Spiritual care training in healthcare: Does it really have an impact?
Spiritual care has formed an integral part of palliative care since its inception. People with advanced illnesses, however, frequently report that their spiritual needs are not attended to by their medical care team. The present study examines and describes the impact of a spiritual care training program on practice and cultural change in our Canadian hospice. A qualitative case study approach was adopted to gather feedback from hospice staff and volunteers using purposive sampling. In-depth interviews were conducted, transcribed, and analyzed using thematic (semantic and latent) analysis. Our data suggest that the program had a profound personal impact on attendees and contributed to a slight shift in practice patterns in our organization. Using a program not specifically tailored to our local and organizational cultural contexts resulted in some unanticipated challenges such as the range of tensions between personal and cultural boundaries. Although some people criticized parts of the program or questioned the program's value, a general agreement suggests that the program had a positive impact and meaningfully benefited our hospice. "What will happen next?" was the question most frequently voiced by interviewees. Although the program may not have been a perfect fit for our organization, its use instigated a process of cultural change that unfolds today. The present study suggests that a systematic approach to spiritual care training that includes the concepts of workplace spirituality and sensitive practice offer useful frameworks for the development and implementation of spiritual care training in other institutions.


Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss.
Mutations of the human SLC26A4/PDS gene constitute the most common cause of syndromic and nonsyndromic hearing loss. Definition of the SLC26A4 mutation spectrum among different populations with sensorineural hearing loss is important for development of optimal genetic screening services for congenital hearing impairment. We screened for SLC26A4 mutations among Chinese and U.S. subjects with hearing loss, using denaturing HPLC (DHPLC) and direct DNA sequencing. Fifty-two of 55 Chinese subjects with deafness accompanied by enlargement of the vestibular aqueduct (EVA) exhibited at least one mutant SLC26A4 allele, whereas SLC26A4 mutations were found in only 2 of 116 deaf Chinese patients without EVA. The spectrum of SLC26A4 mutations differed among Chinese and U.S. subjects and included 10 previously unreported SLC26A4 variants: 4 in the Chinese population (p.E303Q, p.X329, p.X467, p.X573) and 6 in the U.S. population (p.V250A, p.D266N, p.F354S, p.D697A, p.K715N, p.E737D). Among the seven novel in-frame missense mutations, five encoded SLC26A4 proteins with substantially reduced Cl(-)/anion exchange activity as expressed and measured in Xenopus oocytes, but four of these were sufficiently active to allow study of anion selectivity. The only mutant polypeptide exhibiting complete loss of anion exchange function, p.E303Q, was expressed at or near the oocyte surface at near-wild-type levels. Two variants, p.F354S and p.E737D, displayed selective reduction in relative rate of Cl(-)/HCO(3)(-) exchange compared with similarly measured rates of Cl(-)/Cl(-) and Cl(-)/I(-) exchange. Our data show that mutation analysis of the SLC26A4 gene is of high diagnostic yield among subjects with deafness and bilateral EVA in both China and the U.S. However, the pathogenicity of monoallelic SLC26A4 gene variants in patients with hearing loss remains unclear in many instances.


Targeted therapies for breast cancer.
In recent years the description of well-defined molecular subtypes of breast cancer, together with the identification of the driving genetic alterations and signaling pathways, has led to the clinical development of a number of successful molecular targeted agents. This is best exemplified in the subset of HER2-amplified breast cancers, in which an increasing number of active agents are changing the natural history of this aggressive disease. Other targets are under exploration, and the clinical development of these agents will require a change from the current large, randomized trials in unselected patient populations to smaller trials in groups with a molecularly defined tumor type. In addition, combinatorial approaches that act on the secondary mutations and/or compensatory pathways in resistant tumors may markedly improve on the effects of targeted agents used alone.


Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes.
The mechanical properties of single cells play important roles in regulating cell-matrix interactions, potentially influencing the process of mechanotransduction. Recent studies also suggest that cellular mechanical properties may provide novel biological markers, or "biomarkers," of cell phenotype, reflecting specific changes that occur with disease, differentiation, or cellular transformation. Of particular interest in recent years has been the identification of such biomarkers that can be used to determine specific phenotypic characteristics of stem cells that separate them from primary, differentiated cells. The goal of this study was to determine the elastic and viscoelastic properties of three primary cell types of mesenchymal lineage (chondrocytes, osteoblasts, and adipocytes) and to test the hypothesis that primary differentiated cells exhibit distinct mechanical properties compared to adult stem cells (adipose-derived or bone marrow-derived mesenchymal stem cells). In an adherent, spread configuration, chondrocytes, osteoblasts, and adipocytes all exhibited significantly different mechanical properties, with osteoblasts being stiffer than chondrocytes and both being stiffer than adipocytes. Adipose-derived and mesenchymal stem cells exhibited similar properties to each other, but were mechanically distinct from primary cells, particularly when comparing a ratio of elastic to relaxed moduli. These findings will help more accurately model the cellular mechanical environment in mesenchymal tissues, which could assist in describing injury thresholds and disease progression or even determining the influence of mechanical loading for tissue engineering efforts. Furthermore, the identification of mechanical properties distinct to stem cells could result in more successful sorting procedures to enrich multipotent progenitor cell populations.


Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.
HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Extensive information is recorded for each variant and mutation, including sequence alterations, biochemical and hematological effects, associated pathology, ethnic occurrence and references. In addition to the regular updates to entries, we report two significant advances: (i) The frequencies for a large number of mutations causing beta-thalassemia in at-risk populations have been extracted from the published literature and made available for the user to query upon. (ii) HbVar has been linked with the GALA (Genome Alignment and Annotation database, available at http://globin.cse.psu.edu/gala/) so that users can combine information on hemoglobin variants and thalassemia mutations with a wide spectrum of genomic data. It also expands the capacity to view and analyze the data, using tools within GALA and the University of California at Santa Cruz (UCSC) Genome Browser.


Pyoderma gangrenosum-a novel approach?
Pyoderma gangrenosum (PG) represents a rare skin disorder, with several clinical variants and still not fully understood ethiopathogenesis. Often associated with inflammatory or neoplastic disease, PG is nowadays considered an inflammatory neutrophilic disease with common underlying morbidity. Modern treatment options are oriented towards key mechanisms underlying the pathogenesis of the disease, namely inflammatory mediators, and seem to be the most effective treatment currently available. Although promising, the results are not invariable and these treatments are sometimes surrounded by controversy, as recent studies have reported cases that are refractory to therapy with biological agents. It is possible that refractoriness to the use of biological agents as monotherapy stems from the fact that a single agent is not able to affect the entire inflammatory cascade, or to simultaneously influence all of its levels. Based on the pathogenesis of inflammation, we can suggest that an ideal targeted therapy should be able to induce the following changes: 1) reduction of the secretion of interleukin (IL)-1a/b from the inflammasome with subsequent blocking of its biological effect (by therapy with IL-1 receptor antagonists); 2) blocking of the activation of the secreted procytokines in their active form (by therapy with caspase-1 inhibitors; 3) blocking of the effect of the already released active cytokines (by therapy with tumour necrosis factor alpha, TNF-α, inhibitors); 4) blocking of the effector action of the cytokines on the target intracellular molecules (by therapy with kinase inhibitors). The specific therapy should aim to attack more than one link in the inflammatory cascade, in order to achieve maximum therapeutic effectiveness. Most surely, this could be achieved with combined therapy with different groups of biological agents (for example a combined therapy with IL-1 receptor antagonist and a TNF-α inhibitor). Currently, no data in the literature exist to support this statement, and there are no safety data relating to such approaches. We focus this review on the novel etiopathogenetic concepts of PG and the future therapeutic approaches based on blocking different levels of the inflammatory cascade, which seems to be the most promising weapon in the target-oriented treatment options.


Neurons in the nucleus accumbens promote selection bias for nearer objects.
Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level.


Genetics, Transcriptional Profiles, and Catalytic Properties of the UDP-Arabinose Mutase Family from Barley.
Four members of the UDP-Ara mutase (UAM) gene family from barley have been isolated and characterized, and their map positions on chromosomes 2H, 3H, and 4H have been defined. When the genes are expressed in Escherichia coli, the corresponding HvUAM1, HvUAM2, and HvUAM3 proteins exhibit UAM activity, and the kinetic properties of the enzymes have been determined, including Km, Kcat, and catalytic efficiencies. However, the expressed HvUAM4 protein shows no mutase activity against UDP-Ara or against a broad range of other nucleotide sugars and related molecules. The enzymic data indicate therefore that the HvUAM4 protein may not be a mutase. However, the HvUAM4 gene is transcribed at high levels in all the barley tissues examined, and its transcript abundance is correlated with transcript levels for other genes involved in cell wall biosynthesis. The UDP-l-Arap → UDP-l-Araf reaction, which is essential for the generation of the UDP-Araf substrate for arabinoxylan, arabinogalactan protein, and pectic polysaccharide biosynthesis, is thermodynamically unfavorable and has an equilibrium constant of 0.02. Nevertheless, the incorporation of Araf residues into nascent polysaccharides clearly occurs at biologically appropriate rates. The characterization of the HvUAM genes opens the way for the manipulation of both the amounts and fine structures of heteroxylans in cereals, grasses, and other crop plants, with a view toward enhancing their value in human health and nutrition, and in renewable biofuel production.


