Airway microbial communities, smoking and asthma in a general population sample.
Normal airway microbial communities play a central role in respiratory health but are poorly characterized. Cigarette smoking is the dominant global environmental influence on lung function, and asthma has become the most prevalent chronic respiratory disease worldwide. Both conditions have major microbial components that are incompletely defined. We investigated airway bacterial communities in a general population sample of 529 Australian adults. Posterior oropharyngeal swabs were analyzed by sequencing of the 16S rRNA gene. The microbiota were characterized according to their prevalence, abundance and network memberships. The microbiota were similar across the general population, and were strongly organized into co-abundance networks. Smoking was associated with diversity loss, negative effects on abundant taxa, profound alterations to network structure and expansion of Streptococcus spp. By contrast, the asthmatic microbiota were selectively affected by an increase in Neisseria spp. and by reduced numbers of low abundance but prevalent organisms. Our study shows that the healthy airway microbiota in this population were contained within a highly structured ecosystem, suggesting balanced relationships between the microbiome and human host factors. The marked abnormalities in smokers may contribute to chronic obstructive pulmonary disease (COPD) and lung cancer. The narrow spectrum of abnormalities in asthmatics encourages investigation of damaging and protective effects of specific bacteria. The study was funded by the Asmarley Trust and a Wellcome Joint Senior Investigator Award to WOCC and MFM (WT096964MA and WT097117MA). The Busselton Healthy Ageing Study is supported by the Government of Western Australia (Office of Science, Department of Health) the City of Busselton, and private donations.


The whole-body withdrawal response of Lymnaea stagnalis. II. Activation of central motoneurones and muscles by sensory input.
The role of centrally located motoneurones in producing the whole-body withdrawal response of Lymnaea stagnalis (L.) was investigated. The motoneurones innervating the muscles used during whole-body withdrawal, the columellar muscle (CM) and the dorsal longitudinal muscle (DLM) were cells with a high resting potential (-60 to -70 mV) and thus a high threshold for spike initiation. In both semi-intact and isolated brain preparations these motoneurones showed very little spontaneous spike activity. When spontaneous firing was seen it could be correlated with the occurrence of two types of spontaneous excitatory postsynaptic potential (EPSP). One was a unitary EPSP that occasionally caused the initiation of single action potentials. The second was a larger-amplitude, long-duration (presumably compound) EPSP that caused the motoneurones to fire a burst of high-frequency action potentials. This second type of EPSP activity was associated with spontaneous longitudinal contractions of the body in semi-intact preparations. Tactile stimulation of the skin of Lymnaea evoked EPSPs in the CM and DLM motoneurones and in some other identified cells. These EPSPs summated and usually caused the motoneurone to fire action potentials, thus activating the withdrawal response muscles and causing longitudinal contraction of the semi-intact animal. Stimulating different areas of the body wall demonstrated that there was considerable sensory convergence on the side of the body ipsilateral to stimulation, but less on the contralateral side. Photic (light off) stimulation of the skin of Lymnaea also initiated EPSPs in CM and DLM motoneurones and in some other identified cells in the central nervous system (CNS). Cutting central nerves demonstrated that the reception of this sensory input was mediated by dermal photoreceptors distributed throughout the epidermis. The activation of the CM and DLM motoneurones by sensory input of the modalities that normally cause the whole-body withdrawal of the intact animal demonstrates that these motoneurones have the appropriate electrophysiological properties for the role of mediating whole-body withdrawal.


Accurate sensitivity analysis of photonic devices exploiting the finite-difference time-domain cavity adjoint variable method.
For what is believed to be the first time, the central adjoint variable method (CAVM) is applied to the sensitivity analysis of photonic devices using the finite-difference time-domain (FDTD) technique. The FDTD-CAVM technique obtains accurate sensitivities of any desired response with respect to the different design parameters. Our technique requires only one extra FDTD simulation to extract the sensitivities with respect to all the design parameters regardless of their number. Cost-free sensitivities of the power reflectivity are also derived without any additional simulation. The results show a very good agreement between the CAVM sensitivities and those obtained using the expensive central finite difference approximation.


Crystal Structure of Hexaazaoctadecahydrocoronene Dication [HAOC]2+, a Singlet Benzene Dication.
The structures of hexaazaoctadecahydrocoronene, [HAOC](n) (n = O, + 2), have been determined by single-crystal x-ray diffraction. Although HAOC is aromatic, its dication has a localized structure that is based upon Jahn-Teller-distorted cyanine/p-phenylenediammonium fragments. The structure is consistent with the singlet ground state as determined by magnetic susceptibility and contrasts with the simplest Hückel expectation of a triplet ground state.


Integrative Computational Approaches to Inform Relative Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances Across Species.
Predictive toxicology is increasingly reliant on innovative computational methods to address pressing questions in chemicals assessment. Of importance is the evaluation of contaminant impact differences across species to inform ecosystem protection and identify appropriate model species for human toxicity studies. Here we evaluated 2 complementary tools to predict cross-species differences in binding affinity between per- and polyfluoroalkyl substances (PFAS) and the liver fatty acid-binding protein (LFABP): the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool and molecular dynamics (MD). SeqAPASS determined that the structure of human LFABP, a key determinant of PFAS bioaccumulation, was conserved in the majority of vertebrate species, indicating these species would have similar PFAS bioaccumulation potentials. Level 3 SeqAPASS evaluation identified several potentially destabilizing amino acid differences across species, which were generally supported by DUET stability change predictions. Nine single-residue mutations and 7 whole species sequences were selected for MD evaluation. One mutation (F50V for PFNA) showed a statistically significant difference with stronger affinity than wild-type human LFABP. Predicted binding affinities for 9 different PFAS across 7 species showed human, rat, chicken, and rainbow trout had similar binding affinities to one another for each PFAS, whereas Japanese medaka and fathead minnow had significantly weaker LFABP-binding affinity for some PFAS. Based on these analyses, the combined use of SeqAPASS and MD provides rapid screening for potential species differences with deeper structural insight. This approach can be easily extended to other important biological receptors and potential ligands.


Interventions aimed at reducing obesity in early childhood: a meta-analysis of programs that involve parents.
Obesity is a growing problem even in very young childhood, resulting in high costs for individuals and society. As a response, numerous obesity prevention and intervention programs have been developed. Previous research has shown that early intervention programs are more effective when parents are involved, but the effectiveness of specific aspects of programs with parental involvement has not been investigated. This meta-analysis aims to investigate the features related to the effectiveness of different types of obesity intervention programs involving parents and targeting young children (0-6-year-olds). The Web of Science, PubMed, PsycInfo, CINAHL, and ERIC databases were searched for childhood obesity prevention and intervention programs involving parents. Data were analyzed using the Comprehensive Meta-analysis (CMA) software. Fifty studies with effect sizes measured at short-term follow-up (within 3 months from the end of the intervention) and 26 studies with effect sizes measured at long-term follow-up (all reported in a total of 49 publications) were identified. The combined effect size of interventions was small but significant at short-term follow-up (d = .08, p < .01). The results suggested the presence of a potential publication bias in studies providing results at long-term follow-up, with a nonsignificant adjusted effect size (d = .02), which indicated that obesity interventions were not effective at long-term follow-up. Multivariate meta-regression analyses showed that interventions were more effective when including either interactive sessions or educational materials as opposed to those including both interactive sessions and noninteractive educational materials. No other moderators regarding sample characteristics, study design, or methodological quality were significant. Interventions targeting young children that require parental involvement are effective at short-term follow-up, specifically when interventions include one mode of intervention rather than two. However, results were not retained in the long run.


Immunoreactive glandular kallikrein in plasma during alterations of urinary kallikrein excretion.
To determine whether maneuvers known to modify immunoreactive urinary kallikrein excretion (iUKK) also alter the concentration of immunoreactive glandular kallikrein (iGKK) in plasma, we measured iGKK in the plasma and urine of rats before, at 1 week, and at 3 weeks after induction of two-kidney, one clip hypertension, low sodium intake, and DOCA-salt hypertension. Glandular kallikrein in plasma and urine was measured by radioimmunoassay. Clipping of a renal artery decreased iUKK from 11.7 +/- 0.5 microgram/24 hr/100 g body weight (BW) to 7.8 +/- 0.5 and 8.2 +/- 0.5 at 1 and 3 weeks after surgery without significantly changing iGKK in plasma. The level of iGKK in the plasma did not correlate significantly with iUKK in the clipped group. Low sodium intake significantly increased iUKK, which rose from 6.6 +/- 0.3 microgram/24 hr/100 g BW to 9.6 +/- 0.5 and 13.9 +/- 0.7 after 1 and 3 weeks. In addition, low sodium intake appeared to increase iGKK in plasma, and a significant positive correlation was observed between iUKK and iGKK in plasma in the group on low sodium diet (r = 0.65, p less than 0.01). DOCA-salt treatment increased iUKK significantly from 10.4 +/- 0.6 microgram/24 hr/100 g BW to 17.1 +/- 1.4 and 22.6 +/- 2.3 at 1 and 3 weeks after. The iGKK in plasma increased from 13.8 +/- 0.5 to 15.4 +/- 0.7 ng/ml (p less than 0.05) at 1 week after the DOCA-salt treatment began, but it returned to pretreatment levels 3 weeks later (14.5 +/- 0.7 ng/ml, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)


Projecting the Impact of Socioeconomic and Policy Factors on Greenhouse Gas Emissions and Carbon Sequestration in U.S. Forestry and Agriculture.
Understanding greenhouse gas mitigation potential of the U.S. agriculture and forest sectors is critical for evaluating potential pathways to limit global average temperatures from rising more than 2° C. Using the FASOMGHG model, parameterized to reflect varying conditions across shared socioeconomic pathways, we project the greenhouse gas mitigation potential from U.S. agriculture and forestry across a range of carbon price scenarios. Under a moderate price scenario ($20 per ton CO2 with a 3% annual growth rate), cumulative mitigation potential over 2015-2055 varies substantially across SSPs, from 8.3 to 17.7 GtCO2e. Carbon sequestration in forests contributes the majority, 64-71%, of total mitigation across both sectors. We show that under a high income and population growth scenario over 60% of the total projected increase in forest carbon is driven by growth in demand for forest products, while mitigation incentives result in the remainder. This research sheds light on the interactions between alternative socioeconomic narratives and mitigation policy incentives which can help prioritize outreach, investment, and targeted policies for reducing emissions from and storing more carbon in these land use systems.


