Outcomes following coronary stenting in the era of bare-metal vs the era of drug-eluting stents.
Although drug-eluting stents reduce restenosis rates relative to bare-metal stents, concerns have been raised that drug-eluting stents may also be associated with an increased risk of stent thrombosis. Our study focused on the effect of stent type on population-based interventional outcomes. To compare outcomes of Medicare beneficiaries who underwent nonemergent coronary stenting before and after the availability of drug-eluting stents. Observational study of 38,917 Medicare patients who underwent nonemergent coronary stenting from October 2002 through March 2003 when only bare-metal stents were available (bare-metal stent era cohort) and 28,086 similar patients who underwent coronary stenting from September through December 2003, when 61.5% of patients received a drug-eluting stent and 38.5% received a bare-metal stent (drug-eluting stent era cohort). Follow-up data were available through December 31, 2005. Coronary revascularization (percutaneous coronary intervention, coronary artery bypass surgery), ST-elevation myocardial infarction, survival through 2 years of follow-up. Relative to the bare-metal stent era, patients treated in the drug-eluting stent era had lower 2-year risks for repeat percutaneous coronary interventions (17.1% vs 20.0%, P < .001) and coronary artery bypass surgery (2.7% vs 4.2%, P < .01). The difference in need for repeat revascularization procedures between these 2 eras remained significant after risk adjustment (hazard ratio, 0.82; 95% confidence interval, 0.79-0.85). There was no difference in unadjusted mortality risks at 2 years (8.4% vs 8.4%, P =.98 ), but a small decrease in ST-elevation myocardial infarction existed (2.4% vs 2.0%, P < .001). The adjusted hazard of death or ST-elevation myocardial infarction at 2 years was similar (hazard ratio, 0.96; 95% confidence interval, 0.92-1.01). The widespread adoption of drug-eluting stents into routine practice was associated with a decline in the need for repeat revascularization procedures and had similar 2-year risks for death or ST-elevation myocardial infarction to bare-metal stents.


Prospective MEG biomarkers in ASD: pre-clinical evidence and clinical promise of electrophysiological signatures.
Autism spectrum disorders (ASD) are characterized by social impairments and restricted/stereotyped behaviors and currently affect an estimated 1 in 68 children aged 8 years old. While there has been substantial recent focus on ASD in research, both the biological pathology and, perhaps consequently, a fully effective treatment have yet to be realized. What has remained throughout is the hypothesis that ASD has neurobiological underpinnings and the observation that both the phenotypic expression and likely the underlying etiology is highly heterogeneous. Given the neurodevelopmental basis of ASD, a biologically based marker (biomarker) could prove useful not only for diagnostic and prognostic purposes, but also for stratification and response indices for pharmaceutical development. In this review, we examine the current state of the field for MEG-related biomarkers in ASD. We describe several potential biomarkers (middle latency delays [M50/M100], mismatch negativity latency, gamma-band oscillatory activity), and investigate their relation to symptomology, core domains of dysfunction (e.g., language impairment), and putative biological underpinnings.


Are values related to culture, identity, community cohesion and sense of place the values most vulnerable to climate change?
Values related to culture, identity, community cohesion and sense of place have sometimes been downplayed in the climate change discourse. However, they have been suggested to be not only important to citizens but the values most vulnerable to climate change. Here we test four empirical consequences of the suggestion: (i) at least 50% of the locations citizens' consider to be the most important locations in their municipality are chosen because they represent these values, (ii) locations representing these values have a high probability of being damaged by climate change induced sea level rise, (iii) citizens for which these values are particularly strongly held less strongly believe in the local effects of climate change, and (iv) citizens for which these values are particularly strongly held less strongly believe that they have experienced the effects of climate change. The tests were made using survey data collected in 2014 from 326 citizens owning property in Höganäs municipality, Sweden, and included values elicited using a new methodology separating instrumental values from end values, and using the former (which strictly speaking should be seen as estimates of usefulness rather than as aims in themselves) as stepping stones to pinpoint the latter, that represent the true interests of the respondents. The results provide the first evidence that, albeit frequent, values related to culture, identity, community cohesion and sense of place are not the values most vulnerable to climate change. This in turn indicates a need to further investigate the vulnerability of these values to climate change, using a methodology that clearly distinguishes between instrumental and end values.


Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.
A detailed understanding of the mechanisms by which tumors acquire resistance to targeted anticancer agents should speed the development of treatment strategies with lasting clinical efficacy. RAF inhibition in BRAF-mutant melanoma exemplifies the promise and challenge of many targeted drugs; although response rates are high, resistance invariably develops. Here, we articulate overarching principles of resistance to kinase inhibitors, as well as a translational approach to characterize resistance in the clinical setting through tumor mutation profiling. As a proof of principle, we performed targeted, massively parallel sequencing of 138 cancer genes in a tumor obtained from a patient with melanoma who developed resistance to PLX4032 after an initial dramatic response. The resulting profile identified an activating mutation at codon 121 in the downstream kinase MEK1 that was absent in the corresponding pretreatment tumor. The MEK1(C121S) mutation was shown to increase kinase activity and confer robust resistance to both RAF and MEK inhibition in vitro. Thus, MEK1(C121S) or functionally similar mutations are predicted to confer resistance to combined MEK/RAF inhibition. These results provide an instructive framework for assessing mechanisms of acquired resistance to kinase inhibition and illustrate the use of emerging technologies in a manner that may accelerate personalized cancer medicine.


Injury to articular cartilage joint surfaces: II. Displaced fractures of underlying bone. A histopathologic study of human tissue specimens.
Thirty-two pathologic specimens from patients who previously had sustained intraarticular fractures, usually of either the radial head or the patella, and subsequently had excision of the affected bone, were analyzed with respect to the healing mechanisms of articular fractures in humans. The cases were divided into five groups based on the duration of the time interval between fracture and joint-surface resection. The fracture clefts were sometimes perpendicular to the joint surface but often were more complex, and microscopically showed far more comminution than was appreciated from the gross examination. In all cases the articular chondrocytes demonstrated minimal reactive or reparative response to the injuries, even those cells that were situated directly adjacent to a fracture cleft. All significant repair was derived from the fracture-exposed bone marrow. At early stages, this consisted of granulation tissue. Later specimens showed fibrous tissue bridging the cartilage fracture gaps. Chondrous metaplasia within the surface layers of this fibrous callus could be observed occasionally, particularly in specimens with older fractures. However, it was often absent. In the cancellous bone, the healing of the fractures was by osseous, not chondroosseous, callus. In comminuted fractures areas of osteonecrosis were demonstrated in a number of cases.


Adipose Mesenchymal Extracellular Vesicles as Alpha-1-Antitrypsin Physiological Delivery Systems for Lung Regeneration.
Accumulating evidence shows that Mesenchymal Stem/Stromal Cells (MSCs) exert their therapeutic effects by the release of secretome, made of both soluble proteins and nano/microstructured extracellular vesicles (EVs). In this work, for the first time, we proved by a proteomic investigation that adipose-derived (AD)-MSC-secretome contains alpha-1-antitrypsin (AAT), the main elastase inhibitor in the lung, 72 other proteins involved in protease/antiprotease balance, and 46 proteins involved in the response to bacteria. By secretome fractionation, we proved that AAT is present both in the soluble fraction of secretome and aggregated and/or adsorbed on the surface of EVs, that can act as natural carriers promoting AAT in vivo stability and activity. To modulate secretome composition, AD-MSCs were cultured in different stimulating conditions, such as serum starvation or chemicals (IL-1β and/or dexamethasone) and the expression of the gene encoding for AAT was increased. By testing in vitro the anti-elastase activity of MSC-secretome, a dose-dependent effect was observed; chemical stimulation of AD-MSCs did not increase their secretome anti-elastase activity. Finally, MSC-secretome showed anti-bacterial activity on Gram-negative bacteria, especially for Klebsiellapneumoniae. These preliminary results, in addition to the already demonstrated immunomodulation, pave the way for the use of MSC-secretome in the treatment of AAT-deficiency lung diseases.


