Performance and Accuracy of Lightweight and Low-Cost GPS Data Loggers According to Antenna Positions, Fix Intervals, Habitats and Animal Movements.
Recently developed low-cost Global Positioning System (GPS) data loggers are promising tools for wildlife research because of their affordability for low-budget projects and ability to simultaneously track a greater number of individuals compared with expensive built-in wildlife GPS. However, the reliability of these devices must be carefully examined because they were not developed to track wildlife. This study aimed to assess the performance and accuracy of commercially available GPS data loggers for the first time using the same methods applied to test built-in wildlife GPS. The effects of antenna position, fix interval and habitat on the fix-success rate (FSR) and location error (LE) of CatLog data loggers were investigated in stationary tests, whereas the effects of animal movements on these errors were investigated in motion tests. The units operated well and presented consistent performance and accuracy over time in stationary tests, and the FSR was good for all antenna positions and fix intervals. However, the LE was affected by the GPS antenna and fix interval. Furthermore, completely or partially obstructed habitats reduced the FSR by up to 80% in households and increased the LE. Movement across habitats had no effect on the FSR, whereas forest habitat influenced the LE. Finally, the mean FSR (0.90 ± 0.26) and LE (15.4 ± 10.1 m) values from low-cost GPS data loggers were comparable to those of built-in wildlife GPS collars (71.6% of fixes with LE < 10 m for motion tests), thus confirming their suitability for use in wildlife studies.


Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice.
Chemerin, acting through its receptor ChemR23, is an adipokine associated with inflammatory response, glucose and lipid metabolism and vascular function. Although this adipokine has been associated with the development and progression of kidney disease, it is not clear whether the chemerin/ChemR23 system plays a role in renal function in the context of diabetes. Therefore, we sought to determine whether ChemR23 receptor blockade prevents the development and/or progression of diabetic nephropathy and questioned the role of oxidative stress and Nrf2 in this process. Renal redox state and function were assessed in non-diabetic lean db/m and diabetic obese db/db mice treated with vehicle or CCX832 (ChemR23 antagonist). Renal reactive oxygen species (ROS) production, which was increased in diabetic mice, was attenuated by CCX832. This was associated with an increase in Nox 4 expression. Augmented protein oxidation in db/db mice was not observed when mice were treated with CCX832. CCX832 also abrogated impaired Nrf2 nuclear activity and associated downregulation in antioxidants expression in kidneys from db/db mice. Our in vivo findings highlight the role of the redox signaling and Nrf2 system as renoprotective players during chemerin receptor blockade in diabetic mice. The chemerin/ChemR23 system may be an important target to limit renal dysfunction associated with obesity-related diabetes.


[An analysis of the referrals of primary care physicians to a hospital hypertension unit].
To describe the referral of hypertense patients from primary care to a hospital arterial hypertension unit, the quality of the information sent and the profile of the referred patients. A descriptive crossover study. The Hospital Clínico of San Carlos in Madrid. A simple random sample of 368 clinical records belonging to patients attended at the unit over the last 3 years. 54.6% of patients were referred from primary care. 48.9% of the interclinical (IC) notes were high-quality, with 28.7% acceptable. 36.8% of referrals were considered incorrect, 30.3% because of false unresponsiveness to treatment. Good or acceptable IC notes were associated with 94.1% of correct referrals and only 65.4% of incorrect referrals. A high proportion of referrals which were incorrect by the consensus criteria were detected and were caused by inadequate or insufficient medical treatment. There was a statistically significant relationship found between correct referrals and the quality of information sent in the IC note.


Physiological and morphological factors influencing wear resistance and recovery in C3 and C4 turfgrass species.
High turfgrass wear resistance and recovery are the most sought after characteristics in turfgrass species when used for sports turf, but they are also very important in home gardens and public parks. Several wear resistance investigations have been conducted in field conditions in recent years, but these investigations involved the use of machinery and techniques that are not able to segregate the plant wounding and death effects from soil compaction effects that are generally associated with turfgrass wear. The same can be said of wear recovery investigations, with an extensive use of agronomical machinery for field trials. This study focussed on the wear resistance and recovery of mature swards of Cynodon dactylon (L.) Pers. var. dactylon×C. transvaalensis Burt-Davy cv. Tifway 419, Zoysia matrella (L.) Merr. cv. Zeon and Paspalum vaginatum Swartz. cv. Salam and a typical sports-type mix of Lolium perenne L. (cvv. Speedster 35% and Greenway 35%)+Poa pratensis L. (cvv. SR2100 15% and Greenknight 15%). The goal of this trial was to evaluate turfgrass wear resistance and recovery devoid of climatic and soil effects and thus, sward growing, wear simulation and recovery were conducted in controlled environment. Furthermore, wear simulation was conducted with FIFA-approved, numerical control machinery (Lisport). Wear resistance and recovery data was plotted against results from laboratory investigations on key tissue constituents. Zoysia matrella proved to be the most wear resistant, but the slowest in recovery, whereas the bermudagrass hybrid showed the exact opposite behaviour. Lignin and carbohydrate concentrations proved to be the two factors most closely correlated with wear resistance and recovery respectively. These two classes of compounds were present in an equilibrium that was species specific, with a frequent mutual exclusion between lignin and starch concentrations that deserves further investigation at the intra-specific level.


Macular degeneration associated with aberrant expansion of trinucleotide repeat of the SCA7 gene in 2 Japanese families.
To evaluate the macular function of Japanese patients with a trinucleotide repeat expansion in the spinocerebellar ataxia type 7 (SCA7) gene. Ophthalmic findings in patients whose DNA analysis revealed expanded alleles of the trinucleotide repeat in the SCA7 gene were evaluated. Trinucleotide repeat was expanded from 40 to 48 in affected patients (control subjects, 12 repeats). Affected patients were characterized by different degrees of visual acuity decrease (0.09-0.9), a tritan axis color vision, a coarse granular appearance of the macular region on scanning laser ophthalmoscopy, depression of multifocal electroretinograms, and macular degeneration. However, pigmentary changes were not observed in the retina. The trinucleotide repeat was longer and the onset of macular dysfunction was earlier in the younger generation. One patient in a family manifested decreased visual acuity 10 years preceding other neurologic signs. Patients with SCA7 mutations showed macular dysfunction or degeneration with expansion of CAG repeat in the SCA7 gene. However, the lesions were less pigmented than those previously reported. Patients also showed ophthalmologic anticipation, which has not been reported for the ocular changes in other patients who have trinucleotide repeat expansion of the responsible genes.


The effect of nebulized antibiotics in children with tracheostomy.
Children with tracheostomy have an increased risk of bacterial colonization and infection of the lower respiratory tracts. This study aimed to investigate the effects of nebulized antibiotics on the bacterial load, the need for oral antibiotics, the number of hospitalizations, and the length of stay in the intensive care unit in tracheotomised children with persistent colonization. Children with tracheostomy and persistent bacterial colonization who were started on nebulized antibiotic therapy after a lower respiratory tract infection were included in the study. Nebulized gentamicin or colistin were used according to the results of the tracheal aspirate cultures. Demographic and clinic characteristics were recorded from one year prior until one year after initiation of nebulized antibiotic treatment. Nebulized antibiotic treatment was initiated in 22 patients. Nebulized gentamicin was administered to 14 patients (63.6%) and colistin to 8 patients (36.4%). The median duration of treatment was 3 months (range 2-5 months). Following nebulized antibiotic treatment, median number of hospitalizations decreased from 2 (range 1.0-3.5) to 1 (range 0.0-1.5) (p = 0.04). The median length of stay in the intensive care unit reduced significantly from 89.5 days (range 43.0-82.5) to 25 days (range 7.75-62.75) after starting nebulized antibiotics (p = 0.028). Following nebulized antibiotic treatment median bacterial colony count also decreased (from 105 CFU/ml (range 105-106) to 6 × 104 CFU/ml (range 104-105); p = 0.003). There were no significant side effects during nebulized antibiotic therapy. The use of nebulized antibiotics reduced the number of hospitalizations, length of stay in the intensive care unit, and bacterial load in tracheotomised children with persistent airway colonization without significant side effects. The use of nebulized antibiotics showed a statistically significant decrease in the measures studied. Use of nebulized antibiotics may help to decrease the health care burden of these children, families and health care system. Further studies are needed to determine the indications and optimal duration of long-term nebulized antibiotic treatment in children with tracheostomy.


SARS-CoV-2 Infection and the Liver.
A novel strain of coronoviridae (SARS-CoV-2) was reported in Wuhan China in December 2019. Initially, infection presented with a broad spectrum of symptoms which typically included muscle aches, fever, dry cough, and shortness of breath. SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract. However, there is evidence that these receptors are abundant throughout the body, and just as abundant in cholangiocytes as alveolar cells, posing the question of possible direct liver injury. While liver enzymes and function tests do seem to be deranged in some patients, it is questionable if the injury is due to direct viral damage, drug-induced liver injury, hypoxia, or microthromboses. Likely, the injury is multifactoral, and management of infected patients with pre-existing liver disease should be taken into consideration. Ultimately, a vaccine is needed to aid in reducing cases of SARS-CoV-2 and providing immunity to the general population. However, while considering the types of vaccines available, safety concerns, particularly of RNA- or DNA-based vaccines, need to be addressed.