Heritability of carotid artery intima-medial thickness in type 2 diabetes.
Carotid artery intima-medial thickness (IMT), a marker of subclinical atherosclerosis, is a strong predictor of subsequent cardiovascular morbidity. The role of genetic factors in thickening of the carotid wall remains largely unknown. We hypothesize that in families with multiple members having diabetes, carotid IMT is likely to be associated with both inherited and environmental factors. To determine the extent of the familial aggregation of carotid IMT in the presence of type 2 diabetes, we studied 252 individuals with type 2 diabetes (mean age 60.6 years) from 122 families. Common carotid artery IMT was measured by high-resolution B-mode ultrasonography. Other measured factors included lipid levels, body mass index, fasting glucose, hemoglobin A1c, albumin/creatinine ratio, and self-reported medical history. Heritability estimates were obtained by using variance component methodology, as implemented in the SOLAR software package. Tests for association between carotid IMT and variables were performed by using mixed model analysis while accounting for the correlation due to family structure. The age-, sex-, and race-adjusted heritability estimate for carotid IMT was 0.32 (SE 0.17, P=0.02). Further adjustment for total cholesterol, hypertension status, and current smoking status resulted in a heritability estimate of 0.41 (SE 0.16, P=0.004). The strongest predictors of carotid IMT, after adjusting for age and sex, were ethnicity (African American versus white), total cholesterol, and smoking status. These data provide empirical evidence that subclinical cardiovascular disease has a significant genetic component and merits a search for the genes involved in susceptibility to the atherosclerotic complications of diabetes.


Role of impulsivity in the relationship between depression and alcohol problems among emerging adult college drinkers.
Depression is common among college students and higher levels of depression are associated with greater alcohol-related problems. However, depression is frequently not found to be directly associated with more alcohol use. This study examined whether various aspects of impulsivity (negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and delay discounting) and drinking to cope with negative affect help to account for the relationship between depression and alcohol problems among emerging adult college drinkers who reported at least a minimal level of depressive symptoms. In this cross-sectional study, 143 emerging adult (between 18 and 25 years old) female (69.9%, n = 100) and male (30.1%, n = 43) college drinkers with at least minimal depressive symptoms completed measures of depression, alcohol use and problems, drinking to cope, and impulsivity. A multiple mediation analysis revealed that only negative urgency and drinking to cope partially mediated the depression-alcohol problems relationship. Moderated mediation analyses revealed that impulsivity-related constructs did not significantly interact with drinking to cope to increase alcohol problems. It appears that alcohol use is particularly problematic for students with elevated depression, and this is partly attributable to depression's association with negative urgency, in addition to its association with drinking to cope. Our findings suggest that students who suffer from depression may engage in problematic drinking behavior in part because negative affect is detrimental to their short-term impulse control and decision making, independent of maladaptive attempts to regulate affect through drinking to cope.


Antibacterial Effect of Chitosan-Gold Nanoparticles and Computational Modeling of the Interaction between Chitosan and a Lipid Bilayer Model.
Pathogenic bacteria have the ability to develop antibiotic resistance mechanisms. Their action consists mainly in the production of bacterial enzymes that inactivate antibiotics or the appearance of modifications that prevent the arrival of the drug at the target point or the alteration of the target point itself, becoming a growing problem for health systems. Chitosan-gold nanoparticles (Cs-AuNPs) have been shown as effective bactericidal materials avoiding damage to human cells. In this work, Cs-AuNPs were synthesized using chitosan as the reducing agent, and a systematic analysis of the influence of the synthesis parameters on the size and zeta potential of the Cs-AuNPs and their UV-vis spectra was carried out. We used a simulation model to characterize the interaction of chitosan with bacterial membranes, using a symmetric charged bilayer and two different chitosan models with different degrees of the chitosan amine protonation as a function of pH, with the aim to elucidate the antibacterial mechanism involving the cell wall disruption. The Cs-AuNP antibacterial activity was evaluated to check the simulation model.


Morphological types and morphometrical measurements of the suprascapular notch in both dry bones and human cadavers: anatomical study to improve the outcomes of the diagnostic and interventional procedures in the shoulder region.
Understanding the anatomy of suprascapular area helps the clinicians and surgeons in management of any disability at the shoulder region. This work aimed to clear the different morphological and morphometrical types of suprascapular notch (SSN). Unknown 120 dry human scapulae of both sides and 60 formalin-embalmed cadaveric upper limbs (40 males and 20 females) were used in the present study. Three main morphological forms of SSN were reported: J, U, and V-shaped. J-shaped notch showed the highest incidence followed by U-shaped then V-shaped one. Morphometrically, type (III) notch was the most prevalent in both dry bones and cadavers, while the incidence of type (II) was the lowest form. Also, the measurements of superior transverse diameter, middle transverse diameter and vertical dimension of the different types of the notch showed no side or sex significant difference. The suprascapular foramen with ossified superior transverse scapular ligament (STSL) was seen in 5.8% of dry bones and 10% of cadaveric specimens. Fan and band-shaped ossified transverse scapular ligaments were reported. Absence of SSN was seen in 10.8% of dry bones, 7.5% of male and 10% of female specimens with left side predominance. V-shaped, absence, and ossified STSL were considered as predisposing factors of suprascapular nerve entrapment syndrome. Knowledge of the morphology and morphometric parameters of SSN is of great clinical significance for anatomists, radiologists, physiotherapists, orthopedics and neurosurgeons to perform good diagnosis and best planning for surgical or arthroscopic interventions within the shoulder region.


Effects of Recreational Ski Mountaineering on Cumulative Muscle Fatigue - A Longitudinal Trial.
Sport is known to have many positive effects on mental and physical health. High-intensity exercise is considered to decrease muscle strength and induce muscle fatigue, which is associated with a higher risk of injury. In recreational alpine skiers, a decrease of eccentric peak hamstring torque, as an indication of muscle fatigue, occurs even after 1 day of skiing. The popularity of ski mountaineering is increasing enormously, but no studies are available on its effects on muscle strength. Therefore, the present study examined the consequences of ski mountaineering on muscle fatigue of the concentric/eccentric quadriceps and/or hamstrings. In addition, a possible role of myofascial foam rolling in reducing muscle fatigue was evaluated. Fifty recreational ski mountaineers (27 males, 23 females) completed five consecutive tours of ski mountaineering within 1 week. After each day of skiing, participants underwent an isokinetic muscle test assessing the concentric and eccentric muscle strength of both thighs. One group completed an additional session of myofascial foam rolling. Right and left concentric quadriceps peak torque, left hamstrings peak torque, left eccentric quadriceps peak torque, as well as right and left hamstring peak torque, were reduced after a single day of ski mountaineering (p ≤ 0.016 for all). However, no cumulative muscle fatigue was detected and we could not demonstrate any effect of myofascial foam rolling. The results show conclusively that a single day of ski mountaineering leads to a significant decrease of concentric and eccentric quadriceps and hamstring strength. Therefore, in order to improve muscle strength for the ski mountaineering season, a physical training program including concentric and eccentric methods can be recommended.


Water quality analysis based on LSTM and BP optimization with a transfer learning model.
In the urban water environmental management, a fast and effective method for water quality analysis should be established with the rapid urbanization. In this study, the Beijing's sub-center was chosen as a case study, and long short-term memory (LSTM) and back propagation (BP) models were built, then a transfer learning model was proposed and applied to optimize the two models on the base of the upstream and downstream relationships in the rivers. The results indicated that the proposed deep learning model could improve NSE by 7% and 9% for LSTM and BP at the Dongguan Bridge gauge, respectively. At the Xugezhuang gauge in the Liangshui River, NSE was improved by 11% and 17%, respectively. At the Yulinzhuang gauge, it was improved by 16% and 13%, respectively. Because the upstream and downstream relationships were considered in the learning model, the model performance was obviously better. In brief, this method would provide an idea for the effective water quality model construction in the ungauged basins or regions.


Propagation and primary isolation of JCV and BKV in urinary epithelial cell cultures.
Human papovavirus JC, previously passaged in amnion cells, produced a cytopathic effect in urine-derived epithelial cells, and virus-specific antigens were demonstrable by indirect immunofluorescence. The hemagglutinating titer of JCV purified from infected cell cultures was generally 100- to 1000-fold higher than the amount of viral hemagglutinin used to initiate infection. Amnion-passaged JCV was readily adapted to growth in urine-derived epithelial cells. The prototype strain of human papovavirus BK, adapted to growth in human embryonic lung cells, also productively infected urine-derived epithelial cells. Primary human fetal glial cells and urine-derived cells were used in parallel experiments for primary isolation of JCV from diseased brain tissue. For this purpose, primary human fetal glial cells were more sensitive than urine-derived epithelial cells. Primary isolations of JCV and BKV from urine sediments of transplant patients and a normal male were made in urine-derived cells. Two renal transplant patients were identified as simultaneously excreting JCV and BKV. Both JCV and BKV genomes were molecularly cloned from one urine specimen of a double excretor. Although direct comparisons between primary human fetal glial and urine-derived epithelial cells were not made, it appears that the latter may be more suitable for primary isolation of JCV from urine.