Effects of prior culture or isoproterenol injections on the regeneration of rat submandibular gland autografts.
This study compares the acinar cell regenerative response in submandibular gland (SMG) autografts that were cultured before grafting to the rat tongue with the acinar cell regenerative response in direct SMG autografts to the tongue. In addition, the effects of isoproterenol on direct SMG autografts were studied. A portion of the left SMG was excised from each rat and cut into fragments which were autografted either immediately into the middle one-third of the rat's tongue; or were cultured for 1, 4, or 7 days and then autografted to the donor's tongue. After 8 weeks the rats were killed and the tongues were removed and processed for light microscopic study. The histologic preparations showed evidence of cytodifferentiation into acinar cells in four of the previously cultured SMG autografts. Some of the direct SMG autografts did not contain acinar cells, whereas other direct SMG autografts contained numerous acinar cells and even striated ducts. In the SMG autografts that were cultured for 1 day before autografting and in the direct SMG autografts, the most pronounced regenerative responses were seen in autografts that contained ductlike structures that were apparently connected to the epithelial surface of the tongue. Lastly, isoproterenol appeared to accelerate the regenerative response in some of the direct SMG autografts, and the drug caused acinar cell hypertrophy in two of the direct SMG autografts.


GNSS Positioning by CORS and EGM2008 in Jilin Province, China.
The Continuously Operating Reference Station (CORS) technique has been widely applied in land resource management, surveying, mapping, deformation monitoring, precise navigation, etc. This article analyzed the positioning method using EGM2008 and CORS of Jilin Province, China. The vertical transformation of EGM2008 from WGS84 to China's CGCS2000 datum and the horizontal coordinate transformation from CGCS2000 to a triangulation coordinate system were discussed. The results indicated that a local geoid with respect to CGCS2000 can be transferred from EGM2008 with the same accuracy, and the geoid correction between CGCS2000 and WGS84 varied from 0.023 m to 0.111 m. The coordinate transformation method based on the curve surface approximation method indicated that the theoretical error was less than 0.09 m in the grid within 10° longitudinal and 5° latitudinal, and less than 0.3 m in large area and 0.1 m in small area in field validation. The method proposed in this article expanded the positioning result and its application for JLCORS and other CORS with local datum.


Carbon dioxide hydrate as a recovery tool after fatigue of the plantar flexors.
This study investigated the effects of cooling the triceps surae with carbon dioxide hydrate (CDH), which is a gas hydrate, a crystalline structure belonging to the clathrates, on the recovery from muscle fatigue. Thirty-six healthy young men were equally and randomly assigned to an ICE group, a CDH group, or a non-cooling (NON) group. All participants performed 80 maximal voluntary isometric contractions (MVCs) of the plantar flexors as a fatiguing task. MVC torque and voluntary activation were determined before, immediately after, and 20 min after the fatiguing task. Evoked torque was similarly assessed except for immediately after the task. In the ICE and CDH groups, the triceps surae was cooled for 5 min using ice and CDH, starting 5 min after the fatiguing task, respectively. The MVC torque and voluntary activation were higher in order of before >20 min after >immediately after the fatiguing task regardless of group, and those time-course changes did not differ between the groups. A decrease in the evoked torque from before to 20 min after the fatiguing task was observed in the ICE and NON groups but not in the CDH group. These results suggest that cooling muscle with CDH can facilitate recovery from peripheral muscle fatigue. This may be due to an increase in blood flow caused by carbon dioxide contained within the CDH, and indicates the potential of CDH as a recovery tool after fatiguing exercise.


Unprecedented Fine Structure of a Solar Flare Revealed by the 1.6 m New Solar Telescope.
Solar flares signify the sudden release of magnetic energy and are sources of so called space weather. The fine structures (below 500 km) of flares are rarely observed and are accessible to only a few instruments world-wide. Here we present observation of a solar flare using exceptionally high resolution images from the 1.6 m New Solar Telescope (NST) equipped with high order adaptive optics at Big Bear Solar Observatory (BBSO). The observation reveals the process of the flare in unprecedented detail, including the flare ribbon propagating across the sunspots, coronal rain (made of condensing plasma) streaming down along the post-flare loops, and the chromosphere's response to the impact of coronal rain, showing fine-scale brightenings at the footpoints of the falling plasma. Taking advantage of the resolving power of the NST, we measure the cross-sectional widths of flare ribbons, post-flare loops and footpoint brighenings, which generally lie in the range of 80-200 km, well below the resolution of most current instruments used for flare studies. Confining the scale of such fine structure provides an essential piece of information in modeling the energy transport mechanism of flares, which is an important issue in solar and plasma physics.


Airborne pollen and suicide mortality in Tokyo, 2001-2011.
Prior research has indicated that pollen might be linked to suicide mortality although the few studies that have been undertaken to date have produced conflicting findings and been limited to Western settings. This study examined the association between the level of airborne pollen and suicide mortality in Tokyo, Japan in the period from 2001 to 2011. The daily number of suicide deaths was obtained from the Japanese Ministry of Health, Labour and Welfare, with pollen data being obtained from the Tokyo Metropolitan Institute of Public Health. A time-stratified case-crossover study was performed to examine the association between different levels of pollen concentration and suicide mortality. During the study period there were 5185 male and 2332 female suicides in the pollen season (February to April). For men there was no association between airborne pollen and suicide mortality. For women, compared to when there was no airborne pollen, the same-day (lag 0) pollen level of 30 to <100 grains per cm2 was associated with an approximately 50% increase in the odds for suicide (e.g. 30 to <50 grains per cm2: odds ratio 1.574, 95% confidence interval 1.076-2.303, p=0.020). The estimates remained fairly stable after adjusting for air pollutants and after varying the cut-points that defined the pollen levels. Our results indicate that pollen is associated with female suicide mortality in Tokyo.


Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi.
Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.


Integrating family planning into Ethiopian voluntary testing and counselling programmes.
Governments and donors encourage the integration of family planning into voluntary testing and counselling (VCT) services. We aimed to determine if clients of VCT services have a need for and will accept quality family planning services. 'Voluntary HIV counselling and testing integrated with contraceptive services' is a proof-of-concept study that interviewed 4019 VCT clients before the addition of family planning services and 4027 different clients after family planning services were introduced. Clients attended eight public VCT facilities in the Oromia region, Ethiopia. The intervention had four components: development of family planning counselling messages for VCT clients, VCT provider training, contraceptive supply provision and monitoring. Ethiopia's population of 80 million is increasing rapidly at an annual rate of 2.5%. Contraceptive prevalence is only 15%. The estimated adult HIV prevalence rate is 2.1%, with more than 1.1 million people infected. The number of VCT facilities increased from 23 in 2001 to more than 1000 in 2007, and the number of HIV tests taken doubled from 1.7 million tests in 2007 to 3.5 million in 2008. Clients interviewed after the introduction of family planning services received significantly more family planning counselling and accepted significantly more contraceptives than those clients served before the intervention. However, three-quarters of the clients were not sexually active. Of those clients who were sexually active, 70% were using contraceptives. The study demonstrated that family planning can be integrated into VCT clinics. However, policy-makers and programme managers should carefully consider the characteristics and reproductive health needs of target populations when making decisions about service integration.


Impact of economic fluctuations on suicide mortality in Canada (1926-2008): Testing the Durkheim, Ginsberg, and Henry and Short theories.
Three theories have been proposed to explain the relationship between suicide and economic fluctuations, including the Durkheim (nonlinear), Ginsberg (procyclical), and Henry and Short (countercyclical) theories. This study tested the effect of economic fluctuations, measured by unemployment rate, on suicide rates in Canada from 1926 to 2008. Autoregressive integrated moving average time-series models were used. The results showed a significant relationship between suicide and economic fluctuation; this association was positive during the contraction period (1926-1950) and negative in the period of economic expansion (1951-1973). Males and females showed differential effects in the period of moderate unemployment (1974-2008). In addition, the suicide rate of mid-adults (45-64) was most impacted by economic fluctuations. Our study tends to support Durkheim's theory and suggests the need for public health responses in times of economic contraction and expansion.


