Risk indicators for peri-implant mucositis: a systematic literature review.
To examine the existing evidence in identifying risk indicators in the aetiology of peri-implant mucositis. A search was performed in PubMed, Web of Science (WOS) and The Cochrane Library databases for articles published until June 2014. This search gave 3135 results of which 15 studies fulfilled the inclusion criteria. The current review revealed that only a few studies provided data on risk indicators for the development of peri-implant mucositis. Based on the data available, there is evidence that plaque is a risk indicator for peri-implant mucositis. Smoking has also been identified as an independent risk indicator whereas the overall evidence for surface roughness, residual cement, the dimension of the keratinized tissue and time of implant in function is weak. There are limited data available to support systemic conditions as risk indicators for peri-implant mucositis. Plaque accumulation at implants will result in development of peri-implant mucositis. Smoking should also be considered as a risk indicator for the development of peri-implant mucositis.


Retinal ganglion cell death after different transient periods of pressure-induced ischemia and survival intervals. A quantitative in vivo study.
To quantitate in vivo retinal ganglion cell (RGC) survival after transient periods of pressure-induced ischemia of the rat retina and after different survival intervals. In adult rats, RGCs were labeled with fluorogold applied to their main targets in the brain. Seven days later, in several groups of rats, the left retinas were subjected to transient periods of ischemia of 30, 45, 60, 75, 90, 105, or 120 minutes, respectively, by increasing the intraocular pressure (IOP) of the left eye above systolic values. Five, 7, 14, and 30 days later, the rats were killed, and their retinas were prepared as wholemounts for examination under fluorescence microscopy to estimate RGC survival. The authors found that periods of ischemia of 30 and 45 minutes do not induce RGC death; longer periods of transient ischemia induce the death of a proportion of RGCs, and the proportion increases with the duration of the ischemia; RGC death, which can be observed as early as 5 days after ischemia, continues during the 30-day study period; and periods of ischemia that last 90 minutes or more cause the death of approximately 95% of the RGC population 30 days later. Increases of the IOP above systolic levels for periods of 60 minutes or more result in RGC loss in the rat retina. Both the duration of the initial transient period of ischemia and the duration of the survival period influence the proportion of RGC death.


Health information needs of professional nurses required at the point of care.
Professional nurses work in dynamic environments and need to keep up to date with relevant information for practice in nursing to render quality patient care. Keeping up to date with current information is often challenging because of heavy workload, diverse information needs and the accessibility of the required information at the point of care. The aim of the study was to explore and describe the information needs of professional nurses at the point of care in order to make recommendations to stakeholders to develop a mobile library accessible by means of smart phones when needed. The researcher utilised a quantitative, descriptive survey design to conduct this study. The target population comprised 757 professional nurses employed at a state hospital. Simple random sampling was used to select a sample of the wards, units and departments for inclusion in the study. A convenience sample of 250 participants was selected. Two hundred and fifty structured self-administered questionnaires were distributed amongst the participants. Descriptive statistics were used to analyse the data. A total of 136 completed questionnaires were returned. The findings highlighted the types and accessible sources of information. Information needs of professional nurses were identified such as: extremely drug-resistant tuberculosis, multi-drug-resistant tuberculosis, HIV, antiretrovirals and all chronic lifestyle diseases. This study has enabled the researcher to identify the information needs required by professional nurses at the point of care to enhance the delivery of patient care. The research results were used to develop a mobile library that could be accessed by professional nurses.


Comparative study of sorption and solubility of heat-cure and self-cure acrylic resins in different solutions.
The objective of this study was to compare the sorption and solubility of heat-cure and self-cure acrylic resins in different solutions. One heat-cure acrylic resin (Trevalon) and one self-cure acrylic resin (Rapid Repair) were studied. Five groups of square-shaped specimens (20 mm × 20 mm × 2 mm) were prepared for each acrylic resin and then immersed in five solutions: distilled water, artificial saliva, denture cleansing solution, distilled water, and denture cleaning solution for 12 h alternatively, artificial saliva and denture cleaning solution for 12 h alternatively at 37 ± 2°C, and tested sorption and solubility by weight gain/loss method, respectively, after 1, 6, and 11 weeks. The data were analyzed by one-way analysis of variance followed by post hoc Tukey's test. Water sorption mean values varied from 17.5 ± 0.88 to 27.25 ± 1.04 μg/mm 3 for heat cure and from 12.75 ± 0.55 to 19.75 ± 1.04 μg/mm 3 for self-cure in the different solutions after different interval periods of 1, 6, and 11 weeks. These values were statistically significant (P< 0.001). Water solubility mean values varied from 0.25 ± 0.55 to 1.5 ± 0.55 μg/mm 3 for heat cure and from 1.5 ± 0.55 to 6.5 ± 0.55 μg/mm 3 for self-cure in the different solutions after different interval periods of 1, 6, and 11 weeks. These values were statistically not significant (P > 0.05). There was no linear correlation between sorption and solubility values. Overall, analysis of results showed the maximum sorption value in denture cleansing solution followed by alternative soaking in distilled water and artificial saliva. Least sorption was observed with artificial saliva followed by distilled water. Both heat-cure and self-cure acrylic resins showed varying water sorption and solubility. The results of both water sorption and solubility showed compliance with the International Standards Organization specification. No correlation was found between water sorption and solubility. Artificial saliva solution is a better storage medium than distilled water and denture cleansing solution for both heat-cure and self-cure acrylic resins.


Mutational load may predict risk of progression in patients with Barrett's oesophagus and indefinite for dysplasia: a pilot study.
Mutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett's oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND. This is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not. Thirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%. These results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.


Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression.
Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.


Injections, cocktails and diviners: therapeutic flexibility in the context of malaria elimination and drug resistance in Northeast Cambodia.
Adherence to effective malaria medication is extremely important in the context of Cambodia's elimination targets and drug resistance containment. Although the public sector health facilities are accessible to the local ethnic minorities of Ratanakiri province (Northeast Cambodia), their illness itineraries often lead them to private pharmacies selling "cocktails" and artemether injections, or to local diviners prescribing animal sacrifices to appease the spirits. The research design consisted of a mixed methods study, combining qualitative (in-depth interviews and participant observation) and quantitative methods (household and cross-sectional survey). Three broad options for malaria treatment were identified: i) the public sector; ii) the private sector; iii) traditional treatment based on divination and ceremonial sacrifice. Treatment choice was influenced by the availability of treatment and provider, perceived side effects and efficacy of treatments, perceived etiology of symptoms, and patient-health provider encounters. Moreover, treatment paths proved to be highly flexible, changing mostly in relation to the perceived efficacy of a chosen treatment. Despite good availability of anti-malarial treatment in the public health sector, attendance remained low due to both structural and human behavioral factors. The common use and under-dosage of anti-malaria monotherapy in the private sector (single-dose injections, single-day drug cocktails) represents a threat not only for individual case management, but also for the regional plan of drug resistance containment and malaria elimination.


TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis.
Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.


Time-resolved FTIR study on the structural switching of human galectin-1 by light-induced disulfide bond formation.
Disulfide bonds play a fundamental role in controlling the tertiary structure of proteins; the formation or cleavage of some disulfide bonds can switch the structures and/or functions of proteins. Human galectin-1 (hGal-1), which is a lectin protein, exemplifies how both structure and function are changed by disulfide bonds; the structure and sugar-binding ability of hGal-1 are altered by the formation and cleavage of its three intra-molecular disulfide bonds. In the present study, the dynamics of the structural change of hGal-1 by the formation of disulfide bonds were investigated by time-resolved FTIR spectroscopy combined with a modification in which its thiol groups (-SH) were replaced with S-nitrosylated groups (SNO). Photodissociation of NO from SNO in reduced hGal-1 induced disulfide bond formation and transformed it into the oxidised form. The structural change to the oxidised form involved three distinct kinetics with fast (<300 s), middle (∼600 s), and slow (∼6400 s) lifetimes. In an examination of hGal-1 in the lactose-bound form, structural changes owing to the release of substrate lactose were also observed upon disulfide bond formation. The present method using the photodissociation of NO is useful for monitoring the dynamics of structural changes following disulfide formation.


Dimensional analysis of visual signals.
The classical radiance-luminance parallelism of units for the measurement of emission and reception of flux applies when visual processing is modeled on principles of physics or engineering. "Energy" has a defined meaning in these disciplines: it is the time integral of flux; the time rate of transfer of flux has the dimension of power. Hence energy is appropriate only when light stimuli are delimited in time, else power is the applicable word. To conform to dimensional specifications in physics, energy models in vision would deal with packets of stimuli of fixed duration, not the time rate of excitation, and have magnitudes expressed in the form of the square root of the integrated squared spatial or spatio-temporal distributions.


