How should one study brain adrenergic receptors in aging?
Contradictory findings and lack of definitive information regarding adrenergic receptors in aging results in part from problems related to the methodology that has been used to study this question. Limitations of available techniques and new biochemical, molecular biological, and physiological methods that may prove particularly helpful for future studies are discussed.


Roll-your-own cigarette smoking among youth experiencing homelessness.
Roll-your-own (RYO) cigarette smoking is uncommon among young smokers in the U.S. but may be more widespread among those experiencing homelessness as it is a less expensive source of cigarettes. This study examines the prevalence and correlates of RYO use among young cigarette smokers experiencing homelessness. The analytic sample consisted of 433 unaccompanied homeless youth who reported past month use of factory-manufactured cigarettes. Participants were sampled from 25 street and service sites in Los Angeles County, and completed a survey on their tobacco-related behaviors and cognitions. RYO use was reported by 43% of cigarette smokers. Among those who filled RYOs with tobacco, 87% rolled them with used tobacco (typically mixed with new tobacco). Most RYO smokers reported engaging in high-risk smoking practices, such as smoking discarded cigarettes. Although RYO smokers were more likely than other smokers to perceive RYOs as less risky in general, these groups did not differ in the perceived relative harm, expense, and ease of access of RYOs compared to regular cigarettes. Multivariable analyses indicated that RYO use was associated with older age, less perceived riskiness of RYOs, greater exposure to RYO smokers, and stronger future intentions to smoke. RYOs may encourage continued tobacco use among youth experiencing homelessness and pose additional health risks despite users' beliefs to the contrary. Future research is needed to obtain more detailed information on RYO practices and motivations for use, as well as how to address RYOs in efforts to reduce tobacco use in this population.


Antihypertensive therapy and orthostatic hemodynamic responses in acute stroke.
It is not known whether antihypertensive medications affect orthostatic blood pressure (BP) regulation in the early period after stroke. Knowledge of this may have implications for clinical practice. A total of 40 acute ischemic stroke patients (mild-to-moderate severity) taking antihypertensive drugs, and 40 patients with acute stroke of similar severity not receiving such drugs were studied. Blood pressure and heart rate were measured while supine, and then for 5 min while sitting up and for 5 min in the standing posture. This was performed < or =3 days poststroke (day 1) and 1 week after the first study (week 1). In both groups of patients on day 1 and week 1, there was no significant fall in mean arterial pressure and heart rate after sitting up and standing up. Logistic regression analysis showed that only cardiac dysfunction was associated with orthostatic hypotension on univariate analysis (odds ratio 4.0, P = .02) and multivariate analysis when age, hypertension, stroke severity, and treatment were included (odds ratio 3.5, P = .05). Use of antihypertensive therapy was not associated with orthostatic hypotension on univariate or multivariate analysis. Use of antihypertensive drugs in the early period poststroke is not detrimental to postural BP regulation. Antihypertensive therapy may therefore be used when indicated in acute stroke, without having to restrict early mobilization; but the results cannot be extrapolated to the postacute phase.


A cross-sectional study of the prevalence of psychopathology in adults with congenital heart disease.
Several studies have suggested high levels of psychopathology in children and adolescents with congenital heart disease (CHD). However, little information is published relating to psychopathology in adults with CHD. We wanted to estimate the prevalence of psychopathology in adults with CHD. A cross-sectional study of attenders at an adult CHD clinic compared with orthopaedic outpatients of the same hospital. A tertiary CHD clinic in South Wales, the comparison group being recruited from the orthopaedic outpatient clinic in the same teaching hospital. One hundred and one individuals attending the CHD clinic were identified, 87 successfully completed questionnaires. Forty-five from 80 randomly selected orthopaedic outpatients completed questionnaires. The General Health Questionnaire 30 (GHQ30) and the Hospital Anxiety and Depression Scale (HADS). We found a statistically significant difference in the mean GHQ 30 score between the CHD and comparison groups, the CHD group having lower scores. The difference remained after adjustment for age and sex. The mean HADS scores differed in the same direction, and were of borderline statistical significance. In this study, adult subjects with CHD had a lower prevalence of psychopathology. Possible explanations for this finding are discussed.


A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).
Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.


