Additional Plate Fixation of Hinge Fractures After Varisation Distal Femoral Osteotomies Provides Favorable Torsional Stability: A Biomechanical Study.
Hinge fractures are considered risk factors for delayed or nonunion of the osteotomy gap in distal femoral osteotomies (DFOs). Limited evidence exists regarding the treatment of hinge fractures after DFO, which could improve stability and thus bone healing. To (1) examine the effect of hinge fractures on the biomechanical properties of the bone-implant construct, (2) evaluate the biomechanical advantages of an additional fixation of a hinge fracture, and (3) test the biomechanical properties of different types of varisation DFOs. Controlled laboratory study. A total of 32 fresh-frozen human distal femora equally underwent medial closing wedge DFO or lateral opening wedge DFO using a unilateral locking compression plate. The following conditions were serially tested: (1) preserved hinge; (2) hinge fracture along the osteotomy plane; (3) screw fixation of the hinge fracture; and (4) locking T-plate fixation of the hinge fracture. Using a servo-hydraulic materials testing machine, we subjected each construct to 15 cycles of axial compression (400 N; 20 N/s) and internal and external rotational loads (10 N·m; 0.5 N·m/s) to evaluate the stiffness. The axial and torsional hinge displacement was recorded using a 3-dimensional optical measuring system. Repeated-measures 1-way analysis of variance and post hoc Bonferroni correction were used for multiple comparisons. Statistical significance was set at P < .05. Independent from the type of osteotomy, a fractured hinge significantly (P < .001) increased rotational displacement and reduced stiffness of the bone-implant construct, resulting in ≥1.92 mm increased displacement and ≥70% reduced stiffness in each rotational direction, while the axial stiffness remained unchanged. For both procedures, neither a screw nor a plate could restore intact rotational stiffness (P < .01), while only the plate was able to restore intact rotational displacement. However, the plate always performed better compared with the screw, with significantly higher and lower values for stiffness (+38% to +53%; P < .05) and displacement (-55% to -72%; P < .01), respectively, in ≥1 rotational direction. At the same time, the type of osteotomy did not significantly affect axial and torsional stability. Hinge fractures after medial closing wedge DFO and lateral opening wedge DFO caused decreased bone-implant construct rotational stiffness and increased fracture-site displacement. In contrast, the axial stiffness remained unchanged in the cadaveric model. When considering an osteosynthesis of a hinge fracture in a DFO, an additional plate fixation was the construct with the highest stiffness and least displacement, which could restore intact hinge rotational displacement.


Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.
Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.


Improved Methane Production by Photocatalytic CO2 Conversion over Ag/In2O3/TiO2 Heterojunctions.
In this work, the role of In2O3 in a heterojunction with TiO2 is studied as a way of increasing the photocatalytic activity for gas-phase CO2 reduction using water as the electron donor and UV irradiation. Depending on the nature of the employed In2O3, different behaviors appear. Thus, with the high crystallite sizes of commercial In2O3, the activity is improved with respect to TiO2, with modest improvements in the selectivity to methane. On the other hand, when In2O3 obtained in the laboratory, with low crystallite size, is employed, there is a further change in selectivity toward CH4, even if the total conversion is lower than that obtained with TiO2. The selectivity improvement in the heterojunctions is attributed to an enhancement in the charge transfer and separation with the presence of In2O3, more pronounced when smaller particles are used as in the case of laboratory-made In2O3, as confirmed by time-resolved fluorescence measurements. Ternary systems formed by these heterojunctions with silver nanoparticles reflect a drastic change in selectivity toward methane, confirming the role of silver as an electron collector that favors the charge transfer to the reaction medium.


Use of Predictive Modeling to Plan for Special Event Medical Care During Mass Gathering Events.
In 2010, South Africa (SA) hosted the Fédération Internationale de Football Association (FIFA) World Cup (soccer). Emergency Medical Services (EMS) used the SA mass gathering medicine (MGM) resource model to predict resource allocation. This study analyzed data from the World Cup and compared them with the resource allocation predicted by the SA mass gathering model. Prospectively, data were collected from patient contacts at 9 venues across the Western Cape province of South Africa. Required resources were based on the number of patients seeking basic life support (BLS), intermediate life support (ILS), and advanced life support (ALS). Overall patient presentation rates (PPRs) and transport to hospital rates (TTHRs) were also calculated. BLS services were required for 78.4% (n = 1279) of patients and were consistently overestimated using the SA mass gathering model. ILS services were required for 14.0% (n = 228), and ALS services were required for 3.1% (n = 51) of patients. Both ILS and ALS services, and TTHR were underestimated at smaller venues. The MGM predictive model overestimated BLS requirements and inconsistently predicted ILS and ALS requirements. MGM resource models, which are heavily based on predicted attendance levels, have inherent limitations, which may be improved by using research-based outcomes.


Insights into hospital readmission patterns of atrial fibrillation patients.
Patients admitted to the hospital with atrial fibrillation have associated morbidity and mortality and incur significant costs. Data characterizing atrial fibrillation patients at high risk for readmission are scarce. We sought to inform this area by characterizing and categorizing unplanned readmissions of atrial fibrillation patients. Retrospective data were abstracted from the charts of patients discharged from 2008 to 2012 after an index hospitalization for atrial fibrillation and referred to the nurse practitioner-led transitional care program, Bridging the Discharge Gap Effectively. Unplanned readmissions were dichotomized as early (⩽30 days) or late (31-180 days) and further classified as either "atrial fibrillation/atrial fibrillation-related" (AF/AF-related), "Cardiac; not AF/AF-related," or "Not cardiac-related." Case classifications were adjudicated by a senior cardiologist. Patient demographics and readmission characteristics were then compared. Of 255 patients, 97 (38.0%) had unplanned readmissions within 180 days of discharge; 45 (46.4%) were early and 52 (53.6%) were late. Atrial fibrillation and cardiac causes accounted for 68.9% (n=31) of early readmissions and 65.4% (n=34) of late. Patients with late readmissions were more likely to have diabetes (32.7% vs. 17.7%, p=.022) and higher CHA2DS2VASc scores (3.63 vs. 2.98, p=0.026) than those not readmitted. No other differences in baseline characteristics were seen within or between groups. The 30-day all-cause readmission rate in this sample was 17.6% (n=45). Readmissions following hospital discharge for atrial fibrillation are common; approximately 50% of these readmissions are for reasons unrelated to atrial fibrillation. In order to reduce atrial fibrillation-related readmissions, further research is needed to characterize predictors of readmission and to develop effective transitional care interventions.


Multilevel X-Pol: a fragment-based method with mixed quantum mechanical representations of different fragments.
The explicit polarization (X-Pol) method is a fragment-based quantum mechanical model, in which a macromolecular system or other large or complex system in solution is partitioned into monomeric fragments. The present study extends the original X-Pol method, where all fragments are treated using the same electronic structure theory, to multilevel representations, called multilevel X-Pol, in which different electronic structure methods are used to describe different fragments. The multilevel X-Pol method has been implemented into a locally modified version of Gaussian 09. A key ingredient that is used to couple interfragment electrostatic interactions at different levels of theory is the use of the response density for the post-self-consistent-field energy. (The response density is also called the generalized density.) The method is useful for treating fragments in a small region of the system such as a solute molecule or the substrate and amino acids in the active site of an enzyme with a high-level theory, and the fragments in the rest of the system by a lower-level and computationally more efficient method. Multilevel X-Pol is illustrated here by applications to hydrogen bonding complexes in which one fragment is treated with the hybrid M06 density functional, Møller-Plesset perturbation theory, or coupled cluster theory, and the other fragments are treated by Hartree-Fock theory or the B3LYP or M06 hybrid density functionals.


Functional genomics of Enterococcus faecalis: multiple novel genetic determinants for biofilm formation in the core genome.
The ability of Enterococcus faecalis to form robust biofilms on host tissues and on abiotic surfaces such as catheters likely plays a major role in the pathogenesis of opportunistic antibiotic-resistant E. faecalis infections and in the transfer of antibiotic resistance genes. We have carried out a comprehensive analysis of genetic determinants of biofilm formation in the core genome of E. faecalis. Here we describe 68 genetic loci predicted to be involved in biofilm formation that were identified by recombinase in vivo expression technology (RIVET); most of these genes have not been studied previously. Differential expression of a number of these determinants during biofilm growth was confirmed by quantitative reverse transcription-PCR, and genetic complementation studies verified a role in biofilm formation for several candidate genes. Of particular interest was genetic locus EF1809, predicted to encode a regulatory protein of the GntR family. We isolated 14 independent nonsibling clones containing the putative promoter region for this gene in the RIVET screen; EF1809 also showed the largest increase in expression during biofilm growth of any of the genes tested. Since an in-frame deletion of EF1809 resulted in a severe biofilm defect that could be complemented by the cloned wild-type gene, we have designated EF1809 ebrA (enterococcal biofilm regulator). Most of the novel genetic loci identified in our studies are highly conserved in gram-positive bacterial pathogens and may thus constitute a pool of uncharacterized genes involved in biofilm formation that may be useful targets for drug discovery.