Structure and function of the methanogenic archaeal community in stable cellulose-degrading enrichment cultures at two different temperatures (15 and 30 degrees C).
Methanogenic cultures were enriched from an air-dried rice field soil and incubated under anaerobic conditions at 30 degrees C with cellulose as substrate (ET1). The culture was then transferred and further incubated at either 15 degrees C (E15) or 30 degrees C (E30), to establish stable cultures that methanogenically degrade cellulose. After five transfers, the rates of CH(4) production became reproducible. At 30 degrees C, CH(4) production rates were (mean+/-S.D.) 15.2+/-0.7 nmol h(-1) ml(-1) culture for the next 16 transfers and at 15 degrees C, they were 0.38+/-0.07 nmol h(-1) ml(-1) for the next six transfers. When E30 was assayed at temperatures between 5-50 degrees C, CH(4) production rates increased with the temperature, reached a maximum at 40 degrees C and then decreased. The same temperature optimum was observed in E15, but with a lower maximum CH(4) production rate. The apparent activation energies of CH(4) production were similar (about 120 kJ mol(-1)4 mM at the beginning of the assay. The structure of the archaeal community was analyzed by molecular techniques. Total DNA was extracted from the microbial cultures before the transfer to different temperatures (ET1) and afterwards (E15, E30). The archaeal small subunit (SSU) ribosomal RNA-encoding genes (rDNA) of these DNA samples were amplified by PCR with archaeal-specific primers and characterized by terminal restriction fragment length polymorphism (T-RFLP). After obtaining a constant T-RFLP pattern in the cultural transfers at 15 and 30 degrees C, the PCR amplicons were used for the generation of clone libraries. Representative rDNA clones (n=10 for each type of culture) were characterized by T-RFLP and sequence analysis. In the primary culture (ET1), the archaeal community was dominated by clones representing 'rice cluster I', a novel lineage of methanogenic Euryarchaeota. However, further transfers resulted in the dominance of Methanosarcinaceae and Methanosaetaceae at 30 and 15 degrees C, respectively. This dominance was confirmed by fluorescence in situ hybridization (FISH) of archaeal cells. Obviously, different archaeal communities were established at the two different temperatures, but their activities nevertheless exhibited similar temperature optima.


Novel properties of statins: suppression of the systemic and bone marrow responses induced by exposure to ambient particulate matter (PM(10)) air pollution.
Exposure to ambient particulate matter (PM(10) elicits systemic inflammatory responses that include the stimulation of bone marrow and progression of atherosclerosis. The present study was designed to assess the effect of repeated exposure of PM(10) on the turnover and release of polymorphonuclear leukocytes (PMNs) from the bone marrow into the circulation and the effect of lovastatin on the PM(10)-induced bone marrow stimulation. Rabbits exposed to PM(10)three times a week for 3 wk, were given a bolus of 5'-bromo-2'-deoxyuridine to label dividing cells in the marrow to calculate the transit time of PMNs in the mitotic or postmitotic pool. PM(10) exposure accelerated the turnover of PMNs by shortening their transit time through the marrow (64.8 ± 1.9 h vs. 34.3 ± 7.4 h, P < 0.001, control vs. PM(10)). This was predominantly due to a rapid transit of PMNs through the postmitotic pool (47.9 ± 0.7 h vs. 21.3 ± 4.3 h, P < 0.001, control vs. PM(10)) but not through the mitotic pool. Lovastatin delayed the transit time of postmitotic PMNs (38.2 ± 0.5 h, P < 0.001 vs. PM(10)) and shifted the postmitotic PMN release peak from 30 h to 48 h. PM(10) exposure induced the prolonged retention of newly released PMNs in the lung, which was reduced by lovastatin (P < 0.01). PM(10) exposure increased plasma interleukin-6 levels with significant reduction by lovastatin (P < 0.01). We conclude that lovastatin downregulates the PM(10)-induced overactive bone marrow by attenuating PM(10)-induced systemic inflammatory responses.


Efficacy of adjunctive ambrisentan treatment for digital ulcers in patients with systemic sclerosis: a case series studyAmbrisentan for digital ulcers.
Purpose: The efficacy of adjunctive ambrisentan treatment in patients with systemic sclerosis (SSc) suffering from digital ulcers (DUs) was investigated.Material and methods: Patients (4 males, 7 females) diagnosed with SSc at our hospital between 2017 and 2022 were enrolled. Ten of them had diffuse SSc, while one had limited SSc. These patients received daily 5 mg doses of ambrisentan in addition to their regular SSc treatment for 16 weeks. Parameters including the total number and size of existing and new DUs, Visual Analog Score (VAS), frequency of Raynaud's phenomenon (RP) attacks, and any adverse effects were assessed.Results: At baseline, the median number and size of DUs was 3.0 (interquartile range (IQR): 2.0-4.0 cm) and 0.4 cm (IQR: 0.3-0.5 cm), respectively. Following the intervention, seven patients with a median of 2.0 DUs and a size of 0.35 cm (IQR: 0.15-0.45 cm) at baseline achieved complete healing. Significant improvements were also observed in other patients. VAS scores decreased from a baseline median of 5.0-0.0 (IQR: 0.0-1.0), and both the frequency and duration of RP attacks notably reduced.Conclusion: Adjunctive ambrisentan therapy proved effective in promoting DU healing and preventing new DUs in SSc patients.


Quality of Life Following Repair of Large Hiatal Hernia is Improved but not Influenced by Use of Mesh: Results From a Randomized Controlled Trial.
Laparoscopic surgery is the treatment of choice for repair of large hiatus hernia, but can be followed by recurrence. Repair with prosthetic mesh has been recommended to prevent recurrence, although complications following mesh repair have generated disagreement about whether or not mesh should be used. The early objective and clinical results of a randomized trial of repair with mesh versus sutures have been reported, and revealed few differences. In the current study, we evaluated quality of life outcomes within this trial at follow-up to 2 years. In a multicenter prospective double-blind randomized trial three methods for repair of large hiatus hernia were compared: sutures versus repair with absorbable mesh (Surgisis) versus non-absorbable (Timesh). Quality of life assessment using the Short-Form 36 (SF-36) questionnaire was undertaken at 3, 6, 12 and 24 months after surgery. SF-36 outcomes (8 individual scales and 2 composite scales) were determined for each group, and compared between groups, and across different follow-up points. 126 patients were enrolled-43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 115 (91.3%) completed a preoperative questionnaire, and 113 (89.7%) completed the post-operative questionnaire at 3 months, 116 (92.1%) at 6 months, 114 (90.5%) at 12 months, and 91 (72.2%) at 24 months. The SF-36 Physical and Mental Component Scores (PCS and MCS) improved significantly following surgery, and this improvement was sustained across 24 months follow-up (p < 0.001 for PCS and MCS at each follow-up point). There were no significant differences between the groups for the component scores or the eight SF-36 subscale scores at each follow-up time. 29 individuals had a recurrence at 6 months follow-up, of which 9 were symptomatic. The PCS were higher in patients with recurrence versus without (p < 0.01), and in patients with a symptomatic recurrence versus asymptomatic recurrence versus no recurrence (p = 0.001). SF-36 measured quality of life improved significantly after repair of large hiatal hernia at up to 2 years follow-up, and there were no differences in outcome for the different repair techniques. The use of mesh versus no mesh in repair of large hiatal hernia did not influence quality of life.


Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial.
The goals were to investigate how many subclinical seizures in full-term neonates with hypoxic-ischemic encephalopathy (HIE) would be missed without continuous amplitude-integrated electroencephalography (aEEG) and whether immediate treatment of both clinical and subclinical seizures would result in a reduction in the total duration of seizures and a decrease in brain injury, as seen on MRI scans. In this multicenter, randomized, controlled trial, term infants with moderate to severe HIE and subclinical seizures were assigned randomly to either treatment of both clinical seizures and subclinical seizure patterns (group A) or blinding of the aEEG registration and treatment of clinical seizures only (group B). All recordings were reviewed with respect to the duration of seizure patterns and the use of antiepileptic drugs (AEDs). MRI scans were scored for the severity of brain injury. Nineteen infants in group A and 14 infants in group B were available for comparison. The median duration of seizure patterns in group A was 196 minutes, compared with 503 minutes in group B (not statistically significant). No significant differences in the number of AEDs were seen. Five infants in group B received AEDs when no seizure discharges were seen on aEEG traces. Six of 19 infants in group A and 7 of 14 infants in group B died during the neonatal period. A significant correlation between the duration of seizure patterns and the severity of brain injury in the blinded group, as well as in the whole group, was found. In this small group of infants with neonatal HIE and seizures, there was a trend for a reduction in seizure duration when clinical and subclinical seizures were treated. The severity of brain injury seen on MRI scans was associated with a longer duration of seizure patterns.


Catalytic Stereoselective Conversion of Biomass-Derived 4'-Methoxypropiophenone to Trans-Anethole with a Bifunctional and Recyclable Hf-Based Polymeric Nanocatalyst.
Anethole (AN) is widely used as an odor cleaner in daily necessities, and can also be applied in the fields of food additives, drug synthesis, natural preservatives, and polymeric materials' preparation. Considering environmental and economic benefits, the use of biomass raw materials with non-precious metal catalysts to prepare high-value fine chemicals is a very promising route. Here, we developed an acid-base bifunctional polymeric material (PhP-Hf (1:1.5)) composed of hafnium and phenylphosphonate in a molar ratio of 1:1.5 for catalytic conversion of biomass-derived 4'-methoxypropiophenone (4-MOPP) to AN via cascade Meerwein-Pondorf-Verley (MPV) reduction and dehydration reactions in a single pot. Compared with the traditional catalytic systems that use high-pressure hydrogen as a hydrogen donor, alcohol can be used as a safer and more convenient hydrogen source and solvent. Among the tested alcohols, 2-pentanol was found to be the best candidate in terms of pronounced selectivity. A high AN yield of 98.1% at 99.8% 4-MOPP conversion (TOF: 8.5 h-1) could be achieved over PhP-Hf (1:1.5) at 220 °C for 2 h. Further exploration of the reaction mechanism revealed that the acid and base sites of PhP-Hf (1:1.5) catalyst synergistically promote the MPV reduction step, while the Brønsted acid species significantly contribute to the subsequent dehydration step. In addition, the PhP-Hf polymeric nanocatalyst can be recycled at least five times, showing great potential in the catalytic conversion of biomass.