TiO2/S-Doped Carbons Hybrids: Analysis of Their Interfacial and Surface Features.
Hybrids containing approximately equal amounts of P25 TiO2 and S-doped porous carbons were prepared using a water-based slurry mixing method. The materials were extensively characterized by adsorption of nitrogen, potentiometric titration, thermal analysis in air and in helium, XRD, XPS and SEM. The collected results showed the significant blockage of carbon micropores by TiO2 particles deposited on their outer surface. The formation of a new interface, especially for the S-rich samples, might also contribute to the porosity alteration. Analysis of surface chemistry suggested the presence of Ti-S bonds with an involvement of sulfur from thiophenic species in the carbon phase. The latter, especially when polymer-derived, was mainly deposited on the TiO2 nanoparticles. Formation of Ti-S stabilized sulfur and increased the ignition temperature of the hybrids, especially those with a high content of sulfur, in comparison with the ignition temperature of carbons. The surfaces of hybrid with S-containing carbons was also thermally very stable and of basic chemical nature. The formation of interfacial structures Ti-C was detected by XPS analysis suggesting a partial reduction of the Ti.


Gold patterned biochips for on-chip immuno-MALDI-TOF MS: SPR imaging coupled multi-protein MS analysis.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of immuno-captured target protein efficiently complements conventional immunoassays by offering rich molecular information such as protein isoforms or modifications. Direct immobilization of antibodies on MALDI solid support enables both target enrichment and MS analysis on the same plate, allowing simplified and potentially multiplexing protein MS analysis. Reliable on-chip immuno-MALDI-TOF MS for multiple biomarkers requires successful adaptation of antibody array biochips, which also must accommodate consistent reaction conditions on antibody arrays during immuno-capture and MS analysis. Here we developed a facile fabrication process of versatile antibody array biochips for reliable on-chip MALDI-TOF-MS analysis of multiple immuno-captured proteins. Hydrophilic gold arrays surrounded by super-hydrophobic surfaces were formed on a gold patterned biochip via spontaneous chemical or protein layer deposition. From antibody immobilization to MALDI matrix treatment, this hydrophilic/phobic pattern allowed highly consistent surface reactions on each gold spot. Various antibodies were immobilized on these gold spots both by covalent coupling or protein G binding. Four different protein markers were successfully analyzed on the present immuno-MALDI biochip from complex protein mixtures including serum samples. Tryptic digests of captured PSA protein were also effectively detected by on-chip MALDI-TOF-MS. Moreover, the present MALDI biochip can be directly applied to the SPR imaging system, by which antibody and subsequent antigen immobilization were successfully monitored.


Differences in the Density of Fungiform Papillae and Composition of Saliva in Patients With Taste Disorders Compared to Healthy Controls.
This study investigated the relation of the fungiform taste papillae density and saliva composition with the taste perception of patients suffering from diagnosed taste disorders. For this purpose, 81 patients and 40 healthy subjects were included. Taste was measured by means of regional and whole mouth chemosensory tests, and electrogustometry. Olfaction was assessed using the Sniffin Sticks. Fungiform papillae were quantified using the "Denver Papillae Protocol for Objective Analysis of Fungiform Papillae". In addition, salivary parameters [flow rate, total proteins, catalase, total anti-oxidative capacity (TAC), carbonic anhydrase VI (caVI), and pH] were determined and the Beck Depression Inventory was administered. Patients showed less taste papillae compared to healthy subjects. The number of papillae correlated with total taste strip score and salivary flow rate. Regarding salivary parameters, the flow rate, protein concentration, and TAC of patients were higher compared to controls. In addition, salivary flow rate, protease, caVI, and catalase values correlated with the summed taste strip score. Regarding various taste disorders, salty-dysgeusia patients showed the lowest taste test scores compared to those with bitter or metal-dysgeusia. Olfactory function of patients was significantly worse compared to healthy controls. This difference was most pronounced for ageusia patients. Compared to controls, patients also exhibited higher depressive symptoms. The density of fungiform papillae seemed to be positively associated with taste perception. Furthermore, patients exhibited changes in saliva composition (higher salivary flow rate, increased protein concentration, proteolysis, and TAC) compared to controls indicating that assessment of saliva may be critical for the diagnostic procedure in taste disorders.


Evaluation of laser power stability of repeatedly used SubCyclo probe in micropulse transscleral cyclophotocoagulation for glaucoma: A step towards sustainable ophthalmic surgery.
To evaluate the laser power stability of the SubCyclo probe for micropulse transscleral cyclophotocoagulation after repeated use. This experimental study involved 6 new probes. Each probe was connected to the SubCyclo mode (2,000 mW power, 31.3% duty cycle, and 100 seconds duration) of the Vitra 810 laser delivery system (Quantel Medical, France). Laser power measurements were taken using a calibrated laser power meter (Nova, Ophir Optronics Solutions, Israel) every 10 seconds from 10 to 90 seconds during each of the 40 cycles. Intra-rater reliability was assessed using intraclass correlation (ICC). A linear mixed model for repeated measures and pairwise comparisons with Bonferroni adjustment were used for the analysis. The mean (SD) power outputs of all probes for the first cycle and all cycles were 421.9 (19.7) mW and 436.7 (16.1) mW, respectively. During the first cycle, the mean (SD) laser power gradually decreased from 444.3 (13.4) mW at 10 seconds to 407.3 (17.0) mW at 90 seconds (Fig 3). For all cycles, the power was 446.0 (13.6) mW at 10 seconds and gradually declined to 426.8 (21.0) mW at 90 seconds. Pairwise comparisons revealed significant differences in mean laser power outputs after 16 cycles of repeated use compared to the first cycle. The ICC estimate (95% CI) for intra-rater reliability was 0.96 (0.89, 0.99). The SubCyclo probe maintains stable laser power outputs throughout repeated use for up to 16 cycles, with a significant increase observed after 16 cycles.


Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263) that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability.


Morbidity associated with iliac crest harvesting in the treatment of maxillary and mandibular atrophies: a 10-year analysis.
The iliac crest provides an important donor site for cancellous, cortical, and corticocancellous bone because it has the highest concentration of osteocompetent cells, offers sufficient volume, and is readily accessible. Although iliac crest harvesting is considered a common procedure in different medical specialities, donor site morbidity is a subject that requires further discussion. Moreover, the increasing number of bone grafts being undertaken stresses the importance of donor site morbidity in surgical planning and for patient consent. This study evaluated morbidity associated with iliac crest harvesting over a 10-year period and patients' overall satisfaction. This prospective study involved 235 patients who were scheduled for iliac harvesting procedures from April 2001 through May 2010. A standardized surgical procedure with an anterior approach was used for the harvesting of all iliac crest grafts. The following variables were considered: pain, discomfort, presence of functional disorders, presence of sensory disturbances, esthetic outcome, and patients' general satisfaction, which were evaluated using specific tests or questionnaires. Ninety-nine percent of patients complained of mild pain 1 week after intervention but the pain rapidly disappeared after a few weeks. Functional disorders such as alterations in walking and lifting strength were reported by 100% of patients after intervention, but after 5 weeks this percentage had decreased substantially. Sensory disturbances such as hypoesthesia were recognized as transitory complications of iliac crest harvesting. A large percentage of patients were satisfied with the esthetic outcome of the intervention. Although the anterior iliac crest is a donor site with low morbidity, many studies have reported contrasting results. These data support the idea that the surgical approach plays a crucial role in decreasing postoperative morbidity. Moreover, this study confirmed that the anterior iliac crest can be considered a first-rate option for bone-defect reconstruction because of its low morbidity. However, future improvements in bone substitutes may well change this situation.


Subglottic stenosis in newborn intensive care unit graduates.
Five infants with postintubation subglottic stenosis were identified among 64 intubated patients in a follow-up clinic. The presence of laryngeal lesions was not suspected until three weeks to three months after discharge from their initial hospitalization. The onset of stridor, often precipitated by respiratory illness, led to the diagnosis, which in one case was delayed for as long as three months. No correlation was found between the presence of the severity of laryngeal pathology and the gestational age of the infants or the duration of intubation in this study. In spite of the precautions taken for the intubation of neonates requiring assisted ventilation, subglottic stenosis may develop in these infants and should always be considered in newborn intensive care unit graduates when they manifest refractory or recurrent respiratory obstruction in the first year of life. Routine follow-up of all intubated neonates to detect subglottic stenosis is recommended.