Optimal Entry Point and Trajectory for Anterior C1 Lateral Mass Screw.
A radiographic analysis of the anatomy of the C1 lateral mass using computed tomography (CT) scans and Mimics software. To define the anatomy of the C1 lateral mass and make recommendations for optimal entry point and trajectory for anterior C1 lateral mass screws. Although various posterior insertion angles and entry points for screw insertion have been proposed for posterior C1 lateral mass screws, no large series have been performed to assess the ideal entry point and optimal trajectory for anterior C1 lateral mass screw placement. The C1 lateral mass was evaluated using CT scans and a 3-dimensional imaging application (Mimics software). Measuring the space available for the anterior C1 lateral mass screw (SAS) at different camber angles from 0 to 30 degrees (5-degree intervals) was performed to identify the ideal camber angle of insertion. Measuring the range of sagittal angles was performed to calculate the ideal sagittal angle. Other measurements involving the height of the C1 lateral mass were also made. The optimal screw entry point was found to be located on the anterior surface of the atlas 12.88 mm (±1.10 mm) lateral to the center of the anterior tubercle. This optimal entry point was found to be 6.81 mm (±0.59 mm) superior to the anterior edge of the atlas inferior articulating process. The mean ideal camber angle was 20.92 degrees laterally and the mean ideal sagittal angle was 5.80 degrees downward. These measurements define the optimal entry point and trajectory for anterior C1 lateral mass screws and facilitate anterior C1 lateral mass screw placement. A thorough understanding of the local anatomy may decrease the risk of injury to the spinal cord, vertebral artery, and internal carotid artery. Delineating the anatomy in each case with preoperative 3D CT evaluation is recommended.


Evaluation of Delirium in Critically Ill Patients Prescribed Melatonin or Ramelteon.
An impaired sleep-wake cycle may be one factor that affects the development of delirium in critically ill patients. Several small studies suggest that exogenous melatonin or ramelteon may decrease the incidence and/or duration of delirium. To compare the effect of prophylactic administration of melatonin, ramelteon, or no melatonin receptor agonist on the development of delirium in the intensive care unit (ICU). This was a single-center, retrospective, observational cohort study of nondelirious patients in the ICU who received melatonin, ramelteon, or no melatonin receptor agonist. The primary end point was the incidence of delirium. Secondary end points included assessments of daily level of sedation and daily utilization of antipsychotic, sedative, and opioid agents. No difference was observed in the incidence of delirium among the melatonin, ramelteon, and placebo cohorts (18.7% vs 14.3% vs 13.8%; P = 0.77). A difference was observed in the rate of agitation and sedation among the 3 groups, with the greatest observed in the melatonin cohort. Additionally, there was a difference in the use of propofol, dexmedetomidine, and opioids. Overall, there was no difference in clinical outcomes, including duration of mechanical ventilation and ICU or hospital length of stay. Therapy with melatonin, ramelteon, and no melatonin receptor agonist resulted in similar rates of delirium in a mixed ICU population. Despite significant differences in agitation, sedation, and medication utilization, there was no differences in the clinical outcomes evaluated.


Homology modeling and structure-based design improve hydrophobic interaction chromatography behavior of integrin binding antibodies.
Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack of solubility. In this work, we optimized a candidate integrin α11-binding mAb for developability using molecular modeling, rational design, and hydrophobic interaction chromatography (HIC). A homology model of the parental mAb Fv region was built, and this revealed hydrophobic patches on the surface of the complementarity-determining region loops. A series of 97 variants of the residues primarily responsible for the hydrophobic patches were expressed and their HIC retention times (RT) were measured. As intended, many of the computationally designed variants reduced the HIC RT compared to the parental mAb, and mutating residues that contributed most to hydrophobic patches had the greatest effect on HIC RT. A retrospective analysis was then performed where 3-dimentional protein property descriptors were evaluated for their ability to predict HIC RT using the current series of mAbs. The same descriptors were used to train a simple multi-parameter protein quantitative structure-property relationship model on this data, producing an improved correlation. We also extended this analysis to recently published HIC data for 137 clinical mAb candidates as well as 31 adnectin variants, and found that the surface area of hydrophobic patches averaged over a molecular dynamics sample consistently correlated to the experimental data across a diverse set of biotherapeutics.


Prevalence and distribution of sesamoid bones and accessory ossicles of the foot as determined by digital tomosynthesis.
We previously reported that digital tomosynthesis (DTS) is a reliable tool for evaluating bony structures of the hand. The current study aimed to identify the prevalence and distribution of sesamoid bones and accessory ossicles of the foot using DTS and to compare the results to those of conventional radiography (CR). Foot images (DTS, 213; CR, 44) of 213 patients taken at a tertiary hospital were retrospectively reviewed. Sesamoid bones were identified in the metatarsaophalangeal (MTP), distal interphalangeal (DIP) and interphalangeal (IP) joints of the great (I), second (II), third (III), fourth (IV), and fifth (V) toes. Accessory ossicles were observed in the midfoot and hindfoot. The mean number of sesamoid bones and accessory ossicles was 3.9 ± 1.3 for the left foot and 3.7 ± 1.0 for the right foot on CR; and 3.9 ± 1.4 for the left foot and 3.9 ± 1.3 for the right foot on DTS. Sesamoid bones were observed in MTP I (100%), MTP II (5%), MTP III (2%), MTP IV (2%), MTP V (14%), and IP (68%) on CR. Sesamoid bones were observed in MTP I (100%), MTP II (8%), MTP III (1%), MTP IV (2%), MTP V (25%), and IP I(65%) on DTS. Among accessory ossicles, the most common bone identified was os tibiale externum (23% on CR and 33% on DTS) andos peroneum (14% on CR and 21% on DTS), and os trigonum (32% on CR and 0.5% on DTS). DTS was useful for finding sesamoid bones and accessory ossicles, although there were some limitations in observing the hindfoot. Clin. Anat. 30:1072-1076, 2017. © 2017 Wiley Periodicals, Inc.


[Pharmacological cardioversion with intravenous propafenone in atrial fibrillation].
The efficacy and safety of intravenous propafenone for conversion of recent-onset and chronic atrial fibrillation was assessed in 46 patients. 40 with atrial fibrillation associated with or without structural heart disease (mean age 63 +/- 14 years) and 6 patients with atrial fibrillation related to the Wolff-Parkinson-White syndrome (mean age 34.8 +/- 13 years). Propafenone treatment was administered at 2 mg/kg over 15 minutes under continuous electrocardiographic monitoring. In 28 of 32 (87.5%) patients with paroxysmal and/or recent-onset atrial fibrillation a stable sinus rhythm was restored within 1 hour after propafenone (mean 17 +/- 11 minutes) and in only 3 of 8 (37.5%) with chronic atrial fibrillation (p < 0.05). Conversion to sinus rhythm was obtained in 5 of 6 (83.3%) patients with atrial fibrillation related ventricular preexcitation, mean time 21 +/- 12 minutes. Propafenone had an additional effect reducing mean heart rate (141 +/- 21 to 102 +/- 15 beat per minute, p < 0.05) and the shortest preexcited R-R intervals was increased, mean 231.6 +/- 27.8 to 355 +/- 37.2 milliseconds (p < 0.001) in cases associated with ventricular preexcitation. Dizziness, hypotension and transient conduction disturbances occurred in only one patient with rheumatic valvular heart disease: EF 40%. Propafenone is an effective and safe antiarrhythmic drug for converting paroxysmal and/or recent-onset atrial fibrillation of various origins with a more limited efficacy in chronic atrial fibrillation.


Carotid Sinus Massage in Syncope Evaluation: A Nonspecific and Dubious Diagnostic Method.
Carotid sinus hypersensitivity (CSH) is a frequent finding in the evaluation of syncope. However, its significance in the clinical setting is still dubious. A new criterion was proposed by Solari et al. with a symptomatic systolic blood pressure (SBP) cut-off value of ≤ 85 mmHg to refine the vasodepressor (VD) response diagnosis. To determine and compare the response to carotid sinus massage (CSM) in patients with and without syncope according to standard and proposed criteria. CSM was performed in 99 patients with and 66 patients without syncope. CSH was defined as cardioinhibitory (CI) for asystole ≥ 3 seconds, or as VD for SBP decrease ≥ 50 mmHg. No differences in the hemodynamic responses were observed during CSM between the groups, with 24.2% and 25.8% CI, and 8.1% and 13.6% VD in the symptomatic and asymptomatic groups, respectively (p = 0.466). A p value < 0.050 was considered statistically significant. During the maneuvers, 45 (45.45%) and 34 (51.5%) patients in the symptomatic and asymptomatic groups achieved SBP below ≤ 85 mmHg. Symptoms were reported especially in those patients in whom CSM caused a SBP decrease to below 90 mmHg and/or asystole > 2.5 seconds, regardless of the pattern of response or the presence of previous syncope. The response to CSM in patients with and without syncope was similar; therefore, CSH may be an unspecific condition. Clinical correlation and other methods of evaluation, such as long-lasting ECG monitoring, may be necessary to confirm CSH as the cause of syncope.


Prevalence and morbidity of primary immunodeficiency diseases, United States 2001-2007.
Few studies have estimated population prevalence and morbidity of primary immunodeficiency diseases (PIDD). We used administrative healthcare databases to estimate the prevalence of PIDD diagnoses in the United States from 2001 to 2007. MarketScan databases compile claims from commercial health insurance plans and Medicaid, recording individual diagnoses for outpatient encounters and hospital stays. We used a cross sectional survey to estimate prevalence of PIDD using related ICD-9 codes (279.0, 279.1, 279.2, 279.8, 279.9, 288.1 and 288.2). Persons with secondary immunodeficiency diagnoses were excluded from analysis. Between 2001 and 2007, prevalence of any PIDD diagnosis increased from 38.9 to 50.5 per 100,000 among privately insured and from 29.1 to 41.1 per 100,000 among publicly insured persons. B cell defects predominated. Prevalence was more than twice as high among Whites as among Blacks or Hispanics. In this large database, we found a higher prevalence of diagnosed PIDD than has been reported previously from registries. Increased awareness may have contributed to the increasing prevalence.