Biphasic change in BDNF gene expression following antidepressant drug treatment explained by differential transcript regulation.
Brain-derived neurotrophic factor (BDNF) has been suggested as a possible target for the treatment of depression. The effect by antidepressant drugs on BDNF mRNA expression is, however, strictly dependent on both treatment duration and time after the last administration. The rat BDNF gene itself is complex and expresses four different mRNA isoforms which can be regulated by different signaling cascades. The aim of the present study was to test the hypothesis that the previously shown biphasic action by the antidepressant drugs on total BDNF expression is explained by differential BDNF transcript regulation. For this purpose, we used in situ hybridization with exon-specific oligo nucleotides for exon V (total BDNF mRNA), exon I (protein synthesis-dependent transcripts), exon III and exon IV (immediate early-gene like-transcripts). Following an acute injection, all three drugs tested: fluoxetine, desipramine and TCP decreased total BDNF mRNA (exon V) as well as exon IV mRNA, while no significant effect was recorded for exons I and III mRNAs. In contrast chronic administration of all three drugs resulted in increased expression of exon V- and exon I-containing transcripts (fluoxetine and TCP only) but no significant changes were recorded for exon III and IV mRNAs. Electroconvulsive shock administration showed up-regulation of all four BDNF mRNAs following a single shock, but after repeated administration increases were restricted to exons I- and V-containing transcripts. In summary, this study shows clear evidence of differential BDNF transcript regulation following acute and chronic antidepressant drug treatment.


Revelation of Interfacial Energetics in Organic Multiheterojunctions.
Efficient charge generation via exciton dissociation in organic bulk heterojunctions necessitates donor-acceptor interfaces, e.g., between a conjugated polymer and a fullerene derivative. Furthermore, aggregation and corresponding structural order of polymer and fullerene domains result in energetic relaxations of molecular energy levels toward smaller energy gaps as compared to the situation for amorphous phases existing in homogeneously intermixed polymer:fullerene blends. Here it is shown that these molecular energy level shifts are reflected in interfacial charge transfer (CT) transitions and depending on the existence of disordered or ordered interfacial domains. It can be done so by systematically controlling the order at the donor-acceptor interface via ternary blending of semicrystalline and amorphous model polymers with a fullerene acceptor. These variations in interfacial domain order are probed with luminescence spectroscopy, yielding various transition energies due to activation of different recombination channels at the interface. Finally, it is shown that via this analysis the energy landscape at the organic heterojunction interface can be obtained.


Did the call for boycott by the Catholic bishops affect the polio vaccination coverage in Kenya in 2015? A cross-sectional study.
Polio eradication is now feasible after removal of Nigeria from the list of endemic countries and global reduction of cases of wild polio virus in 2015 by more than 80%. However, all countries must remain focused to achieve eradication. In August 2015, the Catholic bishops in Kenya called for boycott of a polio vaccination campaign citing safety concerns with the polio vaccine. We conducted a survey to establish if the coverage was affected by the boycott. A cross sectional survey was conducted in all the 32 counties that participated in the campaign. A total of 90,157 children and 37,732 parents/guardians were sampled to determine the vaccination coverage and reasons for missed vaccination. The national vaccination coverage was 93% compared to 94% in the November 2014 campaign. The proportion of parents/guardians that belonged to Catholic Church was 31% compared to 7% of the children who were missed. Reasons for missed vaccination included house not being visited (44%), children not being at home at time of visit (38%), refusal by parents (12%), children being as leep (1%), and various other reasons (5%). Compared to the November 2014 campaign, the proportion of children who were not vaccinated due to parent's refusal significantly increased from 6% to 12% in August 2015. The call for boycott did not affect the campaign significantly. However, if the call for boycott is repeated in future it could have some significant negative implication to polio eradication. It is therefore important to ensure that any vaccine safety issues are addressed accordingly.


Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions.
The human parvovirus adeno-associated virus (AAV) infects a broad range of cell types, including human, nonhuman primate, canine, murine, and avian. Although little is known about the initial events of virus infection, AAV is currently being developed as a vector for human gene therapy. Using defined mutant CHO cell lines and standard biochemical assays, we demonstrate that heparan sulfate proteoglycans mediate both AAV attachment to and infection of target cells. Competition experiments using heparin, a soluble receptor analog, demonstrated dose-dependent inhibition of AAV attachment and infection. Enzymatic removal of heparan but not chondroitin sulfate moieties from the cell surface greatly reduced AAV attachment and infectivity. Finally, mutant cell lines that do not produce heparan sulfate proteoglycans were significantly impaired for both AAV binding and infection. This is the first report that proteoglycan has a role in cellular attachment of a parvovirus. Together, these results demonstrate that membrane-associated heparan sulfate proteoglycan serves as the viral receptor for AAV type 2, and provide an explanation for the broad host range of AAV. Identification of heparan sulfate proteoglycan as a viral receptor should facilitate development of new reagents for virus purification and provide critical information on the use of AAV as a gene therapy vector.


Kinetic properties and tissular distribution of mammalian phosphomannomutase isozymes.
Human tissues contain two types of phosphomannomutase, PMM1 and PMM2. Mutations in the PMM2 gene are responsible for the most common form of carbohydrate-deficient glycoprotein syndrome [Matthijs, Schollen, Pardon, Veiga-da-Cunha, Jaeken, Cassiman and Van Schaftingen (1997) Nat. Genet. 19, 88-92]. The protein encoded by this gene has now been produced in Escherichia coli and purified to homogeneity, and its properties have been compared with those of recombinant human PMM1. PMM2 converts mannose 1-phosphate into mannose 6-phosphate about 20 times more rapidly than glucose 1-phosphate to glucose 6-phosphate, whereas PMM1 displays identical Vmax values with both substrates. The Ka values for both mannose 1,6-bisphosphate and glucose 1,6-bisphosphate are significantly lower in the case of PMM2 than in the case of PMM1. Like PMM1, PMM2 forms a phosphoenzyme with the chemical characteristics of an acyl-phosphate. PMM1 and PMM2 hydrolyse different hexose bisphosphates (glucose 1,6-bisphosphate, mannose 1,6-bisphosphate, fructose 1,6-bisphosphate) at maximal rates of approximately 3.5 and 0.3% of their PMM activity, respectively. Fructose 1,6-bisphosphate does not activate PMM2 but causes a time-dependent stimulation of PMM1 due to the progressive formation of mannose 1,6-bisphosphate from fructose 1,6-bisphosphate and mannose 1-phosphate. Experiments with specific antibodies, kinetic studies and Northern blots indicated that PMM2 is the only detectable isozyme in most rat tissues except brain and lung, where PMM1 accounts for about 66 and 13% of the total activities, respectively.


Socially intelligent robots: dimensions of human-robot interaction.
Social intelligence in robots has a quite recent history in artificial intelligence and robotics. However, it has become increasingly apparent that social and interactive skills are necessary requirements in many application areas and contexts where robots need to interact and collaborate with other robots or humans. Research on human-robot interaction (HRI) poses many challenges regarding the nature of interactivity and 'social behaviour' in robot and humans. The first part of this paper addresses dimensions of HRI, discussing requirements on social skills for robots and introducing the conceptual space of HRI studies. In order to illustrate these concepts, two examples of HRI research are presented. First, research is surveyed which investigates the development of a cognitive robot companion. The aim of this work is to develop social rules for robot behaviour (a 'robotiquette') that is comfortable and acceptable to humans. Second, robots are discussed as possible educational or therapeutic toys for children with autism. The concept of interactive emergence in human-child interactions is highlighted. Different types of play among children are discussed in the light of their potential investigation in human-robot experiments. The paper concludes by examining different paradigms regarding 'social relationships' of robots and people interacting with them.


Wolbachia pipientis Associated With Tephritid Fruit Fly Pests: From Basic Research to Applications.
Members of the true fruit flies (family Tephritidae) are among the most serious agricultural pests worldwide, whose control and management demands large and costly international efforts. The need for cost-effective and environmentally friendly integrated pest management (IPM) has led to the development and implementation of autocidal control strategies. These approaches include the widely used sterile insect technique and the incompatible insect technique (IIT). IIT relies on maternally transmitted bacteria (namely Wolbachia) to cause a conditional sterility in crosses between released mass-reared Wolbachia-infected males and wild females, which are either uninfected or infected with a different Wolbachia strain (i.e., cytoplasmic incompatibility; CI). Herein, we review the current state of knowledge on Wolbachia-tephritid interactions including infection prevalence in wild populations, phenotypic consequences, and their impact on life history traits. Numerous pest tephritid species are reported to harbor Wolbachia infections, with a subset exhibiting high prevalence. The phenotypic effects of Wolbachia have been assessed in very few tephritid species, due in part to the difficulty of manipulating Wolbachia infection (removal or transinfection). Based on recent methodological advances (high-throughput DNA sequencing) and breakthroughs concerning the mechanistic basis of CI, we suggest research avenues that could accelerate generation of necessary knowledge for the potential use of Wolbachia-based IIT in area-wide integrated pest management (AW-IPM) strategies for the population control of tephritid pests.