Childhood autism in the UK and Greece: a cross-national study of progress in different intervention contexts.
Aim: This is a cross-national study with the aim to explore the development of children with autism over time in the UK and Greece. The focus of the study was to investigate the differences in language and social skills between children with autism across the two countries who were receiving different types of treatment: speech and language therapy, psychoanalytic/psychodynamic psychotherapy, and occupational therapy. Study design: A cross-national longitudinal design with a mixed (between-subjects and within-subjects) design. Participants: A sample of 40 children in total. In the UK, 20 children with autism who had received psychotherapy (n = 10) and speech and language therapy (n = 10) were recruited and monitored post-therapy twice over a two-year period. In Greece, 20 children with autism who received occupational therapy (n = 10) and speech and language therapy (n = 10) were recruited and monitored post-therapy twice over a two-year period. Results: All children changed significantly over time on all aspects of measurement, demonstrating that children with autism are developing in a very similar way across the two countries. With respect to the effect of the therapy context on the development of children with autism, it was found that there were no differences across intervention contexts at the start of the study, and there were mainly nonsignificant interactions in the rate of change across the differing types of intervention. However, further analysis showed some important differences: speech and language therapy participants presented more widespread change on language scores across the measures; psychotherapy participants showed significant greater increase in imagination and decrease in stereotypical behavior; and occupational therapy participants presented significant reduction of stereotypical behavior. Conclusions: This study can help professionals who work with children with autism further their understanding of the disorder and how it manifests through time in order to provide appropriate services based on each child's needs. Keywords: Childhood autism, speech and language therapy, psychotherapy, occupational therapy, UK, Greece.


A pragmatic approach to intravenous anaesthetics and electroencephalographic endpoints for the treatment of refractory and super-refractory status epilepticus in critical care.
Status epilepticus is a common neurological emergency, with overall mortality around 20%. Over half of cases are first time presentations of seizures. The pathological process by which spontaneous seizures are generated arises from an imbalance in excitatory and inhibitory neuronal networks, which if unchecked, can result in alterations in intracellular signalling pathways and electrolyte shifts, which bring about changes in the blood brain barrier, neuronal cell death and eventually cerebral atrophy. This narrative review focusses on the treatment of status epilepticus in adults. Anaesthetic agents interrupt neuronal activity by enhancing inhibitory or decreasing excitatory transmission, primarily via GABA and NMDA receptors. Intravenous anaesthetic agents are commonly used as second or third line drugs in the treatment of refractory status epilepticus, but the optimal timing and choice of anaesthetic drug has not yet been established by high quality evidence. Titration of antiepileptic and anaesthetic drugs in critically ill patients presents a particular challenge, due to alterations in drug absorbtion and metabolism as well as changes in drug distrubution, which arise from fluid shifts and altered protein binding. Furthermore, side effects associated with prolonged infusions of anaesthetic drugs can lead to multi-organ dysfunction and a need for critical care support. Electroencelography can identify patterns of burst suppression, which may be a target to guide weaning of intravenous therapy. Continuous elctroencephalography has the potential to directly impact clinical care, but despite its utility, major barriers exist which have limited its widespread use in clinical practice. A flow chart outlining the timing and dosage of anaesthetic agents used at our institution is provided.


Barb geometry of asymmetrical feathers reveals a transitional morphology in the evolution of avian flight.
The geometry of feather barbs (barb length and barb angle) determines feather vane asymmetry and vane rigidity, which are both critical to a feather's aerodynamic performance. Here, we describe the relationship between barb geometry and aerodynamic function across the evolutionary history of asymmetrical flight feathers, from Mesozoic taxa outside of modern avian diversity (Microraptor, Archaeopteryx, Sapeornis, Confuciusornis and the enantiornithine Eopengornis) to an extensive sample of modern birds. Contrary to previous assumptions, we find that barb angle is not related to vane-width asymmetry; instead barb angle varies with vane function, whereas barb length variation determines vane asymmetry. We demonstrate that barb geometry significantly differs among functionally distinct portions of flight feather vanes, and that cutting-edge leading vanes occupy a distinct region of morphospace characterized by small barb angles. This cutting-edge vane morphology is ubiquitous across a phylogenetically and functionally diverse sample of modern birds and Mesozoic stem birds, revealing a fundamental aerodynamic adaptation that has persisted from the Late Jurassic. However, in Mesozoic taxa stemward of Ornithurae and Enantiornithes, trailing vane barb geometry is distinctly different from that of modern birds. In both modern birds and enantiornithines, trailing vanes have larger barb angles than in comparatively stemward taxa like Archaeopteryx, which exhibit small trailing vane barb angles. This discovery reveals a previously unrecognized evolutionary transition in flight feather morphology, which has important implications for the flight capacity of early feathered theropods such as Archaeopteryx and Microraptor. Our findings suggest that the fully modern avian flight feather, and possibly a modern capacity for powered flight, evolved crownward of Confuciusornis, long after the origin of asymmetrical flight feathers, and much later than previously recognized.


Hypercholesterolemia and related risk factors in a cohort of patients with diabetes and hypertension in Maputo, Mozambique.
some studies reported that 25.5% of African population presents hypercholesterolemia; however, epidemiology of hypercholesterolemia in Africa is poorly described. Mozambique is experiencing a constant growth of non-communicable diseases, but scarce data are available about hypercholesterolemia. Our study aims at describing the prevalence of hypercholesterolemia in patients with diabetes and hypertension in Mozambique and investigate possible risk factors. we conducted a cross-sectional study involving all the patients diagnosed with hypertension and/or diabetes from June 2018 to November 2020 in the Zimpeto DREAM Centre (Maputo, Mozambique). For each patient, anthropometric, clinical and laboratory data were collected. Hypercholesterolemia was defined as total blood cholesterol >200 mg/dL. Univariable and multivariable analysis were perfumed. a total of 885 patients were included, 76.2% (n=674) female. Hypertension alone was diagnosed in 670 (75.7%) patients, diabetes in 109 (12.3%) patients and 106 (11.9%) both diseases. Hypercholesterolemia was present in 410 (46.3%) patients and it was more prevalent in patients diagnosed with both diabetes and hypertension (52.8%), as compared to the patients diagnosed with hypertension (46.9%) or diabetes alone (36.7%). In the multivariable analysis, the only factors independently associated with hypercholesterolemia were female sex (aOR 1.77, 95% CI 1.26-2.48, p=0.001) and a body mass index >25kg/m2 (aOR 1.50, 95% CI 1.11-2.04, p=0.008). our results highlight the need for a specific focus on female and obese/overweight patients, especially if diagnosed with both hypertension and diabetes, to promptly detect metabolic disorders and establish temporary preventive measures for cardiovascular events.


Effect of salinity and temperature on the expression of genes involved in branchial ion transport processes in European sea bass.
The responses of European sea bass to temperature increase and salinity decrease were investigated measuring mRNA expression levels of main genes involved in ion transport. Juvenile fish were pre-acclimated to seawater (SW) at 18 °C (temperate) or 24 °C (warm) for two weeks and then transferred for two weeks to either fresh water (FW) or SW at the respective temperature. Unlike temperate conditions, there is no change in Na+/K+-ATPase α1a (nka α1a) and Na+/H+ exchanger 3 (nhe3) mRNA expression following FW transfer in warm conditions. This is linked to the high expression of these genes in warm SW compared to temperate SW. Na+/Cl--cotransporter (ncc2a) expression however is increased following FW transfer in temperate and warm conditions. Main transporters involved in ion excretion (Na+/K+/2Cl--1 cotransporter, nkcc1 and cystic fibrosis transmembrane conductance regulator, cftr) as well as nitrogen excretion (Rh-glycoproteins, rhcg1 and rhbg) and acid-base regulation (V-H+-ATPase, vha-a and b) are highly expressed in SW warm conditions vs FW warm. Overall, our results suggest a higher activation of ion transport processes in warm conditions and more strikingly in SW. This is linked to a strong interplay between diverse ion transporters in order to coordinate physiological responses at the gill level.


