits of active learning and the importance of collaboration skills, the higher education system has started to transform toward utilization of group activities into lecture hall culture. In this study, a novel interaction has been introduced, wherein a social robot facilitated a small collaborative group activity of students in higher education. Thirty-six students completed a 3 h activity that covered the main content of a course in Human Computer Interaction. In this within-subject study, the students worked in groups of four on three activities, moving between three conditions: instructor facilitation of several groups using pen and paper for the activity; tablets facilitation, also used for the activity; and robot facilitation, using tablets for the activity. The robot facilitated the activity by introducing the different tasks, ensuring proper time management, and encouraging discussion among the students. This study examined the effects of facilitation type on attitudes toward the activity facilitation, the group activity, and the robot, using quantitative, and qualitative measures. Overall students perceived the robot positively, as friendly and responsive, even though the robot did not directly respond to the students' verbal communications. While most survey items did not convey significant differences between the robot, tablet, or instructor, we found significant correlations between perceptions of the robot, and attitudes toward the activity facilitation, and the group activity. Qualitative data revealed the drawbacks and benefits of the robot, as well as its relative perceived advantages over a human facilitator, such as better time management, objectivity, and efficiency. These results suggest that the robot's complementary characteristics enable a higher quality learning environment, that corresponds with students' requirements and that a Robot Supportive Collaborative Learning (RSCL) is a promising novel paradigm for higher education.


Utility of MR proton density fat fraction and its correlation with ultrasonography and biochemical markers in nonalcoholic fatty liver disease in overweight adolescents.
Background Clinical or biochemical markers that have good correlation with magnetic resonance proton density fat fraction (MR PDFF) can be used as simple tools for the screening for nonalcoholic fatty liver disease (NAFLD) and in determining the degree of fatty infiltration of the liver. The objective of this study was to determine the degree of relationship between MR PDFF and ultrasonography (USG) grades of fatty liver, and clinical and biochemical parameters of adolescents and to determine the sensitivity and specificity of USG for diagnosis of NAFLD. Methods This prospective study included 34 overweight adolescents (mean age, 12.1 ± 1.5 years; range, 10-15.1 years; 10 girls and 24 boys) who underwent both USG and magnetic resonance imaging (MRI). Correlation analysis was performed between MR fat fraction and USG grades of fatty liver, and clinical and biochemical parameters of fatty liver disease. Results MR fat fraction had a moderate positive correlation with serum alanine transaminase (ALT) and aspartate transaminase (AST) (ρ = 0.634, p < 0.001, ρ = 0.516, p = 0.002, respectively) and had a negligible or weak correlation with body mass index (BMI), BMI standard deviation score (SDS), waist circumference (WC), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol levels. The sensitivity and specificity of USG in the diagnosis of NAFLD were 81% (95% confidence interval 54%-95%) and 50% (27%-73%), respectively. The MR fat fraction had a moderate positive correlation with ultrasound grades of fatty liver (ρ = 0.487, p = 0.003). Conclusions Serum ALT and AST are potential biochemical markers to assess the degree of hepatic steatosis in NAFLD, which needs validation in further studies. USG can be used as a screening tool for NAFLD, but the diagnosis should be confirmed by estimating the MR fat fraction.


The effect of initial local anesthetic dose with continuous interscalene analgesia on postoperative pain and diaphragmatic function in patients undergoing arthroscopic shoulder surgery: a double-blind, randomized controlled trial.
Interscalene block (ISB) is commonly performed using 20-40 mL of local anesthetic. Spread to adjacent structures and consequent adverse effects including paralysis of the ipsilateral hemidiaphragm are frequent. Pain ratings, analgesic requirements, adverse events, satisfaction, function and diaphragmatic excursion were compared following interscalene block (ISB) with reduced initial bolus volumes. Subjects undergoing arthroscopic rotator cuff repair were randomized to receive 5, 10, or 20 mL ropivacaine 0.75% for ISB in a double-blind fashion (N = 36). Continuous infusion with ropivacaine 0.2% was maintained for 48 h. Pain and diaphragmatic excursion were assessed before block and in the recovery unit. Pain ratings in the recovery room were generally less than 4 (0-10 NRS) for all treatment groups, but a statistically significant difference was noted between the 5 and 20 mL groups (NRS: 2.67 vs. 0.62 respectively; p = 0.04). Pain ratings and supplemental analgesic use were similar among the groups at 24 h, 48 h and 12 weeks. There were no differences in the quality of block for surgical anesthesia. Dyspnea was significantly greater in the 20 mL group (p = 0.041). Subjects with dyspnea had significant diaphragmatic impairment more frequently (Relative risk: 2.5; 95%CI: 1.3-4.8; p = 0.042). Increased contralateral diaphragmatic motion was measured in 29 of the 36 subjects. Physical shoulder function at 12 weeks improved over baseline in all groups (baseline mean SST: 6.3, SEM: 0.6; 95%CI: 5.1-7.5; 12 week mean SST: 8.2, SEM: 0.46; 95%CI: 7.3-9.2; p = 0.0035). ISB provided reliable surgical analgesia with 5 mL, 10 mL or 20 mL ropivacaine (0.75%). The 20 mL volume was associated with increased complaints of dyspnea. The 5 mL volume was associated with statistically higher pain scores in the immediate postoperative period. Lower volumes resulted in a reduced incidence of dyspnea compared to 20 mL, however diaphragmatic impairment was not eliminated. Compensatory increases in contralateral diaphragmatic movement may explain tolerance for ipsilateral paresis. clinicaltrials.gov. identifier: NCT00672100.


All about Dowels - A Review Part I. Considerations before Cementation.
The optimal way of restoring a non vital tooth with dowel-core technique has long been a controversial matter. The purpose of this review was to assess the factors that may influence the successful restoration of root filled teeth with root canal dowels. The first part of the review discusses indications and physical parameters of dowel. Searches were performed in PubMed/Medline database using single or combined key words to obtain the most relevant list of references. Articles selected in the search process were obtained from the journals and reviewed with every aspect of dowel system for reconstruction of endodontically treated teeth. Medline search showed 228 articles for dowels but after applying exclusion criteria, only 51 articles remained to be included in Part I of this review. Out of which, 49 were in vitro studies and two were clinical studies. Reviewing the literature revealed that clinical data is still missing. Literature emphasizes that dowels should only be used for the retention of core material and not in view of reinforcing the remaining tooth structure. The dowel length is limited by the apical seal of four mm to six mm. Dowel width should be as small as possible. Canal configuration determines the selection between prefabricated and custom cast dowel. Fiber based dowel may be clinically appropriate for restoration of endodontically treated anterior tooth, although clinical studies are lacking.