Critical assessment of nucleic acid electrostatics via experimental and computational investigation of an unfolded state ensemble.
Electrostatic forces, acting between helices and modulated by the presence of the ion atmosphere, are key determinants in the energetic balance that governs RNA folding. Previous studies have employed Poisson-Boltzmann (PB) theory to compute the energetic contribution of these forces in RNA folding. However, the complex interaction of these electrostatic forces with RNA features such as tertiary contact formation, specific ion-binding, and complex interhelical junctions present in prior studies precluded a rigorous evaluation of PB theory, especially in physiologically important Mg(2+) solutions. To critically assess PB theory, we developed a model system that isolates these electrostatic forces. The model system, composed of two DNA duplexes tethered by a polyethylene glycol junction, is an analog for the unfolded state of canonical helix-junction-helix motifs found in virtually all structured RNAs. This model system lacks the complicating features that have precluded a critical assessment of PB in prior studies, ensuring that interhelical electrostatic forces dominate the behavior of the system. The system's simplicity allows PB predictions to be directly compared with small-angle X-ray scattering experiments over a range of monovalent and divalent ion concentrations. These comparisons indicate that PB is a reasonable description of the underlying electrostatic energies for monovalent ions, but large deviations are observed for divalent ions. The validation of PB for monovalent solutions allows analysis of the change in the conformational ensemble of this simple motif as salt concentration is changed. Addition of ions allows the motif to sample more compact microstates, increasing its conformational entropy. The increase of conformational entropy presents an additional barrier to folding by stabilizing the unfolded state. Neglecting this effect will adversely impact the accuracy of folding analyses and models.


Fracture through the stalk of pedunculated osteochondromas. A report of three cases.
Although fracture through the base of an osteochondroma is a well-recognized clinical entity, the fate of such fractures has never been documented. Recommendations concerning the treatment of these fractures are contradictory. Of the three cases of fracture through the base of a pedunculated osteochondroma observed in the last 12 years, two healed without problem, one in a patient with a solitary osteochondroma, the other in a patient with multiple osteochondromas. The third patient remained symptomatic one year after injury, and histologic evaluation of the specimen after surgical excision confirmed the diagnosis of fibrous nonunion of the fracture. Experience with fractures through the base of a pedunculated osteochondroma suggests that the majority of these fractures will heal without complication, regardless of whether they involve solitary or multiple osteochondromas. However, symptomatic fibrous nonunion of such a fracture may occur particularly when an osteochondroma is located near large, mobile tendons.


Travel-related thromboembolism: mechanisms and avoidance.
Evidence regarding the existence of travel-related venous thrombosis and pulmonary embolism is building. Research suggests that travel of all kinds increases the risk by two- to four-fold. Risks are not restricted to air travel alone. For travelers without any known risk factors, the risk of experiencing venous thromboembolism is likely to be very low. However, risks increase significantly in the presence of known risk factors, such as age over 60 years, thrombophilic disorders, varicose veins, history of thromboembolism, obesity, women taking oral contraceptives and travel duration over 12 h. A combination of one or more of these risk factors raises the probability of developing travel-related thromboembolism. Possible contributing factors, such as cramped sitting (with suppressed leg venous flow), moderate hypoxia, low humidity in the aircraft and dehydration, are discussed. Depending on the risk profile of individuals, the use of graduated compression stockings and/or pharmacological interventions (low-molecular-weight heparins are preferred) may be recommended.


Endogenous Bufadienolide, Blood Pressure and Alcohol Withdrawal.
Previously, it was demonstrated that marinobufagenin (MBG) is implicated in the development of ethanol withdrawal in rats. It has been shown that ethanol withdrawal is associated with a pressor response in the alcoholics. We hypothesized that elevated levels of sodium pump ligand, MBG, would underline the increase in systolic blood pressure during alcohol withdrawal in humans. The cohort included 9 patients with the diagnosis "alcohol dependence syndrome" (F10.(1-3) according to ICD-10). The blood samples for measurement of MBG concentration were collected from the subjects on the first day of withdrawal and after 7 days treatment of the abstinence. Arterial blood pressure was measured via plethysmography at the same time points. The beginning of the alcoholic abstinence was associated with the rise of arterial blood pressure with enhanced levels of plasma MBG. At day 7 following withdrawal, the systolic blood pressure and MBG levels were decreased to normal values. The development of alcohol withdrawal is accompanied by an increase in arterial blood pressure, which is associated with increased plasma MBG concentration.


NPD1 induction of retinal pigment epithelial cell survival involves PI3K/Akt phosphorylation signaling.
Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes survival in cells exposed to oxidative stress by inducing the activity of anti-inflammatory mediators and suppressing the expression of pro-inflammatory genes. Though retinal pigment epithelial (RPE) cells naturally produce NPD1 from DHA, investigating the mechanisms through which exogenous NPD1 induces cell survival is essential to assess mechanisms of actions and the potential of this lipid mediator for treatment of retinal degenerative diseases. The PI3K/Akt and mTOR/p70S6K pathways are responsible for supporting cell survival upon exposure to oxidative stress. In human ARPE-19 cells pretreated with NPD1 then exposed to varying concentrations of oxidative stress or repeated exposures to oxidative stress, Akt, mTOR, and p70S6K were phosphorylated to a greater extent and for a greater duration than cells not pretreated with NPD1. In addition to increased phosphorylation, a subsequent decreased rate of apoptosis was observed upon NPD1 treatment. Thus NPD1 bioactivity in RPE cells enhances activation of these pathways and promotes cell integrity and survival.


Effectiveness of lumbar zygapophysial joint blockage for low back pain.
Zygapophysial joints have been a well-recognized source of low back pain. This paper compares the efficacy of lumbar zygapophysial joints blockage and medical therapy in terms of pain relief, loss of working days and recurrence of pain in a population with mechanical low back pain. 80 patients suffering from low back pain were included in the study. Patients were divided into 2 groups. Patients in Group I were given diclofenac sodium, thiocolchicoside and were recommended bed rest. Patients in Group II received zygapophysial joints blockage by prilocaine, bupivacaine and methylprednisolone acetate. Both of the groups were evaluated with a Oswestry low back pain disability questionnaire and visual analog scale for pain. Posttreatment VAS and ODQ scores were significantly lower than pretreatment scores. The decrease in these scores in Group II was greater than those of Group I. Blockage of the lumbar facet joints is a rapid and effective way to reduce pain originating from lumbar facet joints.


Transcript profile of the response of two soybean genotypes to potassium deficiency.
The macronutrient potassium (K) is essential to plant growth and development. Crop yield potential is often affected by lack of soluble K. The molecular regulation mechanism of physiological and biochemical responses to K starvation in soybean roots and shoots is not fully understood. In the present study, two soybean varieties were subjected to low-K stress conditions: a low-K-tolerant variety (You06-71) and a low-K-sensitive variety (HengChun04-11). Eight libraries were generated for analysis: 2 genotypes ×2 tissues (roots and shoots) ×2 time periods [short term (0.5 to 12 h) and long term (3 to 12 d)]. RNA derived from the roots and shoots of these two varieties across two periods (short term and long term) were sequenced and the transcriptomes were compared using high-throughput tag-sequencing. To this end, a large number of clean tags (tags used for analysis after removal of dirty tags) corresponding to distinct tags (all types of clean tags) were identified in eight libraries (L1, You06-71-root short term; L2, HengChun04-11-root short term; L3, You06-71-shoot short term; L4, HengChun04-11-shoot short term; L5, You06-71-root long term; L6, HengChun04-11-root long term; L7, You06-71-shoot long term; L8, HengChun04-11-shoot long term). All clean tags were mapped to the available soybean (Glycine max) transcript database (http://www.soybase.org). Many genes showed substantial differences in expression across the libraries. In total, 5,440 transcripts involved in 118 KEGG pathways were either up- or down-regulated. Fifteen genes were randomly selected and their expression levels were confirmed using quantitative RT-PCR. Our results provide preliminary information on the molecular mechanism of potassium absorption and transport under low-K stress conditions in different soybean tissues.


Evaluation of the microbiological efficacy of cleaning agents for tracheostomy inner cannulas.
Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.


Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2) underlies platelet activation by diesel exhaust particles and other charged/hydrophobic ligands.
Platelets are activated by a range of stimuli that share little or no resemblance in structure to each other or to recognized ligands, including diesel exhaust particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR γ-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using platelets from mice deficient in either or both of these receptors. In addition, all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double-deficient platelets, indicating that they bind to additional surface receptors, although only in the case of dextran sulfate does this lead to activation. DEP, fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC-2 in transfected cell lines as shown using a sensitive reporter assay confirming a direct interaction with the two receptors. We conclude that this miscellaneous group of ligands bind to multiple proteins on the cell surface including GPVI and/or CLEC-2, inducing activation. These results have pathophysiological significance in a variety of conditions that involve exposure to activating charged/hydrophobic agents.