Formation and infrared identification of protonated fluoranthene isomers 3-, 9-, and 10-C16H11+ in solid para-H2.
Polycyclic aromatic hydrocarbons (PAH) and their derivatives are prospective carriers of unidentified infrared (UIR) emission features observed in interstellar media. Fluoranthene (C16H10) is a simple planar PAH with five- and six-membered rings; it can be considered as a fragment of C60, which, along with its cationic counterpart, has been identified in interstellar media. Protonated fluoranthene, C16H11+, was generated upon electron bombardment during deposition at 3.2 K of p-H2 containing fluoranthene in a small proportion. The intensities of infrared features of C16H11+ decreased after maintaining the matrix in darkness because of its neutralization with trapped electrons. According to the correlations in intensities upon neutralization and secondary photolysis, observed lines were classified into three groups which are assigned to isomers 3-C16H11+, 9-C16H11+, and 10-C16H11+. Experimental vibrational wavenumbers and relative IR intensities of the features agree with corresponding calculated values predicted for these three isomers of C16H11+ with the B3PW91/6-311++G(2d,2p) method. 3-C16H11+ and 9-C16H11+ are predicted to have the lowest energy (within 5 kJ mol-1), whereas 10- and 1-C16H11+ are lying above the global minimum 3-C16H11+ by ∼20 kJ mol-1. However, definitive identification of 1-C16H11+ could not be made as only the most intense line is tentatively assigned. Although the observed spectra of these isomers match unsatisfactorily with the UIR bands, they will facilitate the potential terrestrial and extraterrestrial identification of these species.


Expression of CD10 by B-chronic lymphocytic leukemia cells undergoing apoptosis in vivo and in vitro.
B-cell chronic lymphocytic leukemia (B-CLL) is an accumulating disease of slowly proliferating cells. CD10 is not normally expressed on the surface of B-CLL cells. The aim of this study was to ascertain whether B-CLL cells, induced into apoptosis, expressed surface CD10, since a correlation between apoptosis and CD10 expression has been demonstrated. Peripheral blood cells from 31 untreated B-CLL patients were induced into apoptosis by etoposide, fludarabine or Ga(mu)-Ab treatment and tested for CD10 expression by flow cytometry. Normal CD5+ B cells were also induced into apoptosis and tested for CD10 expression. CD10 positive cells were absent in B-CLL cell suspensions, but were detected following in vitro culture, and their appearance paralleled that of apoptotic cells. Treatment with etoposide, fludarabine or Ga(mu)-Ab enhanced both apoptosis and CD10 expression. Inhibition of apoptosis by VAD-fmk or Ga(delta)-Ab prevented CD10 expression. Cell separation tests following induction of apoptosis demonstrated that CD10+ cells were apoptotic. CD10+ cells were observed in the peripheral blood of two patients within a few hours following fludarabine infusion. In another patient, who failed to respond, no CD10+ cells were seen. Expression of CD10 was observed also in normal CD5+ B cells when these were induced into apoptosis. This study demonstrates that B-CLL cells, as well as normal CD5+ B cells, become CD10+ following apoptosis induction in vitro. Some of the data obtained also suggest a use for CD10 to monitor apoptosis of B-CLL in a clinical setting.


Micelle vs. vesicle formation controlled by distal functionalization of C60-PEG conjugates.
An amphiphilic C60-PEG conjugate was modified by the addition of cationic moieties in the hydrophobic C60 part to provide the related bis- and tris-adducts and their self-assembling structures were compared. All of these materials were water-soluble and their supramolecular structures were investigated in the aqueous phase using tensiometry, DLS, and STEM techniques. While mono- and bis-adducts formed micelle-type supramolecular structures, the tris-one with two additional cationic pyrrolidine groups showed the formation of larger particles as indicated by DLS data. Further, the STEM image of the tris-adduct showed a vesicle-type supramolecular structure with, presumably, an internal water-phase inside.


Schuurs-Hoeijmakers syndrome in two patients from Japan.
Schuurs-Hoeijmakers syndrome is a rare disease characterized by intellectual disability and dysmorphic facial features among various physical abnormalities due to PACS1 mutation. To date, 28 patients with a recurrent de novo PACS1 mutation (c.607C > T) have been reported, primarily in Western populations. Here, we describe two Japanese patients with Schuurs-Hoeijmakers syndrome with a recurrent PACS1 mutation. In addition to the typical clinical symptoms, each patient presented novel clinical phenotypes. One patient presented with involuntary movements and was treated with trihexyphenidyl hydrochloride. We hypothesized that the PACS1 mutation leads to an inherent dopaminergic insufficiency that underlies the developing symptoms along with the neurodevelopmental processes. The second patient was diagnosed with lipomyelomeningocele during an examination for severe constipation at the age of 2 years and 8 months. The diagnosis of lipomyelomeningocele in this patient was delayed due to the lack of cutaneous lesions. As the majority of patients with PACS1 mutation present constipation, underdiagnosis of lipomyelomeningocele is a possibility. As the phenotypic expansion of the patients with Schuurs-Hoeijmakers syndrome was not fully recognized, additional studies are needed to clarify the clinical spectrum.


Long-term expansion, enhanced chondrogenic potential, and suppression of endochondral ossification of adult human MSCs via WNT signaling modulation.
Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.


Practical Tips for Successful Implementation of Educational Innovations: Project Management Tools for Health Professional Educators.
This article was migrated. The article was marked as recommended. Background: Growing demands from health professional educators lead to expectations for smooth implementation of high-stake endeavors such as developing and successfully launching educational innovations ranging from curricular sessions to new programs under time constraints. Usually, multiple requirements, resources, and processes need to be identified, evaluated, and effectively utilized, making the process difficult and confusing. Personnel and operations must be aligned to create momentum for a successful workflow, which requires planning and negotiation with stakeholders. Increasingly, project management strategies and skills have been recommended to medical educators for accomplishing these goals; however, to-date no practical tools or templates have been provided to support and guide educational implementation processes in a practical fashion. Aim: Adjusted to the needs of medical educators across all healthcare professions, we provide interactive templates and tools in the appendix, which walk readers through the implementation of a complete educational project from start to finish. Methods: Using project management guidelines established by the Project Management Institute (PMI), the global credentialing body for the project management profession, the tools and templates follow best practices that were aligned with standards of curriculum development (six-step approach) as published by Kern and colleagues ( Thomas, Kern, Hughes & Chen (Eds.), 2016). Results: We identified a practical workflow for implementing educational innovations and developed interactive tools and templates as guides for tracking and presenting progress for the launch of educational projects of any scale, large or small. Conclusions/summary statement: Developing and implementing complex, multistep endeavors such as collaborative educational sessions or programs can be mastered successfully using project management tools and templates. Based on international project management guidelines and best practices, the authors outline how project management tools and templates allow medical educators to streamline successful systematic planning, engage in creative-problem solving and establish consensus under time constraints.


Identification of streptococci to species level by sequencing the gene encoding the manganese-dependent superoxide dismutase.
We have used a PCR assay based on the use of degenerate primers in order to characterize an internal fragment (sodA(int)) representing approximately 85% of the genes encoding the manganese-dependent superoxide dismutase in various streptococcal type strains (S. acidominimus, S. agalactiae, S. alactolyticus, S. anginosus, S. bovis, S. constellatus, S. canis, S. cricetus, S. downei, S. dysgalactiae, S. equi subsp. equi, S. equi subsp. zooepidemicus, S. equinus, S. gordonii, S. iniae, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguis, S. pneumoniae, S. porcinus, S. pyogenes, S. salivarius, S. sanguis, S. sobrinus, S. suis, S. thermophilus, and S. vestibularis). Phylogenetic analysis of these sodA(int) fragments yields an evolutionary tree having a topology similar to that of the tree constructed with the 16S rRNA sequences. We have shown that clinical isolates could be identified by determining the positions of their sodA(int) fragments on the phylogenetic tree of the sodA(int) fragments of the type species. We propose this method for the characterization of strains that cannot be assigned to a species on the basis of their conventional phenotypic reactions.


Origin of INSL3-mediated testicular descent in therian mammals.
Testicular descent is a unique physiological adaptation found in therian mammals allowing optimal spermatogenesis below core body temperature. Recent studies show that INSL3, produced by Leydig cells, and its receptor LGR8 (RXFP2) are essential for mediating the transabdominal phase of testicular descent during early development. However, the origin and genetic basis for this physiological adaptation is not clear. Using syntenic mapping and the functional characterization of contemporary and resurrected relaxin family hormones, we show that derivation of INSL3-mediated testicular descent involved the duplication of an ancestral RLN3-like gene that encodes an indiscriminate ligand for LGR7 (RXFP1) and LGR8. This event was followed by acquisition of the LGR7-selective characteristics by a daughter gene (RLN3) prior to the evolution of the common ancestor of monotremes, marsupials, and placentals. A subsequent mutation of the other daughter gene (INSL3) occurred before the emergence of therian mammals, which then led to the derivation of the reciprocal LGR8-specific characteristics of INSL3. The stepwise evolution of these independent signaling pathways through gene duplication and subsequent divergence is consistent with Darwinian theory of selection and adaptation, and the temporal proximity suggests an association between these genetic events and the concurrent evolution of testicular descent in ancestral therian mammals.