Human interferons: structure and function.
Other relevant areas of research regarding the structure and function of IFNs include the study of IFN fragments and hybrid IFN molecules prepared by recombinant DNA technology, and monoclonal antibodies against IFNs have also made major contributions to our knowledge of IFN structure and function. However, these topics have been addressed in a number of recent reviews (Zoon and Wetzel, 1984; Langer and Pestka, 1985). We are now awaiting the crystal structure of several human IFNs. Once this knowledge has been acquired, we can proceed to envisage at the three-dimensional level how these molecules interact with their receptors to produce their numerous biological activities.


Comparative study of the X-ray reflectivity and in-depth profile of a-C, B₄C and Ni coatings at 0.1-2 keV.
The use of soft X-rays near the carbon edge of absorption (270-300 eV) greatly enhances studies in various branches of science. However, the choice of reflecting coatings for mirrors operating in free-electron and X-ray free-electron laser (FEL and XFEL) beamlines in this spectral range is not so evident and experimental justifications of the mirror efficiency are rather limited. In the present paper it is demonstrated experimentally that the reflectivity of B4C- and Ni-coated grazing-incidence mirrors is high enough for their operation in FEL or XFEL beamlines near the carbon K-edge of absorption. The minimal reflectivity of both mirrors proves to exceed 80% near the carbon absorption edge at a grazing angle of 0.6°. An in-depth profile of the chemical elements composing the reflecting coatings is reconstructed based on analysis of a set of reflectivity curves measured versus the grazing angle at different photon energies in the soft X-ray spectral region. This allows us to predict correctly the mirror reflectivity at any X-ray energy and any grazing angle.


Race and nutrition: an investigation of Black-White differences in health-related nutritional behaviours.
Black-White disparities in the incidence and prevalence of chronic disease and premature morbidity are persistent and well documented in the United States. Prevailing explanations for these disparities have focused upon socioeconomic inequality and related mechanisms as the causal factors. Yet, despite the explanatory power of socioeconomic status in models of health outcomes, an unexplained racial gap in health persists. This research contributes to the study of the Black-White health divergence by exploring a mechanism with the prospect of explaining a portion of the racial gap in health remaining after adjustment for socioeconomic status. Specifically, using random coefficient regression to analyse pooled data from the 1993-1999 California Dietary Practices Survey, I identify significant differences between Blacks and Whites, after adjustment for socioeconomic status and other controls, both in global nutritional healthfulness and across a range of nutritional behaviours with established links to the development of chronic disease. Given the compelling body of literature linking nutritional behaviour to health outcomes, these differences between Blacks and Whites constitute evidence for the potential explanatory value of nutrition in future studies seeking to explain the residual racial gap in health remaining after adjustment for socioeconomic status and correlates of socioeconomic status.


Mature bovine adrenodoxin contains a 14-amino-acid COOH-terminal extension originally detected by cDNA sequencing.
Since the nucleotide sequence of bovine adrenodoxin cDNA is at variance with protein sequencing data in that it encodes an additional 14 amino acids at the COOH terminus, we used a specific antibody raised against this 14-amino-acid segment to examine its presence in: nascent precursor polypeptide chains, the processed mature adrenodoxin and mitochondria of both steroidogenic and nonsteroidogenic tissues. These studies reveal the presence of the extra peptide in the precursor form derived from in vitro translation and in the newly synthesized mature form as shown by [35S]methionine labeling of proteins in adrenocortical cells. Both the purified COOH-terminal synthetic peptide and purified mature adrenodoxin competed with radiolabeled adrenodoxin for immunoprecipitation by the anti-peptide antibody. Immunoblots revealed the presence of the extra peptide in purified adrenodoxin and in bovine adrenocortical, corpus luteal, kidney and liver mitochondria while it was not detectable in heart mitochondria. Thus, we conclude that mature adrenodoxin and its homologs in non-steroidogenic tissues contain the C-terminal extension following uptake into mitochondria. These results indicate structural homology between adrenodoxin and the iron-sulfur proteins of the kidney and liver and also suggest the presence of a second iron-sulfur protein in kidney and liver.


Progesterone lipid nanoparticles: Scaling up and in vivo human study.
This investigation describes a scaling up study aimed at producing progesterone containing nanoparticles in a pilot scale. Particularly hot homogenization techniques based on ultrasound homogenization or high pressure homogenization have been employed to produce lipid nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride. It was found that the high pressure homogenization method enabled to obtain nanoparticles without agglomerates and smaller mean diameters with respect to ultrasound homogenization method. X-ray characterization suggested a lamellar structural organization of both type of nanoparticles. Progesterone encapsulation efficiency was almost 100% in the case of high pressure homogenization method. Shelf life study indicated a double fold stability of progesterone when encapsulated in nanoparticles produced by the high pressure homogenization method. Dialysis and Franz cell methods were performed to mimic subcutaneous and skin administration. Nanoparticles constituted of tristearin in mixture with caprylic/capric triglyceride display a slower release of progesterone with respect to nanoparticles constituted of pure tristearin. Franz cell evidenced a higher progesterone skin uptake in the case of pure tristearin nanoparticles. A human in vivo study, based on tape stripping, was conducted to investigate the performance of nanoparticles as progesterone skin delivery systems. Tape stripping results indicated a decrease of progesterone concentration in stratum corneum within six hours, suggesting an interaction between nanoparticle material and skin lipids.


Isolating and maintaining highly polarized primary epithelial cells from normal human duodenum for growth as spheroid-like vesicles.
A method is described for the three-dimensional (3-D) in vitro culture of nontransformed gastrointestinal epithelial cells from the human duodenal mucosa. Biopsies obtained from human duodenum were finely minced. The tissue fragments were suspended in culture medium supplemented with 5% fetal calf serum and the appropriate antibiotics. The suspended mucosal fragments generated spheroid-like multicellular vesicles consisting of highly prismatic absorptive and goblet cells retaining most of the histological features of the tissue in vivo. We performed immunocytochemical studies to determine the origin of the vesicles using monoclonal antibodies against EP4. The histochemistry of the vesicles showed alkaline phosphatase activity. Ultrastructural studies revealed that these cells exhibit characteristics of normal duodenal cells in vivo: apical microvilli, glycocalyx, tight junctions and desmosomes, lateral membrane interdigitations, mucous droplets, and a well-developed Golgi apparatus. An overgrowth of the vesicles by fibroblasts was not seen during cultivation. In contrast with the two-dimensional cell cultures grown on artificial supports, the vesicle cells show organization similar to that of natural epithelia. The polarization and cytoarchitecture of normal gastrointestinal epithelial cells cultured as 3-D vesicles are comparable to those known for the native tissue. This study was undertaken to provide a morphological baseline for subsequent infection experiments.


Asthma phenotypes according to the timing of smoking onset in young adults.
Whether and how cigarette smoking influences asthma are still matters of debate. To identify risk factors associated with asthma according to whether individuals began active smoking before or after asthma onset. A sample of 544 individuals was examined using the protocol of the European Community Respiratory Health Status, Phase 1. Current active smoking (43.6%) was associated with wheezing during the past year (15.2%, OR 3.7; 95% CI 1.7-8.4), but not with asthma (17.6%, OR 0.78; 95% CI 0.48-1.26). However, active smoking modulated risk factors for asthma. Asthma that developed before smoking and asthma without smoking were both significantly related to nasal allergy, parental asthma and atopy (as assessed by skin prick test positivity and increased total and specific IgE levels). Only a lower FEV1 level was significantly associated with asthma that initiated after beginning smoking. Our data put forward different phenotypes of asthma according to the timing of smoking onset and suggest that asthma either never accompanied by smoking or followed by smoking onset might be characterised by an allergic pattern. Longitudinal studies are warranted to further clarify the relationships among asthma phenotypes according to the sequence of disease onset and smoking.