Polybrominated diphenyl ether flame retardants in eggs may reduce reproductive success of ospreys in Oregon and Washington, USA.
Spatial and temporal assessments and reports of polybrominated diphenyl ether (PBDE) flame retardants in birds remain sparse. In the present study, PBDEs were detected in all 120 osprey (Pandion haliaetus) eggs collected. The eggs were collected from nests along the Columbia, Willamette and Yakima rivers of Oregon (OR) and Washington (WA) and in Puget Sound (WA) between 2002 and 2007. PBDE congeners: 17, 28, 47, 49, 66, 85, 99, 100, 138, 153, 154 (possible coelution with brominated biphenyl 153 [BB153]), 183, 190 (detected in one egg), 209 (not detected), and BB101 (only detected in 2006 and 2007) and total-alpha-hexabromocyclododecane (only detected in five eggs) were analyzed for in the egg samples. Eggs from reservoirs in the forested headwaters of the Willamette River (2002) contained the lowest concentrations of SigmaPBDEs (geometric mean [range], 98 [55.2-275] ng/g wet weight [ww]), while those from the middle Willamette River (2006) contained the highest (897 [507-1,880] ng/g ww). Concentrations in eggs from the Columbia River progressively increased downstream from Umatilla, OR (River Mile [RM] 286) to Skamokoa, WA (RM 29), which indicated additive PBDE sources along the river. In general, regardless of the year of egg collection, differences in PBDE concentrations reported in osprey eggs along the three major rivers studied (Columbia, Willamette and Yakima) seem to reflect differences in river flow (dilution effect) and the extent of human population and industry (source inputs) along the rivers. PBDE concentrations increased over time at two locations (Seattle, WA; Columbia River, RM 29-84) where temporal patterns could be evaluated. Only during 2006 (on the middle Willamette River, RM 61-157) and 2007 (on the lower Columbia River, RM 29-84) did SigmaPBDE concentrations in osprey eggs exceed 1,000 ng/g ww with negative relationships indicated at both locations between productivity and SigmaPBDE concentrations in eggs (P = 0.008, P = 0.057). Osprey eggs from Everett, WA contained nearly twice the SigmaPBDE concentration (geometric mean 239 vs. 141 ng/g ww, range 124-384 vs. 22.2-819 ng/g ww, P < or = 0.05) as double-crested cormorant (Phalacrocorax auritus) eggs collected at the same location and time, which is likely due to dietary differences. No significant relationship (all Ps > 0.147) was indicated between PBDE congeners (including SigmaPBDEs) and eggshell thickness at the concentrations observed in this study.


Systematic comparison of the response properties of protein and RNA mediated gene regulatory motifs.
We present a framework enabling the dissection of the effects of motif structure (feedback or feedforward), the nature of the controller (RNA or protein), and the regulation mode (transcriptional, post-transcriptional or translational) on the response to a step change in the input. We have used a common model framework for gene expression where both motif structures have an activating input and repressing regulator, with the same set of parameters, to enable a comparison of the responses. We studied the global sensitivity of the system properties, such as steady-state gain, overshoot, peak time, and peak duration, to parameters. We find that, in all motifs, overshoot correlated negatively whereas peak duration varied concavely with peak time. Differences in the other system properties were found to be mainly dependent on the nature of the controller rather than the motif structure. Protein mediated motifs showed a higher degree of adaptation i.e. a tendency to return to baseline levels; in particular, feedforward motifs exhibited perfect adaptation. RNA mediated motifs had a mild regulatory effect; they also exhibited a lower peaking tendency and mean overshoot. Protein mediated feedforward motifs showed higher overshoot and lower peak time compared to the corresponding feedback motifs.


Oxidation of CO on a carbon-based material composed of nickel hydroxide and hydroxyl graphene oxide, (Ni4(OH)3-hGO)--a first-principles calculation.
Nickel or nickel hydroxide clusters and graphene oxide (GO) composites are novel nanomaterials in the application of electrochemical catalysts. In this work, we calculated the energy of Ni4 adsorbed onto saturated hydroxyl graphene oxide (hGO), which forms a Ni4(OH)3 cluster on the hydroxyl graphene oxide (Ni4(OH)3-hGO) and releases 4.47 eV (5.22 eV with DFT-D3 correction). We subsequently studied the oxidation of CO on the Ni4(OH)3-hGO system via three mechanisms - LH, ER and carbonated mechanisms. Our results show that the activation energy for oxidation of the first CO molecule according to the ER mechanism is 0.14 eV (0.12 eV with DFT-D3 correction), much smaller than that with LH (Ea = 0.65 eV, 0.61 eV with DFT-D3 correction) and with carbonated (Ea = 1.28 eV, 1.20 eV with DFT-D3 correction) mechanisms. The barrier to oxidation of the second CO molecule to CO2 with the ER mechanism increases to 0.43 eV (0.37 eV with DFT-D3 correction), but still less than that via LH (Ea = 1.09 eV, 1.07 eV with DFT-D3 correction), indicating that CO could be effectively oxidized through the ER mechanism on the Ni4(OH)3/hGO catalyst.


Is it the athlete or the equipment? An analysis of the top swim performances from 1990 to 2010.
O'Connor, LM and Vozenilek, JA. Is it the athlete or the equipment? An analysis of the top swim performances from 1990 to 2010. J Strength Cond Res 25(12): 3239-3241, 2011-Forty-three world record swims were recorded at the 2009 Fédération Internationale de Natation (FINA) World Championship meet in Rome. Of the 20 FINA recognized long-course (50-m pool) swimming events, men set new world records in 15 of those events, whereas women did the same in 17 events. Each of the men's world records and 14 of the 17 women's records still stand. These performances were unprecedented; never before had these many world records been broken in such a short period of time. There was much speculation that full-body, polyurethane, technical swimsuits were the reason for the conspicuous improvement in world records. Further analysis led the FINA to institute new rules on January 1, 2010, that limited the types of technical swimsuits that could be worn by athletes. No long-course world record has been broken since then. We sought to understand this phenomenon by analyzing publicly available race data and exploring other possible causes including improvements in other sports, improvements in training science, changes in rules and regulations, gender differences, anaerobic vs. aerobic events, unique talent, and membership data.


Preemptive strikes: Fear, hope, and defensive aggression.
Preemptive strikes are costly and harmful. Existing models of defensive aggression focus narrowly on the role fear plays in motivating preemptive strikes. Theoretically integrating the literatures on conflict, decision making, and emotion, the current research investigated how specific emotions associated with certainty or uncertainty, including fear, anger, disgust, hope, and happiness, influence preemptive strikes. Study 1 demonstrated that hope negatively predicts defensive exits from relationships in choice dilemmas. Studies 2 and 3 experimentally manipulated risk of being attacked in an incentivized, interactive decision making task-the Preemptive Strike Game. Risk of being attacked fueled preemptive strikes; reduced feelings of hope partially mediated this effect in Study 3. Studies 4 and 5 investigated preemptive strikes under uncertainty (rather than risk). In Study 4, reasoning about the factors that make one trustful of others curbed preemptive strikes; cogitating about the factors that underlie discrete emotions, however, did not influence defensive aggression. Study 5 demonstrated that the valence and uncertainty appraisals of incidental emotions interact in shaping preemptive strikes. Specifically, recalling an autobiographical emotional experience that produced hope significantly decreased attack rates relative to fear, happiness, and a control condition. Fear, anger, disgust, and happiness were either unrelated to preemptive strikes or showed inconsistent relationships with preemptive strikes across the 5 studies. These findings shed light on how emotions shape defensive aggression, advance knowledge on strategic choice under risk and uncertainty, and demonstrate hope's positive effects on social interactions and relationships. (PsycINFO Database Record


Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus.
Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.


Improving infants' stress-induced cortisol regulation through attachment-based intervention: A randomized controlled trial.
Attachment-based parenting interventions have shown positive effects on early cortisol regulation, a key biomarker. Evaluations to date have focused on diurnal cortisol production in high-risk infants. It is important to understand whether attachment-based intervention may also improve stress-induced cortisol production in typically developing infants. This randomized controlled trial tested an enhanced model of U.S. Early Head Start (EHS) services that combined home-based EHS with a brief, attachment-based parenting intervention, Attachment and Biobehavioral Catch-up (ABC). The trial included 153 low-income mothers and their infants (M age 12.4 months [SD = 4.1]). Control participants received home-based EHS plus 10 weekly books. Intent-to-treat analyses using multilevel models revealed a significant indirect intervention effect on infants' rates of cortisol change in response to a series of mild stressors. The intervention increased maternal sensitivity, which in turn improved cortisol regulation, particularly infants' rates of cortisol recovery. The findings illustrate the efficacy of EHS plus ABC for supporting infants' stress-induced cortisol regulation and implicate sensitive maternal behavior as the underlying driver of the intervention effect. Findings are discussed in terms of the preventative value of attachment-based parenting interventions that improve both parenting and infants' physiological regulation.


Global quantification of mammalian gene expression control.
Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.


Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells.
Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in the 120 kb 3p21.3 critical region contained in nested lung and breast cancer homozygous deletions. Mutation of FUS1 is infrequent in lung cancers which we have confirmed in 40 other primary lung cancers. In addition, we found no evidence for FUS1 promoter region methylation. Because haploinsufficiency or low expression of Fus1 may play a role in lung tumorigenesis, we tested the effect of exogenously induced overexpression of Fus1 protein and found 60-80% inhibition of colony formation for non-small cell lung cancer lines NCI-H1299 (showing allele loss for FUS1) and NCI-H322 (containing only a mutated FUS1 allele) in vitro. By contrast, a similar level of expression of a tumor-acquired mutant form of FUS1 protein did not significantly suppress colony formation. Also, induced expression of Fus1 under the control of an Ecdysone regulated promoter decreased colony formation 75%, increased the doubling time twofold, and arrested H1299 cells in G1. In conclusion, our data are consistent with the hypothesis that FUS1 may function as a 3p21.3 TSG, warranting further studies of its function in the pathogenesis of human cancers.


Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal.
The effects of transedermal nicotine on acute physiologic, performance and subjective measures of tobacco withdrawal were evaluated in a residential, double-blind, placebo-controlled, crossover study. Ten subjects smoked ad libitum for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, three transdermal nicotine delivery systems (patches) that delivered a total of 0, 10, 20 or 30 mg of nicotine were applied for 16 hr. Experimental measures were collected 6 hr after the application of the patches. Plasma levels of nicotine and cotinine indicated that the 20- and 30-mg treatment condition fully replaced the nicotine ordinarily obtained from smoking. During nicotine abstinence (0 mg condition) typical signs of tobacco withdrawal were evident including: decreases in pulse rate, increases in electroencephalographic theta power, increases in subjective measures of tobacco abstinence and slowed performance on computer-delivered cognitive tests. Nicotine patch treatment diminished the physiologic and performance changes, but subjective measures of tobacco abstinence (cigarette craving, increases in withdrawal scores) were not significantly reduced. These data indicate that the nicotine patch may be used to diminish aspects of tobacco abstinence that could affect performance even though withdrawal discomfort may persist.


Hip fractures in institutionalized elderly people: incidence rates and excess mortality.
It is assumed that nursing homes are the setting with the highest incidence of hip fractures. This observation is, however, based on very little data. The aim of this study was to analyze hip fracture rates and the associated excess mortality in a large nursing home population. A cohort of >69,000 women and men newly admitted to German nursing homes were used to calculate sex- and age-specific incidence rates of hip fractures. To calculate excess mortality, a retrospective cohort study was conducted. To each patient with a hip fracture (n = 4342), four residents without hip fracture (n = 17,368) were matched by sex, age, and level of care (measure for the need of care). Hazard regression models were applied. During 91,850 person-years, 4342 hip fractures were observed. The crude incidence rates for hip fractures were 50.8/1000 person-years in women and 32.7/1000 person-years in men. The incidence rates increased with increasing age categories and were highest in the first months after admission to the nursing home. Increasing care need reduced the risk of hip fracture. Mortality in patients with a hip fracture was increased (women: hazard rate ratio for the first 3 mo after fracture, 1.72; 95% CI, 1.59-1.86; men: hazard ratio, 2.14; 95% CI, 1.80-2.53), but excess mortality was limited to the first months after injury. Data are presented for hip fracture rates and excess mortality after a hip fracture. Our results have implications on the timing and the allocation of specific measures for hip fracture prevention.


A team quality improvement sequence for complex problems.
To solve complex quality problems teams need to follow a systematic sequence of inquiry and action. In this article a practical description of a team quality improvement sequence (TQIS) is given based on the experience of the more successful teams in the Norwegian total quality management experiment. There are nine phases in the sequence and teams have the flexibility to choose the best quality methods for completing each phase. The strengths of the framework are in ensuring that personnel time is used cost effectively and that changes are made which result in measurable improvement. One limitation is that the framework has not been as widely tested as FOCUS-PDCA (find, organise, clarify, understand, select-plan, do, check, act) and other frameworks to which the TQIS framework is compared. It is proposed that if team projects are to be the main vehicle for quality improvement, then their work must be made more cost effective. The article aims to stimulate research into the conditions necessary for different quality teams to be successful in health care, and draws on the research to propose a "risk of team failure index" to improve the management of such teams.


Hip Arthroplasty or Medical Management: A Challenging Treatment Decision for Younger Patients.
The two main treatment options for total hip arthroplasty (THA), medical management and surgical intervention, have advantages and disadvantages, creating a challenging decision. Treatment decisions are further complicated in a younger population (≤50) as the potential need for revision surgery is probable. We examined the relationship of selected variables to the decision-making process for younger patients with symptomatic OA. Thirty-five participants chose surgical intervention and 36 selected medical management for their current treatment. Pain, activity restrictions, and total WOMAC scores were statistically significant (P < .05) for patients selecting surgical intervention. No difference in quality of life was shown between groups. Pain was the only predictor variable identified, however, activity restrictions were also influential variables as these were highly correlated with pain.


Linking disease associations with regulatory information in the human genome.
Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.


Development of a DNA Macroarray for the Detection and Identification of Fungal Pathogens Causing Decline of Young Grapevines.
Young vine decline (YVD) is a complex disease caused by at least 51 different fungi and responsible for important economic losses to the grapevine industry worldwide. YVD fungi are known to occur in planting material. Hence, detection prior to planting is critical to assure longevity of newly established vineyards. A DNA macroarray based on reverse dot-blot hybridization containing 102 oligonucleotides complementary to portions of the β-tubulin region was developed for detection of YVD fungi. Specificity of the array was first evaluated against 138 pure fungal cultures representing 72 different taxa from nine genera, including 37 YVD species. In total, 61 species, including 34 YVD pathogens, were detected and identified by the array. The detection limit of the array was below 0.1 pg of genomic DNA. The array was validated against artificially inoculated canes and soil and commercial planting material, with the latter showing a high incidence of YVD fungi in nursery plants otherwise not detected by traditional plating and culturing. This DNA array proved to be a rapid and specific tool to simultaneously detect and identify most YVD fungi in a single test, which has the potential to be used in commercial diagnostics or by the grapevine nursery industry to determine the health status of the planting material.


Predictors of infection in chronic lymphocytic leukaemia (CLL).
A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001).


Atom Probe Tomography of a Cu-Doped TiNiSn Thermoelectric Material: Nanoscale Structure and Optimization of Analysis Conditions.
Cu-doping and crystallographic site occupations within the half-Heusler (HH) TiNiSn, a promising thermoelectric material, have been examined by atom probe tomography. In particular, this investigation aims to better understand the influence of atom probe analysis conditions on the measured chemical composition. Under a voltage-pulsing mode, atomic planes are clearly resolved and suggest an arrangement of elements in-line with the expected HH (F-43m space group) crystal structure. The Cu dopant is also distributed uniformly throughout the bulk material. For operation under laser-pulsed modes, the returned composition is highly dependent on the selected laser energy, with high energies resulting in the measurement of excessively high absolute Ti counts at the expense of Sn and in particular Ni. High laser energies also appear to be correlated with the detection of a high fraction of partial hits, indicating nonideal evaporation behavior. The possible mechanisms for these trends are discussed, along with suggestions for optimal analysis conditions for these and similar thermoelectric materials.


Generation and visualization of four-dimensional MR angiography data using an undersampled 3-D projection trajectory.
Time-resolved contrast-enhanced magnetic resonance (MR) angiography (CE-MRA) has gained in popularity relative to X-ray Digital Subtraction Angiography because it provides three-dimensional (3-D) spatial resolution and it is less invasive. We have previously presented methods that improve temporal resolution in CE-MRA while providing high spatial resolution by employing an undersampled 3-D projection (3D PR) trajectory. The increased coverage and isotropic resolution of the 3D PR acquisition simplify visualization of the vasculature from any perspective. We present a new algorithm to develop a set of time-resolved 3-D image volumes by preferentially weighting the 3D PR data according to its acquisition time. An iterative algorithm computes a series of density compensation functions for a regridding reconstruction, one for each time frame, that exploit the variable sampling density in 3D PR. The iterative weighting procedure simplifies the calculation of appropriate density compensation for arbitrary sampling patterns, which improve sampling efficiency and, thus, signal-to-noise ratio and contrast-to-noise ratio, since it is does not require a closed-form calculation based on geometry. Current medical workstations can display these large four-dimensional studies, however, interactive cine animation of the data is only possible at significantly degraded resolution. Therefore, we also present a method for interactive visualization using powerful graphics cards and distributed processing. Results from volunteer and patient studies demonstrate the advantages of dynamic imaging with high spatial resolution.


Altered Immune Phenotypes and HLA-DQB1 Gene Variation in Multiple Sclerosis Patients Failing Interferon β Treatment.
Interferon beta (IFNβ) has been prescribed as a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) for nearly three decades. However, there is still a lack of treatment response markers that correlate with the clinical outcome of patients. To determine a combination of cellular and molecular blood signatures associated with the efficacy of IFNβ treatment using an integrated approach. The immune status of 40 RRMS patients, 15 of whom were untreated and 25 that received IFNβ1a treatment (15 responders, 10 non-responders), was investigated by phenotyping regulatory CD4+ T cells and naïve/memory T cell subsets, by measurement of circulating IFNα/β proteins with digital ELISA (Simoa) and analysis of ~600 immune related genes including 159 interferon-stimulated genes (ISGs) with the Nanostring technology. The potential impact of HLA class II gene variation in treatment responsiveness was investigated by genotyping HLA-DRB1, -DRB3,4,5, -DQA1, and -DQB1, using as a control population the Milieu Interieur cohort of 1,000 French healthy donors. Clinical responders and non-responders displayed similar plasma levels of IFNβ and similar ISG profiles. However, non-responders mainly differed from other subject groups with reduced circulating naïve regulatory T cells, enhanced terminally differentiated effector memory CD4+ TEMRA cells, and altered expression of at least six genes with immunoregulatory function. Moreover, non-responders were enriched for HLA-DQB1 genotypes encoding DQ8 and DQ2 serotypes. Interestingly, these two serotypes are associated with type 1 diabetes and celiac disease. Overall, the immune signatures of non-responders suggest an active disease that is resistant to therapeutic IFNβ, and in which CD4+ T cells, likely restricted by DQ8 and/or DQ2, exert enhanced autoreactive and bystander inflammatory activities.