A modular design of molecular qubits to implement universal quantum gates.
The physical implementation of quantum information processing relies on individual modules-qubits-and operations that modify such modules either individually or in groups-quantum gates. Two examples of gates that entangle pairs of qubits are the controlled NOT-gate (CNOT) gate, which flips the state of one qubit depending on the state of another, and the gate that brings a two-qubit product state into a superposition involving partially swapping the qubit states. Here we show that through supramolecular chemistry a single simple module, molecular {Cr7Ni} rings, which act as the qubits, can be assembled into structures suitable for either the CNOT or gate by choice of linker, and we characterize these structures by electron spin resonance spectroscopy. We introduce two schemes for implementing such gates with these supramolecular assemblies and perform detailed simulations, based on the measured parameters including decoherence, to demonstrate how the gates would operate.


Case managers' attitudes to the physical health of their patients.
To examine the attitudes and practices of case managers working in Area Mental Health Services (AMHS) towards the physical health of people with chronic mental illness. Case managers at four AMHS in Melbourne participated in focus groups and completed a survey questionnaire. Case managers generally believed that mental illness, psychotropic medication and lifestyle factors contributed to the poor physical health status of their patients. Although many case managers attempted interventions aimed at improving physical health, there was inconsistency regarding the areas targeted. Preventive health measures were often neglected. Overall, there was a sense of pessimism around whether improved physical health was possible for people with chronic mental illness. Lack of coordination among health professionals and the health system may contribute to the poor general health of people with mental illness. Patients often have difficulty accessing general practitioners and the culture within the AMHS can exclude considerations of physical health. Case management should include aspects addressing the physical health issues of AMHS clients.


Epidemiology of injuries in Nigeria-a systematic review of mortality and etiology.
Trauma is a major health issue worldwide, but especially so in developing countries such as Nigeria, where no comprehensive, national, injury data exist. There is a need to better define the epidemiology of injury as a basis for formulation of violence and injury prevention strategy. This is a systematic analysis of published data on the epidemiology of injuries. The objective of this study was to describe the prevalent causes of injury among adults and children, and the causes of injury mortality. The medical records of 15,694 patients from the age of two weeks to 95 years formed the analysed data set. The mean value of their ages was 27 ±13 years and the gender ratio (M:F) 2:1. The injury burden is 11.2/100,000 population. The prevalent causes of injury are: (1) road traffic crashes (RTCs) = 68.4 % of 9939 patients; (2) fall = 5.5%; (3) gunshot injury = 3.2%; and (4) burns = 2.4%. Among children, the leading causes are: (1) RTC = 33.9% of 2,199 patients; (2) fall = 29.1%; (3) foreign body related = 5.5%; (4) bites = 4.9%; and (5) burns = 4%. Mortality resulted mainly from head injury, 26.6% of 575, and hemorrhage 8.3%. Road traffic incidents are the leading cause of injury among adults and children. Falls are six times more prevalent among children than for adults. Burns and firearm injuries are relatively uncommon. Injury mortality results mainly from head injury and hemorrhage.


Diverse genome organization following 13 independent mesopolyploid events in Brassicaceae contrasts with convergent patterns of gene retention.
Hybridization and polyploidy followed by genome-wide diploidization had a significant impact on the diversification of land plants. The ancient At-α whole-genome duplication (WGD) preceded the diversification of crucifers (Brassicaceae). Some genera and tribes also experienced younger, mesopolyploid WGDs concealed by subsequent genome diploidization. Here we tested if multiple base chromosome numbers originated due to genome diploidization after independent mesopolyploid WGDs and how diploidization affected post-polyploid gene retention. Sixteen species representing 10 Brassicaceae tribes were analyzed by comparative chromosome painting and/or whole-transcriptome analysis of gene age distributions and phylogenetic analyses of gene duplications. Overall, we found evidence for at least 13 independent mesopolyploidies followed by different degrees of diploidization across the Brassicaceae. New mesotetraploid events were uncovered for the tribes Anastaticeae, Iberideae and Schizopetaleae, and mesohexaploid WGDs for Cochlearieae and Physarieae. In contrast, we found convergent patterns of gene retention and loss among these independent WGDs. Our combined analyses of genomic data for Brassicaceae indicate that extant chromosome number variation in many plant groups, and especially monophyletic taxa with multiple base chromosome numbers, can result from clade-specific genome duplications followed by diploidization. Our observation of parallel gene retention and loss across multiple independent WGDs provides one of the first multi-species tests of the predictability of patterns of post-polyploid genome evolution.


The gravitational shunt: an alternative approach to cerebrospinal fluid shunting.
Current cerebrospinal fluid shunts use complex differential pressure values to regulate drainage. Such systems are prone to overdrainage and obstruction, and thus have an unpredictable effect on intracranial pressure (ICP). The gravitational shunt (GS) introduces an alternative approach. It uses a single, simple valve to balance the pressures generated within a vertical shunt system. The ICP is then regulated by the position of the valve along the cranioabdominal shunt axis and not by the mechanical properties of the valve. Bench testing demonstrated that when using the GS (1) a linear correlation (r = 0.91, p < 0.001) exists between the ICP and the position of the valve along the vertical shunt axis, (2) positive and negative ICPs are maintained, and (3) the ICP can be predicted by an equation derived from theoretical principles. The GS uses a single, simple valve as a pressure regulator and an antisiphon device. It allows the maintenance of a normal negative ICP in the upright position without risk of over-drainage. The other benefits of this system are discussed.


Efficient ternary blend bulk heterojunction solar cells with tunable open-circuit voltage.
To explore the potential of ternary blend bulk heterojunction (BHJ) photovoltaics as a general platform for increasing the attainable performance of organic solar cells, a model system based on poly(3-hexylthiophene) (P3HT) as the donor and two soluble fullerene acceptors, phenyl-C(61)-butyric acid methyl ester (PC(61)BM) and indene-C(60) bisadduct (ICBA), was examined. In all of the solar cells, the overall ratio of polymer to fullerene was maintained at 1:1, while the composition of the fullerene component (PC(61)BM:ICBA ratio) was varied. Photovoltaic devices showed high short-circuit current densities (J(sc)) and fill factors (FF) (>0.57) at all fullerene ratios, while the open-circuit voltage (V(oc)) was found to vary from 0.61 to 0.84 V as the fraction of ICBA was increased. These results indicate that the V(oc) in ternary blend BHJ solar cells is not limited to the smallest V(oc) of the corresponding binary blend solar cells but can be varied between the extreme V(oc) values without significant effect on the J(sc) or FF. By extension, this result suggests that ternary blends provide a potentially effective route toward maximizing the attainable J(sc)V(oc) product (which is directly proportional to the solar cell efficiency) in BHJ solar cells and that with judicious selection of donor and acceptor components, solar cells with efficiencies exceeding the theoretical limits for binary blend solar cells could be possible without sacrificing the simplicity of a single active-layer processing step.


Plasma Soluble Urokinase Receptor Level Is Correlated with Podocytes Damage in Patients with IgA Nephropathy.
Focal segmental glomerulosclerosis (FSGS) lesions are similar in characteristics to S lesions of the Oxford classification of IgA nephropathy (IgAN) and may predict poor prognosis. In the present study, we aimed to explore the association between plasma soluble urokinase receptor (suPAR) levels and S lesions and podocytes damage in IgAN patients. We enrolled 569 IgAN patients with follow-up data and detected plasma suPAR levels at renal biopsy by enzyme-linked immunosorbent assay. Plasma suPAR levels in IgAN patients with or without S lesions did not differ significantly (P = 0.411). However, suPAR levels were positively correlated with proteinuria (r = 0.202, P < 0.001), and negatively correlated with estimated glomerular filtration rate (eGFR, r = -0.236, P < 0.001). In the partial correlation to adjust for eGFR, plasma suPAR levels remained positively correlated with proteinuria (r = 0.112, P = 0.023). In a Cox proportional hazards model, higher levels of plasma suPAR were not associated with poor renal outcome. Plasma suPAR levels of IgAN and primary FSGS patients with nephrotic syndrome were not significantly different (P = 0.306). Plasma suPAR levels in patients with extensive effacement of the epithelial cell foot processes of glomerular podocytes were significantly higher than those with segmental effacement on the basis of comparable eGFR (P = 0.036). In IgAN patients, plasma suPAR levels were not associated with S lesions. However, they were positively associated with proteinuria and negatively associated with eGFR. In addition, plasma suPAR levels were positively associated with the effacement degree of the foot processes, which might partially contribute to the development of proteinuria in patients with IgAN.


The Role of Electrostatics in Enzymes: Do Biomolecular Force Fields Reflect Protein Electric Fields?
Preorganization of large, directionally oriented, electric fields inside protein active sites has been proposed as a crucial contributor to catalytic mechanism in many enzymes, and it may be efficiently investigated at the atomistic level with molecular dynamics simulations. Here, we evaluate the ability of the AMOEBA polarizable force field, as well as the additive Amber ff14SB and Charmm C36m models, to describe the electric fields present inside the active site of the peptidyl-prolyl isomerase cyclophilin A. We compare the molecular mechanical electric fields to those calculated with a fully first-principles quantum mechanical (QM) representation of the protein, solvent, and ions, and find that AMOEBA consistently shows far greater correlation with the QM electric fields than either of the additive force fields tested. Catalytically relevant fields calculated with AMOEBA were typically smaller than those observed with additive potentials, but were generally consistent with an electrostatically driven mechanism for catalysis. Our results highlight the accuracy and the potential advantages of using polarizable force fields in systems where accurate electrostatics may be crucial for providing mechanistic insights.


