Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles.
Interactions between respiratory viruses during infection affect transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralizing antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses co-localizing at the apical cell surface. Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion.


Drosophila glue protects from predation.
Animals can be permanently attached to a substrate in terrestrial environments at certain stages of their development. Pupa adhesion has evolved multiple times in insects and is thought to maintain the animal in a place where it is not detectable by predators. Here, we investigate whether pupa adhesion in Drosophila can also protect the animal by preventing potential predators from detaching the pupa. We measured the adhesion of Drosophila species sampled from the same area and found that pupa adhesion varies among species, which can be explained by different glue production strategies. Then, we compared attached and manually detached pupae in both field and laboratory assays to investigate the role of pupa adhesion to prevent predation. First, we found that attached pupae remain onsite 30% more than detached pupae in the field after 3 days, probably because they are less predated. Second, we observed that attached pupae are less efficiently predated by ants in the laboratory: they are not carried back to the ant nest and more ants are needed to consume them onsite. Our results show that pupa adhesion can prevent the animal from being taken away by predators and is crucial for Drosophila fly survival.


Postpartum Acute Colonic Pseudo-Obstruction (Ogilvie's Syndrome): A systematic review of case reports and case series.
Ogilvie's Syndrome or Acute Colonic Pseudo-Obstruction (ACPO) is a rare condition characterized by massive dilatation of the colon in the absence of mechanical obstruction. About 10% of all reported cases are related to Obstetric and Gynaecological procedures, Caesarean section being the commonest associated factor. Acute intestinal dilatation, if not treated, may lead to perforation and faecal peritonitis with consequent high morbidity and mortality. An electronic literature searches were performed in PubMed, EMBASE, Google scholar and hand searches for relevant references were included without any language restriction. All the records reported after year 2002 were included for the full review. We analyzed the quality of the reports and the data was further analyzed for their respective risk factors, clinical features, management methods, morbidity and mortality. The results from our searches included a total of 125 cases of postpartum ACPO. A total of 66 cases were reported in 37 publications after year 2002. Details of delivery were recorded in 13(19%), clinical manifestations in 49(69%), imaging results in 43(65%) and management described in 100% of the cases. Although 62(92%) cases were following caesarean section, no specific antepartum or intrapartum factors were associated with ACPO. The caesarean sections performed for indications of preeclampsia, multiple pregnancy, antepartum haemorrhage/placenta previa were more in this group of patients who developed ACPO compared to caesarean sections performed for same indication in general population of England and Wales. Abdominal distension and pain were the commonest symptoms, followed by vomiting. Fever was common in patients with perforation. Twenty eight (43%) patients had intestinal perforation or impending perforation, and 31(47%) patients required laparotomy. Conservative management was successful in 33(50%) patients. All patients with a caecal diameter of more than 12cm perforated compared to 3/17 with a diameter of less than 9cm. Most perforations were diagnosed between postoperative day 3 and day 5. Only one case of mortality has been recorded (1.5%). No specific risk factors could be identified for postpartum ACPO. A postpartum patient with abdominal distension and pain should have appropriate imaging to rule out colonic dilatation and/or perforation. Perforation may occur with a caecal diameter of less than 9cm but it is more likely if the diameter exceeded 12cm. The mortality risk appears to be low in the postpartum group compared to other patients with ACPO. There is a need for establishing national level databases to capture all the relevant data in a consistent manner, to understand this rare disease process.


Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices.
Central sleep apnea is common in heart failure patients. Transvenous phrenic nerve stimulation (TPNS) requires placing a lead to stimulate the phrenic nerve and activate the diaphragm. Data are lacking concerning the safety and efficacy of TPNS in patients with concomitant cardiovascular implantable electronic devices (CIEDs). To report the safety and efficacy of TPNS in patients with concomitant CIEDs. In the remedē System Pivotal Trial, 151 patients underwent TPNS device implant. This analysis compared patients with concomitant CIEDs to those without with respect to safety, implant metrics, and efficacy of TPNS. Safety was assessed using incidence of adverse events and device-device interactions. A detailed interaction protocol was followed. Implant metrics included overall TPNS implantation success. Efficacy endpoints included changes in the apnea-hypopnea index (AHI) and quality of life. Of 151 patients, 64 (42%) had a concomitant CIED. There were no significant differences between the groups with respect to safety. There were 4 CIED oversensing events in 3 patients leading to 1 inappropriate defibrillator shock and delivery of antitachycardia pacing. There was no difference in efficacy between the CIED and non-CIED subgroups receiving TPNS, with both having similar percentages of patients who achieved ≥50% reduction in AHI and quality-of-life improvement. Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, implantation success, and TPNS efficacy. A detailed interaction protocol should be followed to minimize the incidence of device-device interaction.


[Large-scale imaging of corneal nerve fibres by guided eye movements].
The high resolution of corneal confocal microscopy (CCM) allows in vivo imaging of the corneal sub-basal nerve plexus (SNP). The field of view of a single CCM image (0.16 mm²) is not sufficient for the reliable morphometric characterisation of the SNP. Therefore we are developing a highly automated mosaicking technique for large-area imaging of the SNP using CCM image sequences. In order to acquire an image sequence of a larger area of the SNP, the view direction of the patient is guided by a computer-controlled moving fixation target on a display in front of the non-examined eye. The CCM image sequence is recorded with 30 fps. An online calculated mosaic image allows the medical operator to observe the acquisition process and assess the quality and size of the resulting image during the CCM recording process. Remaining image artefacts are corrected in an automated post-processing step. Using a first prototype system and an appropriate fixation target trajectory, a mean growth of the covered SNP area of 0.18 mm²/s could be achieved. Using the presented technology, large-area images of the SNP can be generated. The technology is characterized by a high degree of automation and short examination times.


Synthesis, spectroscopy, and computational analysis of photoluminescent bis(aminophenyl)-substituted thiophene derivatives.
Substituted oligothiophenes have a long history in the field of organic electronics, as they often combine outstanding electro-optical properties with the ease of synthesis. To assist the rational selection of the most promising structures to be synthesized, there is the demand for tools that allow prediction of the properties of the materials. In this study, we present strategies for synthesis and computational characterization, with respect to the fluorescence behavior of oligothiophene-based materials for organoelectronic applications. In a combined approach, sophisticated computational methodologies are directly compared to experimental results. The M06-2X functional in combination with the polarizable continuum model in a state-specific formulation for excited-state solvation proved to be particularly reliable. In addition, a semiclassical approach for describing the vibrational broadening of the spectra is employed. As a result, a robust procedure for the prediction of the fluorescence spectra of oligothiophene derivatives is presented.


Parental manipulation of the behavior of normal and deviant children.
The present study examined the ability of parents to bias home-observation data by influencing their child's behavior in socially desirable and undesirable directions. Parents of 12 deviant and 12 non-deviant boys, aged 4-8, were given the response set to present their child as "good", "bad", and usual (normal) during 6 45-minute observations of family interaction. Deviant and non-deviant children showed significantly more deviant behavior under the bad condition as compared with normal, whereas their good and normal conditions did not differ. Parent positive and negative behaviors were related to changes in child deviant behavior for the deviant sample; parent positive and commanding behaviors were related to changes in child deviant behavior for the nondeviant sample. Parent self-report of behavior change was generally consistent with the observation data. The results suggested implications for naturalistic observations of families and for child behavior change interventions.


DNA-Functionalized Metal-Organic Framework Nanoparticles for Intracellular Delivery of Proteins.
Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular transfection, nucleic acid-metal organic framework nanoparticle (MOF NP) conjugates have been designed and synthesized from NU-1000 and PCN-222/MOF-545, respectively, and phosphate-terminated oligonucleotides. They have been characterized structurally and with respect to their ability to enter mammalian cells. The MOFs act as protein hosts, and their densely functionalized, oligonucleotide-rich surfaces make them colloidally stable and ensure facile cellular entry. With insulin as a model protein, high loading and a 10-fold enhancement of cellular uptake (as compared to that of the native protein) were achieved. Importantly, this approach can be generalized to facilitate the delivery of a variety of proteins as biological probes or potential therapeutics.


Next-Generation Cell-Active Inhibitors of the Undrugged Oncogenic PTP4A3 Phosphatase.
Oncogenic protein tyrosine phosphatases (PTPs) are overexpressed in numerous human cancers but they have been challenging pharmacological targets. The emblematic oncogenic PTP4A tyrosine phosphatase family regulates many fundamental malignant processes. 7-Imino-2-phenylthieno[3,2-c]pyridine-4,6(5H,7H)-dione (JMS-053) is a novel, potent, and selective PTP4A inhibitor but its mechanism of action has not been fully elucidated, nor has the chemotype been fully investigated. Because tyrosine phosphatases are notoriously susceptible to oxidation, we interrogated JMS-053 and three newly synthesized analogs with specific attention on the role of oxidation. JMS-053 and its three analogs were potent in vitro PTP4A3 inhibitors, but 7-imino-5-methyl-2-phenylthieno[3,2-c]pyridine-4,6(5H,7H)-dione (NRT-870-59) appeared unique among the thienopyridinediones with respect to its inhibitory specificity for PTP4A3 versus both a PTP4A3 A111S mutant and an oncogenic dual specificity tyrosine phosphatase, CDC25B. Like JMS-053, NRT-870-59 was a reversible PTP4A3 inhibitor. All of the thienopyridinediones retained cytotoxicity against human ovarian and breast cancer cells grown as pathologically relevant three-dimensional spheroids. Inhibition of cancer cell colony formation by NRT-870-59, like JMS-053, required PTP4A3 expression. JMS-053 failed to generate significant detectable reactive oxygen species in vitro or in cancer cells. Mass spectrometry results indicated no disulfide bond formation or oxidation of the catalytic Cys104 after in vitro incubation of PTP4A3 with JMS-053 or NRT-870-59. Gene expression profiling of cancer cells exposed to JMS-053 phenocopied many of the changes seen with the loss of PTP4A3 and did not indicate oxidative stress. These data demonstrate that PTP4A phosphatases can be selectively targeted with small molecules that lack prominent reactive oxygen species generation and encourage further studies of this chemotype. SIGNIFICANCE STATEMENT: Protein tyrosine phosphatases are emerging as important contributors to human cancers. We report on a new class of reversible protein phosphatase small molecule inhibitors that are cytotoxic to human ovarian and breast cancer cells, do not generate significant reactive oxygen species in vitro and in cells, and could be valuable lead molecules for future studies of PTP4A phosphatases.