[Medical honey in the treatment of wound-healing disorders in the head and neck area].
Already in ancient times honey was used as a drug and for the treatment of wounds. In recent years the different effects of honey on wound-healing processes have been reexamined. Based on this, the antibacterial and fungicidal qualities of honey could be confirmed. Between January 2009 and July 2011 medical honey was used on 36 patients suffering from different wound-healing disorders in the head and neck area after unsuccessful conventional treatment. The healing process was registered by microbiological investigations, measurements of the wound edges and adequate photo documentation. Medical honey can be used without problems or detectable side effects on problematic wounds of the head and neck area. Constant treatment leads to fast wound lavation, granulation, reduction of putrid smells and a decrease in inflammation. In the treatment of poorly healing and infected wounds within the head and neck area, medical honey can be used successfully without problems as an effective alternative to conventional treatment options.


Iodine induced 1-D lamellar self assembly in organic ionic crystals for solid state dye sensitized solar cells.
A novel saturated heterocyclic organic ionic crystal, piperidinium iodide (PiHI), is synthesized by a facile route and applied as a solid electrolyte in Dye Sensitized Solar Cells (ss-DSSCs). Upon addition of a small quantity of iodine, PiHI self-assembles into a 1D lamellar micro crystalline structure that shows anisotropic conductivity. The two-component PiHI was characterized by using electrochemical impedance spectroscopy, cyclic voltammetry, steady state voltammetry, FT-IR, and Raman spectroscopy. Wide angle X-ray diffraction (XRD) measurement confirms the presence of long range 1D lamellar channels that pave the way for the diffusion of the redox couple I-/I3- and exhibit high anisotropic conductivity. The ionic conductivity of 1D PiHI (with I2) aligned perpendicular to the electrode, σ⊥ (15.46 mS cm-1), is 1.5 times higher than that aligned parallel to the electrode σ∥ = 10.32 mS cm-1. The ss-DSSC devices with these self-assembled ordered ionic crystals with a carbazole based sensitizer (SK1) achieved a power conversion efficiency (PCE) of 4.2% and 5.2% for ∥al and ⊥ar arrangement, respectively. The reported PCEs are better than that obtained from a classical liquid electrolyte with SK1 sensitizers. The electron kinetics at various interfaces of ss-DSSC devices was evaluated using Electrochemical Impedance Spectroscopy (EIS) measurements. The presence of a saturated cyclic structure promotes close packing through H-bonding and electrostatic interactions, which make ss-DSSC devices more stable up to 600 h under illumination of 1 sun.


Airway management in the emergency department: a one-year study of 610 tracheal intubations.
To describe the methods, success rates, and immediate complications of tracheal intubations performed in the emergency department of an urban teaching hospital. This was an observational, consecutive series undertaken in an urban university hospital with an emergency medicine residency training program and an annual ED census of 60,000 patients. The study population included all patients for whom intubation was attempted in the ED during a 1-year period (July 1, 1995 through June 30, 1996). At the time of each intubation, the intubator filled out an intubation data collection form. If an intubation was performed in the ED but no form was filled out, the data were obtained from the medical record. A total of 610 patients required airway control in the ED; 569 (93%) were intubated by emergency medicine residents or attending physicians. Rapid-sequence intubation (RSI) was used in 515 (84%). A total of 603 patients (98.9%) were successfully intubated; 7 patients could not be intubated and underwent cricothyrotomy. In 33 patients, inadvertent placement into the esophagus occurred; all such situations were rapidly recognized and corrected. Eight (24%) of the 33 esophageal intubations resulted in a reported immediate complication. Overall, 49 patients (8.0%; 95% confidence interval [CI], 6% to 11%) experienced a total of 57 immediate complications (9.3%; 95% CI, 7% to 12%). Three patients sustained a cardiac arrest after intubation; two of these patients had agonal rhythms before intubation, and one probably had a succinylcholine-induced hyperkalemic cardiac arrest. At this institution, the majority of ED intubations were performed by emergency physicians and RSI was the most common method used. Emergency physicians intubated critically ill and injured ED patients with a very high success rate and a low rate of serious complications.


Convolutional Neural Networks as Summary Statistics for Approximate Bayesian Computation.
Approximate Bayesian Computation is widely used in systems biology for inferring parameters in stochastic gene regulatory network models. Its performance hinges critically on the ability to summarize high-dimensional system responses such as time series into a few informative, low-dimensional summary statistics. The quality of those statistics acutely impacts the accuracy of the inference task. Existing methods to select the best subset out of a pool of candidate statistics do not scale well with large pools of several tens to hundreds of candidate statistics. Since high quality statistics are imperative for good performance, this becomes a serious bottleneck when performing inference on complex and high-dimensional problems. This paper proposes a convolutional neural network architecture for automatically learning informative summary statistics of temporal responses. We show that the proposed network can effectively circumvent the statistics selection problem of the preprocessing step for ABC inference. The proposed approach is demonstrated on two benchmark problem and one challenging inference problem learning parameters in a high-dimensional stochastic genetic oscillator. We also study the impact of experimental design on network performance by comparing different data richness and data acquisition strategies.


[Modified EMJH medium for cultivation of Leptospira interrogans serogroup ballum].
Strains within the Ballum serogroup of spirochete Leptospira show fastidious growth with more exigent nutritional requirements than those of other Leptospira pathogenic strains. The influence of 37 nutritional compounds on the growth of Leptospira interrogans serogroup Ballum was investigated employing the synthetic EMJH medium as the base for the study. Microbial growth was estimated spectrophotometrically and direct counts were performed with a Petroff-Hausser counting chamber. Virulence stability was evaluated by calculating the mean lethal dose in hamsters. Antigenicity stability was evaluated by Western blotting using a specific antiserum. Cell yields commonly obtained in EMJH were triplicated without virulence or antigenicity depletions after culturing in a modified EMJH medium with an increased concentration of Tween 80, and the incorporation of sodium acetate and beef extract. Neither the increased concentration of at least 6 components of EMJH nor the incorporation of a variety of new nutrients stimulated cell yields or the growth rate of the microorganism. The results allow us to make use of an enriched culture medium that promotes high cell yields of this fastidious serogroup most prevalent in humans in Cuba.


The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line.
The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-γ to induce COX-2. At the level of mRNA, COX-2 was induced >1000-fold following 24 h of the treatment. Coincubation with PEA (10 μmol/L) did not affect the levels of COX-2, but reduced the levels of prostaglandins D2 and E2 as well as 11- and 15-hydroxyeicosatetraenoic acid, which can also be synthesised by a COX-2 pathway in macrophages. These effects were retained when hydrolysis of PEA to palmitic acid was blocked. Linoleic acid-derived oxylipin levels were not affected by PEA. No direct effects of PEA upon the oxygenation of either arachidonic acid or 2-arachidonoylglycerol by COX-2 were found. It is concluded that in lipopolysaccharide and interferon-γ-stimulated RAW264.7 cells, PEA reduces the production of COX-2-derived oxylipins in a manner that is retained when its metabolism to palmitic acid is inhibited.


Intra-epithelial vaccination with COPV L1 DNA by particle-mediated DNA delivery protects against mucosal challenge with infectious COPV in beagle dogs.
Protection against viral challenge with canine oral papillomavirus (COPV) was achieved by immunisation via particle-mediated DNA delivery (PMDD) of a plasmid encoding the COPV L1 gene to cutaneous and oral mucosal sites in beagle dogs. The initial dose of approximately 9 microg of DNA was followed by two booster doses at 6 week intervals. A similar approach was used to vaccinate a control group of animals with plasmid DNA encoding the Hepatitis B virus S gene. Following challenge at the oral mucosa with COPV all animals vaccinated with the COPV L1 gene were protected against disease. However five of six animals in the control group developed COPV induced papillomas at the oral mucosa. Both cell-mediated lymphoproliferative and humoral antibody responses to the DNA vaccine were observed. Our data indicate that PMDD of plasmid DNA can protect against mucosal challenge with papillomavirus.


Copy Number Variants Account for a Tiny Fraction of Undiagnosed Myopathic Patients.
Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5⁻9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.