Goal setting and strategies to enhance goal pursuit for adults with acquired disability participating in rehabilitation.
Goal setting is considered a key component of rehabilitation for adults with acquired disability, yet there is little consensus regarding the best strategies for undertaking goal setting and in which clinical contexts. It has also been unclear what effect, if any, goal setting has on health outcomes after rehabilitation. To assess the effects of goal setting and strategies to enhance the pursuit of goals (i.e. how goals and progress towards goals are communicated, used, or shared) on improving health outcomes in adults with acquired disability participating in rehabilitation. We searched CENTRAL, MEDLINE, EMBASE, four other databases and three trials registers to December 2013, together with reference checking, citation searching and contact with study authors to identify additional studies. We did not impose any language or date restrictions. Randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs evaluating the effects of goal setting or strategies to enhance goal pursuit in the context of adult rehabilitation for acquired disability. Two authors independently reviewed search results for inclusion. Grey literature searches were conducted and reviewed by a single author. Two authors independently extracted data and assessed risk of bias for included studies. We contacted study authors for additional information. We included 39 studies (27 RCTs, 6 cluster-RCTs, and 6 quasi-RCTs) involving 2846 participants in total. Studies ranged widely regarding clinical context and participants' primary health conditions. The most common health conditions included musculoskeletal disorders, brain injury, chronic pain, mental health conditions, and cardiovascular disease.Eighteen studies compared goal setting, with or without strategies to enhance goal pursuit, to no goal setting. These studies provide very low quality evidence that including any type of goal setting in the practice of adult rehabilitation is better than no goal setting for health-related quality of life or self-reported emotional status (8 studies; 446 participants; standardised mean difference (SMD) 0.53, 95% confidence interval (CI) 0.17 to 0.88, indicative of a moderate effect size) and self-efficacy (3 studies; 108 participants; SMD 1.07, 95% CI 0.64 to 1.49, indicative of a moderate to large effect size). The evidence is inconclusive regarding whether goal setting results in improvements in social participation or activity levels, body structure or function, or levels of patient engagement in the rehabilitation process. Insufficient data are available to determine whether or not goal setting is associated with more or fewer adverse events compared to no goal setting.Fourteen studies compared structured goal setting approaches, with or without strategies to enhance goal pursuit, to 'usual care' that may have involved some goal setting but where no structured approach was followed. These studies provide very low quality evidence that more structured goal setting results in higher patient self-efficacy (2 studies; 134 participants; SMD 0.37, 95% CI 0.02 to 0.71, indicative of a small effect size) and low quality evidence for greater satisfaction with service delivery (5 studies; 309 participants; SMD 0.33, 95% CI 0.10 to 0.56, indicative of a small effect size). The evidence was inconclusive regarding whether more structured goal setting approaches result in higher health-related quality of life or self-reported emotional status, social participation, activity levels, or improvements in body structure or function. Three studies in this group reported on adverse events (death, re-hospitalisation, or worsening symptoms), but insufficient data are available to determine whether structured goal setting is associated with more or fewer adverse events than usual care.A moderate degree of heterogeneity was observed in outcomes across all studies, but an insufficient number of studies was available to permit subgroup analysis to explore the reasons for this heterogeneity. The review also considers studies which investigate the effects of different approaches to enhancing goal pursuit, and studies which investigate different structured goal setting approaches. It also reports on secondary outcomes including goal attainment and healthcare utilisation. There is some very low quality evidence that goal setting may improve some outcomes for adults receiving rehabilitation for acquired disability. The best of this evidence appears to favour positive effects for psychosocial outcomes (i.e. health-related quality of life, emotional status, and self-efficacy) rather than physical ones. Due to study limitations, there is considerable uncertainty regarding these effects however, and further research is highly likely to change reported estimates of effect.


Heterogeneity of lung disease associated with NK2 homeobox 1 mutations.
We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms.


STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma.
Background: Cancer cells undergoing invasion and metastasis possess a phenotype with attenuated glycolysis, but enhanced fatty acid oxidation (FAO). Calcium (Ca2+)-mediated signaling pathways are implicated in tumor metastasis and metabolism regulation. Stromal-interaction molecule 1 (STIM1) triggered store-operated Ca2+ entry (SOCE) is the major route of Ca2+ influx for non-excitable cells including hepatocellular carcinoma (HCC) cells. However, whether and how STIM1 regulates the invasion and metastasis of HCC via metabolic reprogramming is unclear. Methods: The expressions of STIM1 and Snail1 in the HCC tissues and cells were measured by immunohistochemistry, Western-blotting and quantitative PCR. STIM1 knockout-HCC cells were generated by CRISPR-Cas9, and gene-overexpression was mediated via lentivirus transfection. Besides, the invasive and metastatic activities of HCC cells were assessed by transwell assay, anoikis rate in vitro and lung metastasis in vivo. Seahorse energy analysis and micro-array were used to evaluate the glucose and lipid metabolism. Results: STIM1 was down-regulated in metastatic HCC cells rather than in proliferating HCC cells, and low STIM1 levels were associated with poor outcome of HCC patients. During tumor growth, STIM1 stabilized Snail1 protein by activating the CaMKII/AKT/GSK-3β pathway. Subsequently, the upregulated Snail1 suppressed STIM1/SOCE during metastasis. STIM1 restoration significantly diminished anoikis-resistance and metastasis induced by Snail1. Mechanistically, the downregulated STIM1 shifted the anabolic/catabolic balance, i.e., from aerobic glycolysis towards AMPK-activated fatty acid oxidation (FAO), which contributed to Snail1-driven metastasis and anoikis-resistance. Conclusions: Our data provide the molecular basis that STIM1 orchestrates invasion and metastasis via reprogramming HCC metabolism.


Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.
Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.


A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.
Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.


[Asthma in infants: current concepts].
Early childhood bronchial asthma is defined on a clinical basis as the occurrence of at least three episodes of wheeze before 2 years of age, once excluded a chronic obstructive lung disease, mainly cystic fibrosis. Recent birth cohort studies (Tucson, Wight island) showed that approximately 40% of early childhood asthma remain symptomatic in later childhood. Thus in any young child with asthma the question is raised of its significance, ie transient bronchial hyper-reactivity or first manifestations of a chronic asthma. At the present time, there is no specific marker which may clearly differentiate between these two opposite evolutions, and the evidence for an atopic predisposition remains the best predictive criteria for persistent asthma. This justifies preventive measures directed towards environmental protection of the at risk young child: mainly passive smoking and allergen avoidance.


Vibrational signature of charge solvation vs salt bridge isomers of sodiated amino acids in the gas phase.
The vibrational spectra of the gaseous sodium complexes of glycine (Gly-Na(+)) and proline (Pro-Na(+)) have been recorded in the spectral range 1150-2000 cm(-1). The complexes were formed by matrix-assisted laser desorption-ionization, introduced in the cell of a Fourier transform ion cyclotron resonance mass spectrometer, and their infrared spectra were recorded using photons of variable energy emitted by a free electron laser. Photon absorption was probed by the diminished intensity of the parent ion, due to its infrared-induced dissociation into bare sodium cation and the free amino acid and the appearance of Na(+). The observed absorption bands are assigned using ab initio computations of the IR spectra of the lowest energy isomers in each case. They provide the first experimental evidence that the salt bridge isomer is formed in the case of Pro-Na(+). In contrast, charge solvation by chelation of Na(+) between nitrogen and the carbonyl oxygen seems to be most favorable for Gly-Na(+), but a mixture of isomers cannot be ruled out in this case.


Spacing mutations between the Escherichia coli pBAD RNA polymerase binding site and the araC (I) induction site.
Mutations in the Escherichia coli promoter PBAD have been constructed which alter the spacing of the adjacent RNA polymerase and araC inducer protein binding sites. While deletion of a single base-pair or small insertions do not detectably affect araC protein binding to DNA and they do not alter the conserved sequence of the RNA polymerase binding site, stimulation of PBAD in vivo is greatly reduced. The experiments suggest that the distance or angle between the two proteins on the DNA is critical for promoter function.


Acral erythema with bullous formation: a side effect of chemotherapy in a child with acute lymphoblastic leukemia.
Chemotherapy-induced acral erythema (CIAE) with bullous formation is an uncommon complication in children. We describe herein a child who developed CIAE with bullous formation following high-dose methotrexate and cytarabine for relapsed acute lymphoblastic leukemia. The rash completely resolved within two weeks of the appearance without any specific treatment. CIAE may develop in children with hematological malignancies as a complication of pediatric chemotherapeutic regimens, and pediatricians should be aware of this phenomenon despite its rarity.


Mapping α2 adrenoceptors of the human brain with 11C-yohimbine.
A previous study from this laboratory suggested that (11)C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood-brain clearances, volumes of distribution, and receptor availability by means of PET with (11)C-yohimbine in healthy male adults. We recorded the distribution of (11)C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact (11)C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of (11)C-yohimbine. With the lowest steady-state distribution volume (VT), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of VT ranged from 0.82 mL cm(-3) in the right frontal cortex to 0.46 mL cm(-3) in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6-0.8 in the cortex and 0.2-0.5 in subcortical regions. The maps of (11)C-yohimbine binding to α2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer (11)C-yohimbine for mapping α2 adrenoceptors in human brain in vivo.


Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.
Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii. Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii. The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis. Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.


Finding protein-coding genes through human polymorphisms.
Human gene catalogs are fundamental to the study of human biology and medicine. But they are all based on open reading frames (ORFs) in a reference genome sequence (with allowance for introns). Individual genomes, however, are polymorphic: their sequences are not identical. There has been much research on how polymorphism affects previously-identified genes, but no research has been done on how it affects gene identification itself. We computationally predict protein-coding genes in a straightforward manner, by finding long ORFs in mRNA sequences aligned to the reference genome. We systematically test the effect of known polymorphisms with this procedure. Polymorphisms can not only disrupt ORFs, they can also create long ORFs that do not exist in the reference sequence. We found 5,737 putative protein-coding genes that do not exist in the reference, whose protein-coding status is supported by homology to known proteins. On average 10% of these genes are located in the genomic regions devoid of annotated genes in 12 other catalogs. Our statistical analysis showed that these ORFs are unlikely to occur by chance.