Integrated, long term, sustainable, cost effective biosolids management at a large Canadian wastewater treatment facility.
The Greater Moncton Sewerage Commission's 115,000 m3/d advanced, chemically assisted primary wastewater treatment facility located in New Brunswick, Canada, has developed an integrated, long term, sustainable, cost effective programme for the management and beneficial utilization of biosolids from lime stabilized raw sludge. The paper overviews biosolids production, lime stabilization, conveyance, and odour control followed by an indepth discussion of the wastewater sludge as a resource programme, namely: composting, mine site reclamation, landfill cover, land application for agricultural use, tree farming, sod farm base as a soil enrichment, topsoil manufacturing. The paper also addresses the issues of metals, pathogens, organic compounds, the quality control program along with the regulatory requirements. Biosolids capital and operating costs are presented. Research results on removal of metals from primary sludge using a unique biological process known as BIOSOL as developed by the University of Toronto, Canada to remove metals and destroy pathogens are presented. The paper also discusses an ongoing cooperative research project with the Université de Moncton where various mixtures of plant biosolids are composted with low quality soil. Integration, approach to sustainability and "cumulative effects" as part of the overall biosolids management strategy are also discussed.


Tax1-binding protein 1 is expressed in the retina and interacts with the GABA(C) receptor rho1 subunit.
Macromolecular signalling complexes that link neurotransmitter receptors to functionally and structurally associated proteins play an important role in the regulation of neurotransmission. Thus the identification of proteins binding to neurotransmitter receptors describes molecular mechanisms of synaptic signal transduction. To identify interacting proteins of GABA(C) (where GABA is gamma-aminobutyric acid) receptors in the retina, we used antibodies specific for GABA(C) receptor rho1-3 subunits. Analysis of immunoprecipitated proteins by MALDI-TOF MS (matrix-assisted laser-desorption ionization-time-of-flight MS) identified the liver regeneration-related protein 2 that is identical with amino acids 253-813 of the Tax1BP1 (Tax1-binding protein 1). A C-terminal region of Tax1BP1 bound to an intracellular domain of the rho1 subunit, but not to other subunits of GABA(C), GABA(A) or glycine receptors. Confocal laser-scanning microscopy demonstrated co-localization of Tax1BP1 and rho1 in clusters at the cell membrane of transfected cells. Furthermore, Tax1BP1 and GABA(C) receptors were co-expressed in both synaptic layers of the retina, indicating that Tax1BP1 is a component of GABA(C) receptor-containing signal complexes.


EXTRAPAIR MATE CHOICE AND HONEST SIGNALING IN COOPERATIVELY BREEDING SUPERB FAIRY-WRENS.
In many species of monogamous birds females copulate with males other than their social mates, resulting in extrapair fertilizations. Little is known about how females choose extrapair mates and whether the traits used to choose them are reliable indicators of male quality. Here we identify a novel male trait associated with extra-group mating success in the superb fairy-wren (Malurus cyaneus), a cooperatively breeding bird with one of the highest known frequencies of extra-group mating. Female fairy-wrens chose extra-group mates that molted earlier into breeding plumage. Males molted up to five months before the breeding season began, and only males that molted at least one month prior to its onset gained any extra-group fertilizations. This conclusion held after controlling statistically for the effect of age and social status on molt date. Once males acquired breeding plumage, they began courtship display to females on other territories. Thus, some males were displaying to females for several months before the breeding season began. This extraordinarily long period of advertisement by males may be facilitated by the long-term ownership of territories. We suggest that early acquisition of breeding plumage or the subsequent display behavior can be reliable cues for mate choice because they are costly to acquire or maintain.


Covalent binding of the nitroso metabolite of sulfamethoxazole leads to toxicity and major histocompatibility complex-restricted antigen presentation.
Treatment with sulfamethoxazole (SMX) can lead to hypersensitivity reactions. T cells from hypersensitive patients recognize either the parent drug and/or the reactive nitroso (SMX-NO) metabolite. In this study, using a novel in vitro rat splenocyte assay, we have investigated the toxicological and immunological consequences of cell surface haptenation by SMX-NO. SMX-NO was found to be unstable in solution; spontaneous transformation yielded appreciable amounts of SMX-hydroxylamine, nitro-SMX, and the previously unknown azoxy and azo dimers within 15 min. Irreversible binding of SMX-NO to cellular protein was demonstrated by flow cytometry, with haptenation being greater on the surface of antigen-presenting cells than on T cells. The consequences of irreversible binding of SMX-NO were examined in two ways. First, haptenation above a threshold level led to a proportionate increase in cell death (both apoptosis and necrosis). Indeed, the cells that became haptenated were the same as those that underwent necrotic cell death. Second, sensitized splenocytes proliferated in the presence of major histocompatibility complex (MHC)-restricted antigen derived from both viable and dead cells haptenated with low and high levels of SMX-NO, respectively. However, direct modification of MHC by SMX-NO was not the mechanism of antigen presentation. The antigenic threshold of SMX-NO for T-cell proliferation and toxicity was estimated to be between 0.5 and 1 microM and 5 to 10 microM, respectively. The potential of SMX-NO to generate a potent antigen and cause cytotoxicity may in combination provide the signals necessary to induce a hypersensitivity reaction to SMX.


[Diagnosis and treatment of non-Hodgkin lymphoma in elderly patients].
Non-Hodgkin's lymphoma (NHL) is relatively frequent among elderly patients: more than half of the diagnoses in the Netherlands concern patients aged 65 years or above. The treatment depends on histological type, clinical stage and prognostic group. Increasingly, a treatment decision is made after determination of the prognostic group on the basis of the expected response and survival. In elderly patients intensive treatment frequently has more toxic effects. The expected gain in survival has to be weighed against more toxicity and loss of quality of life during and after the therapy. This is notably important for patients with low grade NHL, which requires only intermittent treatment. It is possible to cure some elderly patients with NHL of intermediate or high grade malignancy provided they are adequately treated with combination chemotherapy. Patients with low grade NHL or poor clinical condition may benefit temporarily from palliative treatment, in the planning of which quality of life has to be taken into account.


Utility of Peripherin Versus MAP-2 and Calretinin in the Evaluation of Hirschsprung Disease.
Hirschsprung disease (HD) is a congenital malformation resulting from the lack of migration of ganglion cells in the colon. The absence of ganglion cells in rectal suction biopsies aids in diagnosis, but evaluation of these small biopsies can be difficult. In this study, we compare the microtubule-associated protein-2 (MAP-2), calretinin, and peripherin immunohistochemical stains in 237 selected biopsies performed to rule out HD. By H&E stain, a total of 78 biopsies had ganglion cells, whereas 83 biopsies had no ganglion cells, and an additional 76 biopsies were equivocal for ganglion cells. Of the 78 biopsies with ganglion cells, MAP-2 was positive in 73 (94%), calretinin in 76 (97%), and peripherin in 78 (100%). Of the 83 biopsies with no ganglion cells, calretinin and peripherin highlighted nerve fibrils and ganglion cells, respectively, in 3 biopsies, whereas MAP-2 was positive in only 1 biopsy. Of the 76 biopsies equivocal for ganglion cells, 16 cases were positive by all 3 stains, an additional case by both calretinin and peripherin, and 2 cases by peripherin only. All of the newly positive biopsies were from patients without HD. This study demonstrates that peripherin is superior in helping to rule out HD in these small biopsies, highlighting ganglion cells in virtually all cases with ganglion cells, whereas MAP-2 and calretinin are less sensitive for identification of ganglion cells and nerve fibrils, respectively. In patients with HD, a panel using calretinin and peripherin with or without MAP-2 may be most helpful in identifying transition zones.