Association of vascular physical examination findings and arteriographic lesions in large vessel vasculitis.
To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu's arteritis (TAK) and giant cell arteritis (GCA). In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%-50%) and good-excellent specificity (range 71%-98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%-100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV.


[Abdominal aorta aneurysm in aged patients. Is an operation worthwhile?].
Although abdominal aortic aneurysm (AAA) is an unpredictable and sometimes fatal condition, it can be cured, and studies have indicated that improved peri-operative care has led to a lowering of the operative risk in the elderly. In this study mortality after AAA repair was 3,8% in patients over 60 years compared with 3,2% in those under 60 years. Eighty-seven per cent of the over-60s regained their physical capacities after the operation, and 92% considered the operation to have been worth while. A plea is made that all patients with AAA be referred to a hospital for objective evaluation of the operative risks with a view to elective surgery, since the mortality from ruptured aneurysms is still in the region of 50%.


[The epidemic process as a system. The social regulators of the epidemic process].
The article deals with the mechanisms of spontaneous (urbanization, the international migration of population, the anthropogenic transformation of nature) and goal-oriented regulatory action on the epidemic process. Social factors have been shown to transform into ecological ones with the subsequent transformation of information in the parasitic system and their reflection in the social subsystem as the indices of the risk of infection and its socio-economical importance. Using the processes of urbanization as an example, the present work demonstrates that the mechanism of transmission acts as a filter whose specific features are determined by a range of social factors playing the most important role in the regulation of the epidemic process on the socio-ecosystemic level of its organization.


Effect of Li concentration-dependent material properties on diffusion induced stresses of a Sn anode.
Sn is one of the promising Li ion battery anode materials with high theoretical capacity and mechanical properties that allow for effective relaxation of Li diffusion-induced stresses. Sn is a low melting point metal with a low modulus and strength and has the ability to relax stresses via plasticity and creep deformations. In this study, concentration-dependent material properties are used in numerical simulations to model the Li diffusion-induced stress evolution in Sn micropillars. Simulation results using concentration-dependent material properties resulted in a completely different failure mode in comparison to that of concentration-independent simulation results. Tensile hoop stress needed for crack propagation was analyzed to be at the core for concentration-independent material properties, and switched to being at the surface for concentration-dependent simulation results. In addition, by incorporating these maximum tensile DIS results, the critical size for the failure of Sn micropillars was determined to be 5.3 μm at C/10 charging rate. This was then correlated with experimental observations, where fracture occurred in Sn micropillars with sizes larger than 6 μm, while 4.4 μm sized Sn micropillars survived the lithiation cycle.


Ascorbic acid reduction pretreatment enhancing metal regulation to improve methane production from anaerobic digestion of waste activated sludge.
Conversion of waste activated sludge (WAS) to methane by anaerobic digestion (AD) is often limited by the slow rate of hydrolysis, and the presence of metal ions in sludge is regarded as a critical factor hindering sludge hydrolysis. This study developed a novel strategy to remove Fe from WAS by using ascorbic acid (VC) as a reducing agent under acidic conditions. The feasibility of reduction pretreatment in improving methane production of AD and its intrinsic mechanism were investigated. Results indicate that, under VC doses of 100 mmol/L and pH of 3.50, pretreatment removed 47.60 % of Fe, 59.88 % of Ca, and 51.86 % of Mg contained in the sludge. The removal of metal ions facilitated the disruption of sludge flocculation structure and extracellular polymeric substance (EPS) layers, leading to a 14.78 % increase in cell lysis and a decrease in fractal dimension values to 2.08. Batch AD experiments showed that VC pretreatment improved methane production, with an optimized net methane yield of 190.22 mL/g·VS, an increase of 134.75 % compared to raw WAS. The pretreatment affected the interfacial interaction energy of the sludge, leading to a transformation in the sludge surfaces from hydrophilic to hydrophobic, reducing the interaction between sludge molecules and increasing the number of binding sites available for enzymatic reactions. According to a study of microbial communities, it was found that VC pretreatment caused an increase in the presence of essential functional microbes responsible for hydrolysis, acidification, and methanation. This increase in acetoclastic and hydrogenotrophic methanogens resulted in a substantial enhancement in methane production. These results can be used to develop better pretreatment methods to enhance AD performance.


Determination of creatinine in human serum by short-end injection capillary zone electrophoresis.
A new ultra-rapid free-solution capillary zone electrophoresis method to measure serum creatinine is presented. Procedural parameters such as injection mode, concentration and pH of phosphate running buffer and acidic deproteinization of serum samples were investigated. Short-end injection permits a decrease of the analysis time by injecting samples at the outlet end of a silica capillary closest to the detection window, so reducing the migration distance. Thus, when a capillary with an effective length of 10.2 cm and a 40 mmol/L sodium phosphate buffer pH 2.35 was used, the obtained migration time of the creatinine peak was the shortest never described before, about 1.1 min. These conditions give a good reproducibility of the migration times (coefficient of variation, CV% < 0.5) and the peak areas (CV% < 2.8). Intra- and interassay CV were 3.06 and 6.26%, respectively, and analytical recovery was 99.4%. We compared our proposed method to Jaffé colorimetric assay, by measuring serum creatinine in 128 normal subjects. The obtained data were analyzed by the Passing and Bablok regression and Bland-Altman test. Creatinine concentration in healthy subjects was also used to investigate on its relationships with plasma thiols levels.


[Laparoscopic restoration of the colon continuity after Hartmann procedure].
Literature data and personal experience with laparoscopic restoration of the continuity of the colon after Hartmann's procedure in 19 patients allowed the authors to conclude that minimally traumatic procedures had a number of advantages over operations of wide laparotomy such as less blood loss, rapid restoration of the intestinal motility, early activation of the patients, shorter postoperative stay at hospital. They are also thought to be effective methods of treatment and prophylactics of peritoneal commissures and their complications.


Malignant thymoma: current status and future directions.
Malignant thymomas are rare indolent tumours of the anterior superior mediastinum. Despite a benign histologic appearance, some thymomas invade nearby structures or metastasize. Patients are commonly asymptomatic, but some may present with unusual paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia. Since tumour biopsy may potentially disrupt the thymic capsule, it is often not performed. Patients are therefore diagnosed and staged at the time of definitive surgery. Thymomas can generally be categorized into two stages: non-invasive and invasive. Prognosis closely parallels the disease stage. Surgery is the principal treatment and is curative in early stage disease. Radiation therapy, either alone or in combination with chemotherapy, is an option for both incompletely or completely resected disease. Chemotherapy is offered to patients with locally advanced, recurrent, or metastatic thymoma, with excellent responses and prolonged survival. Multicentre co-operative group clinical trials are required to assess novel thymoma therapies to maximize patient resources in this uncommon tumour.


[Study of water-protein interaction by high resolution NMR].
The interaction between carbonic anhydrase B in the molten globule state and water molecules was studied by high-resolution NMR spectroscopy. NMR spin diffusion experiments revealed spin diffusion propagation from the protein to waters. This is a process of complex bioexponential kinetics presented in spin diffusion spectra as a change in water signal intensity dependent on the post-excitation time of protein molecules. Its reverse, spin diffusion propagation from waters to the protein, was also found. These phenomena are protein concentration- and temperature-dependent and shown to be possibly explained with the assumption that there exist water-protein complexes provoking the formation of large branched associations. At a temperature above 309 K, a stepwise increase in the interaction between waters and proteins occurs in these complexes. The formation of water-protein associations is induced by increasing temperature and/or protein concentration. In these associations, at normal temperature, the protein mobility is close to that of carbonic anhydrase B dimers.


Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence.
Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorescence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocytes was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunofluorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.


A method for volume determination of the orbit and its contents by high resolution axial tomography and quantitative digital image analysis.
The various congenital and acquired conditions which alter orbital volume are reviewed. Previous investigative work to determine orbital capacity is summarized. Since these studies were confined to postmortem evaluations, the need for a technique to measure orbital volume in the living state is presented. A method for volume determination of the orbit and its contents by high-resolution axial tomography and quantitative digital image analysis is reported. This procedure has proven to be accurate (the discrepancy between direct and computed measurements ranged from 0.2% to 4%) and reproducible (greater than 98%). The application of this method to representative clinical problems is presented and discussed. The establishment of a diagnostic system versatile enough to expand the usefulness of computerized axial tomography and polytomography should add a new dimension to ophthalmic investigation and treatment.