[Patients' opinions and expectations about the dialysis care process].
To determine the experiences and needs of patients on dialysis, in order to identify critical points of the care process and develop proposals for improvement. Qualitative study using semistructured interviews with 22 patients on hemodialysis and peritoneal dialysis, from the Andalusian Health Service. Discourse analysis, using the SERVQUAL model. Triangulation of results. The diagnostic stage is described as the hardest moment as it requires acceptance of the disease. During hemodialysis, we see both positive adaptation and the perception of a diminished quality of life. The technique of peritoneal dialysis is evaluated positively, enabling greater independence, despite requiring more responsibility for self care. The contact with patients' organizations or the provision of a counseling service are valued as an aid in the process. With respect to different dimensions of the SERVQUAL model, human treatment and professional competence are valued. The critical points are lack of coordination, malfunctioning of transportation and lack of transparency in the management of waiting lists. Shortcomings in dealing with informal caregivers and the level of knowledge of professionals from areas other than Nephrology, also appear as deficiencies. The main proposals for improving the dialysis process are: attention to psychosocial aspects, the improvement of organizational aspects such as transport, and greater attention to informal caregivers.


Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft.
Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature. Cultured human PBL distributed in moderate concentrations to intraperitoneal tumor when administered i.p., but not when administered i.v. The poor localization of i.v. injected PBL to tumor may reflect species disparity in homing receptors and/or endothelial ligands, a problem which may be overcome with a syngeneic model. These results suggest that regional therapy with HA antibodies and PBL may offer advantages over systemic therapy for initial clinical trials.


Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies.
Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 gene--member of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders.


"I Wish I Could Die So I Would Not Be in Pain": A Qualitative Study of Palliative Care Needs Among People With Cancer or HIV/AIDS in Vietnam and Their Caregivers.
Although cancer and HIV/AIDS are common causes of death in Vietnam, limited data exist on their palliative care needs. As palliative care becomes part of Universal Health Coverage, evidence is needed to scale up appropriate care. To elicit from people with cancer or HIV/AIDS in Vietnam, and their caregivers, the specific multidimensional symptoms and concerns that cause serious health-related suffering. Semistructured, qualitative, in-depth interviews were conducted with stage III or IV cancer patients, people with HIV/AIDS, and their caregivers at three cancer treatment centers and two HIV/AIDS treatment centers in northern, central, and southern Vietnam. Interviews were analyzed using thematic analysis. Sixty people were interviewed (21 cancer patients, 20 people with HIV/AIDS, 19 caregivers). Pain and other physical symptoms severely impacted their daily lives. Psychological distress-including sadness, depression, worry, and a feeling of having no future-was mentioned frequently, and it was exacerbated by disease progression and by social problems such as financial difficulties and, among people with HIV/AIDS, stigma. Caregivers also suffered physically and psychosocially. Spirituality emerged as a source of strength for patients. Findings highlighted patients' and family caregivers' desire for more information about diagnosis, prognosis, and treatment, a shift toward individual decision-making. The findings demonstrate common, multidimensional, and severe suffering among people living with cancer or HIV/AIDS and their caregivers in Vietnam. These qualitative data should guide development of optimum clinical assessment tools and palliative care services for these populations.


How Prevalent is Hydronephrosis Secondary to Acute Appendicitis: A Cross-Sectional Study.
Right hydronephrosis secondary to acute appendicitis is an under-reported phenomenon with only several case reports published. To assess the incidence of this phenomenon in our database of patients diagnosed with acute appendicitis. Data were collected on 1092 patients who underwent surgery due to acute appendicitis between 2003 and 2007 in our tertiary medical center. The data entailed demographic, surgical, and hospitalization parameters including ultrasound or computed tomography examinations and presence of right hydronephrosis prior to surgery. Out of 1092 patients, appendicitis was eventually diagnosed in 87.4% of the patients. Only 594 (54%) had preoperative imaging performed prior to surgery (ultrasound or computed tomography). Out of these 594 patients, 21 (3.5%) had a new right hydronephrosis diagnosed and all had appendicitis with 15/21 (71%) having a retrocecal appendix. Of those with retrocecal appendix, 10 were pregnant women (48%). Erythrocyturia was present in 15/21 patients (71%) and in 10/11 of patients (91%) after excluding those who were pregnant. No significant differences were seen in patients with hydronephrosis regarding age, hospitalization, and surgery time. In all patients, an ultrasound was performed 2 weeks after surgery demonstrating the disappearance of hydronephrosis. Median follow-up time was 41.7 months (range 14.8-118.4 months). Our study shows that 3.5% of our cohort had right hydronephrosis secondary to acute appendicitis. Although this presentation is very rare, physicians should be aware of this phenomenon and the risk for delayed diagnosis and treatment of acute appendicitis.


Introduction to statistical methods for microRNA analysis.
MicroRNA profiling is an important task to investigate miRNA functions and recent technologies such as microarray, single nucleotide polymorphism (SNP), quantitative real-time PCR (qPCR), and next-generation sequencing (NGS) have played a major role for miRNA analysis. In this chapter, we give an overview on statistical approaches for gene expressions, SNP, qPCR, and NGS data including preliminary analyses (pre-processing, differential expression, classification, clustering, exploration of interactions, and the use of ontologies). Our goal is to outline the key approaches with a brief discussion of problems avenues for their solutions and to give some examples for real-world use. Readers will be able to understand the different data formats (expression levels, sequences etc.) and they will be able to choose appropriate methods for their own research and application. On the other hand, we give brief notes on most popular tools/packages for statistical genetic analysis. This chapter aims to serve as a brief introduction to different kinds of statistical methods and also provides an extensive source of references.


Cutaneous periarteritis nodosa. A case report.
We studied a patient with severe ulcerations on the lower limbs due to cutaneous periarteritis nodosa. Chronic relapsing course during more than 12 years with no systemic involvement was documented.