Quantitative Assessment of Rectal Cancer Response to Neoadjuvant Combined Chemotherapy and Radiation Therapy: Comparison of Three Methods of Positioning Region of Interest for ADC Measurements at Diffusion-weighted MR Imaging.
Purpose To determine the impact of three different methods of region of interest (ROI) positioning for apparent diffusion coefficient (ADC) measurements on the assessment of complete response (CR) to neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer. Materials and Methods Institutional review board approval was obtained for this study; all patients gave written informed consent. ADCs were measured by two radiologists using three circular ROIs (three-ROIs), single-section (SS), and whole-tumor volume (WTV) methods in 62 patients with locally advanced rectal cancer on pre- and post-CRT images. Interobserver variability was analyzed by calculating intraclass correlation coefficient (ICC). Descriptive statistics and areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate performance in determining CR from pre- and post-CRT ADCs and ADC change. Histopathologic tumor regression grade was the reference standard. Results SS and WTV methods yielded higher AUCs than did the three-ROIs method when determining CR from post-CRT ADC (0.874 [95% confidence interval {CI}: 0.778, 0.970] and 0.886 [95% CI: 0.781, 0.990] vs 0.731 [95% CI: 0.583, 0.878], respectively; P = .033 and P = .003) and numeric change (0.892 [95% CI: 0.812, 0.972] and 0.897 [95% CI: 0.801, 0.994] vs 0.740 [95% CI: 0.591, 0.890], respectively; P = .048 and P = .0021). Respective accuracies of SS, WTV, and three-ROIs methods were 79% (49 of 62), 77% (48 of 62), and 61% (38 of 62) for post-CRT, 79% (49 of 62), 86% (53 of 62), and 60% (37 of 62) for numeric ADC change, and 77% (48 of 62), 84% (52 of 62), and 57% (35 of 62) for percentage ADC change (ADC cut-offs: 1.21, 1.30, and 1.05 × 10-3 mm2/sec, 0.33, 0.45, and 0.27 × 10-3 mm2/sec increases, and 40%, 54%, and 27% increases, respectively). Post-CRT and ADC change measurements achieved negative predictive values of 96% (44 of 46) to 100% (39 of 39). Intraobserver agreement was highest for WTV-derived ADCs (ICC, 0.742 [95% CI: 0.316, 0.892] to 0.891 [95% CI: 0.615, 0.956]) and higher for all pretreatment than posttreatment measurements (ICC, 0.761 [95% CI: 0.209, 0.930] and 0.648 [95% CI: 0.164, 0.895] for three-ROIs method, 0.608 [95% CI: 0.287, 0.844] and 0.582 [95% CI: 0.176, 0.870] for SS method, 0.891 [95% CI: 0.615, 0.956] and 0.742 for WTV method [95% CI: 0.316, 0.892]). Conclusion Tumor ADCs are highly dependent on the ROI positioning method used. Larger area measurements yield greater accuracy in response assessment. Post-CRT ADCs and values of ADC changes accurately identify noncomplete responders. WTV measurement of percentage ADC change provides the best results. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on September 19, 2016.


Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen.
Intracellular bacterial pathogens exploit host cell resources to replicate and survive inside the host. Targeting these host systems is one promising approach to developing novel antimicrobials to treat intracellular infections. We show that human macrophage-like cells infected with Brucella abortus undergo a metabolic shift characterized by attenuated tricarboxylic acid cycle metabolism, reduced amino acid consumption, altered mitochondrial localization, and increased lactate production. This shift to an aerobic glycolytic state resembles the Warburg effect, a change in energy production that is well described in cancer cells and also occurs in activated inflammatory cells. B. abortus efficiently uses lactic acid as its sole carbon and energy source and requires the ability to metabolize lactate for normal survival in human macrophage-like cells. We demonstrate that chemical inhibitors of host glycolysis and lactate production do not affect in vitro growth of B. abortus in axenic culture but decrease its survival in the intracellular niche. Our data support a model in which infection shifts host metabolism to a Warburg-like state, and B. abortus uses this change in metabolism to promote intracellular survival. Pharmacological perturbation of these features of host cell metabolism may be a useful strategy to inhibit infection by intracellular pathogens.IMPORTANCEBrucella spp. are intracellular bacterial pathogens that cause disease in a range of mammals, including livestock. Transmission from livestock to humans is common and can lead to chronic human disease. Human macrophage-like cells infected with Brucella abortus undergo a Warburg-like metabolic shift to an aerobic glycolytic state where the host cells produce lactic acid and have reduced amino acid catabolism. We provide evidence that the pathogen can exploit this change in host metabolism to support growth and survival in the intracellular niche. Drugs that inhibit this shift in host cell metabolism inhibit intracellular replication and decrease the survival of B. abortus in an in vitro infection model; these drugs may be broadly useful therapeutics for intracellular infections.


Current perspectives of enteric fever: a hospital-based study from India.
The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid. The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003. The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied. Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 microg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125-0.5 microg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013). The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.


Alveolar soft part sarcoma of the nasal cavity: report of a case and a review of the literature.
A case of alveolar soft part sarcoma of the nasal cavity is presented. Alveolar soft part sarcoma is a rare malignant neoplasm, which often affects females (ratio 2 to 1) in their second decade. It occurs most frequently in the extremities, with an unusual predilection to involve the right side of the body. Excluding the orbit, only a few cases have been reported in the head and neck area. We present the first reported case of alveolar soft part sarcoma limited to the nasal chamber.


Ultrasonographic estimation of fetal weight: acquiring accuracy in residency.
Ultrasonographic imaging is considered an objective means for fetal weight estimation. The goals of this study were to determine the accuracy of ultrasonographic estimates of fetal'weight performed by residents in training and to ascertain how rapidly the residents gained proficiency in this regard. A total of 300 ultrasonographic estimates of fetal weight and corresponding birth weight were collected and stratified into 4 groups by the level of residents' experience, from level 1 (inexperienced, with <6 months of exposure) to level 4 (advanced experience, with at least 24 months of training). The proportional difference between ultrasonographic estimates of fetal weight and birth weight was calculated for each case and grouped according to the level of training of the examiner. The derived data were compared by analysis of variance, linear regression, and chi2 test. Significant increases in the accuracy of ultrasonographic estimates of fetal weight were observed with advancing levels of resident experience (P< .0001). Overall, 30.6% of ultrasonographic estimates of fetal weight fell within 5% of birth weight, and 60.6% fell within 10%. Among the least experienced residents (<6 months of training), 49.4% of estimates fell within 10% of birth weight; among those with 6 to 11 months of experience, 53.5% of estimates fell within 10%; among those with 12 to 23 months of experience, 64.1 % of estimates fell within 10%; and among the most experienced (>24 months), 73.6% of estimates fell within 10%. There is a learning curve for ultrasonographic estimates of fetal weight, with a significant decrease in the percent error seen with advancing training among residents, reaching acceptable levels of more than 70% of estimates within 10% of birth weight after 24 months of ultrasonographic experience.


Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma.
Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database. We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status. Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1-43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4-5.3). Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma. Prognostic and Epidemiological; Level III.


Animal models and the study of atherosclerosis.
Identifications, requirements, and numerous contributions of animal models, as well as different aspects of atherosclerosis that were successfully studied in animals, are reviewed. Suggestions are made for updating the selection of specific animal models that will most satisfactorily fulfill the needs of studies in a particular problem of this disease process. Attention has been called to the importance of the type of atherosclerotic lesions and their dependence on species susceptibility and dietary influence. The role the type of lesion plays in atherosclerosis has been emphasized, especially in studies concerned with the progression and therapy of this disease process. From the variety of animals listed in this review, as well as the number of different problems already studied or awaiting further study, it appears that numerous data can be reconciled to help elucidate many problems and provide information for our better understanding of atherosclerosis. This, in turn, will allow us to make more accurate and effective recommendations leading to prevention and/or treatment of atherosclerosis.


RbBa2(N3)5: a new ternary azide.
Rubidium dibarium pentaazide, RbBa2(N3)5, was prepared from an aqueous solution of the binary azides at room temperature. It crystallizes in the monoclinic system (space group P2/n). Two central atoms of azide groups occupy the 2c (1) and 2b (1) positions, another azide group lies completely on a twofold axis (2f), while Rb atoms are situated in 2e (2) positions. The crystal structure of RbBa2(N3)5 can be regarded as a distorted AlB2-type arrangement of the metal atoms, with the azide groups occupying the voids between the cations. This results in coordination numbers of 8 (Rb) and 10 (Ba). The N-N distances are in the range 1.169 (8)-1.190 (5) A, typical for the azide group.


Surfactant size effect on surface-enhanced Raman scattering intensity from silver nanoparticles.
We report on the synthesis of two types of Ag nanoparticles (NPs) and the influence of adsorbed surfactant size on the NP surface for surface-enhanced Raman scattering (SERS) signals. Both particles were of similar size and morphology but were covered by surfactants of different sizes; one surfactant was sodium citrate (molecular weight: 258) and the other was sodium polyacrylate (molecular weight: 2100). For SERS measurement, 4-mecapobenzoic acid and 4-naphthalene thiol as Raman-active dyes were immobilized on the surface of each AgNP. The signals from Raman-active dyes on AgNPs covered with citrate displayed 10 times higher intensity than those from polyacrylate-stabilized AgNPs. Elemental analysis (EA) revealed that the average weight percentage of sulfur is 0.94 wt% and 0.12 wt% for citrate-stabilized and polyacrylate-stabilized AgNPs, respectively. The sulfur content difference was attributed to the size of the existing surfactant influencing the ligand exchange by steric hindrance and subsequently the amount of sulfur content of the particles. These experimental results suggest that the size of initial surfactant should be taken into account when synthesizing a metal particle for enhancing SERS signal.


Factors that influence the health status of immigrants living in Greece.
To examine the health status of immigrants living in Greece and investigate the factors that influence it. A cross-sectional study with 1152 immigrants (response rate = 60%) was conducted during April 2013 to March 2014. Regarding the sampling method, as there is no accurate census of immigrants in Greece the snowball sampling was used. Data collection included demographic characteristics, health status, medication and self-reported preventive health examinations of immigrants (blood count, blood pressure, cholesterol, and blood sugar measurement). The majority of immigrants originated from Albania (51.4%), while 52.6% were males with mean age 37.6 years. Of those 63.5% were working, 80.9% had legal documents for living and working in Greece and 58.2% had valid health and social security. Most of the immigrants (66.6%) considered their health as good/very good. Immigrants without health insurance, lower monthly family income and worst self-reported health did not adhere with their medication treatment due to cost. Immigrants with legal documents and health insurance performed more often blood count measurement, blood pressure measurement, cholesterol measurement and blood sugar measurement. Increased monthly family income was also associated with higher probability of blood count measurement. Very poor/poor/average self-reported health and increased age were associated with higher probability of taking medicines for chronic diseases. Self-reported health of immigrants in Greece is good/very good while absence of health insurance and legal documents, lower income and worst self-reported health are associated with worst health outcomes.