Effect of implant support on distal-extension removable partial dentures: in vivo assessment.
The use of a limited number of implants for support of a removable partial denture (RPD) changes a Kennedy Class I or II situation to that of a Class III. This in vivo pilot study evaluated implant-supported distal-extension removable partial dentures (RPD) in 5 partially edentulous patients. Two implants (Brånemark TU MK III, Nobel Biocare) were placed in a mandibular Kennedy Class I arch. To fabricate an implant-supported RPD (ISRPD), a conventional RPD base was fitted to the healing abutment with autopolymerizing acrylic resin (Uni-fast II, GC) to support the posterior aspect of the RPD. By changing the healing abutment to a healing cap, there was no connection between the denture base and implant, and the ISRPD became a conventional RPD (CRPD). Using a crossover study design, the masticatory movements (mandibular movements during mastication) of both dentures were measured using a commercially available tracking device (BioPACK, Bioresearch, Japan). The occlusal force and contact area were also measured using pressure-sensitive sheets and an image scanner (T-scan system). Using a visual analog scale (VAS), the 4 criteria of comfort, chewing, retention, and stability were evaluated. All the data obtained were analyzed using Wilcoxen signed rank tests (alpha = .05). There were no significant differences (P > .05) in masticatory movements between the ISRPD and the CRPD (5 patients: 4 women, 1 man). However, the ISRPD had significantly greater force and greater area than the CRPD (P = .043). The center of occlusal force of the ISRPD tended to move more distally compared to the CRPD. All the patients preferred the ISRPD for comfort, chewing, retention, and stability. One implant per edentulous area and a simple attachment technique yielded a stable distal extension RPD.


Simulation of carotid artery stenting reduces training procedure and fluoroscopy times.
Outcomes from carotid artery stenting (CAS) are related to experience and technical expertise of the operator. Simulation of CAS may enhance clinical proficiency. We interrogated the impact of endovascular simulation of CAS procedures in operators who are at various stages of training. Twelve trainees (students [n = 4]; junior surgery residents, postgraduate year [PGY] 1-3 [n = 4]; and senior surgery residents or fellows, PGY 4-7 [n = 4]) were apprised of characteristics of an endovascular simulator and CAS procedures. This was followed by four independent sessions that were assessed for objective measures including procedure and fluoroscopy times and contrast agent use. A qualitative analysis grading steps of CAS by two observers using a Likert scale was performed. One-way analysis of variance and paired t-tests were employed for data analysis. For all participants (n = 12), procedure times (mean, 920 ± 279 seconds for the first session vs 454 ± 156 seconds for the fourth session; P < .01; confidence interval [CI], 315-621) and fluoroscopy cumulative times (mean, 421 ± 230 seconds for the first session vs 222 ± 102 seconds for the fourth session; P < .01; CI, 78-285) decreased with progression of cases. Students and PGY 1-3 residents decreased their procedure times significantly in comparison of initial and final sessions (P < .05 and P < .01, respectively). For all groups, fluoroscopy cumulative times were reduced, and this decrement was significant in the PGY 1-3 cohort (mean, 444 ± 8 seconds for the first session vs 265 ± 51 seconds for the fourth session; P < .01; CI, 81-276). Initial CAS procedure times were significantly different between groups (P < .05), but this was observed to resolve by the final case at study completion. Qualitatively, the Likert scores of students and PGY 1-3 residents significantly improved with case repetition, specifically in the following steps: (1) cannulation of common carotid artery and (2) sizing and deployment of embolic protection device. Senior operators (PGY 4-7) demonstrated consistently better performance overall with minimal change in scoring with case repetition. Practice leads to improvements in endovascular simulator procedure and fluoroscopy times, especially for more novice trainees. Initial operator performance gaps can be approximated with a few sessions to expected proficiency. Incorporation of endovascular simulators in residency training may assist in shortening the learning curve in rarer endovascular procedures.


Characteristics of Chronic Cough in adults in Pakistani population: A cross sectional study.
Data about causes of chronic cough are lacking in our part of world. The aim of our study was to look for spectrum of causes in our setup and to determine a correlation between causes of cough and baseline factors of age, gender, and BMI and compare it to other populations. Total 236 chronic cough patients who attended chest clinic at KRL Hospital Islamabad from January 2018 to June 2019 were included in this cross-sectional study. Chronic cough was defined as cough greater than eight weeks. Main causes of chronic cough taken were cough variant asthma, allergic rhinitis, interstitial lung disease, Gastro-esophageal reflux disease, bronchial hyper-reactivity, ACE-I induced cough and others'. Other demographic and clinical data were also recorded. The mean age was 45.16± 16.50 years and BMI was 26.23 ± 4.68kg/m2. Major cause of chronic cough was cough variant asthma in 111(47%). Age had significant positive correlations with ILD, ACE-I induced cough and CCF, while significant negative correlations with CVA and AR. On gender correlation, ILD and ACE-I cough were significantly found more in females. BMI had significant correlation with ACE-I cough only. Variability of epidemiology of cough variant asthma, allergic rhinitis and ACE-I induced cough is comparable to worldwide data while differences exist with epidemiology of interstitial lung disease. Further research is needed in the field to delineate the local trends in this regard and compare to other population groups.


Designing self-report instruments for family assessment.
As family medicine research expands, more and better self-report measures for quantifying family systems variables will be required. These measures should be developed from an accepted paradigm for instrument design that includes the following. They should be: 1) grounded in a contemporary conceptual framework; 2) constructed following a rational theoretical design that includes the sequential stages of construct identification, construct definition, item generation, item editing, item formatting, and item scoring; 3) analyzed empirically at the item level for item distribution characteristics, item-scale correlation, and item-response style correlations; 4) analyzed at the scale level for scale distribution characteristics, scale-scale correlations, and scale-response style correlation; 5) revised based on editing and empirical analysis; and 6) psychometrically evaluated for reliability (eg, internal consistency, test-retest) and validity (construct related, criterion related, and content related). Normative data from various reference populations must also be obtained to provide a basis for interpreting scores. Finally, test manuals must be written to summarize test development data and provide information on administration procedures, scoring, and interpretation.


Self management programmes for quality of life in people with stroke.
Stroke results from an acute lack of blood supply to the brain and becomes a chronic health condition for millions of survivors around the world. Self management can offer stroke survivors a pathway to promote their recovery. Self management programmes for people with stroke can include specific education about the stroke and likely effects but essentially, also focusses on skills training to encourage people to take an active part in their management. Such skills training can include problem-solving, goal-setting, decision-making, and coping skills. To assess the effects of self management interventions on the quality of life of adults with stroke who are living in the community, compared with inactive or active (usual care) control interventions. We searched the following databases from inception to April 2016: the Cochrane Stroke Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, SCOPUS, Web of Science, OTSeeker, OT Search, PEDro, REHABDATA, and DARE. We also searched the following trial registries: ClinicalTrials.gov, Stroke Trials Registry, Current Controlled Trials, World Health Organization, and Australian New Zealand Clinical Trials Registry. We included randomised controlled trials of adults with stroke living in the community who received self management interventions. These interventions included more than one component of self management or targeted more than a single domain of change, or both. Interventions were compared with either an inactive control (waiting list or usual care) or active control (alternate intervention such as education only). Measured outcomes included changes in quality of life, self efficacy, activity or participation levels, impairments, health service usage, health behaviours (such as medication adherence or lifestyle behaviours), cost, participant satisfaction, or adverse events. Two review authors independently extracted prespecified data from all included studies and assessed trial quality and risk of bias. We performed meta-analyses where possible to pool results. We included 14 trials with 1863 participants. Evidence from six studies showed that self management programmes improved quality of life in people with stroke (standardised mean difference (SMD) random effects 0.34, 95% confidence interval (CI) 0.05 to 0.62, P = 0.02; moderate quality evidence) and improved self efficacy (SMD, random effects 0.33, 95% CI 0.04 to 0.61, P = 0.03; low quality evidence) compared with usual care. Individual studies reported benefits for health-related behaviours such as reduced use of health services, smoking, and alcohol intake, as well as improved diet and attitude. However, there was no superior effect for such programmes in the domains of locus of control, activities of daily living, medication adherence, participation, or mood. Statistical heterogeneity was mostly low; however, there was much variation in the types and delivery of programmes. Risk of bias was relatively low for complex intervention clinical trials where participants and personnel could not be blinded. The current evidence indicates that self management programmes may benefit people with stroke who are living in the community. The benefits of such programmes lie in improved quality of life and self efficacy. These are all well-recognised goals for people after stroke. There is evidence for many modes of delivery and examples of tailoring content to the target group. Leaders were usually professionals but peers (stroke survivors and carers) were also reported - the commonality is being trained and expert in stroke and its consequences. It would be beneficial for further research to be focused on identifying key features of effective self management programmes and assessing their cost-effectiveness.


