Antivenom for European Vipera species envenoming.
European viper bite is relatively uncommon but can cause serious envenoming, particularly swelling and hemorrhage spreading from limb to trunk that can cause long term disability. Systemic features are relatively mild compared to many other venomous species. Moderate-to-severe envenoming requires antivenom, which is given many hundreds of times each year across the continent. Several Vipera spp antivenoms are produced in Europe, but there is little comparative information available for the antivenoms and none is licensed with the European Medicines Agency. We aimed to collect descriptive data on European viper antivenoms and assess their relative effectiveness. A systematic review of articles relating to antivenom in Europe was performed using the Medline medical database. The following keywords "Europ*" or the individual names of each European country and "antiven*" or "immun*" or "envenom*" and "snake" or "viper*" or "adder" were used. Articles published between 1 January 1996 and 11 March 2016 pertaining to clinical outcome, including case reports, were selected. Referenced articles in the indexed articles were explored for suitability and included if they met any of the criteria: specific antivenom used, route of antivenom administration, adverse reactions to antivenom therapy and length of hospital admission. All accepted abstracts from EAPCCT conferences since 2000 were searched and abstracts relating to Vipera spp envenoming were assessed for suitability. We extracted data on study type, safety and effectiveness. We sought information on antivenoms from manufacturers and individual patient data from authors of publications. Since individual patient data were only rarely available, we compared median length of stay between case series reporting each antivenom. We identified 40 papers and six published abstracts, and one unpublished paper that reported clinical cases and case series of envenomed patients treated with antivenom. No publication reported randomized controlled trials comparing any European Vipera antivenom with either placebo or another antivenom. 25 reports were of retrospective hospital- (n = 13) or poison center-based (n = 12) case series including five or more patients; a further 12 reports were either case reports or case series with less than five patients and one paper was a limited literature review. An additional nine papers reported prospective data; seven collected data remotely through poison service telephone communication with the attending physicians. Antivenoms available in Europe: Eight antivenoms are available for European Vipera spp envenoming; a material safety data sheet providing information on manufacture was available for seven. Six are raised against V. berus or V. ammodytes venom; the seventh is raised against a mixture of V. ammodytes, V. aspis and V. berus venom and the eighth is raised against V. ammodytes, Macrovipera lebetina and Montivipera xanthina venom. Six manufacturers recommended intramuscular administration while two recommended intravenous administration. No randomized control trials comparing the effectiveness of antivenoms were identified. Pre-clinical data: We found two papers presenting comparative preclinical data. Clinical data: Clinical studies were predominantly retrospective and contained clinical data on antivenom used in 2602 patients; where the antivenom was identified (n = 2174), 2061 (94.8%) received Zagreb, ViperFAV or ViperaTAb antivenoms. There were few published data on the other antivenoms. Repeated use of antivenom: Repeat doses were reported in 230/1491 of cases (15.4%) where this information was recorded. Outcome and length of hospital stay: Intravenous administration of antivenom was associated with shorter length of hospital stay (median length of hospital stay in studies of intravenous ViperFAV or ViperaTAb ranged from 1 to 4.8 days versus 2 to 18 days for intramuscular Bulbio or Zagreb antivenoms). Antivenom versus no antivenom: Some small studies demonstrated no difference in the length of hospital stay in patients with equivalent envenomation grading who either did or did not receive antivenom. Adverse events: Adverse reactions were reported in 37 of 2408 cases (1.5%) including seven cases of anaphylaxis. There are very limited pre-clinical comparative data and no randomised controlled trials assessing effectiveness of the antivenoms against different Vipera species. Most descriptive data suggest the efficacy of Zagreb, ViperFAV and ViperaTAb antivenoms by the intravenous route but not intramuscular route, although this is level D evidence. Reported adverse reactions were rare, suggesting that the modern intravenous antivenoms are of good quality. Better and more systematic data, including perhaps randomized controlled trials comparing different antivenoms, are required for the many hundreds of antivenom administrations that occur annually across Europe.


Dietary sodium, erythrocyte sodium concentration, sodium-stimulated lithium efflux and blood pressure.
1. There was a significant positive relationship between sodium-stimulated lithium efflux and systolic blood pressure (r = 0.512) in erythrocytes of black school children. Weight was also positively and significantly correlated with blood pressure. Although erythrocyte sodium concentration did not bear any significant relationship with blood pressure, it did bear significant inverse relationship with urinary sodium excretion. 2. High-school students were randomly assigned to either the experimental or the control group. In the former a reduction of about 70% in salt intake was achieved. After 24 days, the erythrocyte sodium concentration was significantly reduced in the experimental group. A non-significant decline in systolic blood pressure was observed in the experimental group; no change was detectable in the control group for either erythrocyte sodium concentration or systolic blood pressure.


Imaging mass spectrometry.
Imaging mass spectrometry combines the chemical specificity and parallel detection of mass spectrometry with microscopic imaging capabilities. The ability to simultaneously obtain images from all analytes detected, from atomic to macromolecular ions, allows the analyst to probe the chemical organization of a sample and to correlate this with physical features. The sensitivity of the ionization step, sample preparation, the spatial resolution, and the speed of the technique are all important parameters that affect the type of information obtained. Recently, significant progress has been made in each of these steps for both secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) imaging of biological samples. Examples demonstrating localization of proteins in tumors, a reduction of lamellar phospholipids in the region binding two single celled organisms, and sub-cellular distributions of several biomolecules have all contributed to an increasing upsurge in interest in imaging mass spectrometry. Here we review many of the instrumental developments and methodological approaches responsible for this increased interest, compare and contrast the information provided by SIMS and MALDI imaging, and discuss future possibilities.


Thirty years of referrals to a community mental health service.
In recent decades mental health services have become increasingly community based and multidisciplinary. However, it is unclear if referrals have changed over this period. The aim of this study was to compare referrals to a community mental health service over a 30-year period. New referrals to a community mental health service were randomly sampled from 4 time points over a 30-year period, 1983, 1993, 2003 and 2013, using a mental health information system. Original referral letters were retrieved and anonymised. Referrals were compared with regard to referral sources, demographics, reason for referral, psychotherapy requests, urgency, risk concerns and subsequent hospital admission. There was a 20-fold increase in the number of new referrals between 1983 and 2013. Over the 30 years there was a significant decrease in the proportion of referrals expressing concern about psychosis, but an increase in the proportion that were deemed urgent and which were concerned with suicidal risk. Referrals in 2013 were longer and more likely to contain requests for psychotherapy. The work of community mental health teams is increasingly concerned with emotional crises. Although services are now more multidisciplinary, they have not been adequately resourced to meet these changing demands.


Open Dialogues in social networks: professional identity and transdisciplinary collaboration.
The aim of this article is to explore the challenges connected to the transformation and emergence of professional identity in transdisciplinary multi-agency network meetings and the use of Open Dialogue. The empirical findings have been taken from a clinical project in southern Norway concerning multi-agency network meetings with persons between 14 and 25 years of age. The project explores how these meetings are perceived by professionals working in various sectors. Data was collected through three interviews conducted with two focus groups, the first comprising health care professionals and the second professionals from the social and educational sectors. Content analysis was used to create categories through condensation and interpretation. The two main categories that emerged were 'professional role' and 'teamwork'. These were analysed and compared according to the two first meeting in the two focus groups. The results indicate different levels of motivation and understanding regarding role transformation processes. The realization of transdisciplinary collaboration is dependent upon the professionals' mutual reliance. The professionals' participation is affected by stereotypes and differences in their sense of belonging to a certain network, and thus their identity transformation seems to be strongly affected. To encourage the use of integrated solutions in mental health care, the professionals' preference for teamwork, the importance of familiarity with each other and knowledge of cultural barriers should be addressed.


Wheelchair interventions, services and provision for disabled children: a mixed-method systematic review and conceptual framework.
Wheelchairs for disabled children (≤ 18 years) can provide health, developmental and social benefits. World Health Organisation and United Kingdom Government reports demonstrate the need for improved access to wheelchairs both locally and internationally. The use of health economics within this field is lacking. Provision of wheelchairs based on cost-effectiveness evidence is not currently possible. We conducted the first systematic review in this field to incorporate evidence of effectiveness, service user perspectives, policy intentions and cost-effectiveness in order to develop a conceptual framework to inform future research and service development. We used an adapted EPPI-Centre mixed-method systematic review design with narrative summary, thematic and narrative synthesis. 11 databases were searched. Studies were appraised for quality using one of seven appropriate tools. A conceptual framework was developed from synthesised evidence. 22 studies and 14 policies/guidelines were included. Powered wheelchairs appear to offer benefits in reduced need for caregiver assistance; improved communicative, personal-social and cognitive development; and improved mobility function and independent movement. From 14 months of age children can learn some degree of powered wheelchair driving competence. However, effectiveness evidence was limited and low quality. Children and parents placed emphasis on improving social skill and independence. Participation in wider society and development of meaningful relationships were key desired outcomes. Policy intentions and aspirations are in line with the perspectives of children and parents, although translation of policy recommendations into practice is lacking. There is a distinct lack of high quality effectiveness and economic evidence in this field. Social and health needs should be seen as equally important when assessing the mobility needs of disabled children. Disabled children and parents placed highest priority on independence and psychosocial outcomes of wheelchair interventions. Translation of policy and guidelines into practice is lacking and more effective implementation strategies are required to improve services and outcomes. Future research should focus on outcome measure development, developing economic evaluation tools and incorporating these into high quality studies to address known research gaps. The novel conceptual framework maps current gaps in evidence and outlines areas for development.