Gain dynamics in Raman fiber lasers and passive pump-to-Stokes RIN suppression.
We report on theoretical and experimental investigations of gain dynamics in Raman fiber lasers in the frequency range of 1 Hz-1 MHz. An analytical solution of the problem is due to the nonlinear nature of the Raman effect not feasible. Thus, we used a numerical simulation to gain general insights. Experimentally and numerically obtained results for a Raman fiber laser emitting at 1180 nm show good qualitative agreement. We also present a potential physical interpretation of the observed dynamical properties. In addition, we report on an experimental proof-of-principle of a passive pump-to-Stokes RIN suppression scheme for the main Stokes order in cascaded Raman fiber lasers utilizing an additional parasitic Stokes order. Again, results from numerical and experimental studies of a cascaded Raman fiber laser at 1180 nm and 1240 nm show good agreement and confirm the passive pump-to-Stokes RIN suppression at 1180 nm. The dependencies between the resonator design and the parameters of the noise suppression are investigated. In addition, it is shown that the scheme can also be applied to cascaded Raman fiber lasers with more then two Stokes shifts. This opens the possibility to design for example low-noise Raman fiber lasers at 1480 nm to pump low-noise Er(3+) doped fiber amplifiers.


Variations in genome-wide RNAi screens: lessons from influenza research.
Genome-wide RNA interference (RNAi) screening is an emerging and powerful technique for genetic screens, which can be divided into arrayed RNAi screen and pooled RNAi screen/selection based on different screening strategies. To date, several genome-wide RNAi screens have been successfully performed to identify host factors essential for influenza virus replication. However, the host factors identified by different research groups are not always consistent. Taking influenza virus screens as an example, we found that a number of screening parameters may directly or indirectly influence the primary hits identified by the screens. This review highlights the differences among the published genome-wide screening approaches and offers recommendations for performing a good pooled shRNA screen/selection.


Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity.
Methotrexate (MTX) is an effective therapy for rheumatoid arthritis (RA) but it is also associated with toxicity. Pharmacogenetics is the systematic evaluation of the role of genetic differences in the efficacy and toxicity of therapeutic interventions. Because the results of small pharmacogenetic studies are often misleading, we undertook a metaanalysis of published studies to determine the role of polymorphisms in the therapeutic efficacy and toxicity of MTX. A search of PubMed produced 55 publications, which were then reviewed for relevance to MTX toxicity and efficacy in patients with RA. To ensure that no study was missed, each polymorphism found was then entered as an independent search string and all results were reviewed again. Only 2 polymorphisms [C677T and A1298C in methylenetetrahydrofolate reductase (MTHFR); total 8 studies] relevant to MTX metabolism and efficacy had sufficient data to allow a metaanalysis of their association with toxicity; there was no polymorphism with sufficient data to perform a metaanalysis of efficacy. In a fixed-effects model, the C677T polymorphism was associated with increased toxicity (OR 1.71, 95% CI 1.32-2.21, p < 0.001). The A1298C polymorphism was not associated with increased toxicity (OR 1.12, 95% CI 0.79-1.6, p = 0.626). As pharmacogenetics evolves, more data are needed to assess the role of various polymorphisms for drug efficacy and toxicity. These results illustrate the paucity of reliable pharmacogenetic data on a commonly used antirheumatic drug and the potential role of pharmacogenetics in tailoring drug therapy for an individual patient.


Pyruvate dehydrogenase phosphatase deficiency: identification of the first mutation in two brothers and restoration of activity by protein complementation.
Pyruvate dehydrogenase phosphatase (PDP) deficiency has been previously reported as an enzymopathy, but the genetic basis for such a defect has never been established. The aim of this study was to identify the cause of the defect in two patients who presented with PDP deficiency. We studied two brothers of consanguineous parents who presented with neonatal hypotonia, elevated lactate, and less than 25% native pyruvate dehydrogenase complex (PDHc) activity in skin fibroblasts compared with controls. The activity of the complex could be restored to normal values by preincubation of the cells with dichloroacetate or by treating cell extracts with calcium. These two individuals were found to be homozygous for a 3-bp deletion in the coding sequence of the PDP isoform 1 (PDP1), which removes the amino acid residue leucine from position 213 of the protein. A recombinant version of this protein was synthesized and found to have a very reduced (<5%) ability to activate purified PDHc. Reduced steady-state levels of PDP1 in the patient's fibroblasts coupled with the low catalytic activity of the mutant PDP1 resulted in native PDHc activity being reduced, but this could be corrected by the addition of recombinant PDP1 (wild type). We have identified mutations in PDP1 in two brothers with PDP deficiency and have proven that the mutation is disease-causing. This is the first demonstration of human disease due to a mutation in PDP1.


Intracellular demonstration of active TGFbeta1 in B cells and plasma cells of autoimmune mice. IgG-bound TGFbeta1 suppresses neutrophil function and host defense against Staphylococcus aureus infection.
Infection remains a leading cause of morbidity and mortality in patients with SLE. To investigate this, previously we assessed the host defense status of autoimmune MRL/lpr mice and found that elaboration of active TGFbeta suppressed neutrophil function and decreased survival in response to Staphylococcus aureus infection. The purpose of the present work was to elucidate the molecular form and the cellular source of the active TGFbeta involved. Here, we report for the first time that TGFbeta1 is found in the active form inside B cells and plasma cells and that it circulates in the plasma complexed with IgG in two murine models of systemic autoimmunity and in some patients with SLE. IgG-bound active TGFbeta1 is many times more potent than uncomplexed active TGFbeta1 for suppression of neutrophil function in vitro and host defense against S. aureus infection in vivo. These data indicate that TGFbeta1 is in the active form inside B cells and plasma cells, that the formation of a complex of IgG and active TGFbeta1 is greatly accelerated in autoimmunity, and that this complex is extremely potent for suppression of PMN function and host defense against bacterial infection.


Developing an index to measure the voluntariness of consent to research.
The goals of the current study were to expand the content domain and further validate the Coercion Assessment Scale (CAS), a measure of perceived coercion for criminally involved substance abusers being recruited into research. Unlike the few existing measures of this construct, the CAS identifies specific external sources of pressure that may influence one's decision to participate. In Phase 1, we conducted focus groups with criminal justice clients and stakeholders to expand the instrument by identifying additional sources of pressure. In Phase 2, we evaluated the expanded measure (i.e., endorsement rates, reliability, validity) in an ongoing research trial. Results identified new sources of pressure and provided evidence supporting the CAS's utility and reliability over time as well as convergent and discriminative validity.


What is the role of lidocaine or phenytoin in tricyclic antidepressant-induced cardiotoxicity?
Tricyclic antidepressant (TCA) poisoning is a relatively common occurrence and remains a significant cause of mortality and morbidity. Deaths from TCA toxicity are typically due to cardiovascular events such as arrhythmias and hypotension. Cardiovascular toxicity may be multifactorial. However, the primary mechanism is a TCA-induced membrane-depressant or "quinidine-like" effect on the myocardium resulting in slowing down of phase 0 depolarization of the cardiac action potential and subsequent impairment of conduction through the His-Purkinje system and myocardium. This effect is manifest as QRS prolongation on the EKG, atrioventricular (AV) block, and impairment in automaticity leading to hypotension and ventricular dysrhythmia. Primary treatment strategies include sodium bicarbonate, hypertonic saline, and correction of any conditions that may aggravate this toxicity such as acidosis, hyperthermia, and hypotension. In cases of severe TCA toxicity, administration of sodium bicarbonate may be insufficient to correct the cardiac conduction defects. Use of lidocaine or phenytoin, both Vaughan Williams Class IB antiarrhythmic agents, has been reported as an effective adjunctive therapy in cases of severe cardiotoxicity. Thirty articles of interest were identified by searching PubMed, abstracts from meetings, and the reference sections of related primary and review articles and toxicological texts. ROLE OF LIDOCAINE AND PHENYTOIN: Lidocaine and phenytoin also cause sodium channel blockade, but unlike Class IA or IC agents do not depress phase 0 depolarization in healthy cardiac tissue. Lidocaine and phenytoin dissociate relatively quickly from cardiac sodium channels. Sodium channels have faster recovery times after exposure to lidocaine (1-2 s) and phenytoin (0.71 s), than with some TCAs such as amitriptyline (13.6 s), but not others (e.g., imipramine at 1.6 s). In experimental models of amitriptyline poisoning, lidocaine co-administration resulted in decreased sodium channel blockade compared to amitriptyline alone. This correlated with clinical improvement, including normalization of QRS interval, improved hypotension, and decreased mortality. It is postulated that lidocaine's rapid binding to the sodium channel may directly displace slower acting agents from the channel, leaving more channels unbound, and therefore be able to facilitate cardiac conduction. Phenytoin may act through a similar mechanism as lidocaine, although experimental studies suggest that it does not compete directly for the same sodium channel binding site as TCAs. Allosteric modulation of the TCA binding site may occur in the setting of phenytoin use. The evidence for using phenytoin in treating TCA-induced sodium channel blockade is less convincing than that for lidocaine. Human trials are limited to case series and, in most human exposures in which there appeared to be efficacy, the toxicity was not severe. Although there appears to be more evidence for the use of lidocaine than phenytoin as adjunctive treatment for TCA-associated cardiotoxicity, specific clinical indications and dosing recommendations remain to be defined. We recommend the use of lidocaine in cases in which cardiotoxicity (arrhythmias, hypotension) is refractory to treatment with sodium bicarbonate or hypertonic saline, or in which physiological derangement (e.g., severe alkalosis or hypernatremia) limits effective use of these primary strategies.


Epidermal inclusion cyst of the breast.
Epidermal inclusion cysts are uncommon in the breast, but the consequences can be severe when these cysts occur in the breast parenchyma. Here, we report two such cases. The patient in case 1 was an 85-year-old woman with a 3-cm palpable mass in the right breast. Mammography revealed a round and smoothly outlined mass, which indicated a benign tumor, and sonography showed an irregularly shaped and heterogeneous hypoechoic mass. Breast cancer was suspected on the basis of the sonographic findings and the age of the patient, but excisional biopsy revealed an epidermal inclusion cyst. The patient in case 2 was a 45-year-old woman with a 9-cm lesion in the left breast. Mammography revealed a round, dense, smoothly outlined mass, and sonography showed a well-defined, central hyperechoic mass. A phyllodes tumor or a giant fibroadenoma was suspected on the basis of clinical and imaging findings, but the resected specimen revealed an epidermal inclusion cyst.