First Reports and Morphological and Molecular Characterization of Pratylenchus delattrei and Quinisulcius capitatus Associated with Chickpea in Ethiopia.
Chickpea (Cicer arietinum L.) is classed among the most important leguminous crops of high economic value in Ethiopia. Two plant-parasitic nematode species, Pratylenchus delattrei and Quinisulcius capitatus, were recovered from chickpea-growing areas in Ethiopia and characterized using molecular and morphological data, including the first scanning electron microscopy data for P. delattrei. New sequences of D2-D3 of 28S, ITS rDNA and mtDNA COI genes have been obtained from these species, providing the first COI sequences for P. delattrei and Q. capitatus, with both species being found for the first time on chickpea in Ethiopia. Furthermore, Pratylenchus delattrei was recovered in Ethiopia for the first time. The information obtained about these nematodes will be crucial to developing effective nematode management plans for future chickpea production.


Parent Support Programs and Coping Mechanisms in NICU Parents.
Many neonatal intensive care unit (NICU) parents experience emotional distress leading to adverse infant outcomes. Parents may not cope positively in stressful situations, and support programs often are underutilized. To determine coping mechanisms utilized by NICU parents, and types of support programs parents are likely to attend. To determine whether sociodemographic and length-of-stay differences impact coping mechanisms utilized, and types of support programs preferred. A correlational cross-sectional survey design was used. The 28-item Brief COPE tool, questions about demographics and preferred support program styles, was distributed to a convenience sample of NICU parents in a level IV NICU in the southeastern United States. One hundred one NICU parents used coping mechanisms, with acceptance emotional support, active coping, positive reframing, religion, planning, and instrumental support being the most common. Preferred support classes were infant development and talking with other NICU parents. Caucasians more commonly coped using active coping, planning, emotional support, acceptance, instrumental support, and venting compared with other races. Women utilized self-blame coping mechanisms more often compared with men. Younger parents were more likely to use venting and denial coping mechanisms. Parents with a shorter stay utilized self-distraction coping and preferred the class of talking with other parents. Support program preference, type of coping mechanism utilized, and sociodemographic factors may be used to guide the creation of NICU support programs. Additional studies are needed to determine whether support program offering according to preferences and sociodemographic characteristics increases attendance and decreases emotional distress.


Possibilities and progress of quantitative pathological examination of ovarian tumours.
Morphometric and flow DNA-cytometric analysis of ovarian tumours of the common epithelial type has an important and strong additional prognostic impact, which is stage-independent, and more important than subjective grade. In stage I cancers, combined morphometric analysis and DNA index assessed with flow-cytometry can indicate a subgroup of patients with an especially poor prognosis. In stage III and IV cancers, morphometric features exceed the prognostic value of cellular DNA content, as far as they allow selection of a small subset of patients with an excellent prognosis. These results indicate that quantitative pathological examination is of essential importance for therapeutic decision-making both in early and late ovarian cancer patients, and therefore should be carried out as a routine procedure in women with this disease.


Minority Identity, Othering-Based Stress, and Sexual Violence.
Some (minority) groups (MGs) are more vulnerable to sexual violence (SV) exposure than others. Othering-based stress (OBS) may mediate the relationship between minority identification and SV. This study aims to assess the prevalence of SV in different MGs to explore the relationship between minority identification and SV, to investigate whether belonging to multiple MGs moderates this relationship, and to explore OBS SV moderation for different MGs. Through an online survey administered to a nationally representative sample in Belgium, data was collected from 4632 persons, of whom 21.01% self-identified as belonging to a MG (SI-Minority). SV prevalence was measured using behaviorally specific questions based on the WHO definition of SV. SI-Minority participants received an additional scale on OBS. SI-Minority participants reported more SV victimization compared to the non-minorities. However, this increased risk was not moderated by minority identification but linked to the socio-demographic SV risk markers common to minority individuals. Multiple-minority participants were found more at risk of SV compared to single-minority respondents. Lesbian, gay, bisexual, pan-/omnisexual, asexual, and other non-heterosexual (LGB+) participants were found more at risk than heterosexual participants. OBS was found to be significantly correlated to SV in sexual and gender minorities and in cultural minorities. This study contributes to our understanding of the relationship between minority identification, OBS, and SV. Studying both specific and common SV vulnerabilities and outcomes within specific societal subgroups and the general population may inform policy makers when allocating resources to those interventions with the largest societal impact.


Vacancy Energetics and Diffusivities in the Equiatomic Multielement Nb-Mo-Ta-W Alloy.
In this work, we study vacancy energetics in the equiatomic Nb-Mo-Ta-W alloy, especially vacancy formation and migration energies, using molecular statics calculations based on a spectral neighbor analysis potential specifically developed for Nb-Mo-Ta-W. We consider vacancy properties in bulk environments as well as near edge dislocation cores, including the effect of short-range order (SRO) by preparing supercells through Metropolis Monte-Carlo relaxations and temperature on the calculation. The nudged elastic band (NEB) method is applied to study vacancy migration energies. Our results show that both vacancy formation energies and vacancy migration energies are statistically distributed with a wide spread, on the order of 1.0 eV in some cases, and display a noticeable dependence on SRO. We find that, in some cases, vacancies can form with very low energies at edge dislocation cores, from which we hypothesize the formation of stable 'superjogs' on edge dislocation lines. Moreover, the large spread in vacancy formation energies results in an asymmetric thermal sampling of the formation energy distribution towards lower values. This gives rise to effective vacancy formation energies that are noticeably lower than the distribution averages. We study the effect that this phenomenon has on the vacancy diffusivity in the alloy and discuss the implications of our findings on the structural features of Nb-Mo-Ta-W.


A national survey of telemedicine use by US emergency departments.
Telemedicine has the potential to improve the delivery of emergency medical care: however, the extent of its adoption in United States (US) emergency departments is not known. Our objective was to characterise the prevalence of telemedicine use among all US emergency departments, describe clinical applications for which it is most commonly used, and identify emergency department characteristics associated with its use. As part of the National Emergency Department Inventory-USA survey, we queried all 5375 US emergency departments open in 2016. Multivariable logistic regression analyses identified characteristics associated with emergency department receipt of telemedicine services. Overall, 4507 emergency departments (84%) responded to our survey, with 4031 responding to both telemedicine questions (75%). Although 1694 emergency departments (42%) reported no telemedicine in 2016, most did: 1923 (48%) emergency departments received telemedicine services, 149 (4%) emergency departments received telemedicine services and were in hospitals that provided telemedicine, and 265 emergency departments (7%) did not receive telemedicine but were in hospitals that provided telemedicine services. Among emergency departments receiving telemedicine, the most common applications were stroke/neurology (76%), psychiatry (38%), and paediatrics (15%). In multivariable analysis, telemedicine-receiving emergency departments had higher annual total visit volume for adults and lower annual total visit volume by children; were less likely to be academic or freestanding; and varied by region. In multivariable analysis, emergency departments in telemedicine-providing hospitals had higher annual total visit volume for adults and children, were more likely to be academic and were less likely to be freestanding. In 2016, telemedicine was used in most US emergency departments (58%), especially for stroke/neurology and psychiatry. Future research is needed to understand the value of telemedicine for different clinical applications, and the barriers to its implementation.


Gastrointestinal bacteria of certain Antarctic birds and mammals.
An investigation was carried out of the aerobic gram-negative intestinal flora of 158 penguins, 30 skuas, and 66 seals from the Antarctic and sub-Antarctic zones and Phillip Island. Among penguins and seals, 17% and 11%, respectively, were devoid of aerobic enteric organisms, but microscopic examination showed the presence of other bacteria. The coliforms outnumbered the paracolons and nonlactosefermenting bacteria; irregular coliform types and Escherichia coli were predominant. The present study indicated the effect of diet on the composition of the intestinal flora of the birds and mammals examined.