Anti-aminoacyl tRNA synthetase immune responses: insights into the pathogenesis of the idiopathic inflammatory myopathies.
One of the most striking humoral characteristics of the idiopathic inflammatory myopathies is the specific targeting of components of the translational machinery by the immune system. The most commonly targeted of these components are the aminoacyl tRNA synthetase (ARS) molecules. However, the relation between the immune responses to these molecules and the pathogenesis of the inflammatory myopathies remains obscure. This review will examine recent evidence that explores the links between the ARS molecules, inflammation, and apoptosis, with the aim of furthering our current understanding of the underlying pathogenesis of the myositis syndromes. Several of the ARS molecules and their proteolytic fragments generated during inflammation and apoptosis have recently been shown to possess chemoattractant properties. The liberation of these fragments in the muscle microenvironment under certain circumstances may provide a proinflammatory context and lead to the influx of lymphocytes, macrophages, and specialized antigen-presenting cells to the site of muscle injury. The subsequent processing and presentation of these autoantigen fragments on major histocompatibility complex class I and II molecules may generate an ARS-specific autoimmune response, which may be responsible for amplification and propagation of muscle injury in these diseases. The striking association between the inflammatory myopathies and anti-ARS antibodies implies a role for the ARS molecules in the pathogenesis of these syndromes. Recent data suggest that ARS molecules and their proteolytic fragments generated during the cell death process may be responsible for priming and sustaining a specific immune response in situ in myositis. How these molecules become altered and access the immune system in the disease microenvironment is an area of ongoing investigation.


The interferon signaling pathway genes as biomarkers of hepatitis C virus disease progression and response to treatment.
Hepatitis C virus is an ever-increasing worldwide health problem with over 350,000 individuals succumbing to hepatitis C virus-related liver diseases each year. The ability to determine the outcome of an acute-phase illness may be useful in terms of implementing treatment strategies; however, to date, the predictive associations in the literature have centered around candidate gene analysis. Much greater advancements have been made in describing biomarkers from the activation of the host innate immune response, such as the interferon system, for prediction of treatment outcome in chronic hepatitis C with the advent of genome-wide association studies. Recent times has seen a major breakthrough in the field with the description of the IL28B genotype as an independent association factor for pegylated IFN-α2b/ribavirin treatment response. The ability to couple this with other easily measured biomarkers such as the interferon-stimulated gene CXCL10, serum concentration may make this predictive marker set very useful in the clinical setting.


Cognitive and anatomic contributions of metabolic decline in Alzheimer disease and cerebrovascular disease.
Alzheimer disease and cerebrovascular disease affect elderly persons through alterations in brain structure and metabolism that produce cognitive decline. Understanding how each disease contributes to dementia is essential from both a pathophysiologic and diagnostic perspective. To elucidate how baseline cognitive function (episodic memory and executive function) and brain anatomy (white matter hyperintensities and hippocampal volume) are associated with baseline (positron emission tomography-1 [PET1]) and longitudinal (PET2) glucose metabolism in 38 subjects older than 55 years ranging from normal cognition, cognitive impairment without dementia, and dementia. Cross-sectional regression analyses across subjects. Multicenter, university-based study of subcortical vascular dementia. Regional cerebral glucose metabolism was the primary outcome, with the major hypotheses that memory and hippocampal volume are related to temporoparietal hypometabolism while executive function and white matter hyperintensities correlate with frontal lobe hypometabolism. Low baseline hippocampal volume predicted longitudinal development (PET2) of medial temporal hypometabolism. Lower memory was associated with parietal and cingulate hypometabolism at PET1, which increased at the 2-year-follow-up (PET2). Executive function was associated with frontal and temporoparietal hypometabolism at PET1 but only with frontal hypometabolism at follow-up. White matter hyperintensities predicted hypometabolism over time in the frontoparietal regions, predicting a rate of metabolic change (PET1 - PET2/time). Low baseline episodic memory and hippocampal volume predict the metabolic alterations associated with Alzheimer disease, whereas elevated baseline white matter hyperintensities predict a different pattern of metabolic decline that is plausibly associated with cerebrovascular disease.


Facile Synthesis of ZnO Nanoparticles on Nitrogen-Doped Carbon Nanotubes as High-Performance Anode Material for Lithium-Ion Batteries.
ZnO/nitrogen-doped carbon nanotube (ZnO/NCNT) composite, prepared though a simple one-step sol-gel synthetic technique, has been explored for the first time as an anode material. The as-prepared ZnO/NCNT nanocomposite preserves a good dispersity and homogeneity of the ZnO nanoparticles (~6 nm) which deposited on the surface of NCNT. Transmission electron microscopy (TEM) reveals the formation of ZnO nanoparticles with an average size of 6 nm homogeneously deposited on the surface of NCNT. ZnO/NCNT composite, when evaluated as an anode for lithium-ion batteries (LIBs), exhibits remarkably enhanced cycling ability and rate capability compared with the ZnO/CNT counterpart. A relatively large reversible capacity of 1013 mAh·g-1 is manifested at the second cycle and a capacity of 664 mAh·g-1 is retained after 100 cycles. Furthermore, the ZnO/NCNT system displays a reversible capacity of 308 mAh·g-1 even at a high current density of 1600 mA·g-1. These electrochemical performance enhancements are ascribed to the reinforced accumulative effects of the well-dispersed ZnO nanoparticles and doping nitrogen atoms, which can not only suppress the volumetric expansion of ZnO nanoparticles during the cycling performance but also provide a highly conductive NCNT network for ZnO anode.


The role of the dentist in genetic counseling.
Professional and lay attitudes about the role of the dentist in the health sciences is changing perceptibly [16-18]. The view that the activities of the dentist are limited to manipulations of the teeth is being replaced by the view that the dentist is an important member of the health team. To be sure, medical colleagues may still ask why a dentist is in the nursery or elsewhere in the hospital and for the lay public may still ask what genetics has to do with dentistry or vice versa. But "the times, they are a-changing." There is an expanded responsibility for dentists in today's world and a significant part of that responsibility involves the provision of genetic services: diagnosis and counseling. There is no doubt in my mind that the following statement that I make to medical students and colleagues is as true for dentists as for physicians: the failure to provide genetic counseling when it is indicated is malpractice.


Serum thyroglobulin in the management of patients with thyroid cancer.
We have reviewed our experience with the management of patients with thyroid cancer to assess the potential benefits of employing the serum thyroglobulin assay in patient management programs and to determine the optimal conditions for this application. Serum thyroglobulin levels were found to be more reliable when obtained from hypothyroid patients. Levels of thyroglobulin greater than 10 ng/mL appeared to be abnormally elevated in both thyroidectomized patients prior to radioactive iodine therapy (group 1) and in thyroidectomized patients after radioactive iodine therapy (group 2). Elevated thyroglobulin levels were found to be useful indicators of the presence of metastatic disease, whereas normal thyroglobulin levels were reliable indicators of the absence of metastases. In group 1 patients, elevated thyroglobulin levels reliably predicted the presence of important total body scan uptake. In group 2 patients, normal thyroglobulin levels reliably predicted the absence of total body scan uptake. The serum thyroglobulin assay can substantially reduce the need for repetitive total body scanning in the follow-up of group 2 patients with thyroid cancer.


Interactions of FliJ with the Salmonella type III flagellar export apparatus.
FliJ, a 17-kDa protein, is a soluble component of the Salmonella type III flagellar protein export system that has antiaggregation properties and several other characteristics that suggest it may have a chaperone-like function. We have now examined this protein in detail. Ten-amino-acid scanning deletions covering the entire 147-amino-acid sequence were tested for complementation of a fliJ null strain; only the first and last deletions complemented. A few of the deletions, especially towards the C terminus, exerted a dominant negative effect on wild-type cells, indicating that they were actively interfering with function. Two truncated versions of FliJ, representing its N- and C-terminal halves, failed to complement and were not dominant. We tested for FliJ self-association by several techniques. Size-exclusion chromatography (Superdex 200) indicated an apparent molecular mass of around 50 kDa, which could reflect either multimerization or an elongated shape or both. Multiangle light scattering gave a peak value of 20 kDa, close to the molecular mass of the monomer. Analytical ultracentrifugation gave evidence for weak self-association as a trimer or tetramer. It was known from previous studies that FliJ interacts with the N-terminal region of FliH, a negative regulator of the ATPase FliI. Using both truncation and deletion versions of FliJ, we now show that it is its C-terminal region that is responsible for this interaction. We also show that FliJ interacts with the soluble cytoplasmic domain of the largest membrane component of the export apparatus, FlhA; although small deletions in FliJ did not interfere with the association, both truncated versions failed to associate, indicating that a substantial amount of the central region of the FliJ sequence participates in the association. We present a model summarizing these multiple interactions.