Domesticating Cancer: An Evolutionary Strategy in the War on Cancer.
Since cancer shares the same molecular machinery as the host, most therapeutic interventions that aim to target cancer would inadvertently also adversely affect the host. In addition, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation suggests that the evolution of cancer, usually seen as a major clinical challenge, may also afford a key opportunity in lowering on-target toxicities accosted with chemotherapy. As an example, by subjecting cancer to specific selection regimes, cancer can in effect be placed on evolutionary trajectories leading to the development of "targetable" phenotypes such as synthetic lethal interactions. However, such a selection regime would have to overcome a range of obstacles such as on-target toxicity and the selection of an evolvable trait. Since the majority of cancer evolution manifests as a loss of function, we suggest that the induction of auxotrophic phenotypes (i.e., where an organism lose the ability to synthesize specific organic compounds required for growth and thus become dependent on it from dietary sources) may represent an attractive therapeutic option. As an example, animals can obtain vitamin C either by de novo synthesis or from their diet. However, since the maintenance of synthetic pathways is costly, such pathways are often lost if no longer necessary, resulting in the organism being auxotrophic toward the dietary compound. Similarly, increasing the maintenance cost of a redundant pathway in cancer cells is likely to select for clones that have lost such a redundant pathway. Inhibition of a pathway, while supporting the activity of a compensating pathway, may thus induce auxotrophism in cancer cells but not in genomic stable host cells.


Soybean protein hydrolysate improves plasma and liver lipid profiles in rats fed high-cholesterol diet.
This investigation attempted to clarify the hypolipidemic effects of non-dialyzed soybean protein hydrolysate (NSPH), which is hydrolyzed by pepsin from soybean acid-precipitated protein (APP), in rats fed a cholesterol-rich diet. Forty Sprague-Dawley rats were divided into four groups as the control group (19.7% casein), the APP group (14.7% casein + 5% APP), the NSPH group (14.7% casein + 5% NSPH), and the ISO group (19.7% casein + 0.0013% soy isoflavone). After 12-week experimental period, the APP and NSPH groups had a significant lower plasma total cholesterol, triglycerides, and LDL-cholesterol concentrations compared with the control group. Additionally, the atherosclerosis index in APP and NSPH group had also markedly decreased. Liver cholesterol and triglyceride contents of the APP and NSPH group were significantly lower than those of the control group. There were no different in plasma LDL-C, liver cholesterol and triglycerides between the ISO group and control group. Fecal excretion of neutral steroids and nitrogen compounds was significantly higher in the APP and NSPH groups than that in the control group. An in vitro study also showed that NSPH, compared with casein, obviously decreased cholesterol micellar solubility. These results suggested that NSPH may decrease lipid accumulation in the liver and have a hypolipidemic effect by enhancing excretion and inhibiting absorption of lipids.


Gyroxin and its biological activity: effects on CNS basement membranes and endothelium and protease-activated receptors.
Gyroxin is a glycoprotein isolated from rattlesnake venom, with known thrombin-like serine protease properties and behavioral action in the CNS. The mechanism of the latter has eluded experimenters for three decades. In this paper about the in vitro chick retina we demonstrate an excitotoxic CNS action of Gyroxin by observing retinal Intrinsic Optical Signals (IOS). These show sudden dynamic changes in the intact tissue due to gyroxin action. The very fast kinetics of this response precludes deep tissue penetration by the protein, a mechanism of tissue response described here for the first time. At nanomolar concentrations, Gyroxin alters profoundly the optical profiles of retinal spreading depression waves (RSDs), suggesting modulation of ionic transport and metabolism. This effect is reversible in contrast with the acute cell lysis induced with gyroxin pulses at higher concentration. Because there may be more than one target of Gyroxine at the retinal inner limiting membrane, additional biochemical assays were performed to study a possible Na/K-ATPase blockade and PAR receptor activation. We conclude that the Gyroxin interaction with basement membranes of CNS and endothelium triggers conformational phase transitions at basement membranes, with multiple functional consequences.


Supervisory attentional control following carbon monoxide poisoning.
This study tested the hypothesis that carbon monoxide poisoning would produce a deficit of attentional control, the supervisory attention system, as indexed by attention switching and attentional scheduling, and that routine attentional orienting would be unaffected. Seventy-three cases of carbon monoxide poisoning were assessed at 3 days and 1 month post poisoning on tasks of attentional orienting, and tasks of the supervisory attention system. The results were compared to a group of 53 healthy community participants. A deficit of the supervisory attentional system was documented on a task of attention switching in survivors of both deliberate and accidental CO poisoning, leaving attentional scheduling intact. There was no deficit of attentional orienting in the current study. Alteration of consciousness was found to predict subsequent supervisory attention system impairment in correlation analyses, and the deficit was persistent for a 1 month follow-up period.


Music as an auditory stimulus in stroke patients.
Auditory stimulation increases mean blood flow velocity (MBFV) in the middle cerebral artery (MCA) in healthy individuals. Our aim was to monitor such changes in the affected MCA of patients with acute ischemic stroke (AIS). The study included 66 non-thrombolysed patients with AIS who were divided into groups according to National Institutes of Health Stroke Scale (NIHSS) score. Group I consisted of patients with NIHSS score 10 and group II with NIHSS score > or =11. Affected MCA was insonated with transcranial Doppler (TCD). MCA MBFVs were monitored during listening to music for 30 minutes. The first response of MBFV increase was measured as time (Tmax) and percentage of amplitude change (Amax). Pearson Chi-Square test was used. In 78.85% of patients there was a significant increase in MBFV compared to baseline values as a reaction to the music. There was no significant difference in Tmax or Amax between the two groups. However, a trend of longer Tmax was observed with every 2 NIHSS score increase. Music is an auditory stimulus in stroke patients and can be measured with TCD as MCA MBFV increase. Although our study showed no significant change of reaction time with the severity of stroke, a trend of prolonged Tmax was observed with NIHSS score increase.


The changing pattern of Tinea capitis in Jamaica.
The species of dermatophyte fungi causing tinea capitis vary from country to country and may also change with time. This study was done to identify the predominant organisms causing tinea capitis in the Jamaican population. It was a retrospective study looking at all fungal culture requests to the Microbiology Department at the University Hospital of the West Indies during the period January 1, 1998 to December 31, 2002. The results showed a gradual switch from the dominance of Microsporum audouinii (61.5%) in 1998 to the dominance of Trichophyton tonsurans (85%) in 2002. The mean age was 8.6. Females constituted 55.7% of positive cases and males, 44.3%.


Differences in conformations of covalent adducts derived from the binding of 5- and 6-methylchrysene diol epoxide stereoisomers to DNA.
The conformations of adducts derived from the covalent binding of four different isomeric diol epoxide derivatives of 5- or 6-methylchrysene to native double-stranded calf thymus DNA were studied by linear dichroism techniques. Out of four isomers investigated here, only the R,S,S,R enantiomer of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene, (+)-5-MeCDE, is highly tumorigenic and mutagenic toward Salmonella typhimurium TA100; the S,R,R,S enantiomer, (-)-5-MeCDE, and the corresponding R,S,S,R and S,R,R,S enantiomers of anti-1,2,-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-methylchrysene are non-tumorigenic and much less mutagenic than (+)-5-MeCDE. [Melikian et al., (1988) Cancer Res., 48, 1781-1787] Only the DNA adducts derived from the binding of (+)-5-MeCDE are characterized by a pronounced positive linear dichroism signal at 308 nm due to the phenanthrenyl residue which is tilted at an angle of 45-48 degrees with respect to the average orientations of the axes of unoriented DNA segments. The phenanthrenyl residues derived from the covalent binding to DNA of the other three inactive or less active isomers appear to be unoriented. The defined orientation of the covalently bound phenanthrenyl residues derived from (+)-5-MeCDE corresponds to adduct conformations which are similar to those obtained from the binding of the highly tumorigenic trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene stereoisomer and other highly active bay-region diol epoxide derivatives to DNA. These findings provide further evidence that there is a correlation between DNA adduct conformation and biological activities for these series of polycyclic aromatic diol epoxide derivatives with R,S,S,R absolute configuration and which are known to bind predominantly to N2 of guanine.