Subfoveal choroidal thickness in 1323 children aged 11 to 12 years and association with puberty: the Copenhagen Child Cohort 2000 Eye Study.
To investigate subfoveal choroidal thickness and ocular- and systemic-associated factors in a population-based cohort of children. Cross-sectional, observational study where 1323 healthy 11- and 12-year-old children were examined with enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT), ocular interferometric biometry, blood pressure manometry, and measurement of height, weight, nonmydriatic refraction, and best-corrected visual acuity. Self-reported stage of pubertal development was classified as Tanner stages 1 through 4. Mean subfoveal choroidal thickness was 369 ± 81 μm in girls and 348 ± 72 μm in boys. Longer axial length was associated with a thinner subfoveal choroid (-27.2 [95% confidence interval (CI) -32.7 to -21.7] μm/mm; P < 0.0001), adjusting for age and sex. There was no difference in choroidal thickness between sexes (P = 0.14) after adjusting for age and axial length. In girls, the choroid was thickest in participants in the more advanced stage of pubertal development (54.2 [95% CI 20.7-87.7] μm for Tanner 4 versus Tanner 1, P = 0.0015) and increased with body height (19.2 [95% CI 10.8-27.5] μm/10 cm, P < 0.0001). There was no effect of height or puberty in boys, who were less sexually mature than girls. Choroidal thickness in girls increased with body height and sexual maturation. The results suggest that puberty promotes choroidal thickening in girls, an effect that may be mediated by the pubertal growth spurt. The lack of pubertal effect in boys may be related to a smaller proportion of boys in this study having entered puberty.


Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats.
Our previous studies demonstrated that the sexually dimorphic pattern of hypertension in the spontaneously hypertensive rat is androgen dependent. Gonadectomy retards the development of hypertension in young males, but not in females, and administration of testosterone propionate to gonadectomized spontaneously hypertensive rats of both sexes confers a male pattern of blood pressure development. The current study tested the hypothesis that renal and hepatic renin and angiotensinogen gene expression are also androgen dependent in the spontaneously hypertensive rat. Male and female spontaneously hypertensive rats underwent gonadectomy or a sham operation at 4 weeks of age. Subgroups of gonadectomized rats of both sexes were implanted with a 15-mm or 30-mm Silastic capsule filled with testosterone at the same time the gonadectomy was performed; a third group received an empty Silastic capsule. Northern and slot blot analyses were used to characterize and quantitate renin and angiotensinogen messenger RNA (mRNA) in the kidney and liver 18 weeks after the gonadectomy. Blood pressure, plasma renin activity, and hepatic angiotensinogen mRNA levels were higher in intact males than in females. Orchidectomy retarded the development of hypertension and lowered plasma renin and renal and hepatic angiotensinogen mRNA levels, and testosterone replacement restored the male pattern of hypertension and plasma renin and increased renal and hepatic angiotensinogen mRNA. Ovariectomy did not alter blood pressure or plasma renin but did lower renal renin and renal and hepatic angiotensinogen mRNA; testosterone increased blood pressure, plasma renin, renal renin and angiotensinogen mRNA, and hepatic angiotensinogen mRNA levels in ovariectomized females.(ABSTRACT TRUNCATED AT 250 WORDS)


Good laboratory practices for waived testing sites: survey findings from testing sites holding a certificate of waiver under the clinical laboratory improvement amendments of 1988 and recommendations for promoting quality testing.
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), simple, low-risk tests can be waived and performed with no routine regulatory oversight in physicians' offices and various other locations. Since CLIA was implemented, waived testing has steadily increased in the United States. Surveys conducted during 1999-2004 by the Centers for Medicare & Medicaid Services and studies funded by CDC during 1999-2003 evaluated testing practices in sites holding a CLIA Certificate of Waiver (CW). Although study findings indicate CW sites generally take measures to perform testing correctly, they raise quality concerns about practices that could lead to errors in testing and poor patient outcomes. These issues are probably caused, in part, by high personnel turnover rates, lack of understanding about good laboratory practices, and inadequate training. This report summarizes study findings and provides recommendations developed by the Clinical Laboratory Improvement Advisory Committee for conducting quality waived testing. These recommendations include considerations before introducing waived testing, such as management responsibility for testing, regulatory requirements, safety, physical and environmental requirements, benefits and costs, staffing, and documentation. They also cover good laboratory practices for the three phases of testing: 1) before testing (test ordering and specimen collection), 2) during testing (control testing, test performance, and result interpretation and recording), and 3) after testing (result reporting, documentation, confirmatory testing, and biohazard waste disposal). They are intended to be used by those who would benefit from improving their knowledge of good laboratory practices. Continued monitoring of waived testing, with a focus on personnel education and training, is needed to improve practices and enhance patient safety as waived testing continues to increase.


Increased granulopoiesis after sequential administration of transforming growth factor-beta 1 and granulocyte-macrophage colony-stimulating factor.
Transforming growth factor-beta 1 (TGF-beta 1) is an inhibitor of the growth and differentiation of immature hematopoietic progenitors in vitro; however, we have demonstrated that TGF-beta 1 can promote granulopoiesis in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We therefore examined the effect of the combined administration of TGF-beta 1 and GM-CSF in vivo. First, TGF-beta 1 enhanced the specific binding of GM-CSF (2.0-fold) on bone marrow cells, reaching a maximum 40 hours after injection, while the specific binding of interleukin-3 (IL-3) was unaffected. Using GM-CSF-specific binding to determine the optimal regimen for cytokine administration in vivo, we found that the administration of TGF-beta 1 and GM-CSF in sequence increased myelopoiesis. Total numbers of colony-forming units-granulocyte/macrophage (CFU-GM) and myeloblasts per femur were increased above the level obtained with the simultaneous injection of TGF-beta 1 plus GM-CSF, GM-CSF alone or TGF-beta 1 alone. Further, the sequential administration of TGF-beta 1 and GM-CSF resulted in enhanced numbers of mature granulocytes in both the bone marrow and peripheral blood. In contrast, the sequential combination of TGF-beta 1 and GM-CSF did not enhance the numbers or increase the recovery of erythroid cells in the bone marrow. These results show that TGF-beta 1 in vivo as in vitro has a multifunctional effect on bone marrow progenitors, and by using an optimal combination of TGF-beta 1 and GM-CSF in vivo, one can selectively increase both the central and peripheral granulopoietic compartments.


Narrative comprehension and engagement with e-books vs. paper-books in autism spectrum condition.
Children with autism spectrum condition often have specific difficulties with narrative comprehension, a skill which has a strong association with both concurrent and longitudinal reading comprehension. A better understanding of narrative comprehension skills in autism spectrum condition has the potential to provide insight into potential later reading comprehension difficulties and inform early targeted intervention. In the current study, the main objective was to investigate how differences in the medium of story presentation (paper-book vs. e-book) and differences in story narration (adult narration vs. in-app narration) would influence narrative comprehension in general, and between groups (autism spectrum condition and a receptive language-matched control group). We were also interested in how task engagement (visual attention and communication) differed between group and conditions and whether task engagement was related to narrative comprehension. Forty-two children with autism spectrum condition and 42 typically developing children were read a story either via a paper-book or an e-book with interactive and multimedia features. The e-book was either narrated by the experimenter (adult narrated iPad condition) or narrated by an in-app voiceover (e-book narrated iPad condition). Children's behaviour during storybook reading was video recorded and coded for engagement (visual attention and communication). They then completed two measures of narrative comprehension: multiple-choice questions (measuring recall of literal information) and a picture ordering task (measuring global story structure). Contrary to predictions, we did not find any significant group or condition differences on either measure of narrative comprehension, and both groups demonstrated a similar level of narrative comprehension across the three conditions. We found differences in engagement between conditions for both groups, with greater visual attention in the e-book conditions compared to the paper-book condition. However, visual attention only significantly correlated with narrative comprehension for the typically developing group. Overall, this study suggests that children with autism spectrum condition are just as able as language-matched peers to comprehend a narrative from storybooks. Presenting a story on an iPad e-book compared to a paper-book does not influence narrative comprehension, nor does adult narration of the story compared to in-app narration. However, on-task engagement is linked to narrative comprehension in typically developing children.Implications: Taken together, our findings suggest that e-books may be more successful than paper-based mediums at encouraging visual attention towards the story, but no better at supporting narrative comprehension and eliciting communication.


c-abl is required for the development of hyperoxia-induced retinopathy.
The requirement for the nonreceptor tyrosine kinase c-abl in the pathogenesis of retinopathy of prematurity (ROP) was examined using the mouse model for ROP and c-abl-deficient mice. Hyperoxia-induced retinal neovascularization was observed in wild-type and heterozygous mice but animals that were homozygous null for c-abl did not develop a vasoproliferative retinopathy in response to hyperoxia. Two gene products, endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF), have been implicated in the pathogenesis of ROP. The mRNA expression of ET-1 and VEGF was assessed in mice maintained in normoxia and in hyperoxia-exposed mice. ET-1 mRNA levels were unchanged in wild-type mice throughout the hyperoxia treatment, suggesting that ET-1 mRNA expression is not regulated by the increase in inspired oxygen. In wild-type mice maintained in room air, VEGF mRNA levels rose threefold from postnatal day 6 (P6) to P17. When wild-type mice were treated with the hyperoxia regimen, a fivefold decrease in VEGF mRNA expression was observed from P7 to P16. However, retinal VEGF expression in hyperoxia-treated homozygous null mice did not decrease and remained at control levels. These data suggest that c-abl is required for the hyperoxia-induced retinal neovascularization and hyperoxia-induced decrease in VEGF mRNA levels.