Governing role of primary afferent drive in increased excitation of spinal nociceptive neurons in a model of sciatic neuropathy.
Previously we reported that the cuff model of peripheral neuropathy, in which a 2 mm polyethylene tube is implanted around the sciatic nerve, exhibits aspects of neuropathic pain behavior in rats similar to those in humans and causes robust hyperexcitation of spinal nociceptive dorsal horn neurons. The mechanisms mediating this increased excitation are not known and remain a key unresolved question in models of peripheral neuropathy. In anesthetized adult male Sprague-Dawley rats 2-6 weeks after cuff implantation we found that elevated discharge rate of single lumbar (L(3-4)) wide dynamic range (WDR) neurons persists despite acute spinal transection (T9) but is reversed by local conduction block of the cuff-implanted sciatic nerve; lidocaine applied distal to the cuff (i.e. between the cuff and the cutaneous receptive field) decreased spontaneous baseline discharge of WDR dorsal horn neurons approximately 40% (n=18) and when applied subsequently proximal to the cuff, i.e. between the cuff and the spinal cord, it further reduced spontaneous discharge by approximately 60% (n=19; P<0.05 proximal vs. distal) to a level that was not significantly different from that of naive rats. Furthermore, in cuff-implanted rats WDR neurons (n=5) responded to mechanical cutaneous stimulation with an exaggerated afterdischarge which was reversed entirely by proximal nerve conduction block. These results demonstrate that the hyperexcited state of spinal dorsal horn neurons observed in this model of peripheral neuropathy is not maintained by tonic descending facilitatory mechanisms. Rather, on-going afferent discharges originating from the sciatic nerve distal to, at, and proximal to the cuff maintain the synaptically-mediated gain in discharge of spinal dorsal horn WDR neurons and hyperresponsiveness of these neurons to cutaneous stimulation. Our findings reveal that ectopic afferent activity from multiple regions along peripheral nerves may drive CNS changes and the symptoms of pain associated with peripheral neuropathy.


Energy expenditure does not differ, but protein oxidation rates appear lower in meals containing predominantly meat versus soy sources of protein.
High protein meals produce 3 relevant effects in weight management: i) higher thermogenic cost, ii) enhanced fat oxidation, and iii) greater satiation. Pork has been reported to be more thermogenic than soy, suggesting meat protein may be superior to plant protein in a high-protein weight loss diet context. In this study, we aimed to compare the effects of high-protein meals using meat, dairy, and soy sources respectively. This crossover feeding trial measured energy expenditure, substrate oxidation, and satiety levels of 12 adults during 8-hour stays in a whole-room calorimeter. The 3 isoenergetic high-protein test meals (30% protein, 40% carbohydrate, 30% fat) contained predominantly meat, dairy, and soy protein. There was no significant difference between meals for effects on energy expenditure (p = 0.987), carbohydrate oxidation (p = 0.951), and fat oxidation (p = 0.997). Protein oxidation was significantly lower in meals with predominantly meat compared to soy sources (p = 0.012). There was no significant difference between meals for reported satiety levels (p = 0.296). High-protein meals may be argued as beneficial for weight loss. Animal protein does not appear to offer superior energy expenditure effects, but there may be protein-sparing effects with meat, which may be beneficial in terms of retaining lean body mass.


Determination of water in NIST reference material for mineral oils
The accuracy of the reference concentrations of moisture in electrical insulating oil RM 8506 and lubricating oil RM 8507 (both of mineral type) and specified by the National Institute of Standards and Technology (NIST) as containing 39.7 and 76.8 ppm (w/w) water, respectively, has recently been the subject of debate in this journal. To shed some further light on this controversy, we report in this correspondence results for these oils obtained by two additional methods, one based on specially designed reagents for diaphragm-free Karl Fischer (KF) coulometry and the other based on the concept of stripping at elevated temperature/continuous KF coulometry. A positive interference effect was shown to take place for RM 8506 when the direct coulometric method was used. If the results are corrected for this, the values including six different procedures varied in the range 13.5-15.6 ppm (w/w). For RM 8507, all values were between 42.5 and 47.2 ppm (w/w), which means that the values recommended by NIST for both reference oils using volumetric titration are about twice as high as those obtained with the other techniques. A possible explanation for this discrepancy is presented.


The development of acamprosate as a treatment against alcohol relapse.
Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate (Campral), one of only three pharmacological treatments approved for the treatment of alcohol dependence, has shown mixed efficacy in clinical trials in maintaining abstinence of detoxified alcoholics since studies began in the 1980s. Yielding inconsistent results, these studies have prompted skepticism. Herein, the authors review the preclinical studies which have assessed the efficacy of acamprosate in various animal models of alcohol dependence and discuss the disparate findings from the major clinical trials. Moreover, the authors discuss the major limitations of these preclinical and clinical studies and offer explanations for the often-contradictory findings. The article also looks at the importance of the calcium moiety that accompanies the salt form of acamprosate and its relevance to its activity. The recent discovery that large doses of calcium largely duplicate the effects of acamprosate in animal models has introduced a serious challenge to the widely held functional association between this drug and the glutamate neurotransmission system. Future research on acamprosate or newer pharmacotherapeutics should consider assessing plasma and/or brain levels of calcium as a correlate or mediating factor in anti-relapse efficacy. Further, preclinical research on acamprosate has thus far lacked animal models of chemical dependence on alcohol, and the testing of rodents with histories of alcohol intoxication and withdrawal is suggested.


Diet and waist-to-hip ratio: important predictors of lipoprotein levels in sedentary and active young men with no evidence of cardiovascular disease.
Healthy, young men were studied to determine the relationship of energy and nutrient intake and physical activity to concentrations of plasma lipoprotein and cholesteryl ester transfer protein. A cross-sectional study compared active and sedentary male subjects (17 to 35 years old) with no personal or family history of coronary heart disease. Participants kept 20-day food and activity journals. Individual intakes of energy, protein, carbohydrate, fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, dietary fiber, and alcohol were evaluated. Measurements of blood lipids (total cholesterol and triglycerides, high- and low-density lipoprotein cholesterol); apolipoproteins; cholesteryl ester transfer protein; anthropometric variables (body mass index, waist-to-hip ratio, percentage of body fat); and aerobic capacity were taken during fall and spring data collection periods. SUBJECT SELECTION: Subjects were selected on the basis of normal blood lipid levels, absence of underlying disease, and willingness to comply with their current level of physical activity for the duration of the study. Minimal sample size for statistical power was 12 men per group: 12 of 15 subjects who exercised and 13 of 15 subjects who were sedentary completed all phases of the study. Statistical analyses consisted of 2-way analysis of variance (activity level and season). Pearson product moment correlations and multiple regression analyses were conducted to assess whether energy and nutrient intakes, physical activity status, and/or anthropometric variables predicted plasma concentrations of lipids and apolipoproteins. Lower waist-to-hip ratio, and not specifically activity level, was associated with higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of low-density lipoprotein cholesterol (LDL-C). Dietary intake of saturated and monounsaturated fats and alcohol predicted changes in some apolipoprotein and lipoprotein levels. Use of waist-to-hip ratio in the primary prevention of coronary heart disease is a simple and cost-effective measure to predict development of abnormal lipoprotein profiles in young men. Specific dietary recommendations include adoption of a heart-healthy diet with emphasis on monounsaturated fatty acids (10% to 12% of energy or one third of total fat intake) and the suggestion that small amounts of alcohol (< 3 drinks per week) may, indeed, be beneficial. Because alcohol and waist-to-hip ratio were both important predictors of LDL-C level, even in active young men, the consumption of low levels of alcohol may be beneficial only if waist-to-hip ratio is maintained within the healthful range by achieving an appropriate balance of physical activity and macronutrient intake.


[Regression analysis of the relation between antitoxic activity of sera (Jensen method) and antibody titers in the passive hemagglutination reaction].
Antidiphtherial and antitetanus antitoxic immunity was determined in the sera of 1588 children (20 experiments) and 611 children and adults (12 experiments) by two methods--on animals and in the passive hemagglutination test (PHT). Factual data were grouped in accordance with a conditioned scale of the antitoxin values in IU composed of the values average for each interval. The series of two-fold dilutions represented a scale of titres of the same sera in the PHT. Mathematical analysis showed that there was a direct linear regressive relationship between the indices of antitoxic immunity obtained by different methods. As a rule, regression coefficients were below a unit, i. e. the rate of increase of the values by the HDT titre scale was somewhat retarded from the growth by the IU titre, this pointing to the difference in their value. The free member of the regression equation (a) characterizing this choice of the sera varied widely. Between the regression coefficients calculated for individual experiments statistically significant differences were revealed in almost 50% of cases. Transformation of quantitative indices of one test into quantitative characteristics obtained by the other method, with the aid of regression equation calculated outside the definite experiment, proved to be unfounded.


Golden perspective: application of laser-generated gold nanoparticle conjugates in reproductive biology.
The current demand for female calves has grown rapidly and controlling the sex of offspring provides an economically flexible management for the livestock producer. The only functioning method of efficiently producing separate populations of X and Y sperm in mammals is based on relative DNA differentiation by high-speed flow cytometry. In this context, gold nanoparticles conjugated to sex chromosome-specific moieties display promising application as novel fluorophor-alternative for the high-throughput screening, since they feature no photo bleaching, high quantum yield, good biocompatibility and the possibility of non-destructive membrane penetration. Especially, gold nanoparticles fabricated by pulsed laser ablation are in the recent focus of interest, due to excellent biocompatibility, fabrication-dependent, tuneable particle size as well as surface charge and ease of (bio)-functionalization with a remarkably strong ligand binding. For the purpose of our studies functionalized gold nanoparticles may be used as novel markers for sex-sorting of mammalian sperm and, depending on the selected probe, also for the selection of sperm with heritable DNA-sequences interesting for animal breeding.