Nocturnal hemodialysis: three-year experience.
There is evidence that high frequency, as well as long duration, hemodialysis provides better clinical outcomes. We developed nocturnal hemodialysis, a new innovative form of renal replacement therapy, which is performed six to seven nights per week for 8 to 10 h during sleep at home. Blood flow was set at 300 ml/min and dialysate flow at 100 ml/min. An internal jugular catheter was used as the vascular access. Special precautions were taken to prevent accidental disconnection during sleep, as well as air embolization. Dialysis functions from the patient's home were monitored continuously via a modem at the nocturnal hemodialysis center. Twelve patients have completed training and have been successfully performing nocturnal hemodialysis for up to 34 mo. This study represents 170 patient months of experience accumulated over 3 yr. There was hemodynamic stability and significant subjective improvement in patient well being. Nightly Kt/V was 0.99. Weekly removal of phosphate was twice as high and beta2 microglobulin 4 times as high as conventional hemodialysis. All patients have discontinued their phosphate binders and have increased dietary phosphate and protein intake. BP control was achieved with fewer medications. Dialyzer reuse has decreased the operating costs to the level of the other form of home dialysis. Complications were infrequent and were related primarily to the dialysis access. Nocturnal hemodialysis represents the most efficient form of dialysis at low cost and should be considered as an option for patients who can be trained for home hemodialysis.


Evidence for the involvement of cyclic electron transport in the protection of photosystem II against photoinhibition: influence of a new phenolic compound.
Organisms that perform oxygenic photosynthesis are subjected to inhibition of their photosynthetic functions when they are exposed to excessive illumination. Photoinhibition occurs mainly at the level of photosystem II, where a cyclic electron transport has often been proposed to be involved in photoprotection. However, a demonstration of direct protection by cyclic photosystem II against photoinhibitory damage has been lacking. In this report, we used the newly characterized compound 4-[methoxybis(trifluoromethyl)methyl]-2,6-dinitrophenylhydrazine methyl ketone (K-15), known to stimulate cyclic electron transport between the acceptor and donor sides of the photosystem [Klimov, V. V., Zharmukhamedov, S. K., Allakhverdiev, S. I., Kolobanova, L. P., & Baskakov, Y. A. (1993) Biol. Membr. 6, 715-732], to verify if photosystem II is significantly protected by cyclic electron transport against aerobic and anaerobic photoinhibitory damage. The photoinhibitory quenching of the maximal level of fluorescence and the decrease of the absorbance change at 685 nm related to pheophytin photoreduction observed during photoinhibitory illumination of untreated or Mn-depleted photosystem II submembrane fractions are significantly attenuated in the presence of K-15. The photodegradation of cytochrome b559 and the photobleaching of beta-carotene and chlorophyll-670 measured in Mn-depleted photosystem II preparations are also strongly retarded when K-15 is present. The detection, by photoacoustic spectroscopy, of the energy stored during the cyclic electron transport is also reported in Mn-depleted photosystem II submembrane fractions and in photosystem II reaction center complexes. This reaction is also gradually photoinhibited due to the progressive photodegradation of the required electron transport intermediates but is significantly more stable in the presence of K-15. It is deduced that cyclic electron transport around photosystem II constitutes an effective protective mechanism against photoinhibitory damage.


RNA folding argues against a hot-start origin of life.
Opinion is strongly divided on whether life arose on earth under hot or cold conditions, the hot-start and cold-start scenarios, respectively. The origin of life close to deep thermal vents appears as the majority opinion among biologists, but there is considerable biochemical evidence that high temperatures are incompatible with an RNA world. To be functional, RNA has to fold into a three-dimensional structure. We report both theoretical and experimental results on RNA folding and show that (as expected) hot conditions strongly reduce RNA folding. The theoretical results come from energy-minimization calculations of the average extent of folding of RNA, mainly from 0-90 degrees C, for both random sequences and tRNA sequences. The experimental results are from circular-dichroism measurements of tRNA over a similar range of temperatures. The quantitative agreement between calculations and experiment is remarkable, even to the shape of the curves indicating the cooperative nature of RNA folding and unfolding. These results provide additional evidence for a lower temperature stage being necessary in the origin of life.


Doping for sex: Bad for mitochondrial performances? Case of testosterone supplemented Hyla arborea during the courtship period.
Sexual selection has been widely explored from numerous perspectives, including behavior, ecology, and to a lesser extent, energetics. Hormones, and specifically androgens such as testosterone, are known to trigger sexual behaviors. Their effects are therefore of interest during the breeding period. Our work investigates the effect of testosterone on the relationship between cellular bioenergetics and contractile properties of two skeletal muscles involved in sexual selection in tree frogs. Calling and locomotor abilities are considered evidence of good condition in Hyla males, and thus server as proxies for male quality and attractiveness. Therefore, how these behaviors are powered efficiently remains of both physiological and behavioral interest. Most previous research, however, has focused primarily on biomechanics, contractile properties or mitochondrial enzyme activities. Some have tried to establish a relationship between those parameters but to our knowledge, there is no study examining muscle fiber bioenergetics in Hyla arborea. Using chronic testosterone supplementation and through an integrative study combining fiber bioenergetics and contractile properties, we compared sexually dimorphic trunk muscles directly linked to chronic sound production to a hindlimb muscle (i.e. gastrocnemius) that is particularly adapted for explosive movement. As expected, trunk muscle bioenergetics were more affected by testosterone than gastrocnemius muscle. Our study also underlines contrasted energetic capacities between muscles, in line with contractile properties of these two different muscle phenotypes. The discrepancy of both substrate utilization and contractile properties is consistent with the specific role of each muscle and our results are elucidating another integrative example of a muscle force-endurance trade-off.


Reductive evolution of bacterial genome in insect gut environment.
Obligate endocellular symbiotic bacteria of insects and other organisms generally exhibit drastic genome reduction. Recently, it was shown that symbiotic gut bacteria of some stinkbugs also have remarkably reduced genomes. Here, we report the complete genome sequence of such a gut bacterium Ishikawaella capsulata of the plataspid stinkbug Megacopta punctatissima. Gene repertoire and evolutionary patterns, including AT richness and elevated evolutionary rate, of the 745,590 bp genome were strikingly similar to those of obligate γ-proteobacterial endocellular insect symbionts like Buchnera in aphids and Wigglesworthia in tsetse flies. Ishikawaella was suggested to supply essential amino acids for the plant-sucking stinkbug as Buchnera does for the host aphid. Although Buchnera is phylogenetically closer to Wigglesworthia than to Ishikawaella, in terms of gene repertoire Buchnera was similar to Ishikawaella rather than to Wigglesworthia, providing a possible case of genome-level convergence of gene content. Meanwhile, several notable differences were identified between the genomes of Ishikawaella and Buchnera, including retention of TCA cycle genes and lack of flagellum-related genes in Ishikawaella, which may reflect their adaptation to distinct symbiotic habitats. Unexpectedly, Ishikawaella retained fewer genes related to cell wall synthesis and lipid metabolism than many endocellular insect symbionts. The plasmid of Ishikawaella encoded genes for arginine metabolism and oxalate detoxification, suggesting the possibility of additional Ishikawaella roles similar to those of human gut bacteria. Our data highlight strikingly similar evolutionary patterns that are shared between the extracellular and endocellular insect symbiont genomes.


Nosocomial bacteriuria in elderly inpatients may be leading to considerable antibiotic overuse: an audit of current management practice in a secondary level care hospital in New Zealand.
Bacteriuria in the form of symptomatic urinary tract infection (UTI) and asymptomatic bacteriuria (ASB) is common in the elderly. There is no clinical benefit obtained by treating elderly individuals with ASB. However, its high prevalence leads to the overdiagnosis of UTI and unnecessary antibiotic use, which can result in adverse events, including Clostridium difficile diarrhea and reinfection with antibiotic-resistant organisms. This was a retrospective audit that assessed the management of nosocomial bacteriuria in elderly patients admitted to the over-65 years rehabilitation unit of a secondary level care hospital in New Zealand. Identified bacteriuria episodes had the timing of sample collection relative to admission, microbial etiology, antibiotic susceptibility profile, inflammatory marker level, and treatment determined. Episodes were classified into six different clinical groups based on the presence or absence of signs and symptoms, urinary catheter status, and systemic inflammatory response. The proportion of bacteriuria episodes by clinical grouping and the level of treatment by clinical group were determined, followed by assessment of the amount of overtreatment in terms of the number of unnecessary antibiotic courses and unnecessary antibiotic treatment days. Significant bacteriuria was identified in 30% of patients, with 35% of urine samples collected in the immediate postadmission period. Fifty-four percent of the bacteriuria episodes were ASB or catheter-associated ASB (CA-ASB) without an inflammatory response, 24% were ASB or CA-ASB with raised inflammatory markers, and 22% were UTI or CA-UTI. The most common cause of bacteriuria was Escherichia coli, although the etiology was diverse, especially after prolonged hospitalization or in catheterized patients. A large proportion of organisms were resistant to one or more of the commonly used oral antibiotics. Treatment of ASB and CA-ASB accounted for 43% of all antibiotic courses received. Furthermore, treatment of ASB and CA-ASB combined with unnecessarily prolonged treatment days for clinically relevant infections accounted for 55% of all antibiotic treatment days received. The results suggest that inappropriate urine screening was occurring and that 43% of antibiotic courses and 55% of all antibiotic treatment days were unnecessary. Current practice is amenable to improvement by performing urine culture only when clinically indicated, focusing on clinical signs and symptoms to diagnose clinically significant UTI rather than a positive culture, and using, where possible, the ecologically least damaging antibiotic for the shortest duration required.