Sodium arsenite administration via drinking water increases genome-wide and Ha-ras DNA hypomethylation in methyl-deficient C57BL/6J mice.
Arsenic is an established human carcinogen. Deficiencies in available animal models have inhibited a detailed analysis of the mechanism of arsenic induced cancer. This study sought to determine the role of a methyl-deficient diet in combination with sodium arsenite on the genomic methylation status and Ha-ras methylation status of C57BL/6J male mice hepatic DNA. Mice were administered arsenic as sodium arsenite via drinking water at 0, 2.6, 4.3, 9.5 or 14.6 mg sodium arsenite/kg/day. Administration occurred 7 days a week for 130 days. Dose-related effects on the liver were evident in mice administered arsenic and methyl-deficient diets. Most prominent were observations of steatosis and microgranulomas. Sodium arsenite increased genomic hypomethylation in a dose dependent manner and methyl-deficiency and sodium arsenite reduced the frequency of methylation at several cytosine sites within the promoter region of the oncogenic gene, Ha-ras. Methylation changes were prominent in a 500 bp non-CpG island-like region of the Ha-ras promoter and less prominent in a 525 bp CpG island-like region. DNA methylation plays an important role in the physiological expression of many genes including Ha-ras. Significantly reduced methylation at a key regulatory region of Ha-ras in the mouse liver may have relevance to understanding arsenic-induced perturbations in the methylation patterns of cellular growth genes involved in the formation of tumors. These findings highlight the effect of sodium arsenite on inherent methylation processes within the hepatic cell.


Pooled Human Serum Increases Regenerative Potential of In Vitro Expanded Stem Cells from Human Extracted Deciduous Teeth.
In regenerative therapy, in vitro expansion of stem cells is critical to obtain a significantly higher number of cells for successful engraftment after transplantation. However, stem cells lose its regenerative potential and enter senescence during in vitro expansion. In this study, the influence of foetal bovine serum (FBS) and pooled human serum (pHS) on the proliferation, morphology and migration of stem cells from human extracted deciduous teeth (SHED) was compared. SHED (n = 3) was expanded in KnockOut DMEM supplemented with either pHS (pHS-SM) or FBS (FBS-SM). pHS was prepared using peripheral blood serum of six healthy male adults, aged between 21 and 35 years old. The number of live SHED was significantly higher, from passage 5 to 7, when cultured in pHS-SM compared to those cultured in FBS-SM (p < 0.05). Number of cells having flattened morphology, characteristics of partially differentiated and senescent cells, was significantly lower (p < 0.05) in pHS-SM (3%) compared to those in FBS-SM (7%). Furthermore, migration of SHED in pHS-SM was found to be more directional. The presence of selected ten paracrine factors known for their proliferation and migration potential was detected in all six individual human sera, used to produce pHS, none of which were detected in FBS. Ingenuity Pathway Analysis showed the possible involvement of the 'ephrin receptor signalling pathway' to regulate the proliferation and migration of SHED in pHS-SM. In conclusion, pHS-SM showed significantly higher proliferation rate and could maintain significantly lower number of senescent cells and support directional migration of cells.


Probing the electronic and vibrational structure of Au2Al2(-) and Au2Al2 using photoelectron spectroscopy and high resolution photoelectron imaging.
The electronic and vibrational structures of Au2Al2(-) and Au2Al2 have been investigated using photoelectron spectroscopy (PES), high-resolution photoelectron imaging, and theoretical calculations. Photoelectron spectra taken at high photon energies with a magnetic-bottle apparatus reveal numerous detachment transitions and a large energy gap for the neutral Au2Al2. Vibrationally resolved PE spectra are obtained using high-resolution photoelectron imaging for the ground state detachment transition of Au2Al2(-) at various photon energies (670.55-843.03 nm). An accurate electron affinity of 1.4438(8) eV is obtained for the Au2Al2 neutral cluster, as well as two vibrational frequencies at 57 ± 8 and 305 ± 13 cm(-1). Hot bands transitions yield two vibrational frequencies for Au2Al2(-) at 57 ± 10 and 144 ± 12 cm(-1). The obtained vibrational and electronic structure information is compared with density functional calculations, unequivocally confirming that both Au2Al2(-) and Au2Al2 possess C2v tetrahedral structures.


Iron chelation therapy as a treatment for Pythium insidiosum in an animal model.
Iron plays an important role in the pathogenesis of Pythium insidiosum. Human pythiosis frequently occurs in iron-overloaded thalassaemic patients and experimentally infected animals develop iron deficiency anaemia. Therefore, we sought to determine the in vitro and in vivo activities of the iron chelator deferasirox against P. insidiosum. In vitro, the MIC and minimum fungicidal concentration (MFC) values of deferasirox for 17 strains of P. insidiosum were determined in accordance with CLSI document M38-A2. In vivo studies were carried out in 20 inoculated rabbits divided into four groups: placebo, immunotherapy obtained from vortexed P. insidiosum cultures (14 day intervals), deferasirox (15 mg/kg/day) and a combination of immunotherapy and deferasirox. Five non-infected animals were used as controls. The MIC and MFC values of deferasirox for P. insidiosum ranged from 12.5 to 50 mg/L and from 50 to 100 mg/L, respectively. Treatment with deferasirox alone ameliorated anaemia and normalized the serum iron levels and hepatic iron concentration in the animals. However, the mean lesion size, although decreased, did not differ significantly from that in the placebo group. The results of immunotherapy plus iron chelation therapy were worse than those of immunotherapy alone. Moreover, the disease spread to the lung tissue in 5 out of 10 deferasirox-treated animals. Despite its limited in vitro and in vivo activity, deferasirox improved iron deficiency anaemia in P. insidiosum-infected rabbits. Further studies are needed to investigate the immunomodulatory properties observed in this study and the benefits and drawbacks of using iron-chelating drugs as an adjuvant therapy in pythiosis.


Nature of Tau-Associated Neurodegeneration and the Molecular Mechanisms.
Neurodegeneration is defined as the progressive loss of structure or function of the neurons. As the nature of degenerative cell loss is currently not clear, there is no specific molecular marker to measure neurodegeneration. Therefore, researchers have been using apoptotic markers to measure neurodegeneration. However, neurodegeneration is completely different from apoptosis by morphology and time course. Lacking specific molecular marker has been the major hindrance in research of neurodegenerative disorders. Alzheimer's disease (AD) is the most common neurodegenerative disorder, and tau accumulation forming neurofibrillary tangles is a hallmark pathology in the AD brains, suggesting that tau must play a critical role in AD neurodegeneration. Here we review part of our published papers on tau-related studies, and share our thoughts on the nature of tau-associated neurodegeneration in AD.


Differential ultrastructural alterations in the Vglut2 glutamatergic input to the substantia nigra pars compacta/pars reticulata following nigrostriatal dopamine loss in a progressive mouse model of Parkinson's disease.
Loss of nigrostriatal dopamine (DA) in Parkinson's disease results in over-activation/bursting of the subthalamic nucleus (STN). The STN projects to the substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr). The vesicular glutamate transporter 2 (Vglut2) is localized within at least STN terminals synapsing within the SN, but it is not known if there are differential changes in the Vglut2+ input to the SNpc versus SNpr following DA loss. The goal/rationale of this current study was to determine whether there were differential changes in the density/levels of glutamate immuno-gold labeling within Vglut2+ nerve terminals synapsing in the SNpc/SNpr and in the proportion of Vglut2+ terminals contacting tyrosine hydroxylase (TH) positively(+) or negatively(-) labeled dendrites following DA loss. Within the SNpc, there was a significant increase (51.3%) in the density of nerve terminal glutamate immuno-gold labeling within Vglut2+ terminals synapsing on TH(-) dendrites following MPTP versus the vehicle (VEH) group. There was a significant decrease (16%) in the percentage of Vglut2+ terminals contacting TH(+) labeled dendrites in the MPTP- versus VEH-treated group within the SNpc. Within the SNpr, there was a significant decrease in the density of glutamate immuno-gold labeling in Vglut2+ terminals contacting TH(+) (71.5%) and TH(-) (55.5%) labeled dendrites, suggesting an increase in glutamate release. There was no change in the percentage of Vglut2+ terminals contacting TH(+) or TH(-) dendrites in the SNpr. We conclude that there is a differential effect following DA loss on the glutamate input from Vglut2+ terminals synapsing within the SNpr versus SNpc.


Changes in circulating follicular helper T-cells in Chinese patients with allergic rhinitis.
Changes of circulating Follicular helper T (cTfh) cells existed in allergic rhinitis (AR) patients, and the severity of disease was associated with a more severe change of cTfh milieu. These results imply that cTfh cells may play a crucial role in the pathology of AR in Chinese patients. The aim of this study was to investigate the changes in cTfh cells in Chinese AR patients. Fifty-two patients were studied (32 in the AR group and 20 in the control group) for this research. The cTfh cell frequency and mRNA levels of transcription factor Bcl-6, B lymphocyte induced maturation protein 1 (BLIMP-1), and related cytokine IL-21 (IL-21 protein was also measured) were analyzed. Clinical severity was evaluated by total serum IgE levels, visual analog scale scores (VAS), and rhino-conjunctivitis quality-of-life questionnaires (RQLQ). The frequency of cTfh cells were elevated in AR groups vs healthy controls (p < 0.05). Levels of IL-21 mRNA, Bcl-6 mRNA and the level of IL-21 protein were also significantly higher in the AR groups (p < 0.05), whereas BLIMP-1 mRNA was decreased (p < 0.05). Furthermore, positive correlations were identified between the frequency of cTfh cells and indicators of clinical severity (p < 0.01).