[The importance of assessing the morphofunctional state of the liver in the diagnosis of fatal alcoholic intoxication].
The morphology and function of the liver was studied by pathomorphological, gas chromatographic, and histochemical analysis in 108 forensic medical expert evaluations of alcohol poisoning, coronary disease, alcohol cardiomyopathy, craniocerebral injury, and mechanical asphyxia. Ethanol concentrations in the blood collected from various parts of the venous system varied: in 69% of cases the level of ethanol was higher in the inferior vena cava than in the portal vein. Histochemical analysis of ethanol-oxidizing enzymatic systems together with pathomorphological findings and alcohol measurements in various parts of the venous system help assess the morphology and function of the liver, define the thanatogenesis, and draw objective expert conclusion on the cause of death.


Triggers of the Postural Display of Courtship in Drosophila persimilis Flies.
D. persimilis courtship shows some flexibility and courting males sometimes perform an elaborate postural display in addition to the standard courtship behaviours shared by most Drosophila species. This postural display includes the acrobatic contortion and tremulation of their abdomen, accompanied by the generation of substrate-borne vibrations, and they proffer a nutritional droplet to the female. Here, we use courtship and choice assays to ask what triggers this display and what advantages males may gain from it during courtship. In pair assays, we found no differences in the courtship duration and copulation success between displaying and non-displaying males. In trio assays, however, the female always mated with the male who performed the display. To investigate what promotes the male display, we varied the level of receptivity of the female and studied the impact of a second male. We found that rejection by the female does not induce the male to display, contrary to what was previously suggested. We present evidence that the male display is in fact promoted by the presence of an attentive and sexually receptive female and the absence of male competition, with the greatest exhibition rate obtained if the courted female is starved. These findings provide valuable information about the social ecology of flies, and how internal and external cues influence sexual behaviours and mate choice.


Association of Mineral Bone Disorder With Decline in Residual Kidney Function in Incident Hemodialysis Patients.
Abnormalities of mineral bone disorder (MBD) parameters have been suggested to be associated with poor renal outcome in predialysis patients. However, the impact of those parameters on decline in residual kidney function (RKF) is uncertain among incident hemodialysis (HD) patients. We performed a retrospective cohort study in 13,772 patients who initiated conventional HD during 2007 to 2011 and survived 6 months of dialysis. We examined the association of baseline serum phosphorus, calcium, intact parathyroid hormone (PTH), and alkaline phosphatase (ALP) with a decline in RKF. Decline in RKF was assessed by estimated slope of renal urea clearance (KRU) over 6 months from HD initiation. Our cohort had a mean ± SD age of 62 ± 15 years; 64% were men, 57% were white, 65% had diabetes, and 51% had hypertension. The median (interquartile range [IQR]) baseline KRU level was 3.4 (2.0, 5.2) mL/min/1.73 m2 . The median (IQR) estimated 6-month KRU slope was -1.47 (-2.24, -0.63) mL/min/1.73 m2 per 6 months. In linear regression models, higher phosphorus categories were associated with a steeper 6-month KRU slope compared with the reference category (phosphorus 4.0 to <4.5 mg/dL). Lower calcium and higher intact PTH and ALP categories were also associated with a steeper 6-month KRU slope compared with their respective reference groups (calcium 9.2 to <9.5 mg/dL; intact PTH 150 to <250 pg/mL; ALP <60 U/L). The increased number of parameter abnormalities had an additive effect on decline in RKF. Abnormalities of MBD parameters including higher phosphorus, intact PTH, ALP and lower calcium levels were independently associated with decline in RKF in incident HD patients. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.


Conidiogenesis in pathogenic hyphomycetes. I. Sporothrix, Exophiala, Geotrichum and Microsporum.
Conidium formation in 5 species of pathogenic hyphomycetous fungi, Sporothrix schenckii, Exophiala salmonis, E. sp., Geotrichum candidum and Microsporum canis were examined using light and scanning electron microscopy. The fungi, grown in pure culture on potato dextrose agar under defined conditions, demonstrated 4 kinds of conidiogenesis. The taxonomic value of the developmental characters in the classification of the Fungi Imperfecti is discussed.


Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo.
Extracellular matrix components must be degraded and resynthesized for vascular remodeling to occur. We hypothesized that the hemodynamic environment regulates activity of matrix metalloproteinases (MMPs), the primary agents for in vivo matrix degradation, during vascular remodeling in response to changes in transmural pressure and shear stress. Pathological hemodynamic conditions were reproduced in an ex vivo system in which we maintained porcine carotid arteries for 24 and 48 h. Total levels of MMP-2 and MMP-9 extracted from tissue homogenates and analyzed by SDS-PAGE zymography were stimulated by transmural pressure and were unaffected by shear stress changes. Degradation of two specific gelatinase substrates, gelatin and elastin, increased with increasing pressure, but the degradation was not affected by shear stress changes in tissue specimens analyzed using in situ zymography (gelatin) and fluorescent measurement of endogenous elastin degradation (elastin). Our results suggest that transmural pressure activates at least two members of the MMP family and that activity of these enzymes is accompanied by degradation of matrix components, effects that may be implicated in hypertensive vascular remodeling.


Modelling outbreak response impact in human vaccine-preventable diseases: A systematic review of differences in practices between collaboration types before COVID-19.
Outbreak response modelling often involves collaboration among academics, and experts from governmental and non-governmental organizations. We conducted a systematic review of modelling studies on human vaccine-preventable disease (VPD) outbreaks to identify patterns in modelling practices between two collaboration types. We complemented this with a mini comparison of foot-and-mouth disease (FMD), a veterinary disease that is controllable by vaccination. We searched three databases for modelling studies that assessed the impact of an outbreak response. We extracted data on author affiliation type (academic institution, governmental, and non-governmental organizations), location studied, and whether at least one author was affiliated to the studied location. We also extracted the outcomes and interventions studied, and model characteristics. Included studies were grouped into two collaboration types: purely academic (papers with only academic affiliations), and mixed (all other combinations) to help investigate differences in modelling patterns between collaboration types in the human disease literature and overall differences with FMD collaboration practices. Human VPDs formed 227 of 252 included studies. Purely academic collaborations dominated the human disease studies (56%). Notably, mixed collaborations increased in the last seven years (2013-2019). Most studies had an author affiliated to an institution in the country studied (75.2%) but this was more likely among the mixed collaborations. Contrasted to the human VPDs, mixed collaborations dominated the FMD literature (56%). Furthermore, FMD studies more often had an author with an affiliation to the country studied (92%) and used complex model design, including stochasticity, and model parametrization and validation. The increase in mixed collaboration studies over the past seven years could suggest an increase in the uptake of modelling for outbreak response decision-making. We encourage more mixed collaborations between academic and non-academic institutions and the involvement of locally affiliated authors to help ensure that the studies suit local contexts.


Role of computed axial tomography of the chest in staging patients with nonmetastatic gestational trophoblastic disease.
Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexate-folinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P less than .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.


A new bacterial white spot syndrome (BWSS) in cultured tiger shrimp Penaeus monodon and its comparison with white spot syndrome (WSS) caused by virus.
This paper describes a new bacterial white spot syndrome (BWSS) in cultured tiger shrimp Penaeus monodon. The affected shrimp showed white spots similar to those caused by white spot syndrome virus (WSSV), but the shrimp remained active and grew normally without significant mortalities. The study revealed no evidence of WSSV infection using electron microscopy, histopathology and nested polymerase chain reaction. Electron microscopy indicated bacteria associated with white spot formation, and with degeneration and discoloration of the cuticle as a result of erosion of the epicuticle and underlying cuticular layers. Grossly the white spots in BWSS and WSS look similar but showed different profiles under wet mount microscopy. The bacterial white spots were lichen-like, having perforated centers unlike the melanized dots in WSSV-induced white spots. Bacteriological examination showed that the dominant isolate in the lesions was Bacillus subtilis. The occurrence of BWSS may be associated with the regular use of probiotics containing B. subtilis in shrimp ponds. The externally induced white spot lesions were localized at the integumental tissues, i.e., cuticle and epidermis, and connective tissues. Damage to the deeper tissues was limited. The BWS lesions are non-fatal in the absence of other complications and are usually shed through molting.


Anxiety disorders in typically developing youth: autism spectrum symptoms as a predictor of cognitive-behavioral treatment.
Symptoms of autism spectrum disorder (ASD) were assessed (Social Responsiveness Scale-Parent (SRS-P); coded in-session behavior) in typically-developing, anxiety-disordered children (N = 50) treated with cognitive-behavioral therapy (CBT). Study 1: children with moderate autistic symptomology (per SRS-P) were significantly more likely to improve from family CBT (FCBT) than individual CBT (ICBT; OR = 8.67). Coded behavior did not predict outcome. Study 2: CBT components were compared by treatment and ASD symptom status. At-home exposure completion was greater in FCBT and there was an interaction in child involvement for treatment and ASD status. Though both treatments reduced anxiety, FCBT outperformed ICBT for children with moderate ASD symptoms, a benefit potentially linked to more at-home exposures and greater child involvement in FCBT.


Proposing the Promiscuous Protein Structures in JNK1 and JNK3 for Virtual Screening in Pursuit of Potential Leads.
Over the past decade, the available crystal structures have almost doubled in Protein Data Bank (PDB) providing the research community with a series of similar crystal structures to choose from for future docking studies. With the steady growth in the number of high-resolution three-dimensional protein structures, ligand docking-based virtual screening of chemical libraries to a receptor plays a critical role in the drug discovery process by identifying new drug candidates. Thus, identifying potential candidates among all the available structures in a database for docking studies is of utmost importance. Our work examined whether one could use the resolution of a number of known structures, without considering other parameters, to choose a good experimental structure for various docking studies to find more useful drug leads. We expected that a good experimental structure for docking studies to be the one that gave favorable docking with the largest number of ligands among the experimental structures to be selected. We chose three protein test systems for our study, all belonging to the family of MAPK: (1) JNK1, (2) JNK2, and (3) JNK3. On analysis of the results, the best resolution structures showed significant variations from the expected values in their result, whereas the poor resolution structures proved to be better candidates for docking studies.


Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance.
Gamma secretase inhibitors (GSIs), initially developed as Alzheimer's therapies, have been repurposed as anticancer agents given their inhibition of Notch receptor cleavage. The success of GSIs in preclinical models has been ascribed to induction of cancer stem-like cell differentiation and apoptosis, while also impairing epithelial-to-mesenchymal transition and sensitizing cells to traditional chemoradiotherapies. The promise of these agents has yet to be realized in the clinic, however, as GSIs have failed to demonstrate clinical benefit in most solid tumors with the notable exceptions of CNS malignancies and desmoid tumors. Disappointing clinical performance to date reflects important questions that remain to be answered. For example, what is the net impact of these agents on antitumor immune responses, and will they require concurrent targeting of tumor-intrinsic compensatory pathways? Addressing these limitations in our current understanding of GSI mechanisms will undoubtedly facilitate their rational incorporation into combinatorial strategies and provide a valuable tool with which to combat Notch-dependent cancers. In the present review, we provide a current understanding of GSI mechanisms, discuss clinical performance to date, and suggest areas for future investigation that might maximize the utility of these agents. IMPLICATIONS FOR PRACTICE: The performance of gamma secretase inhibitors (GSIs) in clinical trials generally has not reflected their encouraging performance in preclinical studies. This review provides a current perspective on the clinical performance of GSIs across various solid tumor types alongside putative mechanisms of antitumor activity. Through exploration of outstanding gaps in knowledge as well as reasons for success in certain cancer types, the authors identify areas for future investigation that will likely enable incorporation of GSIs into rational combinatorial strategies for superior tumor control and patient outcomes.


Using dominant eigenvalue analysis to predict formation of alternans in the heart.
Ventricular fibrillation at the whole heart level is often preceded by the alternation of action potential duration (APD), i.e., alternans, at the cellular level. As proven in many experiments, traditional approaches based on the slope of the restitution curve have not been successful in predicting alternans formation. Recently, a technique has been theoretically developed based on dominant eigenvalue analysis to predict alternans formation in isolated cardiac myocytes. Here, we aimed to demonstrate that this technique can be applied to predict alternans formation at the whole heart level. Optical mapping was performed in Langendorff-perfused hearts from New Zealand white rabbits (n = 4), which were paced at decreasing basic cycle lengths to introduce APD alternans. In each heart, the basic cycle length corresponding to the local onset of alternans, B(onset), was determined and two regions of the heart were identified at B(onset): one region which exhibited alternans (1:1(alt)) and one which did not (1:1). Corresponding two-dimensional eigenvalue (λ) maps were generated using principal component analysis by analyzing action potentials after short perturbations from the steady state, and mean eigenvalues (λ[over ¯]) were calculated separately for the 1:1 and 1:1(alt) regions. We demonstrated that λ[over ¯] calculated at B(onset) was significantly different (p<0.05) between the two regions. Our results suggest that this dominant eigenvalue technique can be used to successfully predict the local alternans formation in the heart.


Hoffmann reflex from foreleg flexor nerves in cats: lateralization, picrotoxin, strychnine, crossed flexor reflex.
Hoffmann (H) reflexes from foreleg flexor nerves were studied in cats. The right and left flexor nerves were stimulated and H reflexes were recorded from the same nerves. Paw preference was assessed by a food reaching test. Stimulation of the right median nerve elicited mono- and polysynaptic reflexes from the left ulnar nerve (crossed flexor nerve). Picrotoxin depressed, and strychnine increased H reflexes from both sides without affecting the spinal motor asymmetry. H reflexes were found to be larger on the left than the right side in right-preferent cats and vice versa in left-preferent cats. The right H-reflex recovery curve was higher than left in right-preferent cats. The inhibitory period of the recovery cycle disappeared after picrotoxin and changed to facilitation for the nonpreferred side. Strychinine caused bilateral, nearly-synchronous motoneuronal discharges from the right and left flexor nerves; the discharges originating from the left side preceded those from the right side in a right-preferent cat. These results indicate that spinal motor activity predominates on the nonpreferred side, which would be a prerequisite for postural adjustments during paw use in cats. This asymmetric motor organization in the forelegs of cats having quadrpedal locomotion seems to be similar to asymmetric motor organization in legs in humans.


Developing a concussion assessment mHealth app for certified Athletic Trainers.
Annually, 1.6-3.8 million concussions occur from sports in the United States, which account for 5-9% of all sports injuries. The dangers of concussions include prolonged post-concussive symptoms, increased risk of subsequent concussions, seizures, mental health issues, and in cases of second-impact syndrome (SIS), possible death. Certified Athletic Trainers (ATC) continue to serve an important role in providing assessment and treatments for athletes with sports-related injuries. They provide a critical safety net due to limited knowledge and misconceptions of concussion held by some youth sports coaches and athletes. However, availability of services from ATCs in rural areas is a challenge. In order to help extend coverage to more rural student athletes, we propose designing a telemedicine app following the mHealth development roadmap from the Center for eHealth Research (CeHRes). In this paper we will document contextual inquiry, user requirements capture, design phases, and app evaluation from the targeted user base.


Emergency department characteristics and associations with intensive care admission among patients with coronavirus disease 2019.
There have been few descriptions in the literature to date specifically examining initial coronavirus disease 2019 (COVID-19) patient presentation to the emergency department (ED) and the trajectory of patients who develop critical illness. Here we describe the ED presentation and outcomes of patients with COVID-19 presenting during our initial local surge. This is a multicenter, retrospective cohort study using data extracted from the electronic health records at 3 hospitals within a single health system from March 1, 2020 to June 1, 2020. Patients were included in the study if they presented to an ED and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the study period. Data elements were extracted from the electronic health record electronically and by trained data abstractors and entered into a secure database. We used multivariable regression analysis to examine ED factors associated with the development of critical illness and mortality, with a primary outcome of ICU admission. A total of 330 patients with laboratory-confirmed SARS-CoV-2 infection were admitted during the study period. Of these, 112 (34%) were admitted to the ICU. Among these patients, 20% were female, 50% were White, the median age was 61 (interquartile range [IQR], 52-72), and the median body mass index (BMI) was 28.1 (IQR, 24.3-35.1). On univariable analysis, a doubling of lactate dehydrogenase (LDH) (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.40-6.27) or high-sensitivity C-reactive protein (hsCRP; OR, 1.32; 95% CI, 1.11-1.57) above the reference range or elevated troponin (OR, 12.1; 95% CI, 1.20-121.8) were associated with ICU admission. After adjusting for age, sex, and BMI, LDH was the best predictor of ICU admission (OR, 3.54; 95% CI, 2.12-5.90). Of the patients, 15% required invasive mechanical ventilation during their hospital course, and in-hospital mortality was 19%. Nearly one-third of ED patients who required hospitalization for COVID-19 were admitted to the ICU, 15% received invasive mechanical ventilation, and 19% died. Most patients who were admitted from the ED were tachypneic with elevated inflammatory markers, and the following factors were associated with ICU admission: elevated hsCRP, LDH, and troponin as well as lower oxygen saturation and increased respiratory rate.


Lyme arthritis with subarticular cyst formation in metacarpal and metatarsal bones.
A young woman was treated for seronegative rheumatoid arthritis for more than 9 years, without clinical improvement, before the diagnosis of chronic Lyme arthritis of the metacarpal and metatarsal phalangeal joints was made. Roentgenograms showed subarticular cyst formation in the metacarpal and metatarsal bones. The patient's response to treatment with a 2-week course of ceftriaxone was dramatic.


Ingestion of glutamine and maltodextrin two hours preoperatively improves insulin sensitivity after surgery: a randomized, double blind, controlled trial.
To investigate whether the abbreviation of preoperative fasting with a drink containing glutamine and dextrinomaltose improves organic response to surgical trauma. Thirty-six female patients adult (18-62 years) candidates for elective laparoscopic cholecystectomy were randomly divided into three groups: conventional fasting (fasting group), and two groups receiving two different diets, eight hours (400ml) and two hours before induction of anesthesia (200ml): carbohydrate (CHO) group (12.5% dextrinomaltose) and the glutamine (GLN) group (12.5% dextrinomaltose and 40 and 10g of glutamine, respectively). Blood samples were collected pre and postoperatively. Twenty-eight patients completed the study. No pulmonary complication occurred. Gastric residual volume was similar between groups (p = 0.95). Postoperatively, all patients from the fasting group had abnormal glucose (> 110mg/dl), this abnormality being of 50% when compared to the CHO group (p = 0.14), and of 22.2% when compared to the GLN group (p = 0.01). All patients who had the fasting period shortened (CHO + GLN) had normal postoperative insulin, contrasting with 66.7% in the fasted group (p = 0.02). The abnormal sensitivity to insulin postoperatively rose from 32.1% to 46.4% of cases (p = 0.24), and it occurred in only 11.1% of patients in GLN group when compared to 55.5% in the fasting group (p = 0.02). the abbreviation of preoperative fasting for two hours with dextrinomaltose and glutamine improves insulin sensitivity in patients undergoing elective laparoscopic cholecystectomy.


Are people adapted to their own glasses?
Negative lenses, either in the form of glasses or contact lenses, can correct nearsightedness. Unlike contact lenses, glasses do not only correct, but also induce optic distortions. In the scientific literature, it has often been assumed that people who wear corrective glasses instantaneously account for these distortions when they put their glasses on. We tested this assumption and found that, when people switched between their contact lenses and their glasses, they made the errors that one would predict based on the optics. This shows that people are not immediately adapted to their own glasses when they put them on.