Prolonged leptin treatment increases transient outward K⁺ current via upregulation of Kv4.2 and Kv4.3 channel subunits in adult rat ventricular myocytes.
Circulating leptin levels are elevated in obesity and hyperleptinaemia has been postulated to be an independent risk factor for the development of cardiovascular diseases. Although many studies have been published on the mechanisms involved in the effects of leptin on cardiac function and pathological remodeling, scarce information is currently available analyzing the influence of prolonged leptin treatment on ionic cardiac channels remodeling in adult ventricular myocytes. Enzymatically isolated adult rat ventricular myocytes were treated with leptin or vehicle for 48h. Real-Time RT-PCR were used to analyze mRNA expression of Kir2.1, Cav1.2, Cav 3.1, Kv4.2 and Kv4.3 α-subunits and KChIP2 auxiliary subunit. The fast transient outward potassium channels (Itof) α-subunits Kv4.2, Kv4.3 and KChIP2 were analyzed by Western-blot. The fast transient outward potassium current and the action potentials were recorded in isolated myocytes by the whole-cell patch-clamp technique. Leptin treatment induced an up-regulation of Kv4.2, Kv4.3 and KChIP2 subunits mRNA expression. However, transcriptional levels of Kir2.1, Cav1.2, or Cav3.1 α-subunit channels were unmodified by leptin. Protein expression levels of Kv4.2, Kv4.3 and KChIP2 subunits were also increased by leptin. The electrophysiological study showed that leptin increases the fast transient outward potassium current amplitudes and densities shortening action potential duration. In addition, leptin activated Akt signaling in cardiomyocytes and this mechanism was involved in the effect of leptin on Itof channels. In conclusión, leptin increases both the expression and function of Itof channels in adult ventricular myocytes and this mechanism involves Akt signaling. Altogether these data suggest that leptin could exert beneficial or detrimental effects depending on the initial ventricular myocyte repolarizing reserve.


Lipid modification of the 17-kilodalton membrane immunogen of Treponema pallidum determines macrophage activation as well as amphiphilicity.
A murine monoclonal antibody specific for a 17-kDa major membrane immunogen of Treponema pallidum was used to select recombinant Escherichia coli clones expressing the molecule from a T. pallidum genomic library. Sequence analysis of the structural gene for the immunogen (designated tpp17) revealed a 468-bp open reading frame encoding a polypeptide of 156 amino acids with a calculated molecular mass of 16,441 Da. The deduced amino acid sequence included a putative leader peptide terminated by a consensus tetrapeptide for the modification and processing of prokaryotic lipoproteins. Immunoprecipitation of the cloned immunogen radiolabeled with [3H]palmitate confirmed that it was a lipoprotein. The amino acid sequence also predicted that the mature protein contains four cysteine residues in addition to the lipid-modified cysteine of the N terminus. The existence of disulfide-bonded multimeric forms of the native immunogen was demonstrated by immunoblotting T. pallidum solubilized in the presence and absence of 2-mercaptoethanol. Triton X-114 phase partitioning of a nonlipidated form of the 17-kDa immunogen cleaved from a glutathione S-transferase fusion protein demonstrated that lipid modification is responsible for the immunogen's hydrophobic character. The same nonlipidated form of the immunogen also was used to demonstrate that lipid modification is essential for the molecule's ability to stimulate production of tumor necrosis factor alpha by murine macrophages. We conclude that covalently attached fatty acids not only anchor T. pallidum lipoproteins to spirochetal membranes but also confer upon these molecules the ability to activate immune effector cells.


Ancestral polymorphism and recent invasion of transposable elements in Drosophila species.
During the evolution of transposable elements, some processes, such as ancestral polymorphisms and horizontal transfer of sequences between species, can produce incongruences in phylogenies. We investigated the evolutionary history of the transposable elements Bari and 412 in the sequenced genomes of the Drosophila melanogaster group and in the sibling species D. melanogaster and D. simulans using traditional phylogenetic and network approaches. Maximum likelihood (ML) phylogenetic analyses revealed incongruences and unresolved relationships for both the Bari and 412 elements. The DNA transposon Bari within the D. ananassae genome is more closely related to the element of the melanogaster complex than to the sequence in D. erecta, which is inconsistent with the species phylogeny. Divergence analysis and the comparison of the rate of synonymous substitutions per synonymous site of the Bari and host gene sequences explain the incongruence as an ancestral polymorphism that was inherited stochastically by the derived species. Unresolved relationships were observed in the ML phylogeny of both elements involving D. melanogaster, D. simulans and D. sechellia. A network approach was used to attempt to resolve these relationships. The resulting tree suggests recent transfers of both elements between D. melanogaster and D. simulans. The divergence values of the elements between these species support this conclusion. We showed that ancestral polymorphism and recent invasion of genomes due to introgression or horizontal transfer between species occurred during the evolutionary history of the Bari and 412 elements in the melanogaster group. These invasions likely occurred in Africa during the Pleistocene, before the worldwide expansion of D. melanogaster and D. simulans.


Co-occurrence of Artemisia and Ambrosia pollen seasons against the background of the synoptic situations in Poland.
The Asteraceae family is one of the largest families, comprising 67 genera and 264 species in Poland. However, only a few genera, including Artemisia and Ambrosia are potential allergenic sources. The aim of the study was to estimate how often and to what degree Artemisia and Ambrosia pollen seasons co-occur intensifying human health risk, and how synoptic situations influence frequency of days with high pollen concentrations of both taxa. Artemisia and Ambrosia pollen data were collected, using the volumetric method, at 8 sites in Poland. Daily concentrations of Artemisia pollen equal to 30 grains or more and Ambrosia pollen equal to 10 grains or more were accepted as high values. Concentrations of more than 10 pollen grains were defined as high in the case of Ambrosia because its allergenicity is considered higher. High concentrations were confronted with synoptic situations. Analysis was performed on the basis of two calendars on circulation types of atmosphere in Poland (Niedźwiedź, 2006, 2015). Co-occurrence of Artemisia and Ambrosia pollen seasons is being found most often, when Ambrosia pollen season starts in the first half of August. If it happens in the last 10 days of August high pollen concentrations of Artemisia and Ambrosia do not occur at the same days. At three sites (Sosnowiec, Rzeszów, Lublin) high Ambrosia pollen concentrations during the Artemisia pollen season appear more often than in other sites under question. The high Artemisia pollen concentrations occur, when continental or polar maritime old air masses inflow into Poland. The impact of air masses on high Ambrosia pollen concentrations depends on site localizations. It is likely, that in the south-eastern part of Poland high Ambrosia pollen concentrations result from the pollen transport from east-south-south-westerly directions and the local sources. Co-occurrence of both taxa pollen seasons depends on the air masses inflow and appears more often in a south-eastern part of Poland.


Acquired immunodeficiency syndrome/human immunodeficiency virus risk behavior among gay men in small cities. Findings of a 16-city national sample.
Most research on acquired immunodeficiency syndrome has been conducted in several of the country's largest cities, and little is known about the current level of human immunodeficiency virus risk taking among gay men in other geographical areas. The purpose of this study was to determine the frequency of risk behavior practices among gay men in smaller communities. A large sample of men who patronized gay bars in 16 small and moderate-size cities drawn from six states in four different regions of the country was surveyed to determine the frequency of high-risk behavior and factors influencing risk taking. Eighty-five percent of men in all cities' bars completed all survey measures. The community samples were 1991 men; mean age, 31.3 years; mean education, 10.6 years; 90% were white and 10% were of other ethnicities. All participants provided detailed information on their sexual behavior practices over the preceding 2 months and completed measures assessing their perceived peer norms concerning safer sex practices and risk avoidance, intentions to avoid risk, personal risk estimation, acquired immunodeficiency syndrome risk knowledge, perceived threat of acquired immunodeficiency syndrome/human immunodeficiency virus, and serostatus testing history. High-risk patterns were still common among gay men in these smaller cities; nearly one third of all men had engaged in unprotected anal intercourse an average of eight times in the past 2 months, usually outside monogamous relationships. High-risk behavior was most strongly associated with beliefs that safer sex practices would not be well accepted by peers, weak intentions to use condoms, underestimation of personal vulnerability to the acquired immunodeficiency syndrome, younger age, and higher levels of overall sexual activity. Nine percent of men tested said they were seropositive. Growing human immunodeficiency virus prevalence and continued high rates of risk behavior indicate that a new "front line" for human immunodeficiency virus prevention among homosexually active men has shifted to the country's smaller cities. Community prevention efforts in these areas are urgently needed to avert sharp increases in future human immunodeficiency virus infections in this population.