Factors associated with cerebral malaria.
We conducted a retrospective unmatched case-control study using the medical records of patients admitted to the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand to investigate factors associated with cerebral malaria. The records of 137 patients with severe Plasmodium falciparum without cerebral malaria and 35 patients with cerebral malaria hospitalized during 1997-2005 were reviewed and compared. Ten factors associated with cerebral malaria were identified: pulmonary edema [odds ratio (OR)= 13.8; 95% confidence interval (CI): 1.3-143.2], splenomegaly (OR=3.7; 95% CI: 1.3-44.7), fever (OR=3.3; 95% CI: 1.7-14.3), day 1 malarial density < or = 249,999/microl (OR=1.6; 95% CI: 1.1-14.6), day 2 malarial density < or =249,999/microl (OR=3.4; 95% CI: 1.3-35.1), dyspnea (OR=1.4; 95% CI: 1.2-12.1), hepatomegaly (OR=1.8; 95% CI: 0.2-12.1), being a referred patient (OR=1.3; 95% CI: 1.0-2.2), a higher systolic blood pressure (OR=1.2; 95% CI: 1.0-2.1) and a higher body mass index (OR=1.6; 95% CI: 1.0-2.6). Pulmonary edema was the strongest factor associated with cerebral malaria in our study. Clinicians who treat patients with severe Plasmodium falciparum malaria should be aware these factors are associated with cerebral malaria.


Preliminary assessment of dietary mannanoligosaccharides on growth performance and health status of gilthead seabream Sparus auratus.
A feeding trial was performed to assess the potential beneficial effect of two levels of mannanoligosaccarides (MOS) on the growth performance, feed utilization, hematological parameters, and liver histopathology of gilthead seabream Sparus auratus (also known as gilthead bream). Mannanoligosaccarides were added at the rates of 2 and 4 g/kg to a fish-meal-based control diet, and each diet was given (twice daily [midmorning and midafternoon] to apparent satiation) to triplicate groups of gilthead seabream growers (mean weight = approximately 170 g) in sea cages. The trial lasted 12 weeks, and the average ambient water temperature ranged from 19.6 degrees C to 24.7 degrees C during the experimental period. At the end of the experiment, fish attained market size (350-450 g) and their health status was evaluated by blood analysis and liver histology. There were no differences in survival rates among fish fed experimental diets. However, there were significant improvements in both growth and feed utilization among fish fed diets supplemented with MOS. Hemoglobin (Hb) and hematocrit (Ht) levels and erythrocyte, leukocyte, and thrombocyte (Thr) counts were unaffected by any dietary MOS. The levels of Hb (g/dL; mean +/- SD) and Ht (%; mean +/- SD) were 11.0 +/- 2.5 and 45.6 +/- 6.7 for the control group, 11.1 +/- 1.7 and 39.3 +/- 8.0 for the 2-g/kg group, and 11.2 +/- 1.9 and 40.2 +/- 8.4 for the 4-g/kg group. The mean Thr count ranged from 47.6 to 53.8 x 10(3)/mm3. Despite the apparently higher Thr counts for fish fed diets supplemented with MOS, these differences were not significant. Moreover, no histopathological differences were observed in liver tissue cross sections between control and treatment groups. These results suggest that supplementation of diets with MOS had no significant effects on general fish health.


trans-Resveratrol ameliorates anxiety-like behaviors and neuropathic pain in mouse model of post-traumatic stress disorder.
trans-Resveratrol has been extensively investigated for its anti-inflammatory, antioxidant, and anti-psychiatric properties. However, whether it could rescue posttraumatic stress disorder-like stress-induced pain abnormality is unknown. The present study examined the effects of trans-resveratrol on anxiety-like behavior and neuropathic pain induced by single-prolonged stress, which is a classical animal model for mimicking posttraumatic stress disorder. The single-prolonged stress-induced anxiety-like behavior and pain response were detected by the novelty suppressed feeding, marble burying, locomotor activity, von Frey, and acetone-induced cold allodynia tests in mice. The serum corticosterone levels and glucocorticoid receptor, protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression were detected by enzyme-linked immunosorbent assay and immunoblot analyses. trans-Resveratrol reversed single-prolonged stress-induced increased latency to feed and the number of marbles buried in the novelty suppressed feeding and marble burying tests, but did not significantly influence locomotion distance in the locomotor activity test. trans-Resveratrol also reversed single-prolonged stress-induced cold and mechanical allodynia. Moreover, single-prolonged stress induced abnormality in the limbic hypothalamus-pituitary-adrenal axis was reversed by trans-resveratrol, as evidenced by the fact that trans-resveratrol reversed the differential expression of glucocorticoid receptor in the anxiety- and pain-related regions. In addition, trans-resveratrol increased protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels, which were decreased in mice subjected to single-prolonged stress. These results provide compelling evidence that trans-resveratrol protects neurons against posttraumatic stress disorder-like stress insults through regulation of limbic hypothalamus-pituitary-adrenal axis function and activation of downstream neuroprotective molecules such as protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression.


Changes in the Oral Moisture and the Amount of Microorganisms in Saliva and Tongue Coating after Oral Ingestion Resumption: A Pilot Study.
Tube feeding has been significantly associated with a higher rate of aspiration pneumonia that is mainly related to oral microorganisms and a reduced salivary flow. Thus, the difference in the mode of nutritional intake is expected to affect the oral environment, but this has not yet been fully clarified. The purpose of this study was to investigate, in tube-fed patients, changes in the oral moisture and the counts of microorganisms in saliva and tongue coating, which occur after oral ingestion resumption. Study participants were 7 tube-fed inpatients of the Niigata University Medical and Dental Hospital (72.7±8.5 years old) who received dysphagia rehabilitation at the Unit of Dysphagia Rehabilitation until oral ingestion resumption. Their oral health, swallowing, and nutrition status, oral mucosal moisture, amount of unstimulated saliva and the counts of microorganisms (total microorganisms, streptococci, Candida) in saliva and tongue coating were investigated and compared before and after the recommencement of oral intake. Tongue coating, choking, oral mucosal moisture and amount of unstimulated saliva were improved significantly after resumption of oral ingestion. The other investigated parameters did not significantly change, except for the streptococci in tongue coating, which significantly increased 1 week after oral ingestion recommencement, but decreased thereafter. After oral intake resumption, oral mucosal moisture and amount of unstimulated saliva were improved. However, because of a transitory increase in the counts of streptococci with oral ingestion recommencement, it is important to appropriately manage oral hygiene in these patients, according to the changes in their intraoral microbiota.