Children who have received no vaccines: who are they and where do they live?
Each year 2.1 million children 19 to 35 months of age are undervaccinated. Among these are children who have received no vaccinations. Unvaccinated children are at increased risk of acquiring and transmitting vaccine-preventable diseases. To assess whether the characteristics of children with no vaccinations differ from those of undervaccinated children, to monitor trends in the numbers of unvaccinated children, and to identify states with high rates and counties with large numbers of unvaccinated children. A nationally representative probability sample of children 19 to 35 months of age was collected annually between 1995 and 2001. Vaccination histories were ascertained from children's medical providers. Undervaccinated children had received > or =1 dose of diphtheria-tetanus-pertussis, polio, measles, Haemophilus influenzae type b, hepatitis B, or varicella vaccine but were not fully vaccinated. Unvaccinated children were children who were reported as having no medical providers and having received no vaccinations or children whose medical providers reported administering no vaccinations. A total of 151,720 children sampled between 1995 and 2001, 795 of whom were unvaccinated. Undervaccinated children tended to be black, to have a younger mother who was not married and did not have a college degree, to live in a household near the poverty level, and to live in a central city. Unvaccinated children tended to be white, to have a mother who was married and had a college degree, to live in a household with an annual income exceeding 75,000 dollars, and to have parents who expressed concerns regarding the safety of vaccines and indicated that medical doctors have little influence over vaccination decisions for their children. Unvaccinated children were more likely to be male than female. Annually, approximately 17,000 children were unvaccinated. The largest numbers of unvaccinated children lived in counties in California, Illinois, New York, Washington, Pennsylvania, Texas, Oklahoma, Colorado, Utah, and Michigan. States that allowed philosophical exemptions to laws mandating vaccinations for children as they entered school had significantly higher estimated rates of unvaccinated children. Unvaccinated children have characteristics that are distinctly different from those of undervaccinated children. Unvaccinated children are clustered geographically, increasing the risk of transmitting vaccine-preventable diseases to both unvaccinated and undervaccinated children.


Spread of Chikungunya Virus East/Central/South African Genotype in Northeast Brazil.
We investigated an outbreak of exanthematous illness in Maceió by using molecular surveillance; 76% of samples tested positive for chikungunya virus. Genetic analysis of 23 newly generated genomes identified the East/Central/South African genotype, suggesting that this lineage has persisted since mid-2014 in Brazil and may spread in the Americas and beyond.


Development of a food handling practices assessment tool based on the Sri Lanka food regulations.
Neither the current assessment tool of Sri Lanka for food establishments is based on prevailing Food Regulations 2011 nor did its focus cover serious adaptions for precautions upon prevention of the diseases. The study aims to develop a food handling practices assessment tool based on the Sri Lanka Food Regulations 2011 and to assess food handling practices using a developed tool in the Regional Director of Health Services area, Kalutara. The study consisted of developing food establishments' assessment tool (FEAT) in accordance with Food (Hygiene-1742/26) Regulations of Sri Lanka 2011 and assessing the food establishments using the developed tool in the Regional Director of Health Services area, Kalutara, Sri Lanka. The development of FEAT was carried out to mark inspection scores for food establishments conforming to Food Regulations, others reviewed international food safety protocols and agreements following key informant interviews and focus group discussions. Fully developed FEAT was transferred to a mobile application for ease of use, and assessments were conducted among 421 food establishments in three Medical Officer of Health areas. FEAT contained 11 domains including 75 items with more than 100 assessment points including a guide to conducting an assessment of food handling, compared to the current version of the assessment tool in Sri Lanka. The majority of participants included in the qualitative assessment agreed to include a 1-5 scoring scale to report hygiene levels and to use hygiene regulation to develop FEAT as a legal basis. The highest percentage of food establishments (69.4%) in the "Good" category were in the Bandaragama Medical Officer of Health Area and the highest percentage of food establishments (54.5%) in the "very poor" category were in the Walallawita Medical Officer of Health Area. Food establishments taking precautionary measures, which are not assessed in the current tool, were good, but maintenance of processing area and installation of overhead structures and fitting were poor in food establishments in all three Medical Officer of Health Areas. The novel food assessment tool FEAT is a completely valid instrument for food establishments. It is designed for easy administration and supports reliable assessments. Overall food handling practices of food establishments in the Kalutara Regional Director of Health Services area following assessment with FEAT were in the "satisfactory" category.


Mechanism of suppression of macrophage nitric oxide release by IL-13: influence of the macrophage population.
IL-13 is a cytokine produced by T lymphocytes, mast cells, basophils, and certain B cell lines that up-regulates or inhibits various macrophage functions. In the present study we analyzed the mechanisms of suppression of nitric oxide (NO) release by IL-13 in the macrophage cell line J774A.1 and in thioglycolate-elicited mouse peritoneal macrophages. In both cell types efficient reduction (>80%) of NO production required treatment of the macrophages with IL-13 for at least 7 h before stimulation with IFN-gamma and LPS. In J774A.1 cells, increasing concentrations of IFN-gamma partially antagonized the suppression mediated by IL-13, whereas in peritoneal macrophages, the inhibitory effect of IL-13 was largely independent of the concentrations of IFN-gamma and LPS. In J774A.1 cells, IL-13 strongly reduced both the mRNA and protein levels of inducible nitric oxide synthase (iNOS, NOS-2), as determined by Northern blot analysis and immunoprecipitation. In peritoneal macrophages, in contrast, IL-13 decreased iNOS protein and enzyme activities after 8 to 48 h of stimulation, without altering the expression of iNOS mRNA. Pulse labeling with [35S]methionine revealed that IL-13 caused a 4.7-fold reduction of the de novo synthesis of iNOS protein in these cells. These data demonstrate for the first time that IL-13 is capable of regulating iNOS at both the mRNA and translational levels and underline the important influence of the macrophage population when studying mechanisms of cytokine functions.


Implementing Physical Activity Recommendations in a Tri-Ethnic Rural Community through a Community-University Partnership.
A tri-ethnic rural community with limited resources and a university Prevention Research Center (PRC) developed a partnership to promote evidence-based physical activity. The purpose of this study was to investigate how a community-university partnership can disseminate and implement ἀe Commu nity Guide's recommendations for increasing physical activity and create a model for other under-resourced communities experiencing high rates of chronic disease. Qualitative data collected through 47 semistructured interviews, meeting minutes, and local newspaper articles were coded for themes and analyzed for patterns across the data. Implementation resulted in the creation of new paths and trails, increased walkability throughout the community, local park enhancements, and a community-wide campaign. Lessons learned included the importance of community-defined goals and outcomes, leadership, volunteerism, mutually beneficial goals, synergy, and having nontraditional partners. This research provides a community-university partnership model for implementing evidence-based strategies to increase physical activity in rural communities.


Glanzmann's thrombasthenia associated with gastrointestinal angiodysplasias successfully treated with bevacizumab.
Glanzmann's Thrombasthenia (GT) is a rare hemorrhagic condition caused by a platelet surface receptor disorder of the glycoprotein (GP) IIb/IIIa. Symptoms of GT are various forms of hemorrhages, such as purpura, epistaxis and menorrhagia. Gastrointestinal bleeding (GIB) is a rare expression of the condition and may occur due to traumas in the GI tract or as a consequence of gastrointestinal angiodysplasia (GIADs). In this case report, we present a middle-aged woman with recurrent GIB consequent to GIADs with persistent melena and iron deficiency anemia. After several unsuccessful therapeutic interventions, the patient was studied by the hereditary hemorrhagic telangiectasia's (HHT - Osler-Weber-Rendu disease) unit, where she received bevacizumab, showing a complete improvement in symptoms as well as a reduction in her GIADs. This case shows that bevacizumab could be a possible line of treatment for patients with coagulation disorders with GIADs.


TCR beta-chain variable region-driven selection and massive expansion of HLA-class I-restricted antitumor CTL lines from HLA-A*0201+ melanoma patients.
Recognition of a given melanoma Ag involves a limited array of T cell clones bearing a structurally defined TCR. The aim of this study was to verify whether this information can be used to isolate and expand such anti-tumor effectors from fresh lymphocyte populations. We found that one to three different TCR beta-chain variable (TCRBV) regions were significantly expanded in 4-wk mixed lymphocyte-tumor cultures (MLTC) from six HLA-A*0201+ melanoma patients, and that the T cells expressing the expanded TCRBV regions were involved in HLA class I-restricted lysis of the tumor. T cell activation by mAbs to MLTC-selected TCRBV region and CD28 resulted in large scale expansion (1-10 x 10(9) cells) of T cell lines, highly enriched for the expression of a single TCRBV region and for CD8+ T cells. The TCRBV-driven selection was equally effective when applied to patients' or healthy donors' lymphocytes, and the T cell lines isolated from melanoma patients exerted HLA class I-restricted lysis of the autologous tumor. MLTC and TCRBV-selected lines recognized allogeneic melanomas sharing HLA-A and -B alleles with the autologous tumor, but only two of the HLA-A2-restricted lines were directed to a known peptide from melanoma-associated Ags. Single-strand conformation polymorphism analysis indicated a polyclonal composition of both MLTC and TCRBV-selected lines, but expansion of clonotypes with identical CDR3 length was observed only in the MLTC lines. Thus, TCRBV-driven selection can be exploited to obtain large scale expansion of antitumor CTL lines from melanoma patients.