Perceptions, attitudes and practices on schistosomiasis in Delta State, Nigeria.
Urinary schistosomiasis, which is one of the commonest forms of the parasitic disease is a major debilitating disease characterized by blood in urine. The main objective of the study reported here was to assess the knowledge, attitude/perception and practices of the people in Oshimili South and Ndokwa Northeast Local Government Areas of Delta State in Nigeria. A cross-sectional study of 400 randomly selected persons aged > or =15 years was undertaken using a uniform set of structured interview schedule administered by trained field assistants. This was supported with some qualitative data collected from in-depth interview with community leaders and school teachers as well as focus group discussions with community members. One-third of the people interviewed were aware of the schistosomiasis. For a majority however, the perceived causes of the disease included witchcraft and sexual or body contact with infected persons. For some of the respondents, the disease is not serious since it does not harm or prevent the victim from eating. In many cases the disease was not treated because of the belief that there is no effective cure for it and that it reoccurs after treatment. But perhaps more importantly, the infection is not treated because it is considered a normal growing up process, which the infected person outgrows. A very high proportion of people depended on the schistosomiasis-infected river for all the domestic needs even where there are alternative sources of water. People argued that the river/ stream give them purer water than the hand dug wells. Furthermore, swimming is a popular activity in the river during all seasons, irrespective of sex and age. In conclusion, the study has identified gaps in the knowledge of the cause and means of transmission, poor perception and management practices, which calls for systematic health education on schistosomiasis in the communities


Peribrachiocephalic approaches to the anterior cervicothoracic spine.
This cadaveric study aims to reexamine the corridors to the anterior cervicothoracic junction, relative to the left brachiocephalic vein, and to present these working corridors as either supra- or infra-brachiocephalic. The anterior cervicothoracic junction incorporates the seventh cervical vertebrae through the fourth thoracic vertebrae (C7-T4) and involves critical anatomical structures. Operative approaches to this area are well described in the literature, with the predominant implementation of three surgical corridors. We used three embalmed, human, cadaveric specimens for this study. No pathology involving the cervicothoracic junction was noted. While dissecting, we tried to imitate the actual surgery. For each surgical step, photographs were taken, drawing attention to the critical structures and highlighting the different corridors to the spine relative to the left brachiocephalic vein. It is possible to access the cervicothoracic junction relative to the brachiocephalic vein from the left. The supra-brachiocephalic approach gives access to the C7-T4 vertebrae, whereas if T4-T5 is the goal, the infra-brachiocephalic approach may be utilized. In the supra-brachiocephalic approach, the brachiocephalic artery can be either medialized or lateralized as needed. A re-examination of the anterior cervicothoracic junction anatomy has allowed us to classify approaches relative to the left brachiocephalic vein. Identifying and understanding the approaches relative to this structure will assist in safe and effective spinal surgery in this area.


Integration of nurse practitioners into Ontario's primary health care system: variations across practice settings.
Annual tracking surveys of nurse practitioners in the Canadian province of Ontario conducted by the Centre for Rural and Northern Health Research for the Ministry of Health and Long-Term Care provide a picture of current employment and practice. The authors present an update on the most recent survey of primary health care nurse practitioners (PHC NPs), conducted in 2008.The study sample consisted of 378 NPs registered in Ontario in 2008 and practising in PHC. Differences in demographic, employment, and practice characteristics in a variety of practice settings are explored. Geographic distribution, education, autonomy of the NP, and the practice profiles varied across settings. The findings document the integration of NPs into Ontario's health-care system and suggest a need to further describe the models of practice and their impact on PHC outcomes.


Mediating Mechanisms in a Physical Activity Intervention: A Test of Habit Formation.
A recent randomized controlled trial found that an intervention focused on developing an exercise habit increased weekly minutes of moderate to vigorous physical activity (MVPA) over 8 wk compared to a control group. The purpose of the current study was to test if changes in habit, as well as other behavioral strategy constructs from the Multi-Process Action Control Test, mediated between group condition and MVPA (self-report and accelerometry). Inactive new gym members (N = 94) were randomized into control or experimental (habit-building) groups. No construct entirely explained mediation condition (experimental and control) and changes in MVPA measured by accelerometry. Self-report MVPA found affective judgments, behavioral regulation, and preparatory habit to be mediated between group (experimental/control conditions) and changes in behavior (β = 0.36, 95% confidence interval [.05-.78]). Self-reported and objectively measured behavior models demonstrated complete and partial mediation, respectively. New gym members could benefit from successful behavioral enactment by developing constructs to support habit formation.


Analysis of the lung allocation score estimation of risk of death in patients with pulmonary arterial hypertension using data from the REVEAL Registry.
Waitlist mortality for patients with pulmonary arterial hypertension (PAH) has not improved after implementation of the lung allocation score (LAS). We analyzed data from patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) as a means to compare observed mortality with predicted mortality from the LAS to identify key prognostic parameters that may be incorporated into the LAS to improve waitlist mortality for patients with PAH. Of the 2967 patients with PAH enrolled in REVEAL, 2327 had all required variables available to compute the LAS. Univariable and multivariable analyses were conducted to compare waitlist survival predicted by the LAS formula with that observed in the REVEAL cohort. Two variables were independently associated with increased mortality compared with that predicted by the LAS in multivariable analysis using a Cox proportional hazards model: mean right atrial pressure (mRAP) more than or equal to 14 mm Hg and 6-min walk test distance (6-MWD) less than or equal to 300 m. A modified LAS system was developed, updating the waitlist survival component of the calculation as follows: modified waitlist exponent equals original waitlist exponent plus 0.7; if mRAP is more than or equal to 14 mm Hg, minus 0.35; for every 100 m of 6-MWD, plus 1.0. The LAS is reevaluated every 6 months after the initial 3-year trial period. Our results suggest that an LAS model that includes both 6-MWD and mRAP better discriminates waitlist urgency for patients with PAH than the current LAS.


Comparison of histopathology and RT-qPCR amplification of guanylyl cyclase C for detection of colon cancer metastases in lymph nodes.
In colorectal cancer (CRC), the presence of lymph node (LN) metastases is an important prognostic factor. Approximately 20% of patients diagnosed as having node-negative (pN0) CRC will relapse. Pathological nodal stage misclassification due to sampling error resulting from the small volume of tissue tested has been proposed to explain this recurrence rate in pN0 patients. The authors compared the assessment of node positivity by histopathology (HP) with a molecular method which can accommodate larger tissue volumes. Detection rate of guanylyl cyclase C (GCC) mRNA was determined in 1,495 LNs from 99 CRC patients. Using a subset of 647 LNs, multiple levels of HP analysis were compared with GCC mRNA molecular detection. Finally, clinicopathological factors were correlated with the molecular detection of GCC and clinical outcome in 123 patients with pN0 colon cancer. GCC mRNA was detected in 8.0% of the 560 nodes initially identified as HP-negative, whereas two repeat HP examinations detected 3.0% of these cases. In HP-positive LNs, the GCC mRNA detection rate was 90% (78/87) when half-LN were tested. Testing the entire LN remaining after HP by GCC increased the detection rate of HP-positive LNs to 95% (p=0.027). In comparison, 75% (65/87) and 92% (80/87) of the LN positive by clinical HP remained positive when one or two subsequent sections were examined by HP. Finally, patients with pN0 disease who were GCC-positive exhibited an earlier time of recurrence (hazard ratio, 3.54; 95% CI 1.40 to 8.98; p=0.0077). Molecular detection of tumour cells in LNs may have prognostic value in identifying patients diagnosed as having pN0 colon cancer who will relapse following surgery.


Localized surface plasmon-enhanced near-ultraviolet emission from InGaN/GaN light-emitting diodes using silver and platinum nanoparticles.
We demonstrate localized surface plasmon (LSP)-enhanced near-ultraviolet light-emitting diodes (NUV-LEDs) using silver (Ag) and platinum (Pt) nanoparticles (NPs). The optical output power of NUV-LEDs with metal NPs is higher by 20.1% for NUV-LEDs with Ag NPs and 57.9% for NUV-LEDs with Pt NPs at 20 mA than that of NUV-LEDs without metal NPs. The time-resolved photoluminescence (TR-PL) spectra shows that the decay times of NUV-LEDs with Ag and Pt NPs are faster than that of NUV-LEDs without metal NPs. The TR-PL and absorbance spectra of metal NPs indicate that the spontaneous emission rate is increased by resonance coupling between excitons in the multiple quantum wells and LSPs in the metal NPs.