Protein kinase C regulates human pluripotent stem cell self-renewal.
The self-renewal of human pluripotent stem (hPS) cells including embryonic stem and induced pluripotent stem cells have been reported to be supported by various signal pathways. Among them, fibroblast growth factor-2 (FGF-2) appears indispensable to maintain self-renewal of hPS cells. However, downstream signaling of FGF-2 has not yet been clearly understood in hPS cells. In this study, we screened a kinase inhibitor library using a high-throughput alkaline phosphatase (ALP) activity-based assay in a minimal growth factor-defined medium to understand FGF-2-related molecular mechanisms regulating self-renewal of hPS cells. We found that in the presence of FGF-2, an inhibitor of protein kinase C (PKC), GF109203X (GFX), increased ALP activity. GFX inhibited FGF-2-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β), suggesting that FGF-2 induced PKC and then PKC inhibited the activity of GSK-3β. Addition of activin A increased phosphorylation of GSK-3β and extracellular signal-regulated kinase-1/2 (ERK-1/2) synergistically with FGF-2 whereas activin A alone did not. GFX negated differentiation of hPS cells induced by the PKC activator, phorbol 12-myristate 13-acetate whereas Gö6976, a selective inhibitor of PKCα, β, and γ isoforms could not counteract the effect of PMA. Intriguingly, functional gene analysis by RNA interference revealed that the phosphorylation of GSK-3β was reduced by siRNA of PKCδ, PKCε, and ζ, the phosphorylation of ERK-1/2 was reduced by siRNA of PKCε and ζ, and the phosphorylation of AKT was reduced by PKCε in hPS cells. Our study suggested complicated cross-talk in hPS cells that FGF-2 induced the phosphorylation of phosphatidylinositol-3 kinase (PI3K)/AKT, mitogen-activated protein kinase/ERK-1/2 kinase (MEK), PKC/ERK-1/2 kinase, and PKC/GSK-3β. Addition of GFX with a MEK inhibitor, U0126, in the presence of FGF-2 and activin A provided a long-term stable undifferentiated state of hPS cells even though hPS cells were dissociated into single cells for passage. This study untangles the cross-talk between molecular mechanisms regulating self-renewal and differentiation of hPS cells.


Continuous Spinning of High-Tough Hydrogel Fibers for Flexible Electronics by Using Regional Heterogeneous Polymerization.
Hydrogel fibers have attracted substantial interest for application in flexible electronics due to their ionic conductivity, high specific surface area, and ease of constructing multidimensional structures. However, universal continuous spinning methods for hydrogel fibers are yet lacking. Based on the hydrophobic mold induced regional heterogeneous polymerization, a universal self-lubricating spinning (SLS) strategy for the continuous fabrication of hydrogel fibers from monomers is developed. The universality of the SLS strategy is demonstrated by the successful spinning of 10 vinyl monomer-based hydrogel fibers. Benefiting from the universality of the SLS strategy, the SLS strategy can be combined with pre-gel design and post-treatment toughening to prepare highly entangled polyacrylamide (PAM) and ionic crosslinked poly(acrylamide-co-acrylic acid)/Fe3+ (W-PAMAA/Fe3+ ) hydrogel fibers, respectively. In particular, the W-PAMAA/Fe3+ hydrogel fiber exhibited excellent mechanical properties (tensile stress > 4 MPa, tensile strain > 400%) even after 120 days of swelling in the pH of 3-9. Furthermore, owing to the excellent multi-faceted performance and one-dimensionality of W-PAMAA/Fe3+ hydrogel fibers, flexible sensors with different dimensions and functions can be constructed bottom-up, including the one-dimensional (1D) strain sensor, two-dimensional (2D) direction sensor, three-dimensional (3D) pressure sensor, and underwater communication sensor to present the great potential of hydrogel fibers in flexible electronics.


Complete Genome Sequences of Two Plant Growth-Inhibiting Bacteria, Acinetobacter ursingii M3 and Asticcacaulis excentricus M6, Isolated from Duckweed (Lemna minor).
Acinetobacter ursingii M3 and Asticcacaulis excentricus M6 are plant growth-inhibiting bacteria that reduce the yield of the duckweed Lemna minor. We report here the complete genome sequences of A. ursingii M3 and A. excentricus M6, sequenced using the PacBio RS II platform.


Immunotherapy: A New Approach to Treating Multiple Myeloma with Daratumumab and Elotuzumab.
To review the clinical pharmacology, efficacy, and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma (RRMM). A literature search of MEDLINE, PubMed, the US National Institutes of Health Clinicaltrials.gov, the Food and Drug administration, and relevant meeting abstracts was conducted using the terms daratumumab, elotuzumab, multiple myeloma, anti-CD38, HuMax-CD38, HuLuc63, SLAMF7, and anti-CS1 STUDY SELECTION/DATA EXTRACTION: Human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daratumumab and elotuzumab for MM were identified. Daratumumab (anti-CD38) and elotuzumab (anti-CS1) have been recently FDA approved for the treatment of RRMM after showing efficacy in clinical trials. Elotuzumab approval was based on phase III data, and daratumumab gained accelerated approval based on phase I/II trials. Daratumumab has demonstrated significant single-agent activity, with an overall response rate (ORR) of 36% in patients with a median of 4 prior lines of therapy. Elotuzumab has not been shown to have single-agent activity. But the efficacy of both these antibodies in combination with lenalidomide and dexamethasone in RRMM showed an ORR exceeding 80%. Tolerability of elotuzumab and daratumumab seems to be acceptable, with the most common adverse event being infusion reactions. Daratumumab and elotuzumab have shown encouraging results in RRMM that led to their FDA approval. Both are well tolerated with minimal toxicities. Phase III clinical trials will define optimal combination and place in therapy of daratumumab and elotuzumab.


Ascites or pleural effusion? CT and ultrasound differentiation.
The differentiation of fluid immediately above the diaphragm, i.e., pleural effusion, from subdiaphragmatic fluid, i.e., ascites, can be difficult. Freely mobile pleural effusions are easily proven with decubitus chest films, but loculated subpulmonic effusions can mimic intraabdominal fluid. The simultaneous presence of both ascites and pleural effusion is difficult to identify with plain radiographs. Both computed tomography (CT) and ultrasound (US) can be used to differentiate ascites from pleural effusion. Four criteria have been described to differentiate ascites from pleural effusion by CT. These four signs (the diaphragm sign, the displaced crus sign, the interface sign, and the bare area sign) are reliable when only one abnormal fluid collection is present. When both a pleural effusion and ascites are present, none of these criteria can reliably identify both fluid collections. The combined use of the four criteria, however, leads to a correct identification of abnormal fluid collections in the region of the diaphragm. US examination can differentiate ascites from pleural effusion using three of the above-mentioned signs (the diaphragm sign, the displaced crus sign, and the bare area sign). We will review the four signs and discuss the limitation of these signs in clinical practice. A thorough understanding of these CT and US criteria will allow for accurate identification of all juxtadiaphragmatic fluid collections.


Strengthened structure-function relationships of the corticospinal tract by free water correction after stroke.
The corticospinal tract is the most intensively investigated tract of the human motor system in stroke rehabilitative research. Diffusion-tensor-imaging gives insights into its microstructure, and transcranial magnetic stimulation assesses its excitability. Previous data on the interrelationship between both measures are contradictory. Correlative or predictive models which associate them with motor outcome are incomplete. Free water correction has been developed to enhance diffusion-tensor-imaging by eliminating partial volume with extracellular water, which could improve capturing stroke-related microstructural alterations, thereby also improving structure-function relationships in clinical cohorts. In the present cross-sectional study, data of 18 chronic stroke patients and 17 healthy controls, taken from a previous study on cortico-cerebellar motor tracts, were re-analysed: The data included diffusion-tensor-imaging data quantifying corticospinal tract microstructure with and without free water correction, transcranial magnetic stimulation data assessing recruitment curve properties of motor evoked potentials and detailed clinical data. Linear regression modelling was used to interrelate corticospinal tract microstructure, recruitment curves properties and clinical scores. The main finding of the present study was that free water correction substantially strengthens structure-function associations in stroke patients: Specifically, our data evidenced a significant association between fractional anisotropy of the ipsilesional corticospinal tract and its excitability (P = 0.001, adj. R 2 = 0.54), with free water correction explaining additional 20% in recruitment curve variability. For clinical scores, only free water correction leads to the reliable detection of significant correlations between ipsilesional corticospinal tract fractional anisotropy and residual grip (P = 0.001, adj. R 2 = 0.70) and pinch force (P < 0.001, adj. R 2 = 0.72). Finally, multimodal models can be improved by free water correction as well. This study evidences that corticospinal tract microstructure directly relates to its excitability in stroke patients. It also shows that unexplained variance in motor outcome is considerably reduced by free water correction arguing that it might serve as a powerful tool to improve existing models of structure-function associations and potentially also outcome prediction after stroke.


Novel arthropod repellent, BioUD, is an efficacious alternative to deet.
For >50 yr, N,N-diethyl-3-methylbenzamide (deet) has been the standard for arthropod repellents and has been an important tool to protect people from disease agents carried by ticks, mosquitoes, and other arthropods. However, some people avoid using deet because of concerns about adverse health effects. In 2007, a new repellent, BioUD, with the active ingredient 7.75% 2-undecanone, originally derived from wild tomato (Lycopersicon hirsutum Dunal f. glabratum C. H. Müll) plants, was registered by the U.S. Environmental Protection Agency. In the current study, repellent efficacy of BioUD was compared using arm-in-cage studies with 7 and 15% deet against the mosquitoes Aedes aegypti (L.) and Aedes albopictus Skuse. No differences were found in mean repellency over 6 h after application between BioUD versus 7 and 15% deet for Ae albopictus. For Ae. aegypti, no differences were found over the same time period for 7% deet. Compared with 15% deet, BioUD mean repellency was lower over the 6-h test period. Human subject field trials were conducted in North Carolina, United States, and Ontario, Canada, comparing the repellency of BioUD to products containing 25 and 30% deet. BioUD provided the same repellency or was more efficacious than 25 and 30% deet, respectively, in these studies. Laboratory trials were conducted to determine the repellent activity of BioUD against the American dog tick, Dermacentor variabilis (Say), on human skin and cloth. BioUD repelled ticks at least 2.5 h after application to human skin. On cloth, no differences in mean repellency were found through 8 d after application between BioUD and 7% deet. In a two-choice test for BioUD versus 15% deet on filter paper, ticks spent significantly more time on the deet-treated surface than the BioUD-treated surface. Based on these studies in toto, BioUD is an efficacious alternative to deet in its repellent activity.