Head movements produced during whole body rotations and their sensitivity to changes in head inertia in squirrel monkeys.
The head's inertia produces forces on the neck when the body moves. One collective function of the vestibulocollic and cervicocollic reflexes (VCR and CCR) is thought to be to stabilize the head with respect to the trunk during whole body movements. Little is known as to whether their head-movement kinematics produced by squirrel monkeys during whole body rotations are similar to those of cats and humans. Prior experiments with cats and human subjects have shown that yaw head-movement kinematics are unaffected by changes in the head's inertia when the whole body is rotated. These observations have led to the hypothesis that the combined actions of the VCR and CCR accommodate for changes in the head's inertia. To test this hypothesis in squirrel monkeys, it was imperative to first characterize the behavior of head movements produced during whole body rotation and then investigate their sensitivity to changes in the head's inertia. Our behavioral studies show that squirrel monkeys produce only small head movements with respect to the trunk during whole body rotations over a wide range of stimulus frequencies and velocities (0.5-4.0 Hz; 0-100 degrees /s). Similar head movements were produced when only small additional changes in the head's inertia occurred. Electromyographic recordings from the splenius muscle revealed that an active process was utilized such that increases in muscle activation occurred when the inertia of the head was increased. These results are consistent with prior cat and human studies, suggesting that squirrel monkeys have a similar horizontal VCR and CCR.


Predictive Power of Clean Bed Filtration Theory for Fecal Indicator Bacteria Removal in Stormwater Biofilters.
Green infrastructure (also referred to as low impact development, or LID) has the potential to transform urban stormwater runoff from an environmental threat to a valuable water resource. In this paper we focus on the removal of fecal indicator bacteria (FIB, a pollutant responsible for runoff-associated inland and coastal beach closures) in stormwater biofilters (a common type of green infrastructure). Drawing on a combination of previously published and new laboratory studies of FIB removal in biofilters, we find that 66% of the variance in FIB removal rates can be explained by clean bed filtration theory (CBFT, 31%), antecedent dry period (14%), study effect (8%), biofilter age (7%), and the presence or absence of shrubs (6%). Our analysis suggests that, with the exception of shrubs, plants affect FIB removal indirectly by changing the infiltration rate, not directly by changing the FIB removal mechanisms or altering filtration rates in ways not already accounted for by CBFT. The analysis presented here represents a significant step forward in our understanding of how physicochemical theories (such as CBFT) can be melded with hydrology, engineering design, and ecology to improve the water quality benefits of green infrastructure.


Repurposing of an old drug: In vitro and in vivo efficacies of buparvaquone against Echinococcus multilocularis.
The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the lethal disease alveolar echinococcosis. Current chemotherapeutic treatment options are based on benzimidazoles (albendazole and mebendazole), which are insufficient and hence alternative drugs are needed. In this study, we screened the 400 compounds of the Medicines for Malaria Venture (MMV) Pathogen Box against E. multilocularis metacestodes. For the screen, we employed the phosphoglucose isomerase (PGI) assay which assesses drug-induced damage on metacestodes, and identified ten new compounds with activity against the parasite. The anti-theilerial drug MMV689480 (buparvaquone) and MMV671636 (ELQ-400) were the most promising compounds, with an IC50 of 2.87 μM and 0.02 μM respectively against in vitro cultured E. multilocularis metacestodes. Both drugs suggested a therapeutic window based on their cytotoxicity against mammalian cells. Transmission electron microscopy revealed that treatment with buparvaquone impaired parasite mitochondria early on and additional tests showed that buparvaquone had a reduced activity under anaerobic conditions. Furthermore, we established a system to assess mitochondrial respiration in isolated E. multilocularis cells in real time using the Seahorse XFp Analyzer and demonstrated inhibition of the cytochrome bc1 complex by buparvaquone. Mice with secondary alveolar echinococcosis were treated with buparvaquone (100 mg/kg per dose, three doses per week, four weeks of treatment), but the drug failed to reduce the parasite burden in vivo. Future studies will reveal whether improved formulations of buparvaquone could increase its effectivity.


Functional evaluation of a novel vitreous substitute using polyethylene glycol sols injected into a foldable capsular vitreous body.
Polyethylene glycol (PEG) is a short-term (41 days) potential vitreous substitute and is too short for an ideal vitreous substitute. Previously, a foldable capsular vitreous body (FCVB) was designed to mimic vitreous function. The aim of this study is to evaluate whether PEG injected into FCVB can serve as a long-term vitreous substitute. In vitro study, a concentration of 5% (w/v) PEG sols showed natural-like mechanical and optical properties in terms of pH, density, light transmittance, refractive index, interfacial tension, viscosity, rheology, and cytotoxicity. Then in vivo tests, 30 rabbits received standard pars plana vitrectomy, of which 12 eyes were implanted with PEG injected into FCVB, nine eyes were injected with PEG sols alone, and nine others were injected with balance salt solution as control. A clinical evaluation of the anterior segment, fundus, and intraocular pressure was measured pre- and postoperatively up to 180 days, which showed that FCVBs had good retina supporting function, except for a higher incidence of cataracts. Gross pathology, hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining analysis also showed that FCVBs had good biocompatibility, and that all quadrants of the capsular wall fitted well with the retina. This study demonstrated that PEG injected into FCVB can serve as a long-term vitreous substitute and has potential clinical use.


The effects of betulinic acid on neurobehavioral activity, electrophysiology and histological changes in an animal model of the Alzheimer's disease.
Alzheimer's disease (AD) is a common disorder characterized by aggregation and conversion of amyloid beta (Aβ) monomers to fibrils. Betulinic acid (BA) strongly accelerated this pathway through circumventing the oligomeric intermediate state. BA at doses of 0.2 and 0.4μM/10μl/rat (intra-hippocampal or i.h injection, vehicle: DMSO) was bilaterally administrated 180 and 10min before co-administration of Aβ (0.1μM/5μl/rat, i.h injection, vehicle: PBS) and Streptozotocin (STZ, 1.5mg/kg/10μl/rat, intracerebroventricular or i.c.v. injection, vehicle: aCSF). The behavioral assessments (spatial and passive avoidance memory, anxiety, locomotion, depression, and motor coordination), electrophysiological evaluations (hippocampal long- term potentiation (LTP)) as well as histological changes were evaluated 30days after injections. The indices of spatial and passive avoidance memory, anxiety/depression and LTP records were significantly impaired in AD rats in comparison with the sham. Pretreatment of BA (0.4μM) showed a more significant effect on memory, anxiety, all LTP parameters, and histological damage compared to a low dose in contrast to the AD group. Overall, BA pretreatment was able to prevent AD-induced neurobehavioral and LTP deficits in rats and the best effect was observed in molar ratio of 1:4 (Aβ to BA).


The neural basis of video gaming.
Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity.


Combined GC- and UHPLC-HR-MS Based Metabolomics to Analyze Durable Anti-fungal Resistance Processes in Cereals.
Introduction of durable resistance genes in crops is an important strategy to prevent yield loss caused by pathogens. The durable multi-pathogen resistance gene Lr34 originating from wheat is widely used in breeding, and is functionally transferable to barley and rice. The molecular resistance mechanism of Lr34, encoding for an adenosine triphosphate-binding cassette transporter, is not known yet. To understand the molecular function and the defense response of durable disease resistance in cereals, the metabolic response of Lr34 was investigated in, except for the Lr34 gene, genetically identical lines of barley, rice and wheat. A broad range of compounds including primary, secondary and lipophilic metabolites were analyzed by a combination of gas (GC) and liquid chromatography (LC) mass spectrometry (MS) based methods. Data from metabolomics correlated well with transcriptomics data for plant defense responses such as the formation of anti-fungal hordatines or the components of the glyoxylate cycle. Induction of the glyoxylate cycle found in transgenic Lr34 rice grown in the greenhouse was confirmed in field-grown natural Lr34 wheat. Constitutively active plant defense responses were observed in the different cereals.


Association between serum cholesterol and eating behaviours during early childhood: a cross-sectional study.
Modifiable behaviours during early childhood may provide opportunities to prevent disease processes before adverse outcomes occur. Our objective was to determine whether young children's eating behaviours were associated with increased risk of cardiovascular disease in later life. In this cross-sectional study involving children aged 3-5 years recruited from 7 primary care practices in Toronto, Ontario, we assessed the relation between eating behaviours as assessed by the NutriSTEP (Nutritional Screening Tool for Every Preschooler) questionnaire (completed by parents) and serum levels of non-high-density lipoprotein (HDL) cholesterol, a surrogate marker of cardiovascular risk. We also assessed the relation between dietary intake and serum non-HDL cholesterol, and between eating behaviours and other laboratory indices of cardiovascular risk (low-density lipoprotein [LDL] cholesterol, apolipoprotein B, HDL cholesterol and apoliprotein A1). A total of 1856 children were recruited from primary care practices in Toronto. Of these children, we included 1076 in our study for whom complete data and blood samples were available for analysis. The eating behaviours subscore of the NutriSTEP tool was significantly associated with serum non-HDL cholesterol (p = 0.03); for each unit increase in the eating behaviours subscore suggesting greater nutritional risk, we saw an increase of 0.02 mmol/L (95% confidence interval [CI] 0.002 to 0.05) in serum non-HDL cholesterol. The eating behaviours subscore was also associated with LDL cholesterol and apolipoprotein B, but not with HDL cholesterol or apolipoprotein A1. The dietary intake subscore was not associated with non-HDL cholesterol. Eating behaviours in preschool-aged children are important potentially modifiable determinants of cardiovascular risk and should be a focus for future studies of screening and behavioural interventions.