Dorsal subthalamotomy for Parkinson's disease.
We report our experience of unilateral subthalamotomy in patients with Parkinson's disease (PD). Eleven patients were included in a pilot, open-labeled study to assess the effect of unilateral lesion of the subthalamic nucleus (STN) with a minimum of 12 months of follow-up. The guidelines of CAPIT (Core Assessment Program for Intracerebral Transplantation) were followed for recruitment into the study and follow-up assessment. Levodopa equivalents daily intake (mean 967 mg) were unchanged during the first 12 months in all but one patient who stopped medication. The sensorimotor region of the STN was defined by semimicrorecording and stimulation and a thermolytic lesion was placed accordingly. There was a significant reduction in both UPDRS parts II and III in the "off" state at 1-, 6-, and 12-month follow-up. This effect was maintained in four patients up to 24 months. The dyskinesia score did not change postoperatively. Lesion-induced dyskinesias were not a management problem except in one patient who developed a large infarction several days postsurgery. This initial study indicates that a lesion of the STN is not generally associated with hemiballismus in PD. Subthalamotomy may induce considerable motor benefit and could become another surgical option under specific circumstances.


Inhibition of G protein in human sperm and its influence on acrosome reaction and zona pellucida binding.
To evaluate human sperm acrosomal status, zona pellucida (ZP)-binding capacity, and sperm motion characteristics after treatment with pertussis toxin followed by exposure to increasing concentrations of solubilized human ZP. Prospective analytical study. Normal human sperm donors in an academic research environment. Sperm were prepared with a wash and swim-up method and treated with a final concentration of 100 ng/mL pertussis toxin. Acrosomal status were determined using a Pisum sativum agglutinin-fluorescien-isothiocyanate method after exposure of sperm to 0.25, 0.5, 0.75, and 1.00 ZP/microL solutions of human ZP. Zona binding potential was recorded using intact zona-binding assays. Motion characteristics were recorded with a semen analyzer. Percentage acrosome-reacted sperm, number of zona-bound sperm, and sperm motion parameters. Spermatozoa treated with 100 ng/mL pertussis toxin, followed by ZP-mediated acrosome reaction induction, showed a significant decrease in the percentage of acrosome-reacted sperm compared with untreated controls. Motion characteristics of 3-hour capacitated sperm after treatment with either phosphate-buffered saline (PBS) or pertussis toxin were not different. Pertussis toxin-treated sperm populations bound significantly more sperm to the ZP after 4 hours incubation compared with the PBS-control groups: 137.1 +/- 8.0 compared with 96.3 +/- 7.0 (mean +/- SEM). The data support the concept of the controlling mechanism and importance of G proteins during the ZP-mediated acrosome reaction. Intact acrosome correlate with and are needed to ensure tight zona binding.


Atmospheric oxygen, giant Paleozoic insects and the evolution of aerial locomotor performance.
Uniformitarian approaches to the evolution of terrestrial locomotor physiology and animal flight performance have generally presupposed the constancy of atmospheric composition. Recent geophysical data as well as theoretical models suggest that, to the contrary, both oxygen and carbon dioxide concentrations have changed dramatically during defining periods of metazoan evolution. Hyperoxia in the late Paleozoic atmosphere may have physiologically enhanced the initial evolution of tetrapod locomotor energetics; a concurrently hyperdense atmosphere would have augmented aerodynamic force production in early flying insects. Multiple historical origins of vertebrate flight also correlate temporally with geological periods of increased oxygen concentration and atmospheric density. Arthropod as well as amphibian gigantism appear to have been facilitated by a hyperoxic Carboniferous atmosphere and were subsequently eliminated by a late Permian transition to hypoxia. For extant organisms, the transient, chronic and ontogenetic effects of exposure to hyperoxic gas mixtures are poorly understood relative to contemporary understanding of the physiology of oxygen deprivation. Experimentally, the biomechanical and physiological effects of hyperoxia on animal flight performance can be decoupled through the use of gas mixtures that vary in density and oxygen concentration. Such manipulations permit both paleophysiological simulation of ancestral locomotor performance and an analysis of maximal flight capacity in extant forms.


Safe One-to-One Dosage Conversion From Twice-Daily to Once-Daily Tacrolimus in Long-Term Stable Recipients After Liver Transplantation.
Once-daily tacrolimus provides better compliance for transplant recipients. However, the conversion strategies of dosage and concentration from twice- to once-daily are not well studied. The aim of this study was to investigate the dosage of conversion, follow-up strategy, and safety of conversion to once-daily tacrolimus in stable and long-term recipients after living donor liver transplantation (LDLT). From January 2011 to November 2012, we selectively converted 35 stable LDLT recipients to once-daily tacrolimus based on 1-to-1 daily dose. The tacrolimus dosage, trough level, liver and renal function before conversion, 1 month, 3 months, 6 months, and 1 year after conversion were recorded. Tacrolimus trough level dropped significantly after conversion (2.72±1.65 to 1.85±1.25 ng/mL, p<0.001). No biopsy-proved rejection was detected during 1-year follow-up. However, 1 recipient (2.9%) had a 0.5 mg increase due to elevated liver enzymes and clinically diagnosed rejection. No other patients required dose adjustment due to dropped tough level after conversion. One-to-one dosage conversion in stable LDLT recipients is a safe strategy. Dropped trough level is expected and dose adjustment is rarely required.


Global evaluation of closed-loop electron dynamics in quasi-one-dimensional conductors using polarization vortices.
We evaluate the quasi-one-dimensional (1D) electron dynamics in a NbSe3 ring crystal using polarization vortex pulses with various azimuthal distributions. The single particle relaxation component reveals a large anisotropy on the crystal, indicating that the electrons in the ring maintain their 1D character. The results also suggest that the polarization vortex evaluates the global polarization property of the closed-loop electron that plays an important role in the quantum correlation phenomena such as the Aharonov-Bohm effect.


Comparison of in vitro and in situ methods in evaluation of forage digestibility in ruminants.
The objective of this study was to compare the application of different in vitro and in situ methods in empirical and mechanistic predictions of in vivo OM digestibility (OMD) and their associations to near-infrared reflectance spectroscopy spectra for a variety of forages. Apparent in vivo OMD of silages made from alfalfa (n = 2), corn (n = 9), corn stover (n = 2), grass (n = 11), whole crops of wheat and barley (n = 8) and red clover (n = 7), and fresh alfalfa (n = 1), grass hays (n = 5), and wheat straws (n = 5) had previously been determined in sheep. Concentrations of indigestible NDF (iNDF) in all forage samples were determined by a 288-h ruminal in situ incubation. Gas production of isolated forage NDF was measured by in vitro incubations for 72 h. In vitro pepsin-cellulase OM solubility (OMS) of the forages was determined by a 2-step gravimetric digestion method. Samples were also subjected to a 2-step determination of in vitro OMD based on buffered rumen fluid and pepsin. Further, rumen fluid digestible OM was determined from a single 96-h incubation at 38°C. Digestibility of OM from the in situ and the in vitro incubations was calculated according to published empirical equations, which were either forage specific or general (1 equation for all forages) within method. Indigestible NDF was also used in a mechanistic model to predict OMD. Predictions of OMD were evaluated by residual analysis using the GLM procedure in SAS. In vitro OMS in a general prediction equation of OMD did not display a significant forage-type effect on the residuals (observed - predicted OMD; P = 0.10). Predictions of OMD within forage types were consistent between iNDF and the 2-step in vitro method based on rumen fluid. Root mean square error of OMD was least (0.032) when the prediction was based on a general forage equation of OMS. However, regenerating a simple regression for iNDF by omitting alfalfa and wheat straw reduced the root mean square error of OMD to 0.025. Indigestible NDF in a general forage equation predicted OMD without any bias (P ≥ 0.16), and root mean square error of prediction was smallest among all methods when alfalfa and wheat straw samples were excluded. Our study suggests that compared with the in vitro laboratory methods, iNDF used in forage-specific equations will improve overall predictions of forage in vivo OMD. The in vitro and in situ methods performed equally well in calibrations of iNDF or OMD by near-infrared reflectance spectroscopy.