Alpha-bisabolol: unexpected plant-derived weapon in the struggle against tumour survival?
Despite enormous scientific and economic effort tumour still is one of the most terrible pathologies among human population all over the world. Products derived from the plant kingdom have often offered an opportunity to counteract or alleviate this illness. Here, we summarize the short story of the study of an extraordinary effect of one plant compound towards transformed cells derived from highly malignant tumours. Alpha-bisabolol, a sesquiterpene widely present in plants, selectively kills transformed cells by apoptosis without affecting the viability of normal cells. One of its intracellular targets seems to be situated on mitochondria and is possibly identified as the permeability transition pore, as judged from rapid mitochondrial membrane potential dissipation induced by alpha-bisabolol and the failure to kill cells in the presence of cyclosporine A. Preferential adsorption of alpha-bisabolol into lipid rafts, rich in tumour cells, may explain the selective action of this compounds towards tumour cells. Furthermore, Surface Plasmon Resonance analysis indicates that alpha-bisabolol directly interacts with Bid protein, a member of the Bcl2 family deeply involved in apoptosis, suggesting a possibility that Bid, or similar protein(s), may be involved in a putative intracellular transport system of alpha-bisabolol from plasma membrane to mitochondria. Experiments with animals indicate that alpha-bisabolol is not toxic and is accumulated, through blood flow, in every tissues examined. Further animal studies to test its effect are currently under way.


Update on diagnostics of metabolic myopathies.
This review aims to highlight the most relevant clinical and laboratory findings, regarding acute and progressive metabolic myopathies, and to develop an algorithm addressing clinicians to clinical practice. Although diagnosis of metabolic myopathies remains still challenging, the recent identification of new disorders has increased the number of patients requiring specific investigations. Nowadays, a more detailed characterization of the clinical spectrum of metabolic myopathies improved awareness as well as a deeper knowledge on their natural history or multisystem involvement. Diagnostic procedures, as first-line screening tests are necessary for an earlier and more accurate diagnostic work up, not only in infantile cases, but also in adults with suspected metabolic myopathies. New generation diagnostic techniques such as NGS (Next Generation Sequencing) and whole exome/genome sequencing have emerged as innovative tools to extensively evaluate either known genes variants or new candidate genes as possible causes of metabolic myopathies. Diagnosis of metabolic myopathies is still challenging for clinicians because of rarity and clinical heterogeneity which is often overlapping with other neuromuscular disorders. Detailed algorithms supported by advanced laboratory investigations may be helpful to timely reach a diagnosis, so allowing an earlier therapeutic decision.


Factors affecting postmortem tooth loss.
Unassociated human bones are a particular problem during the exhumation of mass graves and a factor that limits anthropological and paleopathological analyses from archaeological contexts. Extensive anthropological literature has focused on the complex taphonomic factors that influences bone assemblages, but little attention has been paid to postmortem tooth loss and factors affecting this process. The following study focuses upon the influence of different factors on postmortem tooth loss. Three samples were investigated in the study: a medieval church cemetery containing 110 individual skeletal remains, and two samples from a series of mass graves made within the same time period in 1999, containing 402 bodies. The frequency of postmortem tooth loss was analyzed relative to postmortem interval for each sample, excavation methods, age distribution, and presence of bone loss associated with periodontal disease. Our results indicate that the degree of alveolar bone loss significantly affected both antemortem and postmortem tooth loss and that the frequency of postmortem tooth loss has the strongest correlation to time since death. These findings suggest that additional care should be taken when exhuming remains from older contexts.


Wide-field optical coherence tomography: imaging of biological tissues.
We describe a two-dimensional optical coherence tomography technique with which we were able to obtain multiple longitudinal slices of a biological sample directly in a single Z scan. The system is based on a femtosecond Cr4+:forsterite laser and an infrared camera for wide-field imaging of the sample with a depth resolution of 5 microm. With this imaging apparatus we were able to investigate human skin and mouse ear samples and to observe the different constitutive tissues.


Cost-effectiveness of the implantable cardioverter-defibrillator: results from the Canadian Implantable Defibrillator Study (CIDS).
In the Canadian Implantable Defibrillator Study (CIDS), we assessed the cost-effectiveness of the implantable cardioverter-defibrillator (ICD) in reducing the risk of death in survivors of previous ventricular tachycardia (VT) or fibrillation (VF). Healthcare resource use was collected prospectively on the first 430 patients enrolled in CIDS (n=212 ICD, n=218 amiodarone). Mean cost per patient, adjusted for censoring, was computed for each group based on initial therapy assignment. Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost (ICD minus amiodarone) to the difference in life expectancy (both discounted at 3% per year). All costs are in 1999 Canadian dollars (C$1 approximately US$0.65). Over 6.3 years, mean cost per patient in the ICD group was C$87 715 versus C$38 600 in the amiodarone group (difference C$49 115; 95% CI C$25 502 to C$69 508). Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone (difference 0.23, 95% CI -0.09 to 0.55), for incremental cost-effectiveness of ICD therapy of C$213 543 per life-year gained. ICD benefit was greater in patients with low left ventricular ejection fraction (<35%), and cost-effectiveness in this group was more attractive (C$108 484). Alternative extrapolations of survival benefit and costs to 12 years indicated cost-effectiveness in the range of C$100 000 to C$150 000 per life-year gained. At C$213 543, the value for the money offered by ICD therapy is not attractive by currently accepted standards. Further research is warranted to identify the indications and patient subgroups for whom ICDs are a cost-effective use of resources.


Interfacial Engineering of Bimetallic Ag/Pt Nanoparticles on Reduced Graphene Oxide Matrix for Enhanced Antimicrobial Activity.
Environmental biofouling caused by the formation of biofilm has been one of the most urgent global concerns. Silver nanoparticles (NPs), owing to their wide-spectrum antimicrobial property, have been widely explored to combat biofilm, but their extensive use has raised growing concern because they persist in the environment. Here we report a novel hybrid nanocomposite that imparts enhanced antimicrobial activity and low cytotoxicity yet with the advantage of reduced silver loading. The nanocomposite consists of Pt/Ag bimetallic NPs (BNPs) decorated on the porous reduced graphene oxide (rGO) nanosheets. We demonstrate that the enhanced antimicrobial property against Escherichia coli is ascribed to the intricate control of the interfaces between metal compositions, rGO matrix, and bacteria, where the BNPs lead to a rapid release of silver ions, and the trapping of bacteria by the porous rGO matrix further provides high concentration silver ion sites for efficient bacteria-bactericide interaction. We envision that our facile approach significantly expands the design space for the creation of silver-based antimicrobial materials to achieve a wide spectrum of functionalities.