Health informatics design for assisted diagnosis of subclinical atherosclerosis, structural, and functional arterial age calculus and patient-specific cardiovascular risk evaluation.
Traditional methods used to assess cardiovascular risk (i.e., the Framingham Risk Score) exhibit clear limitations. To aid in patient-specific risk stratification and diagnosis it has been proposed to evaluate noninvasively structural and functional arterial parameters. A National Public University Center (CUiiDARTE) was created in Uruguay with the aim of developing and applying strategies to improve cardiovascular risk stratification and subclinical vascular disease detection. To this end a health informatics approach and tool was designed, developed, and implemented in CUiiDARTE. Its goals were to: 1) promote screening for subclinical atherosclerosis, 2) develop a centralized database to store information obtained noninvasively from anywhere in our country, 3) develop a biomathematical model integrating values for arterial structure and function into traditional cardiovascular risk assessment, 4) generate a detailed and comprehensive report for the specialist comparing patient data with reference data from the healthy population, 5) generate a similar report (using a structural and functional arterial age calculator) for the patients assessing the state of their arteries. In this paper, we present the main characteristics of the CUiiDARTE health informatics development.


Oxidative stress and neuronal death/survival signaling in cerebral ischemia.
It has been demonstrated by numerous studies that apoptotic cell death pathways are implicated in ischemic cerebral injury in ischemia models in vivo. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides oxygen as a substrate for numerous enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to produce adenosine triphosphate. Oxygen radicals, the products of these biochemical and physiological reactions, are known to damage cellular lipids, proteins, and nucleic acids and to initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways could provide novel therapeutic strategies in clinical stroke.


Cross-sectional imaging of nontraumatic emergencies of the spleen.
Multiple nontraumatic splenic emergencies are encountered during the imaging of patients in emergency room. Occasionally, patients are investigated for symptoms of suspected splenic pathology, such as abscess, infarct, symptomatic splenic artery aneurysm and pseudoaneurysm, splenic torsion, or rupture. More often, however, splenic emergencies, such as splenic masses and splenic vein thrombosis, are detected in patients in the emergency room during the evaluation of nonspecific abdominal pain. It is essential for radiologists to be vigilant in the identification of nontraumatic splenic emergencies and to be familiar with interventional radiology management options for these pathologies. Our aim is to highlight factors affecting lesion detection on multiple imaging modalities and to discuss the advantages of different cross-sectional modalities for the diagnosis of splenic abnormalities. Finally, we review the management options with emphasis on interventional radiology where applicable.


The evolution of species interactions across natural landscapes.
Given the potential for rapid and microgeographical adaptation, ecologists increasingly are exploring evolutionary explanations for community patterns. Biotic selection can generate local adaptations that alter species interactions. Although some gene flow might be necessary to fuel local adaptation, higher gene flow can homogenise traits across regions and generate local maladaptation. Herein, I estimate the contributions of local biotic selection, gene flow and spatially autocorrelated biotic selection to among-population divergence in traits involved in species interactions across 75 studies. Local biotic selection explained 6.9% of inter-population trait divergence, an indirect estimate of restricted gene flow explained 0.1%, and spatially autocorrelated selection explained 9.3%. Together, biotic selection explained 16% of the variance in population trait means. Most biotic selection regimes were spatially autocorrelated. Hence, most populations receive gene flow from populations facing similar selection, which could allow for local adaptation despite moderate gene flow. Gene flow constrained adaptation in studies conducted at finer spatial scales as expected, but this effect was often confounded with spatially autocorrelated selection. Results indicate that traits involved in species interactions might often evolve across landscapes, especially when biotic selection is spatially autocorrelated. The frequent evolution of species interactions suggests that evolutionary processes might often influence community ecology.


[Analysis of thiabendazole in citrus fruits and bananas].
With regard to routine analyses in market control, the authors recommend two methods (according to the expected amounts of active principle) for the determination of thiabendazole residues on citrus fruits and bananas. The ultraviolet spectrophotometric method is preferable in determining thiabendazole contents of more than 1 p.p.m., if the cleaning operations described are respected. For the detection of thiabendazole and for the determination of amounts of less than 1 p.p.m. (the tolerance limit being 0.2 p.p.m. for pomes, berries, stone fruits, kernel fruits and also for potatoes) the thin-layer chromatographic method seems likewise to be suited (also in considering that it is semi-quantitative by nature); especially since the spectrophotometric method yields values by 0.2 p.p.m. too high (due to the measurement of residual absorption of vegetable constituents). The authors are of opinion that such an error must be considered to be too high for contents lower than 1 p.p.m.


Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles.
The four chambers of the human heart play distinct roles in the maintenance of normal cardiac function, and are differentially affected by inherited/acquired cardiovascular disease. To probe the molecular determinants of these functional differences, we examined mRNA and lncRNA expression profiles in the left (LA) and right (RA) atria, the left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8). Analysis of paired atrial and ventricular samples (n = 40) identified 5,747 mRNAs and 2,794 lncRNAs that were differentially (>1.5 fold; FDR < 0.05) expressed. The largest differences were observed in comparisons between the atrial (RA/LA) and ventricular (RV/LV/IVS) samples. In every case (e.g., LA vs LV, LA vs RV, etc.), >2,300 mRNAs and >1,200 lncRNAs, corresponding to 17-28% of the total transcripts, were differentially expressed. Heterogeneities in mRNA/lncRNA expression profiles in the LA and RA, as well as in the LV, RV and IVS, were also revealed, although the numbers of differentially expressed transcripts were substantially smaller. Gender differences in mRNA and lncRNA expression profiles were also evident in non-failing human atria and ventricles. Gene ontology classification of differentially expressed gene sets revealed chamber-specific enrichment of numerous signaling pathways.


Nomenclature in Abdominal Wall Hernias: Is It Time for Consensus?
Abdominal wall reconstruction is a rapidly evolving area of surgical interest. Due to the increase in prevalence and size of ventral hernias and the high recurrence rates, the academic community has become motivated to find the best reconstruction techniques. Whilst interrogating the abdominal wall reconstruction literature, we discovered an inconsistency in hernia nomenclature that must be addressed. The terms used to describe the anatomical planes of mesh implantation 'inlay', 'sublay' and 'underlay' are misinterpreted throughout. We describe the misinterpretation of these terms and give evidence of where it exists in the literature. We give three critical arguments of why these misinterpretations hinder advances in abdominal wall reconstruction research. The correct definitions of the anatomical planes, and their respective terms, are described and illustrated. Clearly defined nomenclature is required as academic surgeons strive to improve abdominal wall reconstruction outcomes and lower complication rates.


Near-Infrared Refractometry of Liquids by Means of Waveguide ?erenkov Second-Harmonic Generation.
A new, to our knowledge, method for measuring the refractive index of liquids in the near infrared by means of waveguide ?erenkov second-harmonic generation is presented. It makes use of a nonlinear planar waveguide whereby the liquid sample is put into place as the cover. By measurement of the output angle of the ?erenkov radiation mode (in the visible) the liquid sample refractive index (in the near infrared) is determined. Experiments were performed by means of a proton-exchanged LiNbO(3) waveguide as the sensor and a set of liquids with known refractive index. The values obtained are in good agreement with the expected ones, and the average accuracy is on the third decimal place.


Significance of cytoreductive surgery including bowel resection for patients with advanced ovarian cancer.
The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.


Neuronal Nitric Oxide Synthase in Nucleus Accumbens Specifically Mediates Susceptibility to Social Defeat Stress through Cyclin-Dependent Kinase 5.
Stress-induced depression is common worldwide. NAc, a "reward" center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5.SIGNIFICANCE STATEMENT Stress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.


Accelerated Scheme to Predict Ring-Opening Polymerization Enthalpy: Simulation-Experimental Data Fusion and Multitask Machine Learning.
Ring-opening enthalpy (ΔHROP) is a fundamental thermodynamic quantity controlling the polymerization and depolymerization of an important class of recyclable polymers, namely, those created from ring-opening polymerization (ROP). Highly accurate first-principles-based computational methods to compute ΔHROP are computationally too demanding to efficiently guide the design of depolymerizable polymers. In this work, we develop a generalizable machine-learning model that was trained on experimental measurements and reliably computed simulation results of ΔHROP (the latter provides a pathway to systematically increase the chemical diversity of the data). Predictions of ΔHROP using this machine-learning model require essentially no time while the prediction accuracy is about ∼8 kJ/mol, approaching the well-known chemical accuracy. We hope that this effort will contribute to the future development of new depolymerizable polymers.