Coffee Intake and Obesity: A Meta-Analysis.
Many studies have explored the relationship between coffee-one of the most commonly consumed beverages today-and obesity. Despite inconsistent results, the relationship has not been systematically summarized. Thus, we conducted a meta-analysis by compiling data from 12 epidemiologic studies identified from PubMed and Embase through February 2019. The included studies assessed obesity by body mass index (BMI, a measure of overall adiposity) or waist circumference (WC, a measure of central adiposity); analyzed the measure as a continuous outcome or binary outcome. Using random effects model, weighted mean difference (WMD) and 95% confidence interval (CI) were obtained for continuous outcomes; summary relative risk (RR) and 95% CI for the highest vs. lowest categories of coffee intake were estimated for binary outcome. For BMI, WMD was -0.08 (95% CI -0.14, -0.02); RR was 1.49 (95% CI 0.97, 2.29). For WC, WMD was -0.27 (95% CI -0.51, -0.02) and RR was 1.07 (95% CI 0.84, 1.36). In subgroup analysis by sex, evidence for an inverse association was more evident in men, specifically for continuous outcome, with WMD -0.05 (95% CI -0.09, -0.02) for BMI and -0.21 (95% CI -0.35, -0.08) for WC. Our meta-analysis suggests that higher coffee intake might be modestly associated with reduced adiposity, particularly in men.


The 2D:4D-Ratio and Neuroticism Revisited: Empirical Evidence from Germany and China.
The 2D:4D-Ratio, as an indirect measure of the fetal testosterone to estradiol ratio, is potentially very important for understanding and explaining different personality traits. It was the aim of the present study to replicate the findings from Fink et al. (2004) about the relation between individual differences in 2D:4D-Ratios and the Five Factor Model in different cultural groups. Therefore a sample of n = 78 Chinese and n = 370 German participants was recruited. Every participant provided hand scans of both hands, from which 2D:4D-Ratios were computed. Moreover, all participants filled in the NEO Five Factor Inventory (NEO-FFI). Significant sex differences were found for ratios of both hands in the expected direction, with females showing higher ratios than males. With respect to links between personality and the digit ratio, a positive association was observed between 2D:4D-Ratio and Neuroticism in females, as shown in the earlier study. These findings were observed in both female subsamples from China and Germany, as well as in the full sample of participants. But in contrast to the results for the whole and the German female sample, where 2D:4D-Ratio of both hands were related to Neuroticism, in the Chinese female sample only left hand 2D:4D-Ratio was significantly and positively related to Neuroticism. There were no significant correlations found in any of the male samples. Thus, prenatal exposure to sex steroids appears to influence the personality factor Neuroticism in females specifically. This finding potentially has implications for mental health, as Neuroticism has been shown to be a risk factor for various forms of psychopathology.


Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. IV. Aminoglycoside-modifying enzyme AAC(6')/APH(2") is responsible for arbekacin-resistance enhanced by bleomycin.
Resistance patterns against various antimicrobial agents including beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides were examined for 58 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from April to November 1992. All the MRSA strains produced type II-coagulase but not beta-lactamase. Regarding aminoglycoside-modifying enzymes, 7 strains (12%) appeared to be producing aminoglycoside 4',4"-adenyltransferase AAD(4',4") encoded by aadD without coproduction of bifunctional aminoglycoside 6'-acetyltransferase/2"-phosphotransferase AAC(6')/APH(2") encoded by aacA-aphD (referred to as tobramycin-resistant type, TOBr). The remaining 51 strains (88%) were phenotypically producers of both enzymes (i.e., mix-resistant type, Mixr). AAD(4',4"), encoded by aadD which was reported to be closely linked with bleomycin (BLM)-resistance determinant, could be seen in 100% MRSA strains and ca. 90% strains expressed AAC(6')/APH(2"). BLM endowed Mixr-type but not TOBr-type MRSA strain with enhanced resistance to arbekacin (ABK) dose-dependently, presumably by modifying the production of AAC(6')/APH(2"). The manifestation of ABK-resistant phenotype by Mixr-type MRSA required the coexistence of BLM. Therefore, ABK must be administered carefully to cure MRSA infection in patients who have been treated with BLM.


Effect of nurse navigation on patient care satisfaction and distress associated with breast biopsy.
Navigation during the biopsy period is a superior approach to delivering care, with those patients receiving services experiencing less distress. Critical nurse navigator roles include providing information and facilitating access to the healthcare system, both of which are influential on distress. The information in this article supports the expansion of navigation programs to include women undergoing biopsy and aids in promoting a higher standard of care. To evaluate the effect of navigation on care satisfaction and distress in women undergoing breast biopsy. A descriptive, cross-sectional survey design from two outpatient radiology clinics in Appalachia was used. Navigated women had lower scores on every distress measure and were less likely to seek information from an outside source. Women who were more satisfied with their care reported decreased distress; the factors influencing distress varied depending on whether they were the recipient of navigation services. In the non-navigated population, general satisfaction with care and accessibility were more likely to influence distress.


Ciliocytophthoria of nasal epithelial cells after viral infection: a sign of suffering cell.
Ciliocytophthoria (CCP) defines a degenerative process of the ciliated cells consequent to viral infections, and it is characterized by typical morphological changes. We evaluated the distinct and characteristic phases of CCP, by means of the optical microscopy of the nasal mucosa (nasal cytology), in 20 patients (12 males and 8 females; aged between 18 and 40 years). Three phases of CCP by nasal cytology are detected. This outcome confirms that CCP represents a sign of suffering nasal epithelial cell.


Brief report: Association between psychological sense of school membership and mental health among early adolescents.
Mental health problems among adolescents are prevalent and are associated with important difficulties for a normal development during this period and later in life. Understanding better the risk factors associated with mental health problems may help to design and implement more effective preventive interventions. Several personal and family risk factors have been identified in their relationship to mental health; however, much less is known about the influence of school-related factors. One of these school factors is school belonging or the psychological sense of school membership. This is a well-known protective factor to develop good academic commitment, but it has been scarcely studied in its relationship to mental health. We explored this association in a sample of early adolescents and found that students who reported having a high level of school membership had lower mental health problems, even after controlling for several personal and family factors.


AQP1 expression in human gingiva and its correlation with periodontal and peri-implant tissue alterations.
Aquaporins (AQPs) are a family of hydrophobic integral membrane proteins that function as transmembrane channels and play an important role in tissue homeostasis. Aquaporin-1 (AQP1), in particular, has been reported to be involved in several biological processes including inflammation, angiogenesis, wound healing and others. Periodontitis and peri-implantitis can be defined as inflammatory processes that affect the tissues surrounding a tooth or an osseointegrated implant, respectively. To date, there are limited data about the involvement of AQPs in these diseases. The aim of this study was to evaluate the possible link between the histomorphological alterations and the expression of AQP1 in healthy, pathological and healed periodontal and peri-implant gingival tissues. The results obtained showed that changes in organization of collagen fibers were observed in periodontitis and peri-implantitis, together with an increase in the percentage of area occupied by inflammatory cell infiltration and an increase of AQP1 immunostaining, which was located in the endothelial cells of the vessels within the lamina propria. Moreover, in healed periodontal and peri-implant mucosa a restoration of histomorphological alterations was observed together with a concomitant decrease of AQP1 immunostaining. These data suggested a possible link between the degree of inflammatory state and the presence of AQP1, where the latter could be involved in the chain of inflammatory reactions triggered at periodontal and peri-implant levels.


Blockade of the ubiquitin protease UBP43 destabilizes transcription factor PML/RARα and inhibits the growth of acute promyelocytic leukemia.
More effective treatments for acute promyelocytic leukemia (APL) are needed. APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARα, which is generated in APL by chromosomal translocation. The E1-like ubiquitin-activating enzyme (UBE1L) associates with interferon-stimulated gene ISG15 that binds and represses PML/RARα protein. Ubiquitin protease UBP43/USP18 removes ISG15 from conjugated proteins. In this study, we explored how RA regulates UBP43 expression and the effects of UBP43 on PML/RARα stability and APL growth, apoptosis, or differentiation. RA treatment induced UBE1L, ISG15, and UBP43 expression in RA-sensitive but not RA-resistant APL cells. Similar in vivo findings were obtained in a transgenic mouse model of transplantable APL, and in the RA response of leukemic cells harvested directly from APL patients. UBP43 knockdown repressed PML/RARα protein levels and inhibited RA-sensitive or RA-resistant cell growth by destabilizing the PML domain of PML/RARα. This inhibitory effect promoted apoptosis but did not affect the RA differentiation response in these APL cells. In contrast, elevation of UBP43 expression stabilized PML/RARα protein and inhibited apoptosis. Taken together, our findings define the ubiquitin protease UBP43 as a novel candidate drug target for APL treatment.