Students with hearing impairment at a South African university: Self-identity and disclosure.
A growing number of students with hearing loss are being granted access to higher education in South Africa due to the adoption of inclusive educational policies. However, available statistics indicate that participation by students with hearing impairments in higher education remains low and research suggests that support provisioning for those who do gain access is inadequate. This article aims to illustrate that the assumed self-identity of students with hearing impairment influences their choice to disclose their disability. The choice not to disclose their hearing loss prevents them from accessing the necessary reasonable accommodations and this in turn may affect their eventual educational success. Reported here is a qualitative descriptive case study at a South African university. Purposive sampling methods were employed. Data were gathered from in-depth interviews with seven students with hearing impairment ranging from moderate to profound, using spoken language. Constructivist grounded theory was used as an approach to the process of generating and transforming the data, as well as the construction of theory. All the student participants identified as having a hearing rather than a D/deaf identity cultural paradigm and viewed themselves as 'normal'. Linked to this was their unwillingness to disclose their hearing impairment and thus access support. It is crucially important for academic, support and administrative staff to be aware of both the assumed 'hearing' identity and therefore subsequent non-disclosure practices of students with a hearing impairment using the oral method of communication. Universities need to put measures in place to encourage students to voluntarily disclose their hearing impairment in order to provide more targeted teaching and learning support. This could lead to improved educational outcomes for students.


Nonotogenic otalgia: diagnosis and treatment.
Nonotogenic otalgia may be due to referred or reflex pain, neuralgia, or to a psychogenic problem. Referred pain is due to irritative lesions involving the fifth, ninth, or tenth cranial nerves and spinal nerves C2 and C3. If pathologic problems in the area supplied by these nerves have been ruled out, the neuralgia should be considered in the differential diagnosis. Psychogenic factors must be identified and treated before any type of surgical therapy is recommended.


[Looking for a more participative healthcare: sharing medical decision making].
The healthcare model is shifting from a paternalistic towards a more inclusive and participative approach, such as shared decision making (SDM). SDM considers patients as autonomous and responsible agents. SDM is a therapeutic approach where healthcare providers and patients share the best evidence available to make a decision according to the values and preferences of the patient. Decision aids are tools that can facilitate this information exchange. These tools help patients to increase knowledge about options, reduce decisional conflict and improve satisfaction. Additionally, communication skills play a key role within the professional-patient relationship, as they facilitate sharing information and preferences in an effective and respectful manner. This therapeutic approach could support the reduction of health inequalities that affect Latin America, as it promotes an active and informed participation of patients in their healthcare process.


Engineered cyclodextrin-based supramolecular hydrogels for biomedical applications.
Cyclodextrin (CD)-based supramolecular hydrogels are polymer network systems with the ability to rapidly form reversible three-dimensional porous structures through multiple cross-linking methods, offering potential applications in drug delivery. Although CD-based supramolecular hydrogels have been increasingly used in a wide range of applications in recent years, a comprehensive description of their structure, mechanical property modulation, drug loading, delivery, and applications in biomedical fields from a cross-linking perspective is lacking. To provide a comprehensive overview of CD-based supramolecular hydrogels, this review systematically describes their design, regulation of mechanical properties, modes of drug loading and release, and their roles in various biomedical fields, particularly oncology, wound dressing, bone repair, and myocardial tissue engineering. Additionally, this review provides a rational discussion on the current challenges and prospects of CD-based supramolecular hydrogels, which can provide ideas for the rapid development of CD-based hydrogels and foster their translation from the laboratory to clinical medicine.


IL-33 modulates inflammatory brain injury but exacerbates systemic immunosuppression following ischemic stroke.
Stroke triggers a complex inflammatory process in which the balance between pro- and antiinflammatory mediators is critical for the development of the brain infarct. However, systemic changes may also occur in parallel with brain inflammation. Here we demonstrate that administration of recombinant IL-33, a recently described member of the IL-1 superfamily of cytokines, promotes Th2-type effects following focal ischemic stroke, resulting in increased plasma levels of Th2-type cytokines and fewer proinflammatory (3-nitrotyrosine+F4/80+) microglia/macrophages in the brain. These effects of IL-33 were associated with reduced infarct size, fewer activated microglia and infiltrating cytotoxic (natural killer-like) T cells, and more IL-10-expressing regulatory T cells. Despite these neuroprotective effects, mice treated with IL-33 displayed exacerbated post-stroke lung bacterial infection in association with greater functional deficits and mortality at 24 hours. Supplementary antibiotics (gentamicin and ampicillin) mitigated these systemic effects of IL-33 after stroke. Our findings highlight the complex nature of the inflammatory mechanisms differentially activated in the brain and periphery during the acute phase after ischemic stroke. The data indicate that a Th2-promoting agent can provide neuroprotection without adverse systemic effects when given in combination with antibiotics.


Finite Element Modeling of Chondrolabral Lesions in Pincer-Type Femoroacetabular Impingement.
The prevalence of chondrolabral lesions due to femoroacetabular impingement (FAI) is 93% in cadaveric material. As a biomechanically determined factor, it can lead to hip destruction and early osteoarthritis in pincer-type impingement. The aim of this work was to study the biomechanism and stress-strain behavior of chondrolabral lesions in pincer-type impingement during daily activity-associated movements. The SolidWorks package was used to build a 3D pelvis model with and without pincer-type impingement in the femoroacetabular (FA) region. Finite element analysis (FEA) in ANSYS was performed to determine von Mises stress, strain and total deformations for the models during 90 hip flexion and 15 internal rotation during daily activities. Maximum stress-strain values increased 2-3.4 times in the bone along the anterior upper acetabular rim, femoral neck and acetabular labrum in the area of the pincer osteophyte compared to the non-pincer condition in the FA model. 1. The increase in stress-strain in the contact area at the pincer osteophyte and femoral neck can be a factor of cam-type osteophyte formation and progression of acetabular rim ossification. 2. Daily activity can lead to an increase in maximum stress, as a factor of chondral delamination and destruction of the acetabular labrum. 3. Early surgery is needed to avoid progression of osteoarthritis in pincer-type impingement.