Purification and some properties of human placental glucose-6-phosphate dehydrogenase.
Glucose-6-phosphate dehydrogenase was purified from human placenta using DEAE-Sepharose fast flow, 2',5'-ADP Sepharose 4B column chromatography, and chromatofocusing on PBE 94 with PB 74. The enzyme was purified with 62% yield and had a specific activity of 87 units per milligram protein. The pH optimum was determined to be 7.8, using zero buffer extrapolation method. The purified placental glucose-6-phosphate dehydrogenase gave two activity bands on native PAGE: one band, constituting about 3--5% of total activity, moved slower than the remaining 95%. Among the activity bands only the faster moving band gave a band on protein staining. The slower moving band, which probably corresponded to the higher polymeric form of the G6PD with high specific activity, was not seen on native PAGE due to insufficient protein for Coomassie brilliant blue staining. The observation of one band on SDS--PAGE with an M(r) of 54 kDa and a specific activity lower than expected, suggests the presence of both forms of the G6PD, the high polymeric form at low concentration and the inactive form at high concentration, in our preparation. Measuring the activities of placental glucose-6-phosphate dehydrogenase between 20 and 50 degrees C, the activation energy, activation enthalpy, and Q(10) were calculated to be 8.16 kcal/mol, 7.55 kcal/mol, and 1.57, respectively. It was found that human placental G6PD obeys Michaelis-Menten kinetics. K(m) values were determined using the concentration ranges of 20--300 microM for G6P and 10--200 microM for NADP(+). The K(m) value for G6P was 40 microM; the K(m) value NADP(+) was found to be 20 microM. Double-reciprocal plots of 1/Vm vs 1/G6P (at constant [NADP(+)]) and of 1/Vm vs 1/NADP(+) (at constant [G6P]) intersected at the same point on the 1/V(m) axis to give V(m) = 87 U/mg protein.


[Initial mechanisms of sepsis].
The author's hypothesis of the most important role of bacterial toxins (rather than not infection) in the pathogenetic basis of sepsis is discussed. This allows one to understand why sepsis is of multiple etiologies and not transmissible as an infectious agent, and why it does not induce the immunity. In the author's opinion, the hypothesis makes it possible to develop specific therapy for sepsis, rather than its symptomatic therapy.


Analysis of clinical trials and off-label drug use in hospitalized pediatric patients.
Introduction. The lack of pediatric clinical trials (PCTs) leads to an off-label drug use (OLDU) in children. Our objective was to analyze the number and design of PCTs and OLDU in children in the past years. Population, material and methods. Observational and retrospective study on PCTs and OLDU in children, conducted from 2007 to 2012 in a 252-bed children's hospital. The number and design of PCTs and OLDU in children were analyzed by year and by characteristics. Results. Eighty-seven PCTs and 449 active ingredients corresponding to 1049 drugs prescribed to hospitalized children were evaluated.Of these, 117 (26%) were used off-label. The number of PCTs increased from 2008 to 2011. In 2011, 52.2% of PCTs were non-randomized and uncontrolled studies, and only 39.1% were randomized, controlled trials. Of all studied drugs, 77% corresponded to off-label use. OLDU in children remained steady throughout the study period. Conclusions. In our hospital, the number of pediatric research studies has increased in the past years, being non-randomized and uncontrolled studies the most frequent. OLDU in children has not changed.


Abstract Action Language Processing in Eleven-Year-Old Children: Influence of Upper Limb Movement on Sentence Comprehension.
Regarding the embodiment of language processing in adults, there is evidence of a close connection between sensorimotor brain areas and brain areas relevant to the processing of action verbs. This thesis is hotly debated and has therefore been thoroughly studied in adults. However, there are still questions concerning its development in children. The present study deals with the processing of action verbs in concrete and abstract sentences in 60 eleven-year-olds using a decision time paradigm. Sixty-five children mirrored arm movements or sat still and rated the semantic plausibility of sentences. The data of the current study suggest that eleven-year-olds are likely to misunderstand the meaning of action verbs in abstract contexts. Their decision times were faster and their error rates for action verbs in concrete sentences were lower. However, the gender of the children had a significant influence on the decision time and the number of errors, especially when processing abstract sentences. Females were more likely to benefit from an arm movement before the decision, while males were better if they sat still beforehand. Overall, children made quite a few errors when assessing the plausibility of sentences, but the female participants more often gave plausibility assessments that deviated from our expectations, especially when processing abstract sentences. It can be assumed that the embodiment of language processing plays some role in 11-year-old children, but is not yet as mature as it is in adults. Especially with regard to the processing of abstract language, the embodied system still has to change and mature in the course of child development.


Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants.
The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure. To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors. Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0-6 months and 30-42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables. Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16). High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.


Competitive binding of fatty acids and the fluorescent probe 1-8-anilinonaphthalene sulfonate to bovine beta-lactoglobulin.
The use of spectroscopy in the study of fatty acids binding to bovine beta-lactoglobulin (BLG) appears to be a difficult task, as these acid compounds, assumed as the protein natural ligands, do not exhibit favorable optical response such as, for example, absorption or fluorescence. Therefore, the BLG fatty-acid equilibrium has been tackled by exploiting the competition between fatty acids and ANS, a widely used fluorescent hydrophobic probe, whose binding sites on the protein have been characterized recently. Two lifetime decays of the ANS-BLG complex have been found; the longer one has been attributed to the internal binding site and the shorter one to the external site. At increasing fatty acids concentration, the fractional weight associated with ANS bound to the internal site drops, in agreement with a model describing the competition of the dye with fatty acids, whereas the external site occupancy appears to be unaffected by the fatty acids binding to BLG. This model is supported by docking studies. An estimate of the acid-binding affinities for BLG has been obtained by implementing the fitting of the bound ANS intensities with a competitive binding model. A relevant dependence has been found upon the solution pH, in the range from 6 to 8, which correlates with the calyx accessibility modulated by the conformation of the EF loop. Fatty acids with longer aliphatic chains (palmitate and laurate) are found to display larger affinities for the protein and the interaction free energy nicely correlates with the number of contacts inside the protein calyx, in agreement with docking simulations.


Genome-wide copy-number variation analysis identifies common genetic variants at 20p13 associated with aggressiveness of prostate cancer.
The genetic determinants for aggressiveness of prostate cancer (PCa) are poorly understood. Copy-number variations (CNVs) are one of the major sources for genetic diversity and critically modulate cellular biology and human diseases. We hypothesized that CNVs may be associated with PCa aggressiveness. To test this hypothesis, we conducted a genome-wide common CNVs analysis in 448 aggressive and 500 nonaggressive PCa cases recruited from Johns Hopkins Hospital (JHH1) using Affymetrix 6.0 arrays. Suggestive associations were further confirmed using single-nucleotide polymorphisms (SNPs) that tagged the CNVs of interest in an additional 2895 aggressive and 3094 nonaggressive cases, including those from the remaining case subjects of the JHH study (JHH2), the NCI Cancer Genetic Markers of Susceptibility (CGEMS) Study, and the CAncer of the Prostate in Sweden (CAPS) Study. We found that CNP2454, a 32.3 kb deletion polymorphism at 20p13, was significantly associated with aggressiveness of PCa in JHH1 [odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.68; P = 0.045]. The best-tagging SNP for CNP2454, rs2209313, was used to confirm this finding in both JHH1 (P = 0.045) and all confirmation study populations combined (P = 1.77 × 10(-3)). Pooled analysis using all 3353 aggressive and 3584 nonaggressive cases showed the T allele of rs2209313 was significantly associated with an increased risk of aggressive PCa (OR = 1.17, 95% CI: 1.07-1.27; P = 2.75 × 10(-4)). Our results indicate that genetic variations at 20p13 may be responsible for the progression of PCa.


Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients.
The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques.


Risk assessment of diabetic retinopathy with machine and deep learning models with PPG signals and PWV.
Retinopathy is one of the most common micro vascular impairments in diabetic subjects. Elevated blood glucose leads to capillary occlusion, provoking the uncontrolled increase in local growth of new vessels in the retina. When left untreated, it can lead to blindness. Traditional approaches for retinopathy detection require expensive devices and high specialized personnel. Being a microvascular complication, the retinopathy could be detected using the photoplethysmography (PPG) technology. In this paper we investigate the predictive value of the pulse wave velocity and PPG signal analysis with machine and deep learning approaches to detect retinopathy in diabetic subjects. PPG signals and pulse wave velocity (PWV) showed promising results in assessing the diabetic retinopathy. The best performances were scored by a LightGBM based model trained over a subset of the available dataset obtaining 80% of specificity and sensitivity.Clinical relevance- PPG based retinopathy detection could make the retinopathy detection more accessible since it does not need neither expensive devices for signal acquisition nor highly specialized personnel to be interpreted.


Investigating the plasmonics of a dipole-excited silver nanoshell: Mie theory versus finite element method.
This report compares COMSOL's finite element method (FEM) algorithm with the Mie theory for solving the electromagnetic fields in the vicinity of a silica-silver core-shell nanoparticle when excited by a radiating dipole. The novelty of this investigation lies in the excitation source of the nanoshell system: an oscillating electric dipole is frequently used as a model for both molecular scattering and molecular fluorescence; moreover, a common classical model of atomic or molecular spontaneous emission is a decaying electric dipole. The radiated power spectra were evaluated both analytically and numerically by integrating the Poynting vector around 20, 60 and 100 nm nanoshells, thereby solving the total and scattered fields generated by a dipole positioned inside the core and in the surrounding air medium, respectively. The agreement was excellent in amplitude, plasmon resonance peak position and full width at half-maximum. The FEM algorithm also generates accurate solutions of the near-field electromagnetics in the spatial domain, where the E-field behavior as a function of polar angle theta for a fixed observation radius was evaluated. The quasistatic approximation, which is valid for small nanoparticles, is also employed to assess its limitations relative to the Mie and FEM algorithms.