A machine learning framework to determine geolocations from metagenomic profiling.
Studies on metagenomic data of environmental microbial samples found that microbial communities seem to be geolocation-specific, and the microbiome abundance profile can be a differentiating feature to identify samples' geolocations. In this paper, we present a machine learning framework to determine the geolocations from metagenomics profiling of microbial samples. Our method was applied to the multi-source microbiome data from MetaSUB (The Metagenomics and Metadesign of Subways and Urban Biomes) International Consortium for the CAMDA 2019 Metagenomic Forensics Challenge (the Challenge). The goal of the Challenge is to predict the geographical origins of mystery samples by constructing microbiome fingerprints.First, we extracted features from metagenomic abundance profiles. We then randomly split the training data into training and validation sets and trained the prediction models on the training set. Prediction performance was evaluated on the validation set. By using logistic regression with L2 normalization, the prediction accuracy of the model reaches 86%, averaged over 100 random splits of training and validation datasets.The testing data consists of samples from cities that do not occur in the training data. To predict the "mystery" cities that are not sampled before for the testing data, we first defined biological coordinates for sampled cities based on the similarity of microbial samples from them. Then we performed affine transform on the map such that the distance between cities measures their biological difference rather than geographical distance. After that, we derived the probabilities of a given testing sample from unsampled cities based on its predicted probabilities on sampled cities using Kriging interpolation. Results show that this method can successfully assign high probabilities to the true cities-of-origin of testing samples. Our framework shows good performance in predicting the geographic origin of metagenomic samples for cities where training data are available. Furthermore, we demonstrate the potential of the proposed method to predict metagenomic samples' geolocations for samples from locations that are not in the training dataset.


How silicene on Ag(111) oxidizes: microscopic mechanism of the reaction of O2 with silicene.
We demonstrate, using first-principles molecular-dynamics simulations, that oxidation of silicene can easily take place either at low or high oxygen doses, which importantly helps clarify previous inconsistent reports on the oxidation of silicene on the Ag(111) substrate. We show that, while the energy barrier for an O2 molecule reacting with a Si atom strongly depends on the position and orientation of the molecule, the O2 molecule immediately dissociates and forms an Si-O-Si configuration once it finds a barrier-less chemisorption pathway around an outer Si atom of the silicene overlayer. A synergistic effect between the molecular dissociation and subsequent structural rearrangements is found to accelerate the oxidation process at a high oxygen dose. This effect also enhances self-organized formation of sp(3)-like tetrahedral configurations (consisting of Si and O atoms), which results in collapse of the two-dimensional silicene structure and its exfoliation from the substrate. We also find that the electronic properties of the silicene can be significantly altered by oxidation. The present findings suggest that low flux and low temperature of the oxygen gas are key to controlling oxidation of silicene.


Sensitive amplified luminescent proximity homogeneous assay for the quantitative detection of CA242.
We here developed a sensitive and stable amplified luminescent proximity homogeneous assay (AlphaLISA) method for fast quantification of CA242 in human serum. Donor and acceptor beads modified with carboxyl groups could be coupled with CA242 antibodies after activation in the AlphaLISA method. CA242 was rapidly detected by the double antibody sandwich immunoassay. The method yielded good linearity (>0.996) and detection range (0.16-400 U/mL). The intra-assay precisions of CA242-AlphaLISA were between 3.43% and 6.81% (< 10%), and the inter-assay precisions were between 4.06% and 9.56% (< 15%). The relative recoveries ranged from 89.61% to 107.29%. Detection time for the CA242-AlphaLISA method was only 20 min. Moreover, results of CA242-AlphaLISA and time-resolved fluorescence immunoassay had satisfactory correlation and consistency (ρ = 0.9852). The method was successfully applied to the analysis of human serum samples. Meanwhile, serum CA242 has a good detection value in the identification and diagnosis of pancreatic cancer and the monitoring of disease degree. Furthermore, the proposed AlphaLISA method is expected to be an alternative to traditional detection methods, laying a good foundation for the further development of kits to detect other biomarkers in future studies.


Comprehensive approach to genes involved in cell wall modifications in Arabidopsis thaliana.
The plant cell wall is of supermolecular architecture, and is composed of various types of heterogeneous polymers. A few thousand enzymes and structural proteins are directly involved in the construction processes, and in the functional aspects of the dynamic architecture in Arabidopsis thaliana. Most of these proteins are encoded by multigene families, and most members within each family share significant similarities in structural features, but often exhibit differing expression profiles and physiological functions. Thus, for the molecular dissection of cell wall dynamics, it is necessary to distinguish individual members within a family of proteins. As a first step towards characterizing the processes involved in cell wall dynamics, we have manufactured a gene-specific 70-mer oligo microarray that consists of 765 genes classified into 30 putative families of proteins that are implicated in the cell wall dynamics of Arabidopsis. By using this array system, we identified several sets of genes that exhibit organ preferential expression profiles. We also identified gene sets that are expressed differentially at certain specific growth stages of the Arabidopsis inflorescence stem. Our results indicate that there is a division of roles among family members within each of the putative cell wall-related gene families.