Agardite-(Y), Cu(2+) 6Y(AsO4)3(OH)6·3H2O.
Agardite-(Y), with a refined formula of Cu(2+) 5.70(Y0.69Ca0.31)[(As0.83P0.17)O4]3(OH)6·3H2O [ideally Cu(2+) 6Y(AsO4)3(OH)6·3H2O, hexa-copper(II) yttrium tris-(arsenate) hexa-hydroxide trihydrate], belongs to the mixite mineral group which is characterized by the general formula Cu(2+) 6 A(TO4)3(OH)6·3H2O, where nine-coordinated cations in the A-site include rare earth elements along with Al, Ca, Pb, or Bi, and the T-site contains P or As. This study presents the first structure determination of agardite-(Y). It is based on the single-crystal X-ray diffraction of a natural sample from Jote West mine, Pampa Larga Mining District, Copiapo, Chile. The general structural feature of agardite-(Y) is characterized by infinite chains of edge-sharing CuO5 square pyramids (site symmetry 1) extending down the c axis, connected in the ab plane by edge-sharing YO9 polyhedra (site symmetry -6..) and corner-sharing AsO4 tetra-hedra (site symmetry m..). Hy-droxyl groups occupy each corner of the CuO5-square pyramids not shared by a neighboring As or Y atom. Each YO9 polyhedron is surrounded by three tubular channels. The walls of the channels, parallel to the c axis, are six-membered hexa-gonal rings comprised of CuO5 and AsO4 polyhedra in a 2:1 ratio, and contain free mol-ecules of lattice water.


Photoactivation turns green fluorescent protein red.
In the few years since its gene was first cloned, the Aequorea victoria green fluorescent protein (GFP) has become a powerful tool in cell biology, functioning as a marker for gene expression, protein localization and protein dynamics in living cells. GFP variants with improved fluorescence intensity and altered spectral characteristics have been identified, but additional GFP variants are still desirable for multiple labeling experiments, protein interaction studies and improved visibility in some organisms. In particular, long-wavelength (red) fluorescence has remained elusive. Here we describe a red-emitting, green-absorbing fluorescent state of GFP that is generated by photoactivation with blue light. GFP can be switched to its red-emitting state easily with a laser or fluorescence microscope lamp under conditions of low oxygen concentration. This previously unnoticed ability enables regional, non-invasive marking of proteins in vivo. In particular, we report here the use of GFP photoactivation to make the first direct measurements of protein diffusion in the cytoplasm of living bacteria.


Oligoantigenic Diet Improves Children's ADHD Rating Scale Scores Reliably in Added Video-Rating.
The influence of food intake on behavioural disorders was already described in the early 20th century. Elimination of individually allergenic food items from individual diets ["oligoantigenic diet" (OD)] showed promise to improve attention-deficit/hyperactivity disorder (ADHD) symptoms. However, only few of the positive results were evaluated by blinded symptom rating. Therefore the present study's purpose was to evaluate the reliability of a non-blinded rating of the ADHD Rating Scale IV (ARS) for the assessment of OD effects in comparison to a blinded rating of the ARS based on pseudonymized video recordings. Ten children (8m/2f) aged 8 to 14 with ADHD according to ICD-10 participated in an uncontrolled, open-label dietary intervention study. Food items, commonly related to intolerances, were eliminated for four weeks. Participants with > 40% improvement in the ARS between T1 (before the diet) and T2 (after the diet) were defined as responders. Nutrients with individual relevance to ADHD symptoms were identified in a following reintroduction phase (T3-T4) lasting 8-16 weeks. The ARS was completed by a non-blinded child and adolescent psychiatrist (T0-T4). Sessions were recorded on video, pseudonymized, and evaluated by three blinded raters. Complete data were captured for eight children. The inter-rater reliability between the non-blinded therapist and every blinded rater was determined by the intra-class correlation coefficient (ICC). Correlations according to Pearson and Spearman between the non-blinded and blinded rating were calculated for each rater. Two blinded raters and the non-blinded rater considered 5 of 8 (62.5%) children as responders, whereas one blinded rater disagreed as to the success of one case thus considering only 4 of 8 children as responders to the diet. Inter-rater reliability was assessed after each rater having scored 33 videos: The intra-class coefficients were >.9 for all raters (rater 1: ICC=.997, rater 2: ICC=.996, rater 3: ICC=.996) and the Spearman rho between the raters were high (n=33; rater 1: rho =.989, p<.0001, rater 2: rho=.987, p<.0001, rater 3: rho=.984, p<.0001), respectively. As both, blinded and non-blinded ratings of the ARS, revealed relevant significant improvement of ADHD scores in children following an OD in this uncontrolled trial, Randomized controlled trials appear as highly desirable in order to replicate these improvements and to establish reliable and unbiased effect sizes thereby fostering further more objective confirmatory measurements.


[Foot injuries in the emergency room : three lesions that should not be missed].
Urgent consultations for foot injuries are common. Trauma injuries are often obvious, such as displaced or open fractures, dislocations, or tissue breakdown. However, they can also have a subtle presentation and still hide severe structural damage. This is the case of «benign» Lisfranc sprains, compartment syndrome or even tendon sections through an apparently benign wound. The purpose of this article is to help the primary care physician to be aware of these subtle and sometimes hidden injuries, to assist him in the diagnosis and to provide the keys to appropriate treatment.


When the protection of a threatened species depends on the economy of a foreign nation.
A significant challenge of conservation biology is to preserve species in places where their critical habitat also attracts significant economic interest. The problem is compounded when species distributions occur across large spatial extents. Threatened boreal caribou (Rangifer tarandus caribou) epitomize this problem: their critical habitat encompasses a vast expanse of forest that also supplies much of Canada's merchantable timber. Boreal caribou were protected under the Canada Species at Risk Act in 2003. We investigated putative drivers of reduced disturbance for caribou habitat since then. Where the cumulative logging footprint slowed within caribou habitat, this has resulted neither from decreases in annual allowable cut of timber nor the creation or expansion of protected areas. Rather, it has fluctuated with the American economy relative to that of Canada. For each $0.05 US lost over the $CAD, 129 km2 of caribou habitat was not disturbed by logging in a given year. Recent population declines have been occurring even though logging typically remained at <70% of allowed levels. Our study raises concerns about how caribou are functionally being conserved under the current application of existing legislation. In this globalized world, the economy of foreign nations is increasingly likely to govern national conservation objectives.