Mitochondrial Function as Related to Psychological Distress in Health Care Professionals.
The present study evaluated the association of psychological distress and radiation exposure as a work-related stressor with mitochondrial function in health care professionals. Health care professionals at a regional hospital in Italy were evaluated for physical health and psychological measures using self-report questionnaires (n = 41; mean age = 47.6 [13.1] years; 66% women). In a second sample, individuals exposed to elevated levels of ionizing radiation (IR; likely effective dose exceeding 6 mSv/y; n = 63, mean age = 45.8 [8.8] years; 62% women) were compared with health care workers with low IR (n = 57; mean age = 47.2 [9.5] years; 65% women) because exposure to a toxic agent might act as a (work-related) stressor. Associations were examined between psychological factors (12-item General Health Questionnaire, Perceived Stress Scale), work ability (Work Ability Index), and IR exposure at the workplace with markers of mitochondrial function, including mitochondrial redox activity, mitochondrial membrane potential, mitochondrial DNA (mtDNA) copy number, biogenesis, and mtDNA damage response measured from peripheral blood mononuclear cells. All participants were in good physical health. Individuals reporting high levels of psychological distress showed lower mitochondrial biogenesis as indicated by peroxisome proliferator-activated receptor-γ coactivator 1-α and lower nuclear factor erythroid 2-related factor 2 (NRF2) expression (2.5 [1.0] versus 1.0 [0.9] relative expression [rel exp], p = .035, and 31.5 [5.0] versus 19.4 [6.9] rel exp, p = .013, respectively). However, exposure to toxic agents (IR) was primarily associated with mitochondrial metabolism and reduced mtDNA integrity. Participants with IR exposure displayed higher mitochondrial redox activity (4480 [1202] mean fluorescence intensity [MFI]/min versus 3376 [983] MFI/min, p < .001) and lower mitochondrial membrane potential (0.89 [0.09] MFI versus 0.95 [0.11] MFI, p = .001), and reduced mtDNA integrity (1.18 [0.21] rel exp versus 3.48 [1.57] rel exp, p < .001) compared with nonexposed individuals. This study supports the notion that psychological distress and potential stressors related to toxic agents might influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria.


Xenon handling in the liver: red cell capacity effect.
Xenon, despite its lack of chemical reactivity, associates preferentially with red cells in blood. To characterize the effect of this and the nature of xenon-tissue interaction in the liver, multiple indicator dilution studies were performed in the anesthetized normal dog through portal vein injection and hepatic vein collection of anaerobic blood samples. Two experimental runs were carried out in each animal, one at the prevailing hematocrit and the other at reduced hematocrit after bleeding and replacement with dextran. For comparison, the injection mixtures contained labeled red blood cells (a vascular reference), sucrose (an interstitial space reference), and labeled water (which freely enters liver cells), as well as labeled xenon. At the higher hematocrit, the labeled xenon curves generally rose earlier, peaked higher, and decayed more quickly than the labeled water curve; at the lower hematocrit, the xenon curve was delayed and diminished in magnitude in relation to the labeled water curves. Analysis of the curve shapes indicated that xenon, like labeled sucrose and water, underwent delayed wave flow-limited distribution. With knowledge of the red cell plasma partition coefficient (2.89 ml/ml), it was possible to both account for the change in form of the xenon curves with hematocrit and to use the data to estimate the liver cell tissue plasma xenon partition coefficient. Values averaged 1.93 ml/ml liver space, or 1.79 ml/g, and did not change significantly from first to second runs. Theoretical analysis indicated that flow cannot be estimated from xenon downslopes.


Regulatory Role of MicroRNAs in Muscle Atrophy during Exercise Intervention.
Skeletal muscle comprising approximately 40% of body weight is highly important for locomotion and metabolic homeostasis. The growth and regeneration of skeletal muscle are highly organized processes; thus, it is not surprising to reveal certain complexity during these regulatory processes. Recently, a large number of evidence indicate that microRNAs can result in obvious impacts on growth, regeneration and metabolism of skeletal muscle. In this review, recent research achievements of microRNAs in regulating myogenesis, atrophy and aging during exercise intervention are discussed, which will provide the guidance for developing potential applications of microRNAs in health promotion and rehabilitation of sports injuries.


Subjective experiences of anesthesiologists undergoing epidural anesthesia.
This study reports subjective experiences of nine anesthesiologists undergoing three consecutive epidural anesthetics. Eight anesthesiologists and one nurse anesthetist, all ASA physical status 1, underwent three lumbar epidural anesthetics as part of another study. Epidural catheters were inserted via a 17-gauge Tuohy needle without sedation after local anesthesia with pH adjusted lidocaine at the second, third, or fourth lumbar interspace. Three local anesthetics (2% lidocaine HCl, 3% chloroprocaine HCl, and 0.75% bupivacaine HCl) were administered each separated by at least 48 hours. The local anesthetic was incrementally injected via the epidural catheter to achieve at least a T-1 dermatome level of analgesia. Each subject completed a written questionnaire at the end of the study regarding their experience. Most of the subjects (7 of 9) had no prior epidural anesthesia. Eight of nine subjects experienced at least one paresthesia during catheter insertion; this was uniformly described as a "poorly localized burning sensation," radiating to the hip or leg. All subjects reported difficulty taking a deep breath and coughing with a T-1 level of analgesia. Eight of nine subjects reported dysphoria during lidocaine epidural anesthesia. Eight of nine subjects reported moderate back pain after dissipation of chloroprocaine epidural anesthesia. All volunteers stated that they would change their anesthetic practice as a result of participation in this study. They believed that having experienced an epidural anesthetic made them better qualified to prepare patients for this anesthetic technique.


Association Between Thyroid Parameters and Subclinical Atherosclerosis in Hospitalised Euthyroid Patients with Type 2 Diabetes Mellitus.
To explore the association between thyroid parameters and subclinical atherosclerosis (AS) in hospitalised euthyroid patients with type 2 diabetes mellitus (T2DM). A retrospective analysis was conducted involving 1245 inpatients with T2DM. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were measured, and carotid artery ultrasonography was performed. Thyroid hormone (TH) sensitivity was evaluated using thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine ratio (FT3/FT4). In inpatients with T2DM having normal thyroid function, the incidence of subclinical AS declined with increasing levels of FT3, FT4, and FT3/FT4 (P trend < 0.05). Logistic regression analysis revealed that FT4 (OR, 0.914; 95% CI, 0.845-0.989), FT3 (OR, 0.374; 95% CI, 0.277-0.504), and FT3/FT4 (OR, 0.036; 95% CI, 0.013-0.061) were independently associated with subclinical AS (P < 0.05). However, TSH, TFQI, TSHI, and TT4RI levels were not associated with subclinical AS (P > 0.05). FT3/FT4 demonstrated superior predictive accuracy for subclinical AS than that of FT3 or FT4 alone (P < 0.001), with a cutoff point of 0.25. In euthyroid inpatients with T2DM, subclinical AS exhibited negative correlation with FT3, FT4, and FT3/FT4 levels, independent of other risk factors for AS. Additionally, FT3/FT4 ratio had a good predictive value for subclinical AS.


Blending studies with selected waterbuck odor constituents or analogues in the development of a potent repellent blend against savannah tsetse.
Previous comparison of the body odors of tsetse-refractory waterbuck and those of tsetse-attractive ox and buffalo showed that a blend of 15 EAG-active compounds specific to waterbuck, including C5-C10 straight chain carboxylic acid homologues, methyl ketones (C8-C12 straight chain homologues and geranyl acetone), phenols (guaiacol and carvacrol) and δ-octalactone, was repellent to tsetse. A blend of four components selected from each class of compounds (δ-octalactone, pentanoic acid, guaiacol, and geranylacetone) showed repellence that is comparable to that of the 15 components blend and can provide substantial protection to cattle (more than 80%) from tsetse bites and trypanosome infections. Structure-activity studies with the lactone and phenol analogues showed that δ-nonalactone and 4-methylguaiacol are significantly more repellent than δ-octalactone and guaiacol, respectively. In the present study, we compared the responses of Glossina pallidipes and Glossina morsitans to i) blends comprising of various combinations of the most active analogues from each class of compounds, and ii) a four-component blend of δ-nonalactone, heptanoic acid, 4-methylguaiacol and geranyl acetone in different ratios in a two-choice wind-tunnel, followed by a field study with G. pallidipes population in a completely randomized Latin Square Design set ups. In the wind tunnel experiments, the blend of the four compounds in 6:4:2:1 ratio was found to be significantly more repellent (94.53%) than that in 1:1:1:1 proportion and those in other ratios. G. m. morsitans also showed a similar pattern of results. In field experiments with G. pallidipes population, the 6:4:2:1 blend of the four compounds also gave similar results. The results lay down useful groundwork in the large-scale development of more effective 'push' and 'push-pull' control tactics of the tsetse flies.