Synthesis of cyclohexylpuromycin and its reaction with N-acetylphenylalanyl-transfer ribonucleic acid on rat liver ribosomes.
1. Cyclohexylpuromycin, an anlogue of puromycin in which a cyclohexane ring replaces the aromatic benzene ring of the L-phenylalanyl moeity of the nucleoside., has been synthesized and examined for its ability to release N-acetylphenylalanine from tRNA attached to rat liver ribosomes. 2.dl-Cyclohexylpuromycin was active in reacting with N-[3H]acetylphenylalanyl-tRNA on rat liver ribosomes to form N-E13H]lacetylphenylalanycyclohexypuromycin. 3. The reaction product N-acetylphenylalanylcyclohexylpuromycin and the corresponding analogue N-acetylphenylalanylpuromycin were chemically synthesized for evaluation of the structure of the released N-acetylphenylalanyl-containing material. 4. The results obtained suggest that the model of Raacke (1971) for purmycin reactivity needs further examination with regard to the role played by the aromatic ring system of the Lphenylalanyl moiety of the nucleoside


Neuromodulation in Chemosensory Pathways.
Interactions with the environment depend not only on sensory perception of external stimuli but also on processes of neuromodulation regulated by the internal state of an organism. These processes allow regulation of stimulus detection to match the demands of an organism influenced by its general brain state (satiety, wakefulness/sleep state, attentiveness, arousal, learning etc.). The sense of smell is initiated by sensory neurons located in the nasal cavity that recognize environmental odorants and project axons into the olfactory bulb (OB), where they form synapses with several types of neurons. Modulations of early synaptic circuits are particularly important since these can affect all subsequent processing steps. While the precise mechanisms have not been fully elucidated, work from many labs has demonstrated that the activity of neurons in the OB and cortex can be modulated by different factors inducing specific changes to olfactory information processing. The symposium "Neuromodulation in Chemosensory Pathways" at the International Symposium on Olfaction and Taste (ISOT 2016) highlighted some of the most recent advances in state-dependent network modulations of the mouse olfactory system including modulation mediated by specific neurotransmitters and neuroendocrine molecules, involving pharmacological, electrophysiological, learning, and behavioral approaches.


Novel PRKAR1A gene mutations in Carney Complex.
Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pigmentation, and endocrine lesions. Many patients with Carney complex have been shown to have a stop codon mutation in the PRKAR1A gene in the 17q22-24 region. Here we present the case of a 57 year-old man with multiple skin lesions and cardiac myxomas. Histology of the skin lesions showed lentigenous melanocytic hyperplasia and cutaneous myxomas, confirming the diagnosis of Carney complex. Lesional and control normal tissue from the patient were identified and sequenced for the PRKAR1A gene. A germline missense mutation was identified at exon 1A. This is the first report of this mutation, and one of the few reported missense mutation associated with Carney complex. This finding strengthens the argument that there are alternative ways in which the protein kinase A 1-alpha subunit plays a role in tumorigenesis.


Re-phrasing the question: A simple tool for evaluation of adherence to therapy in patients with inflammatory bowel disease.
Non-adherence to medication in patients with inflammatory bowel disease (IBD) is a challenging problem which is often overlooked or under-estimated by the physician or denied by the patient. We aimed to examine if re-phrasing the wording of the question used by the physician could help in revealing more patients who are non-adherent, and for whom appropriate counseling may be instituted. A cross-sectional questionnaire-based study of IBD patients treated in a tertiary center was conducted. Patients received a questionnaire detailing their treatments and disease course, as well as their perceptions about disease. Two forms of questions about adherence were deliberately placed in two separate parts of the questionnaire: One was 'are you taking your medications regularly as prescribed?' (Standard question), and the second, more emphatic question, was 'how often does it happen that you miss a drug dosing?' (Re-phrased question). The rate of non-adherence disclosed by each of these questions was compared. Sensitivity, specificity and predicative values were computed for each question against the conventional definition of non-adherence as taking of less than 80% of prescribed medication doses disclosed by any of the methods. Predictors of non-compliance and of denying non-compliance were also explored. Overall, 165 patients were included (49% female, mean age 33.7 ± 12.7 SD, median age 30 years, 29.6% with ulcerative colitis, 62.4% with Crohn's disease). Upon questioning, 50 (30.3%) of the patients admitted to non-adherence in the last month when asked by the emphatic re-phrased question format, compared with only 10 patients (6%) reporting non-adherence when asked directly by the standard question (OR 7.4, 95%CI 3.6-15.2, p < 0.001). Thus, a 'Do you take your medicine regularly' question format disclosed only 20% of genuinely non-compliant patients and had 16% sensitivity and 98.2% specificity for revealing non-adherence (PPV 80%, NPV 72.9%) compared with the reference re-phrased question. The leading cause for non-adherence was skepticism about drug efficacy or safety (20.5%), followed by vacation or weekend (15%), problems with prescription or pharmacy (13.5%) and forgetfulness (10%). No single demographic or clinical factor correlated with non-adherence. The only factor which correlated with higher probability for non-adherence was biological and combination treatment. Non-compliance with treatment is much more common than patients admit. Asking patients how often does it happen that they miss a drug dosing is a simple, practical tool which performs significantly better in disclosing non-adherence compared with asking patients if they take their medication as they should.


The influence of parental smoking and family type on saliva cotinine in UK ethnic minority children: a cross sectional study.
In the United Kingdom, there has been an increase in cigarette smoking in ethnic minority adults since the 1970s; in some groups levels are now similar to that of White British people. We aimed to examine the determinants of exposure to secondhand smoke in ethnic minority children. We hypothesised that exposure to secondhand smoke in children will vary across ethnic groups, but that the correlates of exposure would be similar to that of Whites. The Determinants of Adolescent Social well-being and Health sample comprises 3468 White United Kingdom and ethnic minority (Black Caribbean, Black African, Indian, Pakistani, Bangladeshi) pupils aged 11-13 yrs. Outcome was saliva cotinine concentration. Explanatory variables collected by self-complete questionnaire included ethnicity, child reported household smoking and socio-economic circumstances. Data were analysed using linear regression models with a random intercept function. Ethnic minority children had lower saliva cotinine than Whites, partly explained by less smoking among parents. White and Black Caribbean children had higher cotinine levels if they lived in a household with a maternal smoker only, than with a paternal smoker only. Living in a lone compared to a dual parent household was associated with increased cotinine concentration of 45% (95%CI 5, 99%) in Whites, 27% (95%CI 5,53%) in Black Caribbeans and 21% (95%CI 1, 45%) in Black Africans after adjusting for household smoking status. Material disadvantage was a significant correlate only for White children (40% (95%CI 1, 94%) increase in cotinine in least compared to most advantaged group). Ethnic minority children were less exposed to secondhand smoke than Whites, but the variations within groups were similarly patterned. These findings suggest that it is important not to be complacent about low smoking prevalence in some minority groups.


Expression and self-assembly of recombinant capsid protein from the antigenically distinct Hawaii human calicivirus.
The Norwalk and Hawaii viruses are antigenically distinct members of the family Caliciviridae and are considered to be important etiologic agents of epidemic gastroenteritis, with most studies focusing on the role of Norwalk virus. To further investigate the importance of Hawaii virus, Hawaii virus-like particles (VLPs) were produced by expression of its capsid protein in the baculovirus system and these VLPs were used as the antigen in an enzyme-linked immunosorbent assay that was efficient in the detection of a serologic response to Hawaii virus. The ready availability of Hawaii VLPs should enable larger-scale epidemiological studies to further elucidate the importance of this agent.


Operative drainage following pancreatic resection: analysis of 1122 patients resected over 5 years at a single institution.
The only prospective randomized trial evaluating the use of intraperitoneal drainage following pancreatic resection was published from our institution approximately 10 years ago. The current study sought to evaluate the evolution of practice over the last 5 years. Between June 2006 and June 2011, there were 1122 resections performed. Six surgeons were evenly grouped and compared by practice pattern: routine drainers (drains placed > 95%), selective drainers, and routine nondrainers (drains placed ∼15%). Prospectively recorded preoperative, operative, and morbidity data were assessed in uni- and multivariate models. Our operative drainage rate was 49% and decreased over time (62% 2006-2008 vs 37% 2009-2011, P < 0.001). Patients without operative drains had significantly lower grade ≥3 overall morbidity (26% vs 33%; P = 0.01), shorter hospital stays (7 vs 8 days; P < 0.01), fewer readmissions (20% vs 27%; P = 0.01), and lower rates of grade ≥3 pancreatic fistula (16% vs 20%; P = 0.05). Similar reoperation (both <1%), interventional radiology procedures (15% vs 19%; P = 0.1), and mortality rates (2% vs 1%; P = 0.3) were seen in both groups. There were no differences between the routine drainers group (n = 248) and the nondrainers group (n = 478) in grade ≥3 fistula or need for interventional radiology-guided procedures. In this study, operative drains were used nearly half of the time and were associated with longer hospital stay, and higher grade ≥3 morbidity, fistula, and readmission rates. They did not decrease the need for reintervention or alter mortality rates. Routine prophylactic drainage after pancreatic resection could be safely abandoned.


Use of soil enzyme activities to assess the recovery of soil functions in abandoned coppice forest systems.
Coppicing consists of periodically cutting back tree stems to ground level to stimulate the growth of multiple stems from the stool. In Central Europe, many coppiced forests were abandoned at the beginning of the last century owing to a decline in the demand for charcoal and wood. This was assumed to enable the forests to recover and the properties to become similar to those of unmanaged forest (high forest). Most studies on abandoned coppiced forest have focused on forest recovery, while soil recovery has generally been overlooked. With the aim of filling this gap, this study investigated the effect of coppicing abandonment on soil recovery by analysing the changes in soil enzyme activities (dehydrogenase, β-glucosidase, invertase, urease, acid phosphatase and arylsulphatase). Two differently managed sessile oak (Quercus petraea) forests were selected for study: a former coppice forest, abandoned >90 years ago, and an undisturbed forest. The analytical data were compared to assess the degree of recovery of the soil in the abandoned coppice forest. The soil organic matter content was two times lower in the abandoned coppice than in the high forest, suggesting that organic matter depletion due the past coppicing is a long-term effect. All of the absolute enzyme activities were also two times lower in the abandoned coppice forest soil than in the high forest soil. However, the specific enzyme activities were similar in both types of soil. This indicates that metabolic activity is similar in both soil types, suggesting that it either recovers faster than organic matter and soil enzyme activity or that, despite the depletion in organic matter and enzyme activities, metabolic activity was sustained in coppiced forest soil. However, in the latter case this would imply that organic matter and soil enzymes were lost in exactly the same proportion, which is highly improbable.