Hybrid floral scent novelty drives pollinator shift in sexually deceptive orchids.
Sexually deceptive orchids of the genus Ophrys attract their pollinators, male insects, on a highly specific basis through the emission of odour blends that mimic the female sex pheromone of the targeted species. In this study, we have investigated a contact site between Ophrys arachnitiformis and O. lupercalis, two sympatric orchid species that are usually reproductively isolated via the exploitation of different pollinator "niches", but occasionally hybridise despite their apparent combination of ethological and mechanical isolation barriers. In particular, we have investigated the extent to which these Ophrys hybrids generate "emergent" combinations (i.e. novel and unpredictable from the parents' phenotypes) of floral traits, and how these phenotypic novelties, particularly the odour blends emitted by the flower, could facilitate the invasion of a novel pollinator "niche" and induce the rapid formation of reproductive isolation, a prerequisite for adaptive evolutionary divergence. Our chemical analyses of floral scents show that the Ophrys F1 hybrids investigated here produce more compounds, significantly different ratios (% of odour compounds in the total blend), as well as new compounds in their floral odour compared to their progenitors. When tested for their attractiveness to the pollinator of each parent orchid species, we found that floral scent extracts of the hybrids triggered less inspecting flights and contacts by the male bees with the scented dummy than those of the parental orchid species. However, a series of additional behavioural bioassays revealed that the novel floral scent of the hybrids was significantly more attractive than either of the two parents to a pollinator species not initially involved in the pollination of any of the parent Ophrys species. Collectively, our results illustrate that the process of hybridisation can lead to the generation of evolutionary novelties, and that novel combinations of floral traits can drive pollinator shifts and rapid reproductive isolation in highly specific plant-pollinator interactions.


Advanced glycation end-products in patients with chronic alcohol misuse.
The aim of our study was to determine serum levels of advanced glycation end-products (AGE) in patients with chronic alcohol misuse and to examine their relationship to markers of nutrition and inflammation. The study group consisted of 23 heavy alcohol drinkers treated for chronic alcohol misuse and 22 healthy controls. Studied parameters included AGE (fluorescence, CML - carboxymethyllysine and pentosidine), lipids, glucose, albumin, leptin, prealbumin, C-reactive protein (CRP) and pregnancy-associated plasma protein A (PAPP-A). AGE fluorescence was significantly higher in chronic alcoholic patients than in healthy subjects (4.3 +/- 0.7 x 10(3) vs 3.7 +/- 0.5 x 10(3) AU/g protein, P < 0.005), while CML was only slightly but not significantly elevated (569.1 +/- 106.6 vs 545.5 +/- 85.8 microg/l) and pentosidine levels did not differ (105.4 +/- 29 vs 102.2 +/- 23 nmol/l). In alcoholics, AGE correlate significantly negatively with leptin (r = -0.46, P < 0.05) and pentosidine with prealbumin (r = -0.43, P < 0.05), otherwise there was no relationship between AGE and other biochemical parameters (glucose, cholesterol, albumin, CRP, PAPP-A). Our findings suggest a more complex relationship among advanced glycation, oxidative stress and metabolism of ethanol and their link to nutrition and nutrition-associated parameters. AGE as a result of oxidative stress might be similarly linked to increased cardiovascular risk of heavy alcohol drinkers, as are malnutrition and inflammation; however, further studies are needed to confirm this hypothesis.


Resistance of Staphylococcus aureus to the cationic antimicrobial agent poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is influenced by cell-surface charge and hydrophobicity.
Cationic antimicrobial agents may prevent device-associated infections caused by Staphylococcus epidermidis and Staphylococcus aureus. This study reports that the cationic antimicrobial polymer poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) was more effective at antagonizing growth of clinical isolates of S. epidermidis than of S. aureus. Importantly, mature S. epidermidis biofilms were significantly inactivated by pDMAEMA. The S. aureus isolates tested were generally more hydrophobic than the S. epidermidis isolates and had a less negative charge, although a number of individual S. aureus and S. epidermidis clinical isolates had similar surface hydrophobicity and charge values. Fluorescence spectroscopy and flow cytometry revealed that fluorescently labelled pDMAEMA interacted strongly with S. epidermidis compared with S. aureus. S. aureus ΔdltA and ΔmprF mutants were less hydrophobic and therefore more susceptible to pDMAEMA than wild-type S. aureus. Although the different susceptibility of S. epidermidis and S. aureus isolates to pDMAEMA is complex, influenced in part by surface hydrophobicity and charge, these findings nevertheless reveal the potential of pDMAEMA to treat S. epidermidis infections.


Passive sampling methods to determine household and personal care product use.
Traditionally, use of household and personal care products has been collected through questionnaires, which is very time consuming, a burden on participants, and prone to recall bias. As part of the SUPERB Project (Study of Use of Products and Exposure-Related Behaviors), a novel platform was developed using bar codes to quickly and reliably determine what household and personal care products people have in their homes and determine the amount used over a 1-week period. We evaluated the acceptability and feasibility of our methodology in a longitudinal field study that included 47 California households, 30 with young children and 17 with an older adult. Acceptability was defined by refusal rates; feasibility was evaluated in terms of readable bar codes, useful product information in our database for all readable barcodes, and ability to find containers at both the start and end of the week. We found 63% of personal care products and 87% of the household care products had readable barcodes with 47% and 41% having sufficient data for product identification, respectively and secondly, the amount used could be determined most of the time. We present distributions for amount used by product category and compare inter- and intra-person variability. In summary, our method appears to be appropriate, acceptable, and useful for gathering information related to potential exposures stemming from the use of personal and household care products. A very low drop-out rate suggests that this methodology can be useful in longitudinal studies of exposure to household and personal care products.


Plant-derived alternative treatments for the aging male: facts and myths.
Soy- or red clover- derived products containing isoflavones have been amply studied in climacteric and postmenopausal women, and confusing contradicting results have been published. The beneficial effects on climacteric complaints, cholesterol and the development of osteoporosis are marginally at best and there are no uterine and mammary safety studies. In males, however, isoflavones may protect the prostate to make them less prone to develop cancer. Cell biological and animal experimental data support this notion. Clinical data about possible beneficial effects on cholesterol or in the bone are largely missing. Hence, soy or red clover products containing the mild estrogenic isoflavones with a slightly higher affinity to the estrogen receptor of the beta in comparison to the alpha subtype may prove to have some beneficial effects in males.


Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ.
RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here, we present a new method, Smart-3SEQ, that accurately quantifies transcript abundance even with small amounts of total RNA and effectively characterizes small samples extracted by laser-capture microdissection (LCM) from FFPE tissue. We also obtain distinct biological profiles from FFPE single cells, which have been impossible to study with previous RNA-seq protocols, and we use these data to identify possible new macrophage phenotypes associated with the tumor microenvironment. We propose Smart-3SEQ as a highly cost-effective method to enable large gene expression profiling experiments unconstrained by sample size and tissue availability. In particular, Smart-3SEQ's compatibility with FFPE tissue unlocks an enormous number of archived clinical samples; combined with LCM it allows unprecedented studies of small cell populations and single cells isolated by their in situ context.