Engineering a Transmembrane Nanopore Ion Channel from a Membrane Breaker Peptide.
Re-engineering nature's molecules is an ideal strategy to obtain explicit functionality such as synthetic molecular machines, yet novel strategies for producing engineered molecular channels are few. Here we report a peptide engineering strategy through sequence reversal, which we applied on the first transmembrane peptide of the mycobacteriophage membranoporin protein holin. We have successfully redesigned the membrane rupture property of this peptide to form specific nanopore ion channels. We report the structural characterization and electrophysiology measurements of a library of 28-residue engineered membrane peptides, with remarkable ion channel behavior. We further identify that key residues at the peptide terminus, the central proline, charge distribution, and hydropathy index of the peptide together contribute to the channel properties that we measure. Our sequence reversal strategy for peptide engineering to successfully obtain nanopore channels can pave the way for better biobased design of controlled nanopores, using only natural amino acids.


Gonadal Hormones and Retinal Disorders: A Review.
Gonadal hormones are essential for reproductive function, but can act on neural and other organ systems, and are probably the cause of the large majority of known sex differences in function and disease. The aim of this review is to provide evidence for this hypothesis in relation to eye disorders and to retinopathies in particular. Epidemiological studies and research articles were reviewed. Analysis of the biological basis for a relationship between eye diseases and hormones showed that estrogen, androgen, and progesterone receptors are present throughout the eye and that these steroids are locally produced in ocular tissues. Sex hormones can have a neuroprotective action on the retina and modulate ocular blood flow. There are differences between the male and the female retina; moreover, sex hormones can influence the development (or not) of certain disorders. For example, exposure to endogenous estrogens, depending on age at menarche and menopause and number of pregnancies, and exposure to exogenous estrogens, as in hormone replacement therapy and use of oral contraceptives, appear to protect against age-related macular degeneration (both drusenoid and neurovascular types), whereas exogenous testosterone therapy is a risk factor for central serous chorioretinopathy. Macular hole is more common among women than men, particularly in postmenopausal women probably owing to the sudden drop in estrogen production in later middle age. Progestin therapy appears to ameliorate the course of retinitis pigmentosa. Diabetic retinopathy, a complication of diabetes, may be more common among men than women. We observed a correlation between many retinopathies and sex, probably as a result of the protective effect some gonadal hormones may exert against the development of certain disorders. This may have ramifications for the use of hormone therapy in the treatment of eye disease and of retinal disorders in particular.


Implementing California's Law on Assisted Dying.
On October 5, 2015, Governor Jerry Brown approved bill ABX2 15, the End of Life Option Act, making California the fifth state in the country to allow physician-assisted dying. The law was modeled after Oregon's 1997 Death with Dignity Act. When the legislative special session ended on March 10, 2016, California health care providers had only ninety days to respond to the state mandate before the law would take effect, on June 9, 2016. Experience with the law so far suggests several challenges with implementation.


Self-rated oral health status, oral health service utilization, and oral hygiene practices among adult Nigerians.
There is scarce information available on oral health service utilization patterns and common oral hygiene practices among adult Nigerians. We conducted the 2010-2011 national oral health survey before the introduction of the national oral health policy to determine the prevalence of oral health service utilization, patterns of oral hygiene practices, and self reported oral health status, among adults in various social classes, educational strata, ethnic groups and geopolitical zones in Nigeria. We conducted a cross-sectional survey in North-Central, North-West, South-East, South-South and South-West geopolitical zones of Nigeria. Multi-stage cluster sampling method was used for the sample selection. We administered a structured questionnaire to a total of 7,630 participants. Information on the socio-demographic characteristics, oral hygiene practices and oral health services utilization pattern of participants was obtained. We interviewed 7, 630 participants (55.6% female). The participants ages ranged between 18 and 81 years, mean age was 37.96 (SD = 13.2). Overall 21.2% of the participants rated their oral health status as very good, 37.1% as good and 27.4% as fair. Only 26.4% reported having visited the dentist at least once prior to the conduct of the survey. More than half of these visits (54.9%) were for treatment purpose. Utilization of oral health services was significantly (p < 0.05) associated with being older, more educated and being engaged in a skilled profession. More educated persons, females and younger persons used toothbrushes for daily tooth cleaning. Age, sex, marital status, level of education and occupation were significantly related to daily frequency of tooth cleaning (p < 0.05). Our results show that while most Nigerian adults have a positive view of their oral health status, majority reported poor oral health utilization habits. Older persons resident in the northern zones of the country and less educated persons displayed poorer oral hygiene practices. The study findings suggest that there is low oral health service utilization among adult Nigerians and that socio-demographic variables influence oral health utilization habits and oral hygiene behavior among adult Nigerians Further studies to identify other factors influencing oral health behavior are suggested.


Osteogenic Differentiation of Mesenchymal Stromal Cells: A Comparative Analysis Between Human Subcutaneous Adipose Tissue and Dental Pulp.
White adipose tissue is a source of mesenchymal stromal/stem cells (MSCs) that are actively studied for their possible therapeutic use in bone tissue repair/remodeling. To better appreciate the osteogenic potential of these cells, we compared some properties of MSCs from human subcutaneous adipose tissue [subcutaneous-adipose stromal cells (S-ASCs)] and dental pulp stem cell (DPSCs) of third-impacted molars, the latter representing a well-established MSC source. Both undifferentiated cell types showed similar fibroblast-like morphology and mesenchymal marker expression. However, undifferentiated S-ASCs displayed a faster doubling time coupled to greater proliferation and colony-forming ability than DPSCs. Also, the osteogenic differentiation of S-ASCs was greater than that of DPSCs, as evaluated by the higher levels of expression of early osteogenic markers Runt-related transcription factor-2 (RUNX2) and alkaline phosphatase at days 3-14 and of extracellular matrix mineralization at days 14-21. Moreover, S-ASCs showed a better colonization of the titanium scaffold. In addition, we investigated whether S-ASC osteogenic commitment was enhanced by adenosine A1 receptor (A1R) stimulation, as previously shown for DPSCs. Although A1R expression was constant during DPSC differentiation, it increased in S-ASC at day 21 from osteogenesis induction. Accordingly, A1R stimulation by the agonist 2-chloro-N6-cyclopentyl-adenosine, added to the cultures at each medium change, stimulated proliferation only in differentiating DPSC and enhanced the osteogenic differentiation earlier in DPSCs than in S-ASCs. These effects were counteracted by cell pretreatment with a selective A1R antagonist. Thus, our findings suggest that S-ASCs could be advantageously used in regenerative orthopedics/dentistry, and locally released or exogenously added purines may play a role in bone repair/remodeling, even though this aspect should be more thoroughly evaluated.


May-December lesbian relationships: power storms or blue skies?
What are the implications when there is considerable difference in the ages of partners in a lesbian couple? May-December lesbian relationships are those where partners are at least 10 years apart in age, and where both partners are over 30. These relationships have been either neglected or valorized in the psychological literature. Differences in socially ascribed power, women's socialization against acknowledging power, the value the lesbian community places on egalitarianism, and the interaction of other privileges, combine to impact these couples. The fluid nature of power dynamics in May-December lesbian relationships is highlighted and explored. Finally, ways that age-variant lesbian couples can navigate these power differentials in healthy ways are addressed.


Neonatal telephone consultations in the National Maternity Hospital.
Details of telephone consultations concerning infants were recorded prospectively over a two month period in the National Maternity Hospital (NMH). There were one hundred and forty-six calls recorded. One hundred and sixteen (79.5%) calls were from mothers. The average age of the infants was twenty-eight days. Eighty (54.8%) calls were answered by Nursing Staff while the remainder were taken by Doctors. There were thirty-nine (26.7%) calls relating to the gastrointestinal system. There were twenty-seven (18.5%) calls regarding infants with respiratory concerns. The next most common problem was irritability followed by calls concerning jaundice, rashes and umbilical issues. Fifty-five (37.7%) callers were given home care advice or reassurance. Thirty-six (24.7%) were advised to attend a Paediatric Emergency Department (ED). GP visits and Baby Clinic appointments were advised for twenty-four (16.4%) and twenty-three (15.8%) infants respectively while six (4.1%) of the callers were directed to attend NMH immediately.


Pulmonary ventilatory function decreases in proportion to increasing altitude.
The objective of this study was to examine how pulmonary ventilatory function, including response to bronchodilation, is related to altitude during high-altitude trekking. This cohort experiment consisted of multiple spirometric tests before and after bronchodilation in participants at baseline (1624 m) and at different altitudes (3404-4896 m) during a 2-week trek. The setting was in the Himalayas. Eleven men (ages 22-68 years) and eight women (ages 19-42 years) participated. Interventions were at altitudes of 1624 m to 5265 m; albuterol was administered via Rotahaler. Forced vital capacity (FVC) decreased by an average of 3.8% [95% confidence interval (CI) 1.6 to 6.0] per 1000-m altitude increment. Forced expiratory volume in 1 second (FEV1.0) decreased 3.7% (95% CI 1.9 to 5.5) per each 1000-m altitude increment. Maximal midexpiratory flow rate (FEF25-75%) decreased by 3.6% (95% CI 0.9 to 6.3) per each 1000-m altitude increment. Small, postalbuterol flow increases were present at baseline and at altitude. Ventilatory function returned quickly toward baseline upon descent. One trekker developed cough, dyspnea at rest, extreme weakness, rales, tachycardia, and oxygen desaturation to 71%. His ventilatory measurements did not differ significantly (p > 0.32) from the group means. We concluded that changes in some pulmonary ventilatory parameters (FVC, FEV1.0, and FEF25-75%) were proportional to the magnitude of altitude during a high-altitude trek. These were tolerated well and do not seem to relate to acute mountain sickness. A bronchodilator effect was not increased at altitude.


Intimal Hyperplasia, Stenosis, and Arteriovenous Fistula Maturation Failure in the Hemodialysis Fistula Maturation Study.
Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%-100%), modestly associated with lower fistula blood flow rate (relative change, -2.5%; 95% confidence interval [95% CI], -4.6% to -0.4%; P=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15; P=0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12; P=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.