Diabetes Screening Through Community Pharmacies in England: A Cost-Effectiveness Study.
Community pharmacies are commonly used to screen for patients with diabetes. The aim of this paper is to estimate the cost per test and cost per appropriately referred patient from a pharmacy perspective using a one-year decision tree model. One-way sensitivity analysis was performed to estimate the effect of geographical location and patient self-referral rate. Data was used from 164 patients screened and located in an area with average social deprivation and largely white European inhabitants and 172 patients in an area with higher social deprivation (lower than average ability to access society's resources) and a mixed ethnicity population in England. The diabetes screening consisted of initial risk assessment via questionnaire followed by HbA1c test for those identified as high risk. The cost per person screened was estimated as £28.65. The cost per appropriately referred patient with type 2 diabetes was estimated to range from £7638 to £11,297 in deprived mixed ethnicity and non-deprived areas respectively. This increased to £12,730 and £18,828, respectively, if only 60% of patients referred chose to inform their general practitioner (GP). The cost per test and identification rates through community pharmacies was similar to that reported through medical practices. Locating services in areas of suspected greater diabetes prevalence and increasing the proportion of patients who follow pharmacist advice to attend their medical practice improves cost-effectiveness.


Testing tuberculosis drug efficacy in a zebrafish high-throughput translational medicine screen.
The translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. We investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. As a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. This is important, because despite the many applications of assessing drug efficacy in zebrafish research, the current methods for measuring uptake using mass spectrometry do not take into account the possible adherence of drugs to the larval surface. Our approach combines nanoliter sampling from the yolk using a microneedle, followed by mass spectrometric analysis. To date, no single physicochemical property has been identified to accurately predict compound uptake; our method offers a great possibility to monitor how any novel compound behaves within the system. We have correlated the uptake data with high-throughput drug-screening data from Mycobacterium marinum-infected zebrafish larvae. As a result, we present an improved zebrafish larva drug-screening platform which offers new insights into drug efficacy and identifies potential false negatives and drugs that are effective in zebrafish and rodents. We demonstrate that this improved zebrafish drug-screening platform can complement conventional models of in vivo Mycobacterium tuberculosis-infected rodent assays. The detailed comparison of two vertebrate systems, fish and rodent, may give more predictive value for efficacy of drugs in humans.


Privacy, professionalism and Facebook: a dilemma for young doctors.
This study aimed to examine the nature and extent of use of the social networking service Facebook by young medical graduates, and their utilisation of privacy options. We carried out a cross-sectional survey of the use of Facebook by recent medical graduates, accessing material potentially available to a wider public. Data were then categorised and analysed. Survey subjects were 338 doctors who had graduated from the University of Otago in 2006 and 2007 and were registered with the Medical Council of New Zealand. Main outcome measures were Facebook membership, utilisation of privacy options, and the nature and extent of the material revealed. A total of 220 (65%) graduates had Facebook accounts; 138 (63%) of these had activated their privacy options, restricting their information to 'Friends'. Of the remaining 82 accounts that were more publicly available, 30 (37%) revealed users' sexual orientation, 13 (16%) revealed their religious views, 35 (43%) indicated their relationship status, 38 (46%) showed photographs of the users drinking alcohol, eight (10%) showed images of the users intoxicated and 37 (45%) showed photographs of the users engaged in healthy behaviours. A total of 54 (66%) members had used their accounts within the last week, indicating active use. Young doctors are active members of Facebook. A quarter of the doctors in our survey sample did not use the privacy options, rendering the information they revealed readily available to a wider public. This information, although it included some healthy behaviours, also revealed personal information that might cause distress to patients or alter the professional boundary between patient and practitioner, as well as information that could bring the profession into disrepute (e.g. belonging to groups like 'Perverts united'). Educators and regulators need to consider how best to advise students and doctors on societal changes in the concepts of what is public and what is private.


Role of donor and secondary interactions in the structures and thermal properties of alkaline-earth and rare-earth metal pyrazolates.
The addition of neutral coligands to reduce the aggregation and improve the volatility of potential heavy alkaline-earth metal chemical vapor deposition (CVD) precursors has typically resulted in liberation of the coligand upon heating. A new series of dinuclear alkaline-earth and rare-earth metal pyrazolates, bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)calcium] (1), bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)strontium] (2), and bis[bis(3,5-di-tert-butylpyrazolato)bis(tetrahydrofuran)barium] (3), have been obtained from our previous donor-free oligonuclear complexes [{M(3,5-tBu2pz)2}n] (5, M = Ca, n = 3; 6, M = Sr, n = 4; 7, M = Ba, n = 6) by treatment with tetrahydrofuran (THF). Compounds 1-3, as well as the europium analogue bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)europium(II)] (4), can also be prepared by direct reaction of the metals and pyrazole in THF and anhydrous liquid ammonia. Recrystallization from hexane led to single crystals of 2-4, while the powder diffraction pattern of 1 revealed it to be isostructural with the previously published bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)ytterbium(II)] (8), providing important insight into differences and similarities between the two groups of metals. Detailed structural analysis of the compounds reveals secondary interactions including pi-bonding and agostic interactions, which are considered essential in stabilizing the metal complexes. The direct comparison of structural features and thermal properties (as evaluated by thermogravimetric analysis and sublimation studies) of the donor-free oligonuclear and the donor-containing dinuclear species offers a better understanding of the role of donors and secondary interactions.


Electronic immunization data collection systems: application of an evaluation framework.
Evaluating the features and performance of health information systems can serve to strengthen the systems themselves as well as to guide other organizations in the process of designing and implementing surveillance tools. We adapted an evaluation framework in order to assess electronic immunization data collection systems, and applied it in two Ontario public health units. The Centers for Disease Control and Prevention's Guidelines for Evaluating Public Health Surveillance Systems are broad in nature and serve as an organizational tool to guide the development of comprehensive evaluation materials. Based on these Guidelines, and informed by other evaluation resources and input from stakeholders in the public health community, we applied an evaluation framework to two examples of immunization data collection and examined several system attributes: simplicity, flexibility, data quality, timeliness, and acceptability. Data collection approaches included key informant interviews, logic and completeness assessments, client surveys, and on-site observations. Both evaluated systems allow high-quality immunization data to be collected, analyzed, and applied in a rapid fashion. However, neither system is currently able to link to other providers' immunization data or provincial data sources, limiting the comprehensiveness of coverage assessments. We recommended that both organizations explore possibilities for external data linkage and collaborate with other jurisdictions to promote a provincial immunization repository or data sharing platform. Electronic systems such as the ones described in this paper allow immunization data to be collected, analyzed, and applied in a rapid fashion, and represent the infostructure required to establish a population-based immunization registry, critical for comprehensively assessing vaccine coverage.


Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.


Toward a dimensional model of vocational interests.
Growing evidence on the predictive validity of vocational interests for job performance calls for greater consideration of interest assessment in organizations. However, a consensus on the fundamental dimensions of interests that are aligned with the contemporary world of work is still lacking. In the current research, we developed an organizing framework of vocational interests and empirically validated an 8-dimension model (SETPOINT: Health Science, Creative Expression, Technology, People, Organization, Influence, Nature, and Things). We propose that interests are structured hierarchically, with preferences for specific work activities at the lowest level (assessed using interest items), basic interests for homogeneous classes of activities at the intermediate level (assessed using basic interest scales), and broad-band interest dimensions describing general tendencies of individuals to be drawn to or motivated by broad types of work environments at the top. To derive broad-band interest dimensions, it is necessary to base it on a comprehensive range of content-specific basic interest constructs. In Study 1, we conducted an extensive review of existing basic interest scales and developed a new assessment of basic interests with 41 homogeneous scales across two samples. In Study 2, we demonstrated the structural validity of the proposed dimensional model using second-order confirmatory factor analysis and exploratory structural equation modeling with a large, diverse sample of working adults and supported its predictive validity for occupational membership in new and traditional sectors of work. We discuss implications from the current findings for building interest theory, using interest assessment for organizational research, and evaluating interest structure with appropriate methods. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age.
Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm.