In situ analysis of liposome hard and soft protein corona structure and composition in a single label-free workflow.
Methodological constraints have limited our ability to study protein corona formation, slowing nanomedicine development and their successful translation into the clinic. We determined hard and soft corona structural properties along with the corresponding proteomic compositions on liposomes in a label-free workflow: surface plasmon resonance and a custom biosensor for in situ structure determination on liposomes and corona separation, and proteomics using sensitive nanoliquid chromatography tandem mass spectrometry with open-source bioinformatics platforms. Undiluted human plasma under dynamic flow conditions was used for in vivo relevance. Proof-of-concept is presented with a regular liposome formulation and two light-triggered indocyanine green (ICG) liposome formulations in preclinical development. We observed formulation-dependent differences in corona structure (thickness, protein-to-lipid ratio, and surface mass density) and protein enrichment. Liposomal lipids induced the enrichment of stealth-mediating apolipoproteins in the hard coronas regardless of pegylation, and their preferential enrichment in the soft corona of the pegylated liposome formulation with ICG was observed. This suggests that the soft corona of loosely interacting proteins contributes to the stealth properties as a component of the biological identity modulated by nanomaterial surface properties. The workflow addresses significant methodological gaps in biocorona research by providing truly complementary hard and soft corona compositions with corresponding in situ structural parameters for the first time. It has been designed into a convenient and easily reproducible single-experiment format suited for preclinical development of lipid nanomedicines.


Involvement of the sensorimotor cortex in physiological force and action tremor.
Whole scalp magnetoencephalography (MEG) signals were recorded in 10 healthy subjects simultaneously with the surface electromyogram (EMG) of the contralateral forearm extensor muscles during isometric contraction and phasic movement of the wrist. In eight subjects, coherence and time domain analyses demonstrated correspondence between the MEG signal, originating near or in the hand region of the motor cortex, and the 6-12 Hz EMG recorded during isometric postural contractions. In contrast, we found little evidence for correspondence between the contralateral EMG and the MEG recorded over the Rolandic region during phasic movements. We conclude that the sensorimotor cortex is differentially involved in physiological force and action tremor at the wrist.


Detection of long repeat expansions from PCR-free whole-genome sequence data.
Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.


Theoretical study for safe and efficient energy transfer to deeply implanted devices using ultrasound.
The goal of this paper is to prove that a safe and efficient energy transfer is possible between an external transducer located on the patient's skin and a device deeply implanted in the abdomen. An ultrasound propagation model based on the Rayleigh-Sommerfeld diffraction integral is coupled with the data from the Visible Human Project to account for the geometry of the organs in the body. The model is able to predict the amount of acoustic power received by the device for different acoustic paths. The acoustic model is validated by comparison with measurements in water and in heterogeneous liquid phantoms. Care is taken to minimize adverse bioeffects-mainly temperature rise and cavitation in tissues. Simulations based on the bio-heat transfer equation are performed to check that thermal effects are indeed small.


Improved in vitro development of cloned bovine embryos using S-adenosylhomocysteine, a non-toxic epigenetic modifying reagent.
In this study, fibroblast cells were stably transfected with mouse POU5F1 promoter-driven enhanced green fluorescent protein (EGFP) to investigate the effect of S-adenosylhomocysteine (SAH), the reversible non-toxic inhibitor of DNA-methyltransferases (DNMTs), at different intervals post-fusion on in vitro development of cloned bovine embryos. Treatment with SAH for 12 hr resulted in 54.6 ± 7.7% blastocyst production, which was significantly greater than in vitro fertilized embryos (IVF: 37.2 ± 2.7%), cloned embryos treated with SAH for 72 hr (31.0 ± 7.6%), and control cloned embryos (34.6 ± 3.6%). The fluorescence intensities of the EGFP-POU5F1 reporter gene at all intervals of SAH treatment, except of 72 hr, were significantly higher than control somatic cell nuclear transfers (SCNT) embryos. The intensity of DNA-methylation in cloned embryos treated with SAH for 48 hr was similar to that of IVF embryos, and was significantly lower than the other SCNT groups. The levels of H3K9 acetylation in all SCNT groups were significantly lower than IVF embryos. Real-time PCR analysis of gene expression revealed significantly higher expression of POU5F1 in cloned versus IVF blastocysts. Neither embryo production method (SCNT vs. IVF) nor the SAH treatment interval affected expression of the BCL2 gene. Cloned embryos at all intervals of SAH treatment, except for 24 hr, had significantly increased VEGF transcript compared to IVF and control SCNT embryos. It was suggested that the time interval of DNMT inhibition may have important consequences on different in vitro features of bovine SCNT, and the improving effects of DNMT inhibition on developmental competency of cloned embryos are restricted to a specific period of time preceding de novo methylation.


Finding regulatory DNA motifs using alignment-free evolutionary conservation information.
As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery make use of global or local alignments of orthologous regulatory regions to assess whether a particular DNA site is conserved across related organisms, and thus more likely to be functional. Since binding sites are usually short, sometimes degenerate, and often independent of orientation, alignment algorithms may not align them correctly. Here, we present a novel, alignment-free approach for using conservation information for TF binding site discovery. We relax the definition of conserved sites: we consider a DNA site within a regulatory region to be conserved in an orthologous sequence if it occurs anywhere in that sequence, irrespective of orientation. We use this definition to derive informative priors over DNA sequence positions, and incorporate these priors into a Gibbs sampling algorithm for motif discovery. Our approach is simple and fast. It requires neither sequence alignments nor the phylogenetic relationships between the orthologous sequences, yet it is more effective on real biological data than methods that do.


Histamine-induced intracellular free Ca++, inositol phosphates and electrical changes in murine N1E-115 neuroblastoma cells.
Apparent intracellular free Ca++ concentration [(Ca++]i) was measured in differentiated N1E-115 neuroblastoma by microinjecting cells with aequorin (estimated intracellular concentration, 4 microM) and measuring light emission. Histamine produced a transient, dose-dependent increase in [Ca++]i. Pyrilamine blocked completely the response to histamine whereas cimetidine had no effect. Omitting Ca++ from the external medium reversibly blocked the response. As well as a rise in [Ca++]i, histamine caused a concomitant cell hyperpolarization that was not blocked by ouabain, low Cl-, tetraethylammonium chloride/tetradotoxin or metiamide but was blocked by apamin and pyrilamine. A secondary small depolarization caused by histamine was also blocked by apamin but not by ouabain, low Cl- or tetraethylammonium chloride/tetrodotoxin. Direct iontophoretic injection of Ca++ into cells caused only hyperpolarization. Injection of inositol 1,4,5-trisphosphate [IP3(1,4,5)] caused an increase in [Ca++]i and rapid hyperpolarization. Inositol 1,3,4-trisphosphate [IP3(1,3,4)] caused an increase in [Ca++]i, rapid hyperpolarization and a slower depolarization. Repeated injections of IP3(1,3,4) led to a diminished [Ca++]i response and decreased hyperpolarization but had no effect on depolarization. Inositol 1,3,4,5-tetrakisphosphate was without effect on [Ca++]i or on cellular membrane potential. The results suggest that histamine causes an H1 receptor-dependent increase in [Ca++]i, probably by the increased entry of extracellular Ca++, although there may be a contribution from intracellular Ca++ released by IP3(1,4,5). The increase in [Ca++]i activates K+ channels leading to cell hyperpolarization. IP3(1,3,4) formed from inositol 1,3,4,5-tetrakisphosphate, which is itself a product of IP3(1,4,5), causes a slower depolarization by a mechanism that does not involve Na+ channels or an increase in [Ca++]i.