Enhancement of hematopoietic response of mice by subcutaneous administration of Lactobacillus casei.
Mice that had received heat-killed Lactobacillus casei (LC 9018) subcutaneously (s.c.) showed enhanced resistance to systemic (i.e., intravenous) infection with Listeria monocytogenes, but the antilisterial resistance of mice was less augmented by s.c. administration of Propionibacterium acnes ("Corynebacterium parvum"). Though there was little change in the total number of splenic leukocytes after s.c. administration of LC 9018, the monocyte-macrophage ratio increased after treatment, reaching its peak on day 5 to 7 after injection. The number of progenitor cells that form macrophage colonies under the stimulus of L-cell-conditioned medium in a semisolid agar culture system increased in the spleens of mice pretreated s.c. with LC 9018, showing a peak response on day 5 after injection. The increase corresponded to the increase in the dose administered, and increased numbers were detected even 10 days after treatment. The number of macrophage colonies in the femurs of mice pretreated s.c. with LC 9018 showed a temporary increase on day 3 after injection but then a decrease until day 10. Colony-stimulating activity was detected in the sera of mice administered LC 9018 s.c. 18 h previously, and the colonies produced were of three types: granulocyte (8%), macrophage (56%), and granulocyte-macrophage (36%). Administration of C. parvum s.c. had little effect on these hematopoietic responses of mice.


Ancestral Protein Reconstruction and Circular Permutation for Improving the Stability and Dynamic Range of FRET Sensors.
Small molecule biosensors based on Förster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.


Vibrational Raman scattering from coherently excited molecular ions in a strong laser field.
We report on a pump-probe investigation of vibrational Raman scattering from coherently excited N2+ ions. It is found that the Raman signals produced by the inelastic scattering of the probe pulse from molecular ions can be dramatically enhanced when the probe laser is resonant with electronic transitions in N2+ ions. The Raman signal can be amplified at 428 nm wavelength due to the presence of population inversion in N2+ ions.


Periprosthetic fractures of the femur following hip arthroplasty.
Periprosthetic femoral fractures are one of the leading causes of revision total hip arthroplasty. Risk factors for these fractures include intraoperative factors (ie, use of cemented technique and host factors, such as osteoporosis and osteolysis) and postoperative factors (ie, osteolysis and trauma). This article discusses prevention, evaluation, management, and technique issues of these fractures. A final section discusses the author's preferred treatment choice of these fractures, based on an algorithm developed by Duncan and Masri.


A recombinant Tobacco curly shoot virus causes leaf curl disease in tomato in a north-eastern state of India and has potentiality to trans-replicate a non-cognate betasatellite.
Leaf curl disease is a serious constraint in tomato production throughout India. Several begomoviruses were reported from different parts of the country; however, identity of begomovirus associated with leaf curl disease in tomato in north-eastern states of India was obscured. In the present study, the complete genome of an isolate (To-Ag-1) of begomovirus was generated from a leaf curl sample collected from Tripura state. However, no DNA-B and betasatellite were detected in the field samples. The genome of To-Ag-1 isolate contained 2,755 nucleotides that shared 94.7 % sequence identity with Tobacco curly shoot virus (TbCSV) and 71.3-90.1 % sequence identity with the other tomato-infecting begomoviruses occurring in the Indian subcontinent. Several inter-specific recombination events among different tomato-infecting begomoviruses from India and intra-specific recombination among different isolates of TbCSV reported from China were observed in the genome of To-Ag-1 isolate. Agroinoculation of the virus alone produced leaf curl symptoms in tomato and Nicotiana benthamiana. However, co-inoculation with a non-cognate betasatellite, Croton yellow vein mosaic betasatellite (CroYVMB) with the TbCSV resulted in increased severity of the symptoms both in tomato and N. benthamiana. Systemic distribution of the TbCSV and CroYVMB was detected in the newly developed leaves of tobacco and tomato, which showed ability of TbCSV to trans-replicate CroYVMB. The present study for the first time provides evidence of occurrence of TbCSV in tomato in north-eastern region of India and showed increased virulence of TbCSV with a non-cognate betasatellite.


Geospatial Analysis of Social Vulnerability, Race, and Firearm Violence in Chicago.
Urban firearm violence (UFV) is associated with inequities rooted in structural racism and socioeconomic disparities. Social vulnerability index (SVI) is a composite measure that encompasses both. We sought to understand the relationship between SVI and the incidence of UFV in Chicago using geospatial analysis for the first time. Firearm assaults in Chicago 2001-2019 were obtained from the Trace. Locations of incidents were geocoded using ArcGIS and overlaid with census tract vector files. These data were linked to 2018 SVI measures obtained from the Center for Disease Control and Prevention. Shooting rates were calculated by tabulating the total number of shootings per capita in each census tract. We used Poisson regression with robust error variance to estimate the incident rate of UFV in different levels of social vulnerability and Local Moran's I to evaluate spatial autocorrelation. In total, 642 census tracts were analyzed. The median shooting rate was 2.6 per 1000 people (interquartile 0.77, 7.0). When compared to those census tracts with very low SVI, census tracts with low SVI had a 1.7-time increased incident rate of shootings (incidence rate ratio [IRR] 1.74, 95% CI 1.08, 2.81), tracts with moderate SVI had a 3.1-time increased incident rate (IRR 3.07, 95% CI 2.31, 4.10), and tracts with high SVI had a 7-time increased incident rate (IRR 7.03, 95% CI 5.45, 9.07). In Chicago, social vulnerability has a significant association with rates of firearm violence, providing a focus point for policy intervention to address high rates of interpersonal violence in similar cities.


The Effects of Carvacrol on Transient Receptor Potential (TRP) Channels in an Animal Model of Parkinson's Disease.
In this study, we aimed to investigate the effects of carvacrol (CA), a widely used phytochemical having anti-oxidant and neuroprotective effects, on transient receptor potential (TRP) channels in an animal model of Parkinson's disease (PD). A total of 64 adult male Spraque-Dawley rats were divided into four groups: sham-operated, PD animal model (unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA), 6 µg/µl), PD + vehicle (dimethyl sulfoxide (DMSO)) treatment, and PD + CA treatment (10 mg/kg, every other day, for 14 days). Half of the brain samples of substantia nigra pars compacta (SNpc) and striatum (CPu) were collected for immunohistochemistry and the remaining half were used for molecular analyses. CA treatment significantly increased the density of dopaminergic neurons immunolabeled with tyrosine hydroxylase and transient receptor potential canonical 1 (TRPC1) channel in the SNpc of PD animals. In contrast, the density of astrocytes immunolabeled with glial fibrillary acetic acid and transient receptor potential ankyrin 1 (TRPA1) channel significantly decreased following CA treatment in the CPu of PD animals. RT-PCR and western blot analyses showed that 6-OHDA administration significantly reduced TRPA1 and TPRPC1 mRNA expression and protein levels in both SNpc and CPu. CA treatment significantly upregulated TRPA1 expression in PD group, while TRPC1 levels did not display an alteration. Based on this data it was concluded that CA treatment might protect the number of dopaminergic neurons by reducing the reactive astrogliosis and modulating the expression of TRP channels in both neurons and astrocytes in an animal model of PD.


Self-feeding dependence incidence and predictors among nursing home residents: Findings from a 5 year retrospective regional study.
The aim of this regionally-based, retrospective study was to describe the incidence of self-feeding dependence and predictors among elderly patients admitted from 2008 to 2013 to 105 Italian nursing homes. Data reported in a regional database collected at the time of nursing home admission and every 6 months up to the resident's death were accessed. The self-feeding degree of dependence was the dependent variable; at the individual and nursing home levels, explanatory variables were those collected at nursing home admission and every 6 months. The structural equation model and the ordinal polynomial logit regression analysis were performed. A total of 13 175 records of residents when admitted to the nursing home and their following 69 341 records, were included. At the time of nursing home admission, 6496 residents (49.3%) reported a certain degree of dependence in self-feeding and showed slight worsening in their dependence every 6 months. At the individual level, the increased functional dependence raised the proportional odds ratios of approximately 4.36 times of an increased dependence in self-feeding; the degree of cognitive impairment, the lack of social interactions, the occurrence of pressure sores, comorbidities, as well as the clinical instability and time all raised the risk of self-feeding dependence progression. At the nursing home level, an increased number of beds emerged as a factor also increasing the proportional odds of dependence in self-feeding. Factors affecting self-feeding dependence are multi-faceted at the individual and at the nursing home levels.


Grief: strategies for people anticipating or recovering from a loss.
A comprehensive, compassionate approach to caring for dying patients considers and responds to the needs of their families. Some of the most satisfying moments a nurse can encounter are those experienced while assisting a grieving family. The principal needs of families experiencing anticipatory grief are for honest, frequent information and unrestricted visiting, and accommodation of individual behaviors and rituals. After a death, a bereaved family can benefit from the nurse's attention to supporting grief behaviors and making referrals to community-based supports. Family needs will vary based on personality; coping strengths; supports within the community, family, and hospital; and culture and tradition. Flexible clinicians are able to accommodate most family needs.