Women's experiences of diagnosis and management of polycystic ovary syndrome: a mixed-methods study in general practice.
Polycystic ovary syndrome (PCOS) is a common lifelong metabolic condition with serious associated comorbidities. Evidence points to a delay in diagnosis and inconsistency in the information provided to women with PCOS. To capture women's experiences of how PCOS is diagnosed and managed in UK general practice. This was a mixed-methods study with an online questionnaire survey and semi-structured telephone interviews with a subset of responders. An online survey to elicit women's experiences of general practice PCOS care was promoted by charities and BBC Radio Leicester. The survey was accessible online between January 2018 and November 2018. A subset of responders undertook a semi-structured telephone interview to provide more in-depth data. A total of 323 women completed the survey (average age 35.4 years) and semi-structured interviews were conducted with 11 women. There were five key themes identified through the survey responses. Participants described a variable lag time from presentation to PCOS diagnosis, with a median of 6-12 months. Many had experienced mental health problems associated with their PCOS symptoms, but had not discussed these with the GP. Many were unable to recall any discussion about associated comorbidities with the GP. Some differences were identified between the experiences of women from white British backgrounds and those from other ethnic backgrounds. From the experiences of the women in this study, it appears that PCOS in general practice is not viewed as a long-term condition with an increased risk of comorbidities including mental health problems. Further research should explore GPs' awareness of comorbidities and the differences in PCOS care experienced by women from different ethnic backgrounds.


Differing cytokine responses by ethnic groups to a bout of exercise-induced muscle damage: a preliminary report.
Strenuous exercise has been shown to alter immune and inflammatory responses potentially predisposing athletes to infection and injury. Ethnic disparities have been demonstrated in athletic performance and in the way individuals respond to exercise as well as in the predisposition towards certain diseases however, the information relating to immune and inflammatory responses to exercise between ethnic groups is still limited. The aim of this study was to investigate whether serum cytokine levels respond differently to eccentrically-biased exercise in African and Caucasian males. Seven black and 8 white males (18-22 years), active but untrained, participated in the study. Participants performed a 60-minute downhill run on a treadmill (gradient -13.5%) at a speed eliciting 75% of their VO2peak on a level grade. Venipunctures were performed before, immediately after and then at 3, 6, 9, 12, 24 hours, and 1, 2 and 3 weeks afterwards. The following serum cytokine concentrations were quantified using the Bio-Plex suspension array system: IL-4, IL-6, IL-10, IL-1ra, IL-12p70, IFNγ, IL-7, IL-8, MCP-1, MIP-1β, eotaxin, IP-10, IL-1β, TNFα, GM-CSF, G-CSF, FGF basic and VEGF. Significant differences between the two groups were evident from 6 hours postexercise onwards with the African runners maintaining significantly higher relative cytokine concentrations. IL-6 serum concentrations of the African runners, for example, ranged from 8% to 55.1% higher than that of the Caucasian runners from 6 hours to 2 weeks postexercise (P<0.05). The study demonstrated that the cytokine response to a bout of downhill running differs between African and Caucasian runners indicating that ethnicity may play a role in exercise-induced immune and inflammatory responses.


Can we assume that research participants are utility maximisers?
The objective of this study was to experimentally examine by means of an information manipulation if respondents are adhering to the utility theory axiom of utility maximisation. A repeated measure experimental design was used. Assessments were conducted pre- and post-intervention with self-administered questionnaires. The study participants were 158 (142 after exclusions) first year undergraduate students, Bangor University (UK). The intervention-information manipulation-did not induce the hypothesised changes in the perceived pros and cons of, or desire for, genetic testing and counselling for breast cancer; correlation revealed a weak relationship between the pros and cons of and desire for testing and counselling. We conclude that there was no evidence of utility maximisation-the key tenet of utility theory-being used. Given the contradiction between the findings of this study and others, there is a need to conduct further research into utility maximisation.


Influence of low-level laser on the speed of orthodontic movement.
This study evaluated the effect of low-level laser irradiation on the speed of orthodontic tooth movement of canines submitted to initial retraction. Twenty-six canines were retracted by using NiTi spring (force of 150 g/side). Thirteen of those were irradiated with diode laser (780 nm, 20 mW, 10 sec, 5 J/cm(2)) for 3 days, and the other 13 were not irradiated and thus were considered the control group. Patients were followed up for 4 months, and nine laser applications were performed (three each month). The movement of the canines was evaluated through 3D casts, and the statistical analysis was performed with ANOVA and Tukey tests (p < 0.05). Periapical radiographs of the studied teeth were submitted to Levander, Malmgreen, and alveolar bone ridge analyses to evaluate tissue integrity and were compared with the Wilcoxon test (p < 0.05). A statistically significant increase in the movement speed of irradiated canines was observed in comparison with nonirradiated canines in all evaluation periods. No statistically significant difference was observed in bone and root resorption of canines, whether irradiated or not. The diode laser used within the protocol guidelines increased the speed of tooth movement. This might reduce orthodontic treatment time.


Paternally expressed imprinted genes associate with hybridization barriers in Capsella.
Hybrid seed lethality is a widespread type of reproductive barrier among angiosperm taxa1,2 that contributes to species divergence by preventing gene flow between natural populations3,4. Besides its ecological importance, it is an important obstacle to plant breeding strategies 5 . Hybrid seed lethality is mostly due to a failure of the nourishing endosperm tissue, resulting in embryo arrest3,6,7. The cause of this failure is a parental dosage imbalance in the endosperm that can be a consequence of either differences in parental ploidy levels or differences in the 'effective ploidy', also known as the endosperm balance number (EBN)8,9. Hybrid seed defects exhibit a parent-of-origin pattern3,6,7, suggesting that differences in number or expression strength of parent-of-origin-specific imprinted genes underpin, as the primary or the secondary cause, the molecular basis of the EBN7,10. Here, we have tested this concept in the genus Capsella and show that the effective ploidy of three Capsella species correlates with the number and expression level of paternally expressed genes (PEGs). Importantly, the number of PEGs and the effective ploidy decrease with the selfing history of a species: the obligate outbreeder Capsella grandiflora had the highest effective ploidy, followed by the recent selfer Capsella rubella and the ancient selfer Capsella orientalis. PEGs were associated with the presence of transposable elements and their silencing mark, DNA methylation in CHH context (where H denotes any base except C). This suggests that transposable elements have driven the imprintome divergence between Capsella species. Together, we propose that variation in transposable element insertions, the resulting differences in PEG number and divergence in their expression level form one component of the effective ploidy variation between species of different breeding system histories, and, as a consequence, allow the establishment of endosperm-based hybridization barriers.


Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.
Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10-7). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10-15) in the combined analysis. We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.


Lessons learned from the dog genome.
Extensive genetic resources and a high-quality genome sequence position the dog as an important model species for understanding genome evolution, population genetics and genes underlying complex phenotypic traits. Newly developed genomic resources have expanded our understanding of canine evolutionary history and dog origins. Domestication involved genetic contributions from multiple populations of gray wolves probably through backcrossing. More recently, the advent of controlled breeding practices has segregated genetic variability into distinct dog breeds that possess specific phenotypic traits. Consequently, genome-wide association and selective sweep scans now allow the discovery of genes underlying breed-specific characteristics. The dog is finally emerging as a novel resource for studying the genetic basis of complex traits, including behavior.


Excess polymorphism at the Adh locus in Drosophila melanogaster.
The evolutionary history of a region of DNA encompassing the Adh locus is studied by comparing patterns of variation in Drosophila melanogaster and its sibling species, D. simulans. An unexpectedly high level of silent polymorphism in the Adh coding region relative to the 5' and 3' flanking regions in D. melanogaster is revealed by a populational survey of restriction polymorphism using a four-cutter filter hybridization technique as well as by direct sequence comparisons. In both of these studies, a region of the Adh gene encompassing the three coding exons exhibits a frequency of polymorphism equal to that of a 4-kb 5' flanking region. In contrast, an interspecific sequence comparison shows a two-fold higher level of divergence in the 5' flanking sequence compared to the structural locus. Analysis of the patterns of variation suggest an excess of polymorphism within the D. melanogaster Adh locus, rather than lack of polymorphism in the 5' flanking region. An approach is outlined for testing neutral theory predictions about patterns of variation within and between species. This approach indicates that the observed patterns of variation are incompatible with an infinite site neutral model.


An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study)
Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QTc = QT/square root of RR) proposed in 1920 by Bazett. The QTc formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QTc and linear corrected QT (QTLC). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated.(ABSTRACT TRUNCATED AT 250 WORDS)