Bacteriocin typing of Serratia marcescens isolates of known serotype-group.
The number of isolates of Serratia marcescens that could be typed by sensitivity to bacteriocins was compared with the nature of the serotype/-group of each of the isolates. Ninety-four of 101 isolates (93.1%) could be bacteriocin-typed; this compares with 80 of the isolates (79.2%) that had been serotyped, and with 91 of the isolates (90.1%) that carried determinable O antigens. It is recommended that bacteriocin typing of S. marcescens be adopted by reference laboratories, because this technique is simple, inexpensive, and appears to be of somewhat higher epidemiological resolution than classic serological procedures.


Ectopic cutaneous schistosomiasis: report of two cases and a review of the literature.
Two cases of ectopic cutaneous schistosomiasis are described. Both patients presented with abdominal papular skin lesions, which on biopsy were found to contain granulomas with Schistosoma mansoni eggs. Twenty-five other cases were retrieved from the literature. Most patients were female, mean age 24.9 year, with a predominance of the white race. The most common localization was anterior thorax and abdomen. Usually, the lesions were asymptomatic. In few cases, however, severe clinical syndromes due to the parasite coexisted, such as transverse myelitis or the acute-toxemic form of the disease. Intestinal infection was not frequently demonstrated in these patients. The importance of the recognition of these cutaneous lesions may rest on the opportunity to provide an etiological diagnosis in these difficult cases.


[Alpha interferon interaction with opiate receptors in the rat brain].
The preferential interactions of alpha-interferon (alpha-IFN) with delta and mu opiate receptors were studied. alpha-IFN (specific antiviral activity 2 X 10(3) U/mg protein) was shown to inhibit in the competitive manner 3H-naloxone and 3H-D-ala2, D-leu5-enkephalin (3H-DADL) specific binding to opiate receptor subpopulations. alpha-IFN was much more effective in decreasing 3H-DADL than 3H-naloxone binding in opiate receptors: K1 values averaged 160 +/- 30 and 1150 +/- 80 U/ml, respectively. IFN effective concentrations inhibiting 50% of 3H-naloxone opiate receptor binding in the absence or presence of 100 mmol/l NaCl were similar, and the "sodium shift" value was equal to 1. The independence of alpha-IFN activity of the presence of NA+ cations suggests the antagonist character of alpha-IFN interaction with opiate receptors. Thus, alpha-IFN employed appears to be an alpha-selective ligand displaying the in vitro properties of "pure" morphine antagonists.


Hospital Investment Decisions in Healthcare 4.0 Technologies: Scoping Review and Framework for Exploring Challenges, Trends, and Research Directions.
Alternative approaches to analyzing and evaluating health care investments in state-of-the-art technologies are being increasingly discussed in the literature, especially with the advent of Healthcare 4.0 (H4.0) technologies or eHealth. Such investments generally involve computer hardware and software that deal with the storage, retrieval, sharing, and use of health care information, data, and knowledge for communication and decision-making. Besides, the use of these technologies significantly increases when addressed in bundles. However, a structured and holistic approach to analyzing investments in H4.0 technologies is not available in the literature. This study aims to analyze previous research related to the evaluation of H4.0 technologies in hospitals and characterize the most common investment approaches used. We propose a framework that organizes the research associated with hospitals' H4.0 technology investment decisions and suggest five main research directions on the topic. To achieve our goal, we followed the standard procedure for scoping reviews. We performed a search in the Crossref, PubMed, Scopus, and Web of Science databases with the keywords investment, health, industry 4.0, investment, health technology assessment, healthcare 4.0, and smart in the title, abstract, and keywords of research papers. We retrieved 5701 publications from all the databases. After removing papers published before 2011 as well as duplicates and performing further screening, we were left with 244 articles, from which 33 were selected after in-depth analysis to compose the final publication portfolio. Our findings show the multidisciplinary nature of the research related to evaluating hospital investments in H4.0 technologies. We found that the most common investment approaches focused on cost analysis, single technology, and single decision-maker involvement, which dominate bundle analysis, H4.0 technology value considerations, and multiple decision-maker involvement. Some of our findings were unexpected, given the interrelated nature of H4.0 technologies and their multidimensional impact. Owing to the absence of a more holistic approach to H4.0 technology investment decisions, we identified five promising research directions for the topic: development of economic valuation methodologies tailored for H4.0 technologies; accounting for technology interrelations in the form of bundles; accounting for uncertainties in the process of evaluating such technologies; integration of administrative, medical, and patient perspectives into the evaluation process; and balancing and handling complexity in the decision-making process.


Genetic similarities between tobacco use disorder and related comorbidities: an exploratory study.
Tobacco use disorder (TUD), defined as the use of tobacco to the detriment of a person's health or social functioning, is associated with various disorders. We hypothesized that mutual variation in genes may partly explain this link. The aims of this study were to make a non-exhaustive inventory of the disorders using (partially) the same genetic pathways as TUD, and to describe the genetic similarities between TUD and the selected disorders. We developed a 3 stage approach: (i) selection of genes influencing TUD using Gene2Mesh and Ingenuity Pathway Analysis (IPA), (ii) selection of disorders associated with the selected genes using IPA and (iii) genetic similarities between disorders associated with TUD using Jaccard distance and cluster analyses. Fourteen disorders and thirty-two genes met our inclusion criteria. The Jaccard distance between pairs of disorders ranged from 0.00 (e.g. oesophageal cancer and malignant hypertension) to 0.45 (e.g. bladder cancer and addiction). A lower number in the Jaccard distance indicates a higher similarity between the two disorders. Two main clusters of genetically similar disorders were observed, one including coexisting disorders (e.g. addiction and alcoholism) and the other one with the side-effects of smoking (e.g. gastric cancer and malignant hypertension). This exploratory study partly explains the potential genetic components linking TUD to other disorders. Two principle clusters of disorders were observed (i) coexisting disorders of TUD and (ii) side-effects of TUD disorders. A further deepening of this observation in a real life study should allow strengthening this hypothesis.


Clinical benefits of a consistent reduction in blood pressure.
This paper briefly reviews the epidemiological evidence that hypertension is a major cardiovascular risk factor. It also summarizes the data from controlled intervention trials that show antihypertensive treatment to be accompanied by a reduction in cardiovascular morbidity and mortality. The inability of antihypertensive treatment to offer full protection to the hypertensive individual is then discussed, together with the therapeutic strategies to increase the benefits, particularly with respect to limiting end-organ damage and reduction of cardiovascular events. In this context, emphasis is given to the potential additional benefit conferred by control of 24-h blood pressure and to the compliance advantage of using drugs with a long duration of action. The longevity of the blood pressure lowering effect can compensate for delayed or missed drug consumption, a frequent phenomenon in the chronically treated hypertensive patient.


Non-specific filtering of beta-distributed data.
Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias. We compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets. We found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered.


A Kalman filter-based approach to reduce the effects of geometric errors and the measurement noise in the inverse ECG problem.
In this article, we aimed to reduce the effects of geometric errors and measurement noise on the inverse problem of Electrocardiography (ECG) solutions. We used the Kalman filter to solve the inverse problem in terms of epicardial potential distributions. The geometric errors were introduced into the problem via wrong determination of the size and location of the heart in simulations. An error model, which is called the enhanced error model (EEM), was modified to be used in inverse problem of ECG to compensate for the geometric errors. In this model, the geometric errors are modeled as additive Gaussian noise and their noise variance is added to the measurement noise variance. The Kalman filter method includes a process noise component, whose variance should also be estimated along with the measurement noise. To estimate these two noise variances, two different algorithms were used: (1) an algorithm based on residuals, (2) expectation maximization algorithm. The results showed that it is important to use the correct noise variances to obtain accurate results. The geometric errors, if ignored in the inverse solution procedure, yielded incorrect epicardial potential distributions. However, even with a noise model as simple as the EEM, the solutions could be significantly improved.


Virulence is not conserved in recombinants between herpes simplex virus types 1 and 2.
The virulence of 31 herpes simplex virus type 1 X herpes simplex virus type 2 intertypic recombinants was determined following intraperitoneal inoculation into CBA mice. Only eight of the recombinants killed any of the mice and of these, only one recombinant was as virulent as its type 2 parent, the other seven recombinants being intermediate between their type 1 and type 2 parental viruses in virulence. These results indicate that most heterotypic combinations are attenuated independently of the virulence of the parental viruses and therefore that the virulence of HSV is controlled multigenically.


Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C.
The biosynthesis of the neural cell adhesion molecule (N-CAM) was studied in primary cultures of rat cerebral glial cells, cerebellar granule neurons, and skeletal muscle cells. The three cell types produced different N-CAM polypeptide patterns. Glial cells synthesized a 135,000 Mr polypeptide B and a 115,000 Mr polypeptide C, whereas neurons expressed a 200,000 Mr polypeptide A as well as polypeptide B. Skeletal muscle cells produced polypeptide B. The polypeptides synthesized by the three cell types were immunochemically identical. The membrane association of polypeptide C was investigated with methods that distinguish peripheral and integral membrane proteins. Polypeptide C was found to be a peripheral membrane protein, whereas polypeptides A and B were integral membrane proteins with cytoplasmic domains of approximately 50,000 and approximately 25,000 Mr, respectively. The affinity of the membrane binding of polypeptide C increased during postnatal development. The posttranslational modifications of polypeptide C were investigated in glial cell cultures, and it was found to be N-linked glycosylated and sulfated.


Local and linear chemical reactivity response functions at finite temperature in density functional theory.
We explore the local and nonlocal response functions of the grand canonical potential density functional at nonzero temperature. In analogy to the zero-temperature treatment, local (e.g., the average electron density and the local softness) and nonlocal (e.g., the softness kernel) intrinsic response functions are defined as partial derivatives of the grand canonical potential with respect to its thermodynamic variables (i.e., the chemical potential of the electron reservoir and the external potential generated by the atomic nuclei). To define the local and nonlocal response functions of the electron density (e.g., the Fukui function, the linear density response function, and the dual descriptor), we differentiate with respect to the average electron number and the external potential. The well-known mathematical relationships between the intrinsic response functions and the electron-density responses are generalized to nonzero temperature, and we prove that in the zero-temperature limit, our results recover well-known identities from the density functional theory of chemical reactivity. Specific working equations and numerical results are provided for the 3-state ensemble model.


Empirical measure of multiclass generalization performance: the K-winner machine case.
Combining the K-winner machine (KWM) model with empirical measurements of a classifier's Vapnik-Chervonenkis (VC)-dimension gives two major results. First, analytical derivations refine the theory that characterizes the generalization performances of binary classifiers. Second, a straightforward extension of the theoretical framework yields bounds to the generalization error for multiclass problems.


Instruction in metacognitive strategies to increase deaf and hard-of-hearing students' reading comprehension.
The purpose of this intervention study was to examine the use of a metacognitive strategy--the Comprehension, Check, and Repair Strategy--on strategic reading behavior, nonstrategic reading behavior, and reading comprehension of students who are deaf or hard of hearing (D/HH). A multiple baseline design was used across 3 teacher-student dyads. Frequency data were collected on students' strategic reading behavior. Reading comprehension was assessed by counting the number of details the students retold after reading a content area passage. Results showed (a) an increase in strategic reading behavior for Students A, B, and C; and (b) an increase in reading comprehension for Student A, and possibly for Student B. Social validity data indicated high acceptability of the intervention. Teachers not only continued to use the strategy with their students after the study ended but also introduced it to other students with whom they worked. Instruction in metacognitive strategies to increase strategic reading behavior may be an effective means by which to increase reading comprehension for D/HH students.


A Serratia marcescens PigP homolog controls prodigiosin biosynthesis, swarming motility and hemolysis and is regulated by cAMP-CRP and HexS.
Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment.


European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).
Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially lifesaving treatments for a number of cardiac conditions but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased health care costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well-recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, antibacterial envelopes, prolonged antibiotics post-implantation, and others. When compared with previous guidelines or consensus statements, the present consensus document gives guidance on the use of novel device alternatives, novel oral anticoagulants, antibacterial envelopes, prolonged antibiotics post-implantation, as well as definitions on minimum quality requirements for centres and operators and volumes. The recognition that an international consensus document focused on management of CIED infections is lacking, the dissemination of results from new important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a Novel 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.


Testing Application of Geographical Information Systems, Forensic Geomorphology and Electrical Resistivity Tomography to Investigate Clandestine Grave Sites in Colombia, South America.
Colombian forensic investigators required assistance locating clandestine burials of missing persons related to human right atrocities from 14 years ago. Geoscientific search methods were trialled, including a predictive spatial statistical model, using various input and database information, to select the most likely grave locations in difficult mountainous terrain. Groundwork using forensic geomorphology, near-surface geophysics (ERT) and subsequent probing identified suspect burial positions. One site was in mountainous terrain and the other in former school grounds, both difficult to access and in poor weather conditions. In the mountainous area, a negative resistivity anomaly area was identified and intrusively investigated, found to be a buried rock. In school grounds, after MESP and intelligence were used to identify a burial site, surface depressions were identified, and ERT datasets collected over the highest priority depression; intrusive investigations discovered a hand-dug pit containing animal bones. This approach is suggested for Latin American searches.


Detection and quantification of the age-related point mutation A189G in the human mitochondrial DNA.
Mutation analysis in the mitochondrial DNA (mtDNA) control region is widely used in population genetic studies as well as in forensic medicine. Among the difficulties linked to the mtDNA analysis, one can find the detection of heteroplasmy, which can be inherited or somatic. Recently, age-related point mutation A189G was described in mtDNA and shown to accumulate with age in muscles. We carried out the detection of this 189 heteroplasmic point mutation using three technologies: automated DNA sequencing, Southern blot hybridization using a digoxigenin-labeled oligonucleotide probe, and peptide nucleic acid (PNA)/real-time PCR combined method on different biological samples. Our results give additional information on the increase in mutation frequency with age in muscle tissue and revealed that the PNA/real-time PCR is a largely more sensitive method than DNA sequencing for heteroplasmy detection. These investigations could be of interest in the detection and interpretation of mtDNA heteroplasmy in anthropological and forensic studies.


Effect of infectious bursal disease on natural killer cell activity and mitogenic response of chicken lymphoid cells: role of adherent cells in cellular immune suppression.
A pathogenic isolate of infectious bursal disease virus (IBDV) caused persistent and extensive lesions in the bursa but mild and transient lesions in the thymuses of chickens of lines 63 and P. The effect of IBDV on two cellular immune functions, namely, natural killer cell cytotoxicity and mitogenic response, was studied. The natural killer cell activity was not consistently influenced, but the virus, during the first 2 weeks of infection, caused transient depression of the blastogenic response of spleen cells to phytohemagglutinin. Studies on mitogenic hyporesponsiveness revealed that the functional impairment was mediated by a suppressor cell that shared several characteristics with macrophages; i.e., the suppressor cell was adherent to plastic, was phagocytic, and resisted treatment with antithymocyte and antibursa cell sera. Removal of suppressor cells from the spleens of virus-infected chickens resulted in restoration of the mitogenic response of cells. Further, in mixing experiments, the suppressor cell isolated from the spleens of virus-infected chickens also inhibited the mitogenic response of normal spleen cells. We concluded that reduced mitogenic response of lymphocytes in IBDV-infected chickens was not due to a lack of functional T-cells, as suggested previously by others, but was due to macrophage-like suppressor cells. The suppressor cells, although present in certain normal chickens, became activated during early stages of IBDV infection.


Metal/Semiconductor hybrid nanostructures for plasmon-enhanced applications.
Hybrid nanostructures composed of semiconductor and plasmonic metal components are receiving extensive attention. They display extraordinary optical characteristics that are derived from the simultaneous existence and close conjunction of localized surface plasmon resonance and semiconduction, as well as the synergistic interactions between the two components. They have been widely studied for photocatalysis, plasmon-enhanced spectroscopy, biotechnology, and solar cells. In this review, the developments in the field of (plasmonic metal)/semiconductor hybrid nanostructures are comprehensively described. The preparation of the hybrid nanostructures is first presented according to the semiconductor type, as well as the nanostructure morphology. The plasmonic properties and the enabled applications of the hybrid nanostructures are then elucidated. Lastly, possible future research in this burgeoning field is discussed.


Nuclear quantum effects in water clusters: the role of the molecular flexibility.
With the objective of establishing the importance of water flexibility in empirical models which explicitly include nuclear quantum effects, we have carried out path integral Monte Carlo simulations in water clusters with up to seven molecules. Two recently developed models have been used for comparison: the rigid TIP4PQ/2005 and the flexible q-TIP4P/F models, both inspired by the rigid TIP4P/2005 model. To obtain a starting configuration for our simulations, we have located the global minima for the rigid TIP4P/2005 and TIP4PQ/2005 models and for the flexible q-TIP4P/F model. All the structures are similar to those predicted by the rigid TIP4P potential showing that the charge distribution mainly determines the global minimum structure. For the flexible q-TIP4P/F model, we have studied the geometrical distortion upon isotopic substitution by studying tritiated water clusters. Our results show that tritiated water clusters exhibit an r(OT) distance shorter than the r(OH) distance in water clusters, not significant changes in the Phi(HOH) angle, and a lower average dipole moment than water clusters. We have also carried out classical simulations with the rigid TIP4PQ/2005 model showing that the rotational kinetic energy is greatly affected by quantum effects, but the translational kinetic energy is only slightly modified. The potential energy is also noticeably higher than in classical simulations. Finally, as a concluding remark, we have calculated the formation energies of water clusters using both models, finding that the formation energies predicted by the rigid TIP4PQ/2005 model are lower by roughly 0.6 kcal/mol than those of the flexible q-TIP4P/F model for clusters of moderate size, the origin of this difference coming mainly from the geometrical distortion of the water molecule in the clusters that causes an increase in the intramolecular potential energy.