Accuracy of ultrasonography in diagnosis of testicular rupture after blunt scrotal trauma.
The aim of this study is to determine the accuracy of ultrasonography for the diagnosis of testis rupture after scrotal trauma and its sensitivity and specificity for testis rupture, tunica albuginea breach, testicular hematoma, testis avulsion, epididymis injuries, and hematocele. Between 1996 and 2006, 33 patients underwent surgical exploration for blunt scrotal trauma. All these patients had an emergency scrotal ultrasonography with the use of a 7.5 or 10 MHz linear transducer. Ultrasonographic findings were compared with surgical findings to calculate sensitivity and specificity of ultrasonography for each type of lesion. Of 33 patients, 16 presented a testis rupture. Testis rupture was in all cases suspected ultrasonographically by the loss of contour of the testis and heterogeneous parenchyma. Tunica albuginea breach was visualized in only 8 patients. Sensitivity and specificity of ultrasound for testis rupture were 100% and 65%, respectively. Moreover, ultrasonography allowed diagnosis of hematocele (sensitivity: 87% and specificity: 89%), testicular hematoma (sensitivity: 71%, specificity: 77%), and testis avulsion (sensitivity: 100%, specificity: 97%). Ultrasonography results for epididymis injuries were poor. On 7 patients, 3 epididymis lesions were misdiagnosed by ultrasound examination. Ultrasonography can distinguish various scrotal injuries. Testicular rupture is probably the most severe injury that needs early surgical treatment to improve testis salvage rate. In our work, ultrasonography is highly sensitive in the diagnosis of testis rupture and can provide information on the scrotal contents integrity that can help the physician to determine the optimal treatment.


Impact of emergency department surge and end of shift on patient workup and treatment prior to referral to internal medicine: a health records review.
The goal of this study was to determine if ED surge and end-of-shift assessment of patients affect the extent of diagnostic tests, therapeutic interventions and accuracy of diagnosis prior to referral to internal medicine. This study was a health records review of consecutive patients referred to the internal medicine service with an ED diagnosis of heart failure, chronic obstructive pulmonary disease (COPD) or sepsis starting 1 December 2013 until 100 cases for each condition had been obtained. We developed a scoring system in consultation with emergency and internal medicine physicians to uniformly assess the completeness of treatments and investigations performed. These scores, expressed as percentage of possible points, were compared at high and low surge levels and at middle and end of shift at time of patient referral. End of shift was defined as 7:30-8:30, 15:30-16:30 and 23:30-00:30 as our shift changes occur at 8:00, 16:00 and 24:00. Rate of admission, diversion to other services and diagnosis disagreements were also assessed. We included 308 patients (101 heart failure, 101 COPD, 106 sepsis) with a mean age of 74.7. Comparing middle of shift to end of shift, the mean scores were 91.9% versus 91.8% (difference 0.1% (95% CI -2.4 to 3.0)) for investigations and 73.0% versus 70.4% (difference 2.6% (95% CI -1.8 to 7.4)) for treatments. Comparing low to high surge times, the mean scores were 92.1% versus 91.7% (difference 0.4% (95% CI -1.2 to 2.4)) for investigations and 71.4% versus 73.6% (difference -2.2% (95% CI -5.6 to 1.3)) for treatments. We found low rates of diversion to alternate services (8.9% heart failure, 0% COPD, 6.6% sepsis) and low rates of diagnosis disagreement (4.0% heart failure, 10.9% COPD, 8.5% sepsis). We found no evidence that surge levels and end of shift impact the extent of investigations and treatments provided to patients diagnosed in the ED with heart failure, COPD or sepsis and referred to internal medicine.


The Speckle Tracking Imaging for the Assessment of Cardiac Resynchronization Therapy (START) study.
We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study. METHODS AND RESULTS: Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (Tmax). In segments with multiple peaks on the time-strain curves, time to the first peak (Tfirst) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. Tfirst-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78-25.6). In addition, Tfirst-SD of CS was associated with the clinical endpoints. This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders.


A genome-scale shRNA resource for transgenic RNAi in Drosophila.
Existing transgenic RNAi resources in Drosophila melanogaster based on long double-stranded hairpin RNAs are powerful tools for functional studies, but they are ineffective in gene knockdown during oogenesis, an important model system for the study of many biological questions. We show that shRNAs, modeled on an endogenous microRNA, are extremely effective at silencing gene expression during oogenesis. We also describe our progress toward building a genome-wide shRNA resource.


Bioavailability of intranasal scopolamine in normal subjects.
The bioavailability of scopolamine in three dosage forms was compared in 12 healthy nonsmoking male volunteers. Subjects received 0.4-mg doses of scopolamine bromide in intravenous (i.v.), intranasal (i.n.), or oral (p.o.) dosage forms on three occasions, with at least 2 weeks separating the doses. Scopolamine concentrations in plasma were determined with a combined reverse-phase liquid chromatographic-radioreceptor binding assay. Saliva volume and flow rate and percent suppression of control flow rate were determined from each sample. Absorption after i.n. and po scopolamine administration was rapid; plasma concentrations [1680 (i.n.) and 164 pg/mL (p.o.)] peaked within 1 h of dosing [0.37 (i.n.) and 0.78 h (p.o.)], respectively. i.n. and i.v. scopolamine suppressed salivary flow rate to similar extents (95% and 99.7%), respectively. Times to reach maximum effect were 1.05 and 0.27 h after i.n. and i.v. dosage, respectively. Absolute intranasal bioavailability, calculated from the area under the drug concentration vs time curve, was found to be significantly greater than that of p.o. scopolamine (83% vs 3.7%, p < 0.05). The i.n. route may provide a noninvasive, reliable, fast, and effective route for administering scopolamine.


Two sides to every leaf: water and CO2 transport in hypostomatous and amphistomatous leaves.
Leaves with stomata on both upper and lower surfaces, termed amphistomatous, are relatively rare compared with hypostomatous leaves with stomata only on the lower surface. Amphistomaty occurs predominantly in fast-growing herbaceous annuals and in slow-growing perennial shrubs and trees. In this paper, we present the current understanding and hypotheses on the costs and benefits of amphistomaty related to water and CO2 transport in contrasting leaf morphologies. First, there is no evidence that amphistomatous species achieve higher stomatal densities on a projected leaf area basis than hypostomatous species, but two-sided gas exchange is less limited by boundary layer effects. Second, amphistomaty may provide a specific advantage in thick leaves by shortening the pathway for CO2 transport between the atmosphere and the chloroplasts. In thin leaves of fast-growing herbaceous annuals, in which both the adaxial and abaxial pathways are already short, amphistomaty enhances leaf-atmosphere gas-exchange capacity. Third, amphistomaty may help to optimise the leaf-interior water status for CO2 transport by reducing temperature gradients and so preventing the condensation of water that could limit CO2 diffusion. Fourth, a potential cost of amphistomaty is the need for additional investments in leaf water transport tissue to balance the water loss through the adaxial surface.


Feasibility of transesophageal echocardiography in birds without cardiac disease.
To establish a technique of transesophageal echocardiography (TEE) in birds without cardiac disease and describe the imaging planes obtained. Validation study. 18 birds including 3 pigeons (Columbia livia), 3 barred owls (Strix varia), 2 red-tailed hawks (Buteo jamaicensis), 1 goose (Anser anser), 1 mallard duck (Anas platyrhynchos), 1 Muscovy duck (Cairina moschata), 2 brown pelicans (Pelecanus occidentalis), 2 Hispaniolan Amazon parrots (Amazona ventralis), 2 red-fronted macaws (Ara rubrogenys), and 1 military macaw (Ara militaris). For each bird, anesthesia was induced and maintained by use of isoflurane. A pediatric, multiplane transesophageal ultrasound probe was passed into the esophagus and adjusted to the level of the heart for echocardiography. Probe positions were recorded via fluoroscopy, and associated imaging planes were described. TEE was performed successfully in all birds except the pelicans, 1 Hispaniolan Amazon parrot, and the red-fronted macaws. Five imaging planes of the heart were consistently viewed from 3 positions of the probe (identified as caudal, middle, and cranial positions relative to the cardiac silhouette). M-mode echocardiography of the left ventricle and the aortic root was performed. Color flow and spectral Doppler ultrasonographic images of in- and outflow regions were obtained. One Hispaniolan Amazon parrot died as a result of esophageal perforation. TEE examination of birds was feasible and provided a larger number of imaging planes with better resolution and details than those typically achieved via a transcoelomic approach. However, TEE should be performed with caution in psittacines.