Effects of arterial hemorrhage speed on the blood coagulation/fibrinolysis system and hemodynamics in rats.
: The effects of rapid hemorrhage on coagulopathy have been reported. However, the effects of different hemorrhage speeds on the blood coagulation/fibrinolysis system have not been investigated. This study aimed to compare different hemorrhage speeds for clarifying their effects on the coagulation/fibrinolysis system and circulation disorders in rats. Male Sprague-Dawley rats (301-396 g) were randomly assigned to five groups depending on hemorrhage speed and length of procedure: first, rapid (1.4 ml/min, 30-min bleeding); second, rapid-L (1.4 ml/min, 30-min bleeding and observation until 6 h); third, slow (0.1 ml/min, intermittently, 6-h bleeding); fourth, control (30-min observation); and fifth, control-L (6-h observation). Hemorrhage was induced by withdrawing blood until 40% of the estimated blood volume from the femoral artery. We measured vital signs, hematology, general chemistry, blood gas status, coagulation parameters, fibrinolytic markers [tissue-type plasminogen activator and plasminogen activator inhibitor one (PAI-1)], vascular endothelial damage (syndecan-1), and liver PAI-1 mRNA expression. Rapid hemorrhage induced elevation of lactate and syndecan-1 levels and prolonged prothrombin time and activated partial thromboplastin time in the rapid group. In contrast, slow hemorrhage did not induce these changes. Hemorrhage speed had no effect on plasma tissue-type plasminogen activator and hematology. Plasma PAI-1 levels were significantly increased in the rapid-L group, while liver PAI-1 mRNA levels were increased in the slow group. This study shows changes in the circulatory and fibrinolysis systems, depending on the hemorrhage speed. Hemorrhage might promote production of PAI-1, while tissue hypoxia due to rapid hemorrhage might promote release of PAI-1.


Identification and in silico characterization of soybean trihelix-GT and bHLH transcription factors involved in stress responses.
Environmental stresses caused by either abiotic or biotic factors greatly affect agriculture. As for soybean [Glycine max (L.) Merril], one of the most important crop species in the world, the situation is not different. In order to deal with these stresses, plants have evolved a variety of sophisticated molecular mechanisms, to which the transcriptional regulation of target-genes by transcription factors is crucial. Even though the involvement of several transcription factor families has been widely reported in stress response, there still is a lot to be uncovered, especially in soybean. Therefore, the objective of this study was to investigate the role of bHLH and trihelix-GT transcription factors in soybean responses to environmental stresses. Gene annotation, data mining for stress response, and phylogenetic analysis of members from both families are presented herein. At least 45 bHLH (from subgroup 25) and 63 trihelix-GT putative genes reside in the soybean genome. Among them, at least 14 bHLH and 11 trihelix-GT seem to be involved in responses to abiotic/biotic stresses. Phylogenetic analysis successfully clustered these with members from other plant species. Nevertheless, bHLH and trihelix-GT genes encompass almost three times more members in soybean than in Arabidopsis or rice, with many of these grouping into new clades with no apparent near orthologs in the other analyzed species. Our results represent an important step towards unraveling the functional roles of plant bHLH and trihelix-GT transcription factors in response to environmental cues.


Comparing 3-month recall to daily reporting of sexual behaviours.
This study aimed to examine discrepancies between self-report methods and methodological issues related to sexual risk taking. We examined sexual behaviour assessed via 3-month electronic recall and by daily electronic reporting among a large cohort of patients attending STI clinics. STI clinic attenders (N= 628) aged 15 to 60 years reported on demographic information (at baseline), penile-vaginal sex acts, condom-unprotected penile-vaginal sex and STI history using 3-month recall and daily reports. Additionally, interviewer-participant match related to race and gender, as well as study site were considered as covariates. Concordance between recall and daily reports on penile-vaginal sex was moderately strong (Spearman's r (rs)=0.62; p<0.001). Comparison for reports for condom-unprotected penile-vaginal sex resulted in a correlation coefficient of 0.61 (p<0.001), also indicating moderately strong agreement between the two methods. Two generalised logit models were conducted to explain lack of strong concordance in penile-vaginal sex acts and condom-unprotected penile-vaginal sex. The odds of a female reporting higher frequency of sex in daily reports compared with recall were more than two times that of a male. Every five person increase in the number of lifetime sexual partners was associated with five times the odds of a discrepancy in reporting methods. Age was also significantly associated with unequal daily versus recall sex frequency reporting. Shifting focus to methodological considerations of technological reports can help ensure better investment of resources into sexual health research due to greater understanding of the methodological properties of data collection methods.


Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) ointment: double-blind, randomized trial in the Islamic Republic of Iran.
To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) ointment in patients with cutaneous leishmaniasis caused by Leishmania major in the Islamic Republic of Iran. Double-blind, randomized trial of four weeks of aminosidine ointment (n = 108) vs two weeks of aminosidine ointment and two weeks of placebo (n = 108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures. Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74%) vs 64/108 (59%) clinical cures (P = 0.05) and 47 (44%) vs 26 (24%) clinical and parasitological cures (P = 0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment: 20 (19%) vs 36 (33%) (P = 0.02). On day 105, the results still favoured those who had been allocated four weeks of active treatment, but the differences were no longer as clearly significant. No side-effects were observed or reported. Approximately two-thirds of patients given ointment for four weeks were cured clinically. Although about half of those cured might have recovered spontaneously even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs.


Lacosamide for SCN2A-related intractable neonatal and infantile seizures.
Voltage-gated sodium channel alpha subunit 2 (SCN2A) gene mutations are associated with neonatal seizures and a wide range of epilepsy syndromes. Previous reports suggest that traditional sodium channel blockers (SCBs) such as phenytoin, carbamazepine, and lamotrigine have a beneficial effect on SCN2A-related neonatal seizures, as they counteract the gain-of-function effect of mutated Nav1.2 channels. Additionally, SCBs are beneficial against other sodium and potassium channel-related neonatal seizures. There are, however, few reports describing the effect of the new SCB lacosamide against neonatal and infantile epileptic seizures. We report herein two neonates with intractable neonatal seizures with SCN2A pathogenic missense variants. Both infants showed temporary seizure relief following IV administrations of phenytoin, but were resistant to a combination of antiepileptic drugs, while complete seizure control was achieved following lacosamide administration. We suggest that SCBs, e.g. phenytoin, should be introduced early for refractory neonatal seizures of non-lesional and presumably genetic origin. If any beneficial response to a SCB is noted, this should prompt an initiation of additional SCBs. New clinical trials will provide data on the efficacy and safety of the new SCB lacosamide for genetic neonatal seizures and perhaps neonatal seizures in general.


Deep convolution neural networks to differentiate between COVID-19 and other pulmonary abnormalities on chest radiographs: Evaluation using internal and external datasets.
We aimed to evaluate the performance of convolutional neural networks (CNNs) in the classification of coronavirus disease 2019 (COVID-19) disease using normal, pneumonia, and COVID-19 chest radiographs (CXRs). First, we collected 9194 CXRs from open datasets and 58 from the Korea University Anam Hospital (KUAH). The number of normal, pneumonia, and COVID-19 CXRs were 4580, 3884, and 730, respectively. The CXRs obtained from the open dataset were randomly assigned to the training, tuning, and test sets in a 70:10:20 ratio. For external validation, the KUAH (20 normal, 20 pneumonia, and 18 COVID-19) dataset, verified by radiologists using computed tomography, was used. Subsequently, transfer learning was conducted using DenseNet169, InceptionResNetV2, and Xception to identify COVID-19 using open datasets (internal) and the KUAH dataset (external) with histogram matching. Gradient-weighted class activation mapping was used for the visualization of abnormal patterns in CXRs. The average AUC and accuracy of the multiscale and mixed-COVID-19Net using three CNNs over five folds were (0.99 ± 0.01 and 92.94% ± 0.45%), (0.99 ± 0.01 and 93.12% ± 0.23%), and (0.99 ± 0.01 and 93.57% ± 0.29%), respectively, using the open datasets (internal). Furthermore, these values were (0.75 and 74.14%), (0.72 and 68.97%), and (0.77 and 68.97%), respectively, for the best model among the fivefold cross-validation with the KUAH dataset (external) using domain adaptation. The various state-of-the-art models trained on open datasets show satisfactory performance for clinical interpretation. Furthermore, the domain adaptation for external datasets was found to be important for detecting COVID-19 as well as other diseases.


Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study.
To assess the risk of cerebral thromboembolism in women using low dose oral contraceptives. A retrospective case-control study. All Danish medical, neurological, neurosurgical, and gynaecological departments. All 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack during 1985-9 and 1588 age matched randomly selected controls. Of 692/1584 case/control questionnaires sent out, 590/1396 (85.3%/88.1%) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreliable diagnosis, 40 had had thromboembolic disease previously, 13 were pregnant, and 152 had a disease predisposing to a cerebral thromboembolic attack. Of the 323 cases without a known predisposition, 320 reported use or non-use of oral contraception. Among the 1396 controls, eight refused to participate, were mentally retarded, or lived abroad; 18 returned an uncompleted questionnaire; 17 had had thromboembolic disease previously; 31 were pregnant; and 130 had a disease predisposing to a cerebral thromboembolic attack. Thus 1198 non-predisposed controls were available, among whom 1197 reported use or non-use of oral contraception. Among the 320 cases, 116 (36.3%) were oral contraceptive users at the time of the cerebral thromboembolic attack. By comparison there were 191 users (16.0%) among the 1197 controls, giving a crude odds ratio of 3.0. After multivariate analysis, including confounder control for age, smoking, years of schooling, and trend in use of different types of oral contraceptives during 1985-90, pills containing 50 micrograms oestrogen were associated with an odds ratio for cerebral thromboembolic attack of 2.9 (95% confidence interval 1.6 to 5.4), those containing 30-40 micrograms oestrogen an odds ratio of 1.8 (1.1 to 2.9), those containing progestogen only an odds ratio of 0.9 (0.4 to 2.4). The odds ratio did not change with increasing age or with duration of oral contraceptive use. A 50% increased risk of a cerebral thromboembolic attacks among cigarette smokers (after confounder control) was independent of oral contraception status and age. Low dose oral contraceptives are associated with an increased risk of cerebral thromboembolic attack. Combined or sequential pills containing 30-40 micrograms oestrogen are associated with a one third reduced risk compared with preparations containing 50 micrograms oestrogen. Progestogen only pills did not increase the risk of a cerebral thromboembolic attack.


Identification of Social-Media Platform of Videos through the Use of Shared Features.
Videos have become a powerful tool for spreading illegal content such as military propaganda, revenge porn, or bullying through social networks. To counter these illegal activities, it has become essential to try new methods to verify the origin of videos from these platforms. However, collecting datasets large enough to train neural networks for this task has become difficult because of the privacy regulations that have been enacted in recent years. To mitigate this limitation, in this work we propose two different solutions based on transfer learning and multitask learning to determine whether a video has been uploaded from or downloaded to a specific social platform through the use of shared features with images trained on the same task. By transferring features from the shallowest to the deepest levels of the network from the image task to videos, we measure the amount of information shared between these two tasks. Then, we introduce a model based on multitask learning, which learns from both tasks simultaneously. The promising experimental results show, in particular, the effectiveness of the multitask approach. According to our knowledge, this is the first work that addresses the problem of social media platform identification of videos through the use of shared features.


Na+ channel immunolocalization in peripheral mammalian axons and changes following nerve injury and neuroma formation.
Nerve injury frequently triggers hyperexcitability and the ectopic initiation of impulses in primary afferent axons. An important consequence is neuropathic paresthesias and pain. Electrogenesis in normal afferents depends on appropriate Na+ channel concentrations. Therefore, we have asked whether injury might trigger changes in axolemmal Na+ channel distribution that could account for neuropathic hyperexcitability. We used an Na+ channel-specific antibody, 7493, to immunolocalize Na+ channels ultrastructurally in membranes of normal rat axons, and to assess remodeling following nerve section and neuroma formation. Selective labeling of nodal axolemma and, more weakly, of Schwann cell membrane, confirmed the efficacy of our immunolabeling protocol. In neuromas at postoperative times associated with peak ectopic activity, we found clear evidence of Na+ channel accumulation. Specifically, soon after myelin was stripped from large-diameter axons, the exposed, formerly internodal axolemma became immunopositive. Small-diameter unmyelinated axons and axon sprouts in the neuroma were also marked with 7493 IgG. Activated phagocytic macrophages and endothelial cells were 7493 negative. Both large- and small-diameter axons in neuromas end in swollen, organelle-packed "end bulbs." Most, but not all, of these acquired Na+ channel immunolabeling. We propose that remodeling results from a modification of the normal process of Na+ channel turnover in neural membranes. Na+ channel protein accumulates in preterminal axolemma and neuroma end bulbs due to a combination of permissive factors (especially myelin removal) and promotional factors (removal of normal downstream targets). This accumulation is a likely precursor of afferent hyperexcitability in injured nerve.


FARS2 (Phenylalanyl-tRNA Synthetase 2) Deficiency: A Novel Mutation Associated with EEG Phenotype of Epilepsy of Infancy with Migrating Focal Seizures (EIMFS).
Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare devastating infantile epileptic encephalopathy that is characterized by a unique electroencephalopgraphy (EEG) signature of multifocal simultaneous seizures. Although no definite etiology is understood for EIMFS, mutations in certain ion channels, are implicated. Similarly, phenylalanyl-tRNA synthetase 2 (FARS2) deficiency is a rare, autosomal recessive disorder of dysfunctional mitochondrial translation causing refractory seizures, lactic acidosis, and developmental regression with a variety of EEG findings. However, an EIMFS-like pattern on EEG in FARS2 deficiency has only recently been reported once. Herein, we describe a seven-week-old male with seizures where whole exome sequencing (WES) revealed pathogenic FARS2 variants and an EIMFS pattern on EEG. This case provides an insight on a novel genetic mechanism for EIMFS. We encourage early consideration of WES when EIMFS is detected to evaluate for FARS2 deficiency, especially in the setting of profound lactic acidosis.


The effect of gender on tooth and gingival display in the anterior region at rest and during smiling.
The aim of the present study was to investigate the effect of gender on the degree of maxillary and mandibular anterior teeth and associated gingival display when the lips are at rest and during smiling. A total of 247 subjects (144 females [58.3%]; 103 males [41.7%]) were included in the study. All of the subjects had all natural anterior teeth present with no caries, extreme occlusal wear, restorations, extrusion, obvious deformities, or tooth mobility. Subjects with a history of congenital anomalies, lip trauma, or facial surgery were excluded. Crown length, displayed portions of anterior teeth, and associated gingivae at rest and during smiling were measured using a Fowler electronic digital caliper, which had a resolution of 0.01 mm. The visible portions of the maxillary anterior teeth were measured vertically from the lower border of the upper lip to the incisal edge of the incisors, or cusp tip for the canines. The visible portions of the mandibular anterior teeth were measured vertically from the upper border of the lower lip to the incisal edges of the incisors, or cusp tip for the canines at the midpoint of the tooth. The measurements were taken by two independent clinicians and they were repeated three times and the mean value was calculated for further analysis. SPSS (V 11) software was used to analyse the data. Statistical analyses were performed by Student t test and ANOVA. The significance level was set at 5%. At rest, males displayed significantly more buccal length for maxillary lateral incisors (1.85 +/- 1.27 vs 1.43 +/- 1.37; P < 0.01), maxillary canines (0.94 +/- 0.91 vs 0.35 +/- 0.67; P < 0.0001), mandibular central incisors (1.09 +/- 1.17 vs 0.82 +/- 1.32; P < 0.01), mandibular lateral incisors (0.98 +/- 1.07 vs 0.79 +/- 1.22; P < 0.05), and mandibular canines (0.87 +/- 1.23 vs 0.57 +/- 0.98; P < 0.05) than females. However, no gender differences in the display of buccal length of the maxillary central incisor were recorded at rest and during smiling. During smiling, no gender differences in the display of buccal length of the anterior teeth were recorded. Gingival display during smiling presented significant differences between gender groups in the maxillary anterior region, with females displaying more gingivae of central incisors (1.85 +/- 1.38 vs 1.73 +/- 1.07; P < 0.05), lateral incisors (2.05 +/- 0.93 vs 1.94 +/- 1.23; P < 0.0001), and canines (2.37 +/- 1.24 versus 2.02 +/- 1.49; P < 0.05). However, no gender differences were observed in the gingival display of the mandibular anterior region. Females displayed 29% vs 25% of maxillary central incisor crown length compared to males at rest. However, during smiling, 87% of maxillary anterior teeth were displayed in females compared to less than 80% in males. Males displayed more of the maxillary lateral, canine, and mandibular anterior teeth than females at rest. During smiling, no gender differences in anterior tooth display were recorded; however, females displayed more maxillary gingivae than males.


Tunable white light of a Ce3+,Tb3+,Mn2+ triply doped Na2Ca3Si2O8 phosphor for high colour-rendering white LED applications: tunable luminescence and energy transfer.
A tunable white light emitting Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ phosphor with a high color rendering index (CRI) has been prepared. Under UV excitation, Na2Ca3Si2O8:Ce3+ phosphors present blue luminescence and exhibit a broad excitation ranging from 250 to 400 nm. When codoping Tb3+/Mn2+ ions into Na2Ca3Si2O8, energy transfer from Ce3+ to Tb3+ and Ce3+ to Mn2+ ions is observed from the spectral overlap between Ce3+ emission and Tb3+/Mn2+ excitation spectra. The energy-transfer efficiencies and corresponding mechanisms are discussed in detail. The mechanism of energy transfer from Ce3+ to Tb3+ is demonstrated to be a dipole-quadrupole mechanism by the Inokuti-Hirayama model. The wavelength-tunable white light can be realized by coupling the emission bands centered at 440, 550 and 590 nm ascribed to the contribution from Ce3+, Tb3+ and Mn2+, respectively. The commission on illumination value of color tunable emission can be tuned by controlling the content of Ce3+, Tb3+ and Mn2+. Temperature-dependent luminescence spectra proved the good thermal stability of the as-prepared phosphor. White LEDs with CRI = 93.5 are finally fabricated using a 365 nm UV chip and the as-prepared Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ phosphor. All the results suggest that Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ can act as potential color-tunable and single-phase white emission phosphors for possible applications in UV based white LEDs.