Assessing the effects of head modelling errors and measurement noise on EEG source localization accuracy in preterm newborns: A single-subject study.
The accuracy of electroencephalogram (EEG) source localization is compromised because of head modelling errors. In this study, we investigated the effect of inaccuracy in the conductivity of head tissues and head model structural deficiencies on the accuracy of EEG source analysis in premature neonates. A series of EEG forward and inverse simulations was performed by introducing structural deficiencies into the reference head models to generate test models, which were then used to investigate head modelling errors caused by cerebrospinal fluid (CSF) exclusion, lack of grey matter (GM)-white matter (WM) distinction, fontanel exclusion and inaccuracy in skull conductivity. The modelling errors were computed between forward and inverse solutions obtained using the reference and test models generated for each deficiency. Our results showed that the exclusion of CSF from the head model had a strong widespread effect on the accuracy of the EEG source localization with position errors lower than 4.17 mm. The GM and WM distinction also caused strong localization errors (up to 3.5 mm). The exclusion of fontanels from the head model also strongly affected the accuracy of the EEG source localization for sources located beneath the fontanels with a maximum localization error of 4.37 mm. Similarly, inaccuracies in the skull conductivity caused errors in EEG forward and inverse modelling in sources beneath cranial bones. Our results indicate that the accuracy of EEG source imaging in premature neonates can be largely improved by using head models, which include not only the brain, skull and scalp but also the CSF, GM, WM and fontanels.


Effects of apical vs. basolateral palytoxin on LLC-PK1 renal epithelia.
Research on palytoxin focuses on its action as a tumor promoter and its ionophoretic action in cell membranes. The first property is unusual because palytoxin is not a protein kinase C activator. The second property is remarkable in that it may require interaction with the Na(+)-K(+)-adenosinetriphosphatase (ATPase). Our studies here with palytoxin exposure to the LLC-PK1 renal epithelial cells have yielded the following results: 1) unlike protein kinase C-activating tumor promoters (tetradecanoylphorbol 12,13-acetate or teleocidin), palytoxin does not produce a specific effect on the tight junctions between epithelia; 2) palytoxin instead produces an irreversible cytotoxic effect characterized by a pronounced cell swelling associated with sharply elevated levels of intracellular Na+ and decreased levels of intracellular K+; 3) these fluctuations in intracellular Na+ and K+ levels are explained by marked elevations in the membrane flux of 22Na+ and 86Rb+; 4) the electrophysiological reflection of these altered ion fluxes is a pronounced depolarization of the cell sheet if palytoxin is presented to the basolateral cell surface and a pronounced hyperpolarization (due to sharply elevated apical Na+ flux and transepithelial short-circuit current) if palytoxin is administered apically; 5) the apical effect of palytoxin can be blocked by apical ouabain; and 6) this apical effect of palytoxin decreases as a function of the age of the cell sheet. This first report of palytoxin action in a polar epithelial cell system provides additional evidence for palytoxin effects being mediated by contact with the Na(+)-K(+)-ATPase. It also adds to a growing literature suggesting the existence of Na(+)-K(+)-ATPase in the apical cell surface of epithelia under certain conditions.


Laparoscopic treatment of abdominal hernia - 5 years of experience.
Laparoscopic surgery has become a well approved method of abdominal hernias treatment in recent years. Due to the advancement of laparoscopy and the use of improved synthetic materials laparoscopic surgery is characterized not only by low complication but also by a short period of recovery after surgery. The aim of the study was a retrospective analysis of the results of laparoscopic abdominal hernia surgeries (IPOM). Between year 2007 and 2012, 65 patients aged between 29 to 76 underwent laproscopic abdominal hernia surgeries due to either primary or postoperative abdominal hernias. All patients were examined in perioperative period, after 12 and 24 months after surgery in search of complications, pain and reccurence. Recovery period was also estimated. In most cases postoperative pain was estimated from 1 to 4 on VAS scale. The most frequent complications were seromas that occured in 3 patients. The other complications were pneumothorax, wound hematoma and wound infection that occured once each. One patient required reoperation due to wound hematoma. Chronic postoperative pain was diagnosed in 3 patients and 4 recurrences were stated. Laparoscopic therapy of abdominal hernias is a safe operative method characterized by low recurrence and complication rates as well as short hospital stay and quick recovery. This technique is restricted by high material costs and the lack of full refund for the procedure.


Overcoming the barriers to optimal end of life care in the emergency department.
The focus of care in the emergency department (ED) is on saving or sustaining life, but some patients admitted to the ED die in the ED. Nurses whose focus is on saving lives may therefore find themselves providing end of life care to patients and their families in a stressful and distressing environment. Providing optimal end of life care involves reflecting on what a good death looks like and how patients can be supported to have a good death. This article describes the barriers to optimal end of life care in the ED and prompts nurses to think about how they can enhance their practice when caring for dying patients and their families.


Emission of VOCs from service stations in Beijing: Species characteristics and pollutants co-control based on SOA and O3.
Currently, air pollution is primarily characterized by PM2.5 and O3. Therefore, the co-control of PM2.5 and O3 has become an important task of atmosphere pollution prevention and control in China. However, few studies have been conducted on the emissions from vapor recovery and processes, which is an important source of VOCs. This paper analyzed the VOC emissions of three vapor process technologies in service stations and first proposed key pollutants for priority control based on the coordinated reactivity of O3 and SOA. The concentration of VOCs emitted from the vapor processor was 3.14-9.95 g m-3, compared to 631.2-717.8 g m-3 for uncontrolled vapor. Alkanes, alkenes, and halocarbons accounted for a high proportion of the vapor both before and after control. Among the emissions, i-pentane, n-butane, and i-butane were the most abundant species. Then, the species of OFP and SOAP were calculated through the maximum incremental reactivity (MIR) and fractional aerosol coefficient (FAC). The average source reactivity (SR) value of the VOC emissions from three service stations was 1.9 g g-1, while the OFP ranged from 8.2 to 13.9 g m-3 and SOAP ranged from 0.18 to 0.36 g m-3. By considering the coordinated chemical reactivity of O3 and SOA, a comprehensive control index (CCI) was proposed for the control of key pollutant species that have multiplier effects on environment. For adsorption, trans-2-butene and p-xylene were the key co-control pollutants, while toluene and trans-2-butene were the most important for membrane and condensation + membrane control. A 50% emission reduction of the top two key species that emission account for 4.3% averagely will reduce O3 by 18.4% and SOA by 17.9%.


An anatomic source of false venous reflux with continuous wave Doppler.
The limitations of continuous wave (CW) Doppler have been recognized in the assessment of venous reflux since CW Doppler is not able to distinguish reflux signals from more than one vein. In our experience, some regions with venous reflux suggested by CW Doppler were noted to have no reflux in any individual vein during duplex studies. The aim of the study was to assess the anatomic source of the venous reflux suggested by CW Doppler but not confirmed by duplex ultrasound. Five hundred and fifty-one consecutive lower limbs with primary or recurrent varicose veins were examined with CW Doppler and subsequently by color-coded duplex ultrasound to assess the source of venous reflux. The duplex ultrasound study revealed no reflux in 44 specific regions (8%) where reflux had been indicated by CW Doppler. Two types of anatomy were noted. Two or more superficial veins joined the deep venous system via a common junction in 25 cases. A descending vein joined the deep venous system in 19 cases. A bidirectional Doppler signal in a region of venous junction without any incompetent veins can be misinterpreted as venous reflux. A careful examination of veins not only at the region of the junction, but also at some distance down the stem of the vein is important during CW Doppler or duplex assessment.


Shaping of light beams by 3D direct laser writing on facets of nonlinear crystals.
We demonstrate experimentally spatial-mode conversions of light beams generated in a quadratic nonlinear process by micron-scale structures placed on the facets of nonlinear crystals. These structures were printed on the crystal facets using a three-dimensional (3D) direct laser writing system. The functional structures were designed to modify the phase of the beam at specific wavelengths, thereby enabling conversion of a fundamental Gaussian laser beam into different high-order Hermite-Gaussian modes, Laguerre-Gaussian modes, and zeroth-order Bessel beams of the second harmonic. This facet functionalization opens exciting new opportunities for robust and compact beam shaping in a nonlinear interaction without compromising the conversion efficiency.


Otitis media.
Dysfunction of the eustachian tube is the underlying problem in all types of otitis media. Systemic antibiotics and careful follow-up are the treatment of choice for acute suppurative otitis media, whereas topical antibiotics with saline irrigation are used in patients with a chronic condition. Myringotomy and tube insertion may be required in patients with secretory otitis media that does not undergo spontaneous resolution.


The Protection of Midazolam Against Immune Mediated Liver Injury Induced by Lipopolysaccharide and Galactosamine in Mice.
Objectives: Liver macrophages agitated by Lipopolysaccharide (LPS) can enhance immuno-inflammatory responses in the liver which mediate liver injury and result in dysfunction. Midazolam has been reported to have inhibitory effects on activated immunity and escalated inflammation, however, what the effects of midazolam on the liver injury caused by excessive immuno-inflammatory response in sepsis, and what influence it will exert on inflamed liver macrophages need to be elucidated. Methods: In the present study, LPS and galactosamine-induced acute liver injury mice were used to observe the effect of midazolam in vivo. LPS-stimulated bone marrow cells were used to evaluate the influence of midazolam on monocytes in vitro. Results: Midazolam prevented liver tissue injury and decreased serum alanine transaminase (ALT) level in LPS plus galactosamine treated mice. Mechanistically, midazolam suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) produced by LPS stimulated liver macrophages in vivo and bone marrow monocytes in vitro, and reduced the expression of major histocompatibility complex class II (MHC II), cluster of differentiation 40 and 86 (CD40 and CD86) on the cell surface. These results could be reversed by PK-11195, a peripheral benzodiazepine receptor (PBR) blocker. Conclusion: Midazolam can prevent liver from LPS-induced immune mediated liver injury by inhibiting inflammation and immune activation in liver macrophages.