Elbow Injuries Among MLB Pitchers Increased During Covid-19 Disrupted Season, But Not Other Baseball Injuries.
The 2020 Major League Baseball Season (MLB) demonstrated season disruptions due to the COVID-19 pandemic. Changes in training and seasonal time frames may be associated with higher rates of injury. To use publicly available data to compare injury rates during the 2015-2019 seasons, COVID-19 shortened season (2020), and the 2021 season stratified by body region and position (pitchers versus position players). A retrospective cohort study utilizing publicly available data. MLB players who competed in 1+ seasons between 2015-2021 were included and stratified by position (pitcher, position player). Incidence rate (IR), reported by 1000 x Athlete-Game Exposures (AGEs), was calculated for each season, and stratified by position and body region. Poisson regressions were performed for all injuries and stratified by position to determine association between season and injury incidence. Subgroup analyses were performed on the elbow, groin/hip/thigh, shoulder. Four thousand, two hundred and seventy-four injuries and 796,502 AGEs across 15,152 players were documented. Overall IR was similar across seasons (2015-2019:5.39; 2020:5.85; 2021:5.04 per 1000 AGEs). IR remained high for the groin/hip/thigh for position players (2015-2019:1.7; 2020:2.0; 2021:1.7 per 1000 AGEs). There was no difference in injury rates between 2015-2019 and 2020 seasons [1.1 (0.9-1.2), p=0.310]. The 2020 season demonstrated a significant increase in elbow injuries [2.7 (1.8-4.0), p<0.001]; when stratified by position, this increase remained significant for pitchers [pitchers: 3.5 (2.1-5.9), p<0.001; position players: 1.8 (0.9-3.6), p=0.073]. No other differences were observed. The groin/hip/thigh demonstrated the highest IR in 2020 among position players across all season time frames, indicating that continued injury mitigation for this region is necessary. When stratified by body region, elbow injury rates among pitchers demonstrated 3.5 times the rate of injury in 2020 compared to previous seasons, impacting injury burden for the most vulnerable body region among pitchers. Level III.


Ovarian serous adenocarcinoma identified during IVF: diagnostic approach, surgical management, and reproductive outcome.
To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF) sequence, and report on reproductive outcome after tumour resection and embryo transfer. Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well. Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here.


Assessment of local public health workers' willingness to respond to pandemic influenza through application of the extended parallel process model.
Local public health agencies play a central role in response to an influenza pandemic, and understanding the willingness of their employees to report to work is therefore a critically relevant concern for pandemic influenza planning efforts. Witte's Extended Parallel Process Model (EPPM) has been found useful for understanding adaptive behavior in the face of unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among local public health workers. We thus aim to use the EPPM as a lens for examining the influences of perceived threat and efficacy on local public health workers' response willingness to pandemic influenza. We administered an online, EPPM-based survey about attitudes/beliefs toward emergency response (Johns Hopkins approximately Public Health Infrastructure Response Survey Tool), to local public health employees in three states between November 2006-December 2007. A total of 1835 responses were collected for an overall response rate of 83%. With some regional variation, overall 16% of the workers in 2006-7 were not willing to "respond to a pandemic flu emergency regardless of its severity". Local health department employees with a perception of high threat and high efficacy--i.e., those fitting a 'concerned and confident' profile in the EPPM analysis--had the highest declared rates of willingness to respond to an influenza pandemic if required by their agency, which was 31.7 times higher than those fitting a 'low threat/low efficacy' EPPM profile. In the context of pandemic influenza planning, the EPPM provides a useful framework to inform nuanced understanding of baseline levels of--and gaps in--local public health workers' response willingness. Within local health departments, 'concerned and confident' employees are most likely to be willing to respond. This finding may allow public health agencies to design, implement, and evaluate training programs focused on emergency response attitudes in health departments.


Can preoperative imaging help to predict postoperative outcome after wisdom tooth removal? A randomized controlled trial using panoramic radiography versus cone-beam CT.
The primary objective of the study was to compare the postoperative complications following surgical removal of impacted third molars using panoramic radiography (PAN) images- and cone-beam computed tomography (CBCT)-based surgeries for "moderate-risk" cases of impacted third mandibular molars. The secondary objective was to compare the reliability of CBCT with that of PAN in preoperative radiographic determination of the position of the third molar, number of roots, and apical divergence. A randomized controlled multicenter trial was conducted to compare the surgical complications of PAN- and CBCT-based surgeries of impacted third molars. The sample consisted of impacted third molars from 256 patients with a close relation to the inferior alveolar nerve (IAN). Exclusion criteria were "no risk" and "high risk" of damage to the IAN based on the assessment of the panoramic radiograph. Patients were divided into two groups: the CBCT group (n = 126) and the PAN group (n = 130). The incidences of IAN sensory disturbance and other postoperative complications were recorded for each group at 7 days after surgery. Statistical analysis (kappa values) was used to compare the diagnoses of five trained dentomaxillofacial radiologists and to relate radiologic diagnoses to perioperative findings. Logistic regression was used to determine whether the imaging modality influenced occurrence of postoperative complications. Two extractions (1.5%) in the CBCT group and five (3.8%) in the PAN group resulted in IAN sensory disturbance (p = 0.45). Logistic regression models did not show that CBCT modality decreased postoperative complications following surgical removal of impacted third molars. Yet, CBCT revealed the number of roots and apical divergence of the roots more reliably than panoramic radiographs. CBCT was not better than panoramic radiography in predicting postoperative complications for moderate-risk cases of impacted third mandibular molars. Nonetheless, a CBCT buccolingual view can accurately confirm the number of roots and root morphology of the third molar better than PAN. For management of postoperative complications for moderate-risk cases of impacted mandibular third molars, careful preoperative radiographic planning followed by an atraumatic surgical approach seems to be valuable, irrespective of the 2D or 3D nature of the preoperative images.


Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer.
The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30-40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP‑2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation.


Demographic and reproductive plasticity across the depth distribution of a coral reef fish.
As humans expand into natural environments, populations of wild organisms may become relegated to marginal habitats at the boundaries of their distributions. In the ocean, mesophotic coral ecosystems (30-150 m) at the depth limit of photosynthetic reefs are hypothesized to act as refuges that are buffered from anthropogenic and natural disturbances, yet the viability and persistence of subpopulations in these peripheral habitats remains poorly understood. To assess the potential for mesophotic reefs to support robust coral reef fish populations, we compared population density and structure, growth, size, and reproductive output of the bicolor damselfish (Stegastes partitus) from shallow (<10 m), deep shelf (20-30 m), and mesophotic reefs (60-70 m) across the Florida Platform. Population densities decreased and size and age distributions shifted toward older and larger individuals in deeper habitats. Otolith-derived ages indicated that S. partitus found on mesophotic reefs reach larger asymptotic sizes and have longer lifespans than fish in shallower habitats. Based on measurements of oocyte area and batch fecundity, mesophotic fish also have higher reproductive investment. These demographic patterns indicate that mesophotic fish populations composed of large, fecund individuals produce high condition larvae and rely on longevity of individuals for population persistence and viability.


T-cell-mediated cytotoxic immune responses to F9 teratocarcinoma cells: cytolytic effector T cells lyse H-2-negative F9 cells and syngeneic spermatogonia.
Murine thymus derived (T) lymphocytes primed in vivo to mouse 129 (H-2bc) derived H-2-negative F9 embryonal carcinoma cells and rechallenged in vitro with X-irradiated F9 stimulator cells differentiated into anti-F9 cell immune cytotoxic T lymphocytes (CTL). Using CBA mouse derived splenic responder T cells, F9 stimulator cells triggered a primary cytotoxic anti-F9 response. The CTL generated lysed the F9 antigen-positive target cells F9. PCC3 and PCC4, but not the F9 antigen-negative mouse 129 derived PYS tumor cells, nor LPS induced H-2bc blast cells. Mouse 129 anti-F9 cell antisera but not H-2k anti-H-2bc antisera blocked the lytic interaction with F9 target cells. Similarily unlabeled F9 cells but not H-2bc blast cells inhibited the anti-F9 cell cytotoxicity H-2k anti-F9 cell immune CTL were found to be cytotoxic for syngeneic spermatogonia, known to express the F9 antigen. The results suggest not only that CTL can recognize and lyse H-2-negative target cells, but also that CTL precursors can be sensitized against H-2-negative stimulator cells. From the data available it may be inferred that anti-F9 Cell immune CTL recognize the F9 antigen, known to be linked with the T/t locus. Since anti-F9 cell immune CTL lyse syngeneic spermatogonia, the system may be useful to analyze in vitro the induction and effector phase of a T-cell-mediated cytotoxic autoimmune orchitis.


Global priority areas for ecosystem restoration.
Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity1 and stabilizing the climate of the Earth2. Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO2-30% of the total CO2 increase in the atmosphere since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically.


Avian influenza (H5N1): implications for intensive care.
As influenza A/H5N1 spreads around the globe the risk of an epidemic increases. Review of the cases of influenza A/H5N1 reported to date demonstrates that it causes a severe illness, with a high proportion of patients (63%) requiring advanced organ support. Of these approx. 68% develop multiorgan failure, at least 54% develop acute respiratory distress syndrome, and 90% die. Disease progression is rapid, with a median time from presentation to hospital to requirement for advanced organ support of only 2 days. The infectious nature, severity and clinical manifestations of the disease and its potential for pandemic spread have considerable implications for intensive care in terms of infection control, patient management, staff morale and intensive care expansion.


Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.
Functional nuclei and mitotic spindles are shown to assemble around DNA-coated beads incubated in Xenopus egg extracts. Bipolar spindles assemble in the absence of centrosomes and kinetochores, indicating that bipolarity is an intrinsic property of microtubules assembling around chromatin in a mitotic cytoplasm. Microtubules nucleated at dispersed sites with random polarity rearrange into two arrays of uniform polarity. Spindle-pole formation requires cytoplasmic dynein-dependent translocation of microtubules across one another. It is proposed that spindles form in the absence of centrosomes by motor-dependent sorting of microtubules according to their polarity.


Axiomatic scalable neurocontroller analysis via the Shapley value.
One of the major challenges in the field of neurally driven evolved autonomous agents is deciphering the neural mechanisms underlying their behavior. Aiming at this goal, we have developed the multi-perturbation Shapley value analysis (MSA)--the first axiomatic and rigorous method for deducing causal function localization from multiple-perturbation data, substantially improving on earlier approaches. Based on fundamental concepts from game theory, the MSA provides a formal way of defining and quantifying the contributions of network elements, as well as the functional interactions between them. The previously presented versions of the MSA require full knowledge (or at least an approximation) of the network's performance under all possible multiple perturbations, limiting their applicability to systems with a small number of elements. This article focuses on presenting new scalable MSA variants, allowing for the analysis of large complex networks in an efficient manner, including large-scale neurocontrollers. The successful operation of the MSA along with the new variants is demonstrated in the analysis of several neurocontrollers solving a food foraging task, consisting of up to 100 neural elements.


Substitution of alcohols by N-nucleophiles via transition metal-catalyzed dehydrogenation.
Transition metal-catalyzed substitution of alcohols by N-nucleophiles (or N-alkylation of amines and related compounds with alcohols) avoids the use of alkylating agents by means of borrowing hydrogen (BH) activation of the alcohol substrates. Water is produced as the only by-product, which makes the "BH" processes atom-economic and environmentally benign. Diverse types of homogeneous organometallic and heterogeneous transition metal catalysts, and substrates such as N-nucleophiles including amines, amides, sulfonamides and ammonia, and various alcohols, can be used for this purpose, demonstrating the promising potential of "BH" processes to replace the procedures using traditional alkylating agents in pharmaceutical and chemical industries. Borrowing hydrogen activation of alcohols for C-N bond formation has recently been paid more and more attention, and a lot of new and novel procedures and examples have been documented. This critical review summarizes the recent advances in "BH" substitution of alcohols by N-nucleophiles since 2009. "Semi-BH" N-alkylation processes with or without an external hydrogen acceptor are also briefly presented. Suitable discussion of the "BH" strategy provides new principles for establishing green processes to replace the relevant traditional synthetic methods for C-N bond formation.


The effect of green tea in oxidative stress.
Green tea, an infusion prepared with the leaves of Camellia sinensis is particularly rich in flavonoids, which are strong antioxidants. Tea drinking, by providing antioxidants, may become valuable in several oxidative stress conditions. Our aim was to evaluate the effect of green tea drinking on some factors reflecting the development of oxidative stress in plasma and in erythrocytes. The study was performed in 34 Portuguese subjects. We evaluated the total antioxidant status (TAS), the lipid peroxidation products-malonyldialdehyde (MDA) and malonyldialdehyde+4-hydroxy-2(E)-nonenal (MDA+4-HNE)-and the oxidative changes in erythrocyte membrane, namely membrane bound haemoglobin (MBH) and the band 3 profile. Analytical evaluations were performed after 3 weeks drinking 1l of water daily, and after 4 weeks drinking 1l of green tea daily. Tea was prepared daily at the same conditions of temperature, time of infusion and concentration. After green tea drinking, we found a significant reduction in serum levels of MDA and MDA+4-HNE and in the oxidative stress within the erythrocyte, as suggested by a significantly lower value of MBH and by changes in band 3 profile towards a normal mean profile, namely an increase in the band 3 monomer. A rise in the antioxidant capacity was also observed. Our data suggest for green tea drinking a beneficial effect, by reducing the development or the enhancement of oxidative stress and, therefore, protecting the individual for oxidative stress diseases. Moreover, we propose further studies about the value of band 3 profile and of MBH in providing a cumulative measurement of the effect of green tea drinking upon the oxidative stress in cells. Moreover, further studies are also needed, to clarify the effect of green tea consumption, the value of regular green tea consumption and the way it should be prepared to reach a healthy effect.


Effects of Nocturnal Sleep Quality on Diurnal Cortisol Profiles and Attention in Nurses: A Cross-Sectional Study.
Low sleep quality (LSQ) activates the hypothalamic-pituitary-adrenal (HPA) axis and is related to arousal. Nursing staff, who work in shifts, tend to exhibit LSQ, which affects the level of vigor after awakening. This study investigated the effects of nocturnal sleep quality on diurnal cortisol profiles and sustained attention in day-shift nurses. This study adopted a prospective cross-sectional design. Participants were recruited from a university-affiliated hospital in northern Taiwan. In the initial stage of this study, the Chinese Pittsburgh Sleep Quality Index (PSQI) Questionnaire was administered to 199 participants to categorize them as either LSQ (PSQI > 5) or high sleep quality (HSQ; PSQI ≤ 5). Participants were then randomly sampled from the two groups. Nocturnal sleep data and four diurnal saliva samples were collected for each participant. Sustained attention was measured before they started work. A total of 32 and 29 participants in the HSQ and LSQ groups, respectively, completed the data collection process. Compared with the HSQ group, the LSQ group exhibited earlier wake-up times (p = .02), a flatter cortisol awakening response (CAR) slope (p < .01), a flatter morning-to-evening slope (p < .01), and prolonged reaction speed and mean reaction time before starting work (p < .01). Compared with the HSQ group, the LSQ group exhibited impaired HPA-axis regulation, with a flatter CAR and diurnal cortisol slope and poor sustained attention in the morning. Nursing staff are advised to achieve HSQ to improve attention and performance levels and maintain optimum work safety.


All-polyethylene compared with metal-backed tibial components in total knee arthroplasty at ten years. A prospective, randomized controlled trial.
Several studies have described equivalent performance on radiostereometric analysis at two years for metal-backed compared with all-polyethylene stemmed tibial implants. The purpose of this study was to determine the ten-year survivorship results of these two designs from a large randomized controlled trial. Patients who were fifty years old or more, with no history of infection, and were undergoing primary total knee arthroplasty were randomized at the time of surgery to receive either an all-polyethylene or a metal-backed tibial component. Patients were assessed preoperatively and at one, three, five, eight, and ten years postoperatively. All assessments included a clinical history, a physical examination, and a radiographic evaluation. A total of 510 consecutive patients (566 knees) were recruited from August 1993 to January 1997. The mean age of the patients at the time of the index arthroplasty was 69.3 years, and 299 (59%) were women. The primary diagnosis was osteoarthritis for 458 knees (80.9%) and rheumatoid arthritis for 108 knees (19.1%). Two hundred and ninety-three patients returned for the ten-year follow-up evaluation. A total of twenty-eight knees had been revised. Ten-year survivorship, with revision for any reason (or the time at which patients were documented as requiring revision but were unfit for surgery) as the end point, was 94.5% (95% confidence interval, 90.4% to 96.8%) for the all-polyethylene design and 96% (95% confidence interval, 92.6% to 97.8%) for the metal-backed design. Ten-year survivorship, with aseptic failure as the end point, was 97% (95% confidence interval, 93.3% to 98.7%) for the all-polyethylene design and 96.8% (95% confidence interval, 93.6% to 98.4%) for the metal-backed design. On the basis of the numbers available at ten years, there was no significant difference in survivorship between the two designs (p > 0.05). The long-term results demonstrate excellent survivorship, with revision as the end point, for both the metal-backed and the all-polyethylene tibial component designs with no differences noted between the two.


Injury Risk Factors in a Small-Scale Gold Mining Community in Ghana's Upper East Region.
Occupational injury is one of many health concerns related to small-scale gold mining (ASGM), but few data exist on the subject, especially in sub-Saharan Africa. In 2011 and 2013, we examined accidents, injuries, and potential risk factors in a Ghanaian ASGM community. In 2011, 173 participants were surveyed on occupational history and health, and 22 of these were surveyed again in 2013. Injury rates were estimated at 45.5 and 38.5 injuries per 100 person-years in 2011 and in 2013, respectively; these rates far surpass those of industrialized mines in the U.S. and South Africa. Demographic and job characteristics generally were not predictive of injury risk, though there was a significant positive association with injury risk for males and smokers. Legs and knees were the most common body parts injured, and falling was the most common cause of injury. The most common type of injuries were cuts or lacerations, burns and scalds, and contusions and abrasions. Only two miners had ever received any occupational safety training, and PPE use was low. Our results suggest that injuries should be a priority area for occupational health research in ASGM.


Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.
The nature and identity of the pancreatic beta-cell precursor has remained elusive for many years. One model envisions an early multihormonal precursor that gives rise to both alpha- and beta-cells and the other endocrine cell types. Alternatively, beta-cells have been suggested to arise late, directly from the GLUT2- and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. In this study, we have identified a subset of the PDX1+ epithelial cells that are marked by expression of Neurogenin3 (Ngn3). Ngn3, a member of the basic helix-loop-helix (bHLH) family of transcription factors, is suggested to act upstream of NeuroD in a bHLH cascade. Detailed analysis of Ngn3/paired box factor 6 (PAX6) and NeuroD/PAX6 co-expression shows that the two bHLH factors are expressed in a largely nonoverlapping set of cells, but such analysis also suggests that the NeuroD+ cells arise from cells expressing Ngn3 transiently. NeuroD+ cells do not express Ki-67, a marker of proliferating cells, which shows that these cells are postmitotic. In contrast, Ki-67 is readily detected in Ngn3+ cells. Thus, Ngn3+ cells fulfill the criteria for an endocrine precursor cell. These expression patterns support the notion that both alpha- and beta-cells develop independently from PDX1+/Ngn3+ epithelial cells, rather than from GLU+/INS+ intermediate stages. The earliest sign of alpha-cell development appears to be Brain4 expression, which apparently precedes Islet-1 (ISL1) expression. Based on our expression analysis, we propose a temporal sequence of gene activation and inactivation for developing alpha- and beta-cells beginning with activation of NeuroD expression. Endocrine cells leave the cell cycle before NeuroD activation, but re-enter the cell cycle at perinatal stages. Dynamic expression of Notch1 in PDX+ epithelial cells suggests that Notch signaling could inhibit a Ngn-NeuroD cascade as seen in the nervous system and thus prevent premature differentiation of endocrine cells.


Drd4 gene polymorphisms are associated with personality variation in a passerine bird.
Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, genotype-environment interactions and confounding environmental factors all act to obscure genotype-personality relationships. Such problems can be addressed by measuring personality under standardized conditions and by selection experiments, with both approaches only feasible with non-human animals. Looking for similar Drd4 genotype-personality associations in a free-living bird, the great tit (Parus major), we detected 73 polymorphisms (66 SNPs, 7 indels) in the P. major Drd4 orthologue. Two of the P. major Drd4 gene polymorphisms were investigated for evidence of association with novelty-seeking behaviour: a coding region synonymous single nucleotide polymorphism (SNP830) and a 15bp indel (ID15) located 5' to the putative transcription initiation site. Frequencies of the three Drd4 SNP830 genotypes, but not the ID15 genotypes, differed significantly between two P. major lines selected over four generations for divergent levels of 'early exploratory behaviour' (EEB). Strong corroborating evidence for the significance of this finding comes from the analysis of free-living, unselected birds where we found a significant association between SNP830 genotypes and differing mean EEB levels. These findings suggest that an association between Drd4 gene polymorphisms and animal personality variation predates the divergence of the avian and mammalian lineages. Furthermore, this work heralds the possibility of following microevolutionary changes in frequencies of behaviourally relevant Drd4 polymorphisms within populations where natural selection acts differentially on different personality types.


Temperature-dependent inulin nanoparticles synthesized by Lactobacillus reuteri 121 inulosucrase and complex formation with flavonoids.
Inulin nanoparticles (INNPs) are a biocompatible material which has a potential application for enhancing solubility and preventing degradation of compounds. In this work, we demonstrated that INNPs could be synthesized from sucrose using inulosucrase from Lactobacillus reuteri 121. Noticeably, dynamic light scattering (DLS) analysis showed that the derived INNPs exhibited uniformity in size, which was easily controlled by the reaction temperature. The effect of enzyme and sucrose concentration, as well as reaction time, was explored. Moreover, the solubility of INNPs in various organic solvents was also investigated, and we found that the INNPs were freely regenerated in water even though they had precipitated by organic solvents. Essentially, we demonstrated that the derived INNPs could be applied for flavonoid encapsulation. The solubility and stability of quercetin and fisetin in the INNPs complexes was higher than those of free compounds. These results make the INNPs very promising for many applications.


Reward circuitry activation by noxious thermal stimuli.
Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.


Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.
Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. Depression scores after treatment and adverse effects. Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity. Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.


Epidemic thresholds in dynamic contact networks.
The reproductive ratio, R0, is a fundamental quantity in epidemiology, which determines the initial increase in an infectious disease in a susceptible host population. In most epidemic models, there is a specific value of R0, the epidemic threshold, above which epidemics are possible, but below which epidemics cannot occur. As the complexity of an epidemic model increases, so too does the difficulty of calculating epidemic thresholds. Here we derive the reproductive ratio and epidemic thresholds for susceptible-infected-recovered (SIR) epidemics in a simple class of dynamic random networks. As in most epidemiological models, R0 depends on two basic epidemic parameters, the transmission and recovery rates. We find that R0 also depends on social parameters, namely the degree distribution that describes heterogeneity in the numbers of concurrent contacts and the mixing parameter that gives the rate at which contacts are initiated and terminated. We show that social mixing fundamentally changes the epidemiological landscape and, consequently, that static network approximations of dynamic networks can be inadequate.


ViPR: an open bioinformatics database and analysis resource for virology research.
The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal 'Workbenches' for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.


Radiation-induced eye lens changes and risk for cataract in interventional cardiology.
Recent studies have reported a significant increase in eye lens opacities among staff in the cardiac catheterization laboratory but indicated further studies are needed to confirm the findings. To evaluate the prevalence of opacities in eyes of cardiologists, radiographers and nurses working in interventional cardiology. The eyes of 52 staff in interventional cardiology facilities and 34 age- and sex-matched unexposed controls were screened in a cardiology conference held in Kuala Lumpur by dilated slit-lamp examination, and posterior lens changes were graded. Individual cumulative lens X-ray exposures were calculated from responses to a questionnaire in terms of workload and working practice. The prevalence of posterior lens opacities among interventional cardiologists was 53%, while in nurses and radiographers it was 45%. Corresponding relative risks were 2.6 (95% CI: 1.2-5.4) and 2.2 (95% CI: 0.98-4.9), for interventional cardiologists and support staff, respectively. This study confirms a statistically significant increase in radiation-associated posterior lens changes in the eyes of interventional cardiology staff.


New carotenoid values for foods improve relationship of food frequency questionnaire intake estimates to plasma values.
Carotenoid consumption is of great interest in disease prevention studies. Until recently, carotenoid food composition data have not been available from a single laboratory source with high validity/reliability characteristics. With the availability of a new carotenoid food composition data base, we examined the impact of the new data base on the intake estimates as measured by a food frequency questionnaire and on the relationship of those estimates to plasma values to ascertain what, if any, improvement is achieved through use of the new values. Plasma samples were available for 162 healthy adults participating in cancer prevention studies at the Arizona Cancer Center, including men and women, smokers and nonsmokers. A single laboratory analyzed plasma samples for beta-carotene, alpha-carotene, lutein, and lycopene. All subjects had completed a modified version of the Block food frequency questionnaire, which calculates carotenoids using a literature-based algorithm. A new carotenoid composition data base using recently published data (A.R. Mangels et al., J. Am. Diet. Assoc., 93: 284-296, 1993) was then directly substituted for the Block data base. There were high correlations between intake estimates derived from the two data bases for all four carotenoids (range, r = 0.76-0.96). Average intake estimates based on the Mangels et al. data base were significantly higher for beta-carotene and lycopene; however, correlations between intakes and plasma values were significantly different only for beta-carotene (r = 0.44 for Mangels versus 0.32 for Block, P = 0.015).