PET studies of D2-receptor binding in striatal and extrastriatal brain regions: Biochemical support in vivo for separate dopaminergic systems in humans.
Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [11C]raclopride and [11C]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.


Cutaneous manifestations of systemic viral diseases in neonates: an update.
Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.


Distal-less functions in subdividing the Drosophila thoracic limb primordium.
The thoracic limb primordium of Drosophila melanogaster is a useful experimental model in which to study how unique tissue types are specified from multipotent founder cell populations. The second thoracic segment limb primordium gives rise to three structures: the wing imaginal disc, the leg imaginal disc, and a larval mechanosensory structure called Keilin's organ. We report that most of the limb primordium arises within neurogenic ectoderm and demonstrate that the neural and imaginal components of the primordium have distinct developmental potentials. We also provide the first analysis of the genetic pathways that subdivide the progenitor cell population into uniquely imaginal and neural identities. In particular, we demonstrate that the imaginal gene escargot represses Keilin's organ fate and that Keilin's organ is specified by Distal-less in conjunction with the downstream achaete-scute complex. This specification involves both the activation of the neural genes cut and couch potato and the repression of escargot. In the absence of achaete-scute complex function, cells adopt mixed identities and subsequently die. We propose that central cells of the primordium previously thought to contribute to the distal leg are Keilin's organ precursors, while both proximal and distal leg precursors are located more peripherally and within the escargot domain.


Experimental analysis of tablet properties for discrete element modeling of an active coating process.
Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.


Late relapse from cutaneous stage I malignant melanoma.
In 1,283 patients with cutaneous stage I malignant melanoma who had ten or more years of follow-up, the incidence of late recurrence (first evidence of metastases occurring ten or more years after melanoma diagnosis) was 2.7%. None of the factors of prognostic importance (anatomic site, tumor thickness, ulcerative state of primary lesion, or initial surgical treatment) proved useful in predicting those patients with late recurrence. There was no sex or age difference in either incidence of late recurrence or prognosis subsequent to recurrence. Prognosis subsequent to late recurrence depended on the site of the recurrence. Survival after distant metastases became evident was extremely short. However, in the majority (53%) of patients, late recurrence was local and survival subsequent to treatment of these metastases was often protracted, emphasizing the importance of long-term follow-up in all patients with cutaneous melanoma.


Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Japanese women.
Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).


Physician education in home care.
Home care is a neglected area of study for most medical students. One home care agency has developed a clerkship model with a local university to teach its students about this fast-growing segment of health care.


Alveolar Ridge Splitting Versus Autogenous Onlay Bone Grafting: Complications and Implant Survival Rates.
To compare the complications and implant survival rates of localized alveolar ridge deficiencies in the horizontal dimension reconstructed by alveolar ridge splitting (ARS) or autogenous onlay bone grafting (OBG). Twenty-eight ARS and 28 OBG were performed. The survival rate of the all included implants was evaluated using the clinical and radiographical evaluation criteria of Misch et al. Temporary exposure of graft, mild infection, temporary paresthesia, and bad split were defined as minor complications; permanent exposure of graft, loss of graft, and permanent paresthesia were defined as major complications. Major and minor complications of ARS and OBG groups were statistically compared. When the minor and major complication rates are considered, there was not any statistically significant difference between OBG (P = 0.099) and ARS (P = 0.241) groups. The satisfactory survival rate of OBG group was 92% and was 100% in the ARS group, and the difference was not statistically significant (P = 0.116). When reconstructing vertically sufficient but horizontally insufficient alveolar ridges, ridge splitting technique could shorten the treatment period, decrease postoperative swelling and pain, eliminate the need for a second surgical site, reduce the treatment cost, and ease the patient cooperation to the surgery.


Myo-REG: A Portal for Signaling Interactions in Muscle Regeneration.
Muscle regeneration is a complex process governed by the interplay between several muscle-resident mononuclear cell populations. Following acute or chronic damage these cell populations are activated, communicate via cell-cell interactions and/or paracrine signals, influencing fate decisions via the activation or repression of internal signaling cascades. These are highly dynamic processes, occurring with distinct temporal and spatial kinetics. The main challenge toward a system level description of the muscle regeneration process is the integration of this plethora of inter- and intra-cellular interactions. We integrated the information on muscle regeneration in a web portal. The scientific content annotated in this portal is organized into two information layers representing relationships between different cell types and intracellular signaling-interactions, respectively. The annotation of the pathways governing the response of each cell type to a variety of stimuli/perturbations occurring during muscle regeneration takes advantage of the information stored in the SIGNOR database. Additional curation efforts have been carried out to increase the coverage of molecular interactions underlying muscle regeneration and to annotate cell-cell interactions. To facilitate the access to information on cell and molecular interactions in the context of muscle regeneration, we have developed Myo-REG, a web portal that captures and integrates published information on skeletal muscle regeneration. The muscle-centered resource we provide is one of a kind in the myology field. A friendly interface allows users to explore, approximately 100 cell interactions or to analyze intracellular pathways related to muscle regeneration. Finally, we discuss how data can be extracted from this portal to support in silico modeling experiments.


Device to relate the superficial temperature of the forearm and the muscular conditioning of the flexor muscle for prevention of carpal tunnel syndrome in E-sports.
Currently, various labor and competitive sectors use computing devices as the primary development tool, one of them being e-sports or electronic sports. Constant use of the computer involves repetitive use of the fingers' superficial and deep flexor muscles, which causes the median nerve to squeeze and irritate in the carpal tunnel space causing carpal tunnel syndrome (CTS). There are methods that can minimize stress on the hands and wrists through muscle conditioning. However, there are no quantifiable indicators of the conditioning performed. Therefore, this work aims to develop a device capable of conditioning the flexor muscles and indicate in a quantifiable way the conditioning carried out as prevention of carpal tunnel syndrome. After the analysis of these data, a direct relationship between the surface temperature of the forearm and the muscular conditioning of the flexors is observed. The temperature variation during conditioning is greatest in the distal forearm with a range of [32.76-34.38]°. Post-conditioning temperature retention is greater in the distal forearm over time.