Normative study of theme identifiability: Instructions with and without explanation of the false memory effect.
False-memory illusions have been widely studied using the Deese/Roediger-McDermott paradigm (DRM). In this paradigm, words semantically related to a single nonpresented critical word are studied. In a later memory test, critical words are often falsely recalled and recognized. The present normative study was conducted to measure the theme identifiability of 60 associative word lists in Spanish that include six words (e.g., stove, coat, blanket, scarf, chill, and bonnet) that are simultaneously associated with three critical words (e.g., HEAT, COLD, and WINTER; Beato & Díez, Psicothema, 26, 457-463, 2011). Different levels of backward associative strength were used in the construction of the DRM lists. In addition, we used two types of instructions to obtain theme identifiability. In the without-explanation condition, traditional instructions were used, requesting participants to write the theme list. In the with-explanation condition, the false-memory effect and how the lists were built were explained, and an example of a DRM list and critical words was shown. Participants then had to discover the critical words. The results showed that all lists produced theme identifiability. Moreover, some lists had a higher theme identifiability rate (e.g., 61 % for the critical words LOVE, BOYFRIEND, COUPLE) than others (e.g., 24 % for CITY, PLACE, VILLAGE). After comparing the theme identifiabilities in the different conditions, the results indicated higher theme identifiability when the false-memory effect was explained than without such an explanation. Overall, these new normative data provide a useful tool for those experiments that, for example, aim to analyze the wide differences observed in false memory with DRM lists and the role of theme identifiability.


Sensitivity and specificity of 2010 rheumatoid arthritis classification criteria.
To validate the sensitivity and specificity of the 2010 RA classification criteria. A total of 313 undiagnosed subjects, who first visited Keio University Hospital with joint symptoms, including arthralgia, joint swelling and morning stiffness, without any previous treatment except for NSAIDs, were included in the present study. A clinical diagnosis of RA was made by rheumatologists, and the gold standard diagnosis of RA was defined as an indication for instituting DMARDs for RA. Seventy-six subjects were diagnosed as gold standard RA. Among these, 8 did not have any swollen joints, 50 were classified as definite RA under the 2010 criteria and the other 18 as not having RA. Eighty-two subjects were eligible for the 2010 criteria, and the sensitivity and specificity under the 2010 criteria were 73.5 and 71.4%, respectively, compared with 47.1 and 92.9% under the 1987 criteria. But the sensitivity of the 2010 criteria decreased to 15.8% when both RF and anti-CCP were negative. According to the result of a receiver-operated characteristic (ROC) curve of the scoring system, if swollen joints and differential diagnosis are not accurately detected, it would be better to use a score of 5 as the cut-off level to detect RA. The 2010 classification criteria have a high sensitivity and have been verified to be useful for distinguishing RA at an early stage.


First do no harm: practitioners' ability to 'diagnose' system weaknesses and improve safety is a critical initial step in improving care quality.
Healthcare systems across the world and especially those in low-resource settings (LRS) are under pressure and one of the first priorities must be to prevent any harm done while trying to deliver care. Health care workers, especially department leaders, need the diagnostic abilities to identify local safety concerns and design actions that benefit their patients. We draw on concepts from the safety sciences that are less well-known than mainstream quality improvement techniques in LRS. We use these to illustrate how to analyse the complex interactions between resources and tools, the organisation of tasks and the norms that may govern behaviours, together with the strengths and vulnerabilities of systems. All interact to influence care and outcomes. To employ these techniques leaders will need to focus on the best attainable standards of care, build trust and shift away from the blame culture that undermines improvement. Health worker education should include development of the technical and relational skills needed to perform these system diagnostic roles. Some safety challenges need leadership from professional associations to provide important resources, peer support and mentorship to sustain safety work.


Learning feedback and feedforward control in a mirror-reversed visual environment.
When we learn a novel task, the motor system needs to acquire both feedforward and feedback control. Currently, little is known about how the learning of these two mechanisms relate to each other. In the present study, we tested whether feedforward and feedback control need to be learned separately, or whether they are learned as common mechanism when a new control policy is acquired. Participants were trained to reach to two lateral and one central target in an environment with mirror (left-right)-reversed visual feedback. One group was allowed to make online movement corrections, whereas the other group only received visual information after the end of the movement. Learning of feedforward control was assessed by measuring the accuracy of the initial movement direction to lateral targets. Feedback control was measured in the responses to sudden visual perturbations of the cursor when reaching to the central target. Although feedforward control improved in both groups, it was significantly better when online corrections were not allowed. In contrast, feedback control only adaptively changed in participants who received online feedback and remained unchanged in the group without online corrections. Our findings suggest that when a new control policy is acquired, feedforward and feedback control are learned separately, and that there may be a trade-off in learning between feedback and feedforward controllers.


Effect of environmental temperature on the interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats.
This research was conducted to determine if altered environmental temperatures would affect the interactive developmental toxicity of radiofrequency (RF) radiation and the industrial solvent, 2-methoxyethanol (2ME). This is important because RF radiation is used in a variety of workplaces that have poorly controlled environmental temperatures, and many workers are concurrently exposed to various chemicals. Furthermore, we have previously demonstrated that combined exposure to RF radiation (10 MHz) and 2ME produces enhanced teratogenicity in rats. RF radiation sufficient to maintain colonic temperatures at the control value (38degrees ), 39.0degrees or 40.0 degrees C for 2 or 4 h combined with either 0 or 100 mg/ kg 2ME at environmental temperatures of 18 degrees , 24 degrees and 30 degrees C (65 degrees , 75 degrees , and 85 degrees F) were given on gestation day 13 to Sprague-Dawley rats. Dams were killed on gestation day 20, and the fetuses were examined for external malformations. Environmental temperature does affect the specific absorption rate (SAR) necessary to maintain a specific colonic temperature but does not affect the interactive developmental toxicity of RF radiation and 2ME in rats. These results, consistent with the literature, add to the evidence that the developmental toxicity of RF radiation (combined or alone) is associated with colonic temperature, not with SAR.


Prophylactic antibiotics for inhibiting preterm labour with intact membranes.
The aetiology of preterm birth is complex and there is evidence that subclinical genital tract infection influences preterm labour in some women but the role of prophylactic antibiotic treatment in the management of preterm labour is controversial. Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if the routine administration of antibiotics confers any benefit or causes harm, prior to membrane rupture. To assess the effects of prophylactic antibiotics administered to women in preterm labour with intact membranes, on maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013). Randomised trials that compared antibiotic treatment with placebo or no treatment for women in preterm labour (between 20 and 36 weeks' gestation) with intact membranes. Two review authors independently assessed trial eligibility, and undertook quality assessment and data extraction. We contacted study authors for additional information. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with their respective 95% confidence intervals (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) was calculated where appropriate. In this update (2013), with the addition of three trials (305 women), the large ORACLE II 2001 trial continues to dominate the results of this review. This review now includes a total of 14 studies randomising 7837 women. No significant difference was shown in perinatal or infant mortality for infants of women allocated to any prophylactic antibiotics compared with no antibiotics. However, an increase in neonatal deaths was shown for infants of women receiving any prophylactic antibiotics when compared with placebo (RR 1.57, 95% CI 1.03 to 2.40; NNTH 149, 95% CI 2500 to 61). No reduction in preterm birth or other clinically important short-term outcomes for the infant were shown.Long-term child outcomes to seven years of age were available for infants in the UK enrolled in the ORACLE II trial. Comparing any antibiotics with placebo, a marginally non-statistically significant increase was shown in any functional impairment (RR 1.10, 95% CI 0.99 to 1.23) and cerebral palsy (CP) (RR 1.82, 95% CI 0.99 to 3.34). In subgroup analysis, CP was statistically significantly increased for infants of women allocated to macrolide and beta-lactam antibiotics combined compared with placebo (RR 2.83, 95% CI 1.02 to 7.88; NNTH 35, 95% CI 333 to 9).Further, exposure to any macrolide antibiotics (including erythromycin alone or erythromycin plus co-amoxiclav) versus no macrolide antibiotics (including placebo and co-amoxiclav alone) was shown to increase neonatal death (RR 1.52, 95% CI 1.05 to 2.19; NNTH 139, 95% CI 1429 to 61), any functional impairment (RR 1.11, 95% CI 1.01 to 1.20; NNTH 24, 95% CI 263 to 13) and CP (RR 1.90, 95% CI 1.20 to 3.01; NNTH 64, 95% CI 286 to 29). Exposure to any beta-lactam (beta-lactam alone or in combination with macrolide antibiotics) versus no beta-lactam antibiotics resulted in more neonatal deaths (RR 1.51, 95% CI 1.06 to 2.15; NNTH 143, 95% CI 1250 to 63) and CP (RR 1.67, 95% CI 1.06 to 2.61; NNTH 79, 95% CI 909 to 33), however no difference was shown in functional impairment.Maternal infection was reduced with the use of any prophylactic antibiotics compared with placebo (RR 0.74, 95% CI 0.63 to 0.86; NNTB 34, 95% CI 24 to 63) and any beta-lactam compared with no beta-lactam antibiotics (RR 0.80, 95% CI 0.69 to 0.92; NNTB 47, 95% CI 31 to 119). However, caution should be exercised with this finding due to the possibility of bias shown by funnel plot asymmetry. Any beta-lactam compared with no beta-lactam antibiotics was associated with an increase in maternal adverse drug reaction (RR 1.61, 95% CI 1.02 to 2.54; NNTH 17, 95% CI 526 to 7). This review did not demonstrate any benefit in important neonatal outcomes with the use of prophylactic antibiotics for women in preterm labour with intact membranes, although maternal infection may be reduced. Of concern, is the finding of short- and longer-term harm for children of mothers exposed to antibiotics. The evidence supports not giving antibiotics routinely to women in preterm labour with intact membranes in the absence of overt signs of infection.Further research is required to develop sensitive markers of subclinical infection for women in preterm labour with intact membranes, as this is a group that might benefit from future novel interventions, including new modalities of antibiotic therapy. The results of this review demonstrate the need for future trials in the area of preterm birth to include assessment of long-term neurodevelopmental outcome.


Magnetic nanoparticle-based hyperthermia for cancer treatment.
Nanotechnology involves the study of nature at a very small scale, searching new properties and applications. The development of this area of knowledge affects greatly both biotechnology and medicine disciplines. The use of materials at the nanoscale, in particular magnetic nanoparticles, is currently a prominent topic in healthcare and life science. Due to their size-tunable physical and chemical properties, magnetic nanoparticles have demonstrated a wide range of applications ranging from medical diagnosis to treatment. Combining a high saturation magnetization with a properly functionalized surface, magnetic nanoparticles are provided with enhanced functionality that allows them to selectively attach to target cells or tissues and play their therapeutic role in them. In particular, iron oxide nanoparticles are being actively investigated to achieve highly efficient carcinogenic cell destruction through magnetic hyperthermia treatments. Hyperthermia in different approaches has been used combined with radiotherapy during the last decades, however, serious harmful secondary effects have been found in healthy tissues to be associated with these treatments. In this framework, nanotechnology provides a novel and original solution with magnetic hyperthermia, which is based on the use of magnetic nanoparticles to remotely induce local heat when a radiofrequency magnetic field is applied, provoking a temperature increase in those tissues and organs where the tumoral cells are present. Therefore, one important factor that determines the efficiency of this technique is the ability of magnetic nanoparticles to be driven and accumulated in the desired area inside the body. With this aim, magnetic nanoparticles must be strategically surface functionalized to selectively target the injured cells and tissues.


Don'T fall off the adaptation cliff: when asymmetrical fitness selects for suboptimal traits.
The cliff-edge hypothesis introduces the counterintuitive idea that the trait value associated with the maximum of an asymmetrical fitness function is not necessarily the value that is selected for if the trait shows variability in its phenotypic expression. We develop a model of population dynamics to show that, in such a system, the evolutionary stable strategy depends on both the shape of the fitness function around its maximum and the amount of phenotypic variance. The model provides quantitative predictions of the expected trait value distribution and provides an alternative quantity that should be maximized ("genotype fitness") instead of the classical fitness function ("phenotype fitness"). We test the model's predictions on three examples: (1) litter size in guinea pigs, (2) sexual selection in damselflies, and (3) the geometry of the human lung. In all three cases, the model's predictions give a closer match to empirical data than traditional optimization theory models. Our model can be extended to most ecological situations, and the evolutionary conditions for its application are expected to be common in nature.


Incisional hernia recurrence after open elective repair: expertise in abdominal wall surgery matters.
Recurrence after incisional hernia repair is one of the major problems related with this operation. Our objective is to analyze the influence of abdominal wall surgery expertise in the results of the open elective repair of incisional hernia. We have compiled the data of a cohort of patients who received surgery for an incisional hernia from July 2012 to December 2015 in a University Hospital. Data were collected prospectively and registered in the Spanish Register of Incisional Hernia (EVEREG). The short- and long-term complications between the groups of patients operated on by the Abdominal Wall Surgery (AWS) unit and groups operated on by surgeons outside of the specialized abdominal wall group (GS) were compared. During the study period, a total of 237 patients were operated on by the open approach (114 AWS; 123 GS). One hundred seventy-five patients completed a median follow-up of 36.6 months [standard deviation (SD) = 6]. Groups were comparable in terms of age, sex, body mass index (BMI), comorbidities, and complexity of hernia. Complications were similar in both groups. Patients in the AWS group presented fewer recurrences (12.0% vs. 28.9%; P = 0.005). The cumulative incidence of recurrence was higher in the GS group [log rank 13.370; P < 0.001; odds ratio (OR) = 37.8; 95% confidence interval (CI) = 30.3-45.4]. In the multivariate analysis, surgery performed by the AWS unit was related to fewer recurrences (OR = 0.19; 95%CI = 0.07-0.58; P < 0.001). Incisional hernia surgery is associated with better results in terms of recurrence when it is performed in a specialized abdominal wall unit.


The interdental gingiva, a visible guide for placement of mini-implants.
To determine whether the tip of the interdental gingiva can serve as a visible guide for placement of mini-implants. Computer tomography (CT) images from 15 males and 15 females (mean age 27 years, range: 23-35 years) were used to evaluate the distance from the tip of the interdental gingiva to the alveolar crest from the central incisor to the 1st molar. The distance from a reference point to the tip of interdental gingiva was recorded from study models using a caliper. The distance between the reference point and the alveolar crest was recorded using CT and added to the model recordings thus providing the distance from the tip of interdental gingiva to the alveolar crest for the various interdental sites. Two-way anova and Student-Newman-Keuls test for multiple comparisons were used for the statistical analysis. There was no significant difference in the distance from the tip of interdental gingiva to the alveolar crest between maxilla and mandible. The distance between the tip of interdental gingiva and the alveolar crest at the central/lateral incisors was the shortest compared with that of other sites. There was also a statistically significant difference between the male and female groups except for the maxillary 2nd premolar/1st molar interradicular site. The tip of interdental gingiva appears a reasonable visual guide for the placement of mini-implants for orthodontic anchorage.


Fate of chemical warfare agents and toxic industrial chemicals in landfills.
One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.


Proliferation of peritoneal mast cells in the skin of W/Wv mice that genetically lack mast cells.
Presence of mast cell precursors in the mouse peritoneal cavity was demonstrated, and the precursors were characterized. When a cell suspension, containing mast cell precursor(s), was directly injected into the skin of genetically mast cell-deficient WBB6F1 (WB X C57BL/6)-W/Wv mice, a cluster composed of approximately 2,000 mast cells appeared at the injection site. By determining the proportion of injection sites at which the mast cell cluster appeared, the concentration of mast cell precursors can be calculated by limiting dilution analysis. The concentration in the peritoneal cavity was about five times as great as the concentration in the bone marrow. Although peritoneal mast cell precursors were shown to originate from the bone marrow, physical characterization revealed that the peritoneal precursors differed from the marrow precursors. The peritoneal precursors were less susceptible to irradiation than the marrow precursors; the former were heavier than the latter. When a 95% pure mast cell suspension was prepared from the peritoneal cells by the removal of phagocytes and the density gradient centrifugation, 1 out of 16 cells had the potentiality to make a mast cell cluster in the skin of the W/Wv mice. Moreover, when a single mast cell was identified under the phase contrast microscope and picked up with the micromanipulator, 1 out of 17 mast cells made the cluster. This indicated that some peritoneal mast cells kept extensive proliferative potentiality even after morphological differentiation. In other words, some peritoneal mast cells themselves may function as the committed precursors.


Retention System and Splinting on Morse Taper Implants in the Posterior Maxilla by 3D Finite Element Analysis.
The purpose of this study was to evaluate different retention systems (cement- or screw-retained) and crown designs (non-splinted or splinted) of fixed implant-supported restorations, in terms of stress distributions in implants/components and bone tissue, by 3-dimensional (3D) finite element analysis. Four 3D models were simulated with the InVesalius, Rhinoceros 3D, and SolidWorks programs. Models were made of type III bone from the posterior maxillary area. Models included three 4.0-mm-diameter Morse taper (MT) implants with different lengths, which supported metal-ceramic crowns. Models were processed by the Femap and NeiNastran programs, using an axial force of 400 N and oblique force of 200 N. Results were visualized as the von Mises stress and maximum principal stress (σmax). Under axial loading, there was no difference in the distribution of stress in implants/components between retention systems and splinted crowns; however, in oblique loading, cemented prostheses showed better stress distribution than screwed prostheses, whereas splinted crowns tended to reduce stress in the implant of the first molar. In the bone tissue cemented prostheses showed better stress distribution in bone tissue than screwed prostheses under axial and oblique loading. The splinted design only had an effect in the screwed prosthesis, with no influence in the cemented prosthesis. Cemented prostheses on MT implants showed more favorable stress distributions in implants/components and bone tissue. Splinting was favorable for stress distribution only for screwed prostheses under oblique loading.