Enhancement of the glutaminase activity of carbamyl phosphate synthetase by alterations in the interaction between the heavy and light subunits.
Glutamine-dependent carbamyl phosphate synthetase (from Escherichia coli) was previously shown to be composed of a light subunit (molecular weight similar to 42,000) which has the binding site for glutamine and a heavy subunit (molecular weight similar to 130,000) which has binding sites for the other reactants and allosteric effectors. The subunits may be separated with retention of catalytic activities; only the separated light subunit exhibits glutaminase activity. The previous finding that storage of the native enzyme at pH 9 at 0 degrees increased its glutaminase activity by about 25-fold was further investigated; such storage markedly decreased the glutamine- and ammonia-dependent synthetase activities of the enzyme. Treatment of the enzyme with p-hydroxymercuribenzoate led to transient increase of glutaminase activity followed by inhibition. When the enzyme was treated with N-ethylmaleimide or with 5,5'-dithiobis-(2-nitrobenzoate), the glutaminase activity was increased by about 250-fold with concomitant loss of synthetase activities. The enhancement of glutaminase produced by storage of the enzyme at pH 9 was associated with intermolecular disulfide bond formation and aggregation of the enzyme. Aggregation also was observed after extensive treatment of the enzyme with 5,5'-dithiobis-(2-nitrobenzoate) or N-ethylmaleimide. However, a moderate increase of glutaminase activity (about 30-fold) was observed without aggregation under conditions in which one sulfhydryl group on the light subunit reacted with either reagent. The findings suggest that the increased glutaminase activities observed here are associated with structural changes in the enzyme in which the intersubunit relationship is altered so as to uncouple the catalytic functions of the enzyme and to facilitate access of water to the glutamine binding site on the light subunit.


Phase imaging and nanoscale currents in phase objects imaged with fast electrons.
We derive the magnetic transport-of-intensity equation (MTIE) that links defocused contrast of magnetic nanoobjects imaged by partially coherent electron waves to their micromagnetic parameters. This provides Maxwell's explanation for observable contrast in terms of the Z component of currents existing around vortices in superconductors and domain vortices and walls in ferromagnets. The solution of the MTIE via Fourier transform is used for quantitative mapping of magnetic flux and projected induction in magnetic and superconducting materials imaged by Lorentz microscopy.


GPER-mediated stabilization of HIF-1α contributes to upregulated aerobic glycolysis in tamoxifen-resistant cells.
Tamoxifen is a first-line therapeutic drug for oestrogen-receptor positive breast cancer; however, like other therapeutics, its clinical use is limited by acquired resistance. Tamoxifen-resistant cells have demonstrated enhanced aerobic glycolysis; however, the mechanisms underlying this upregulation remain unclear. Here, we demonstrated that G-protein coupled oestrogen receptor (GPER) was involved in the upregulation of aerobic glycolysis via induction of hypoxia-inducible factor-1α (HIF-1α) expression and transcriptional activity in tamoxifen-resistant cells. Additionally, GPER stabilized HIF-1α through inhibiting its hydroxylation and ubiquitin-mediated degradation, which were associated with upregulation of C-terminal hydrolase-L1 (UCH-L1), downregulation of prolyl hydroxylase 2 (PHD2) and von Hippel-Lindau tumour suppressor protein (pVHL), induction of HIF-1α/UCH-L1 interaction, and suppression of HIF-1α/PHD2-pVHL association. The GPER/HIF-1α axis was functionally responsible for regulating tamoxifen sensitivity both in vitro and in vivo. Moreover, there was a positive correlation between GPER and HIF-1α expression in clinical breast cancer tissues, and high levels of GPER combined with nuclear HIF-1α indicated poor overall survival. High levels of the GPER/HIF-1α axis were also correlated with shorter relapse-free survival in patients receiving tamoxifen. Hence, our findings support a critical role of GPER/HIF-1α axis in the regulation of aerobic glycolysis in tamoxifen-resistant cells, offering a potential therapeutic target for tamoxifen-resistant breast cancer.


Oral leukoplakia, the ongoing discussion on definition and terminology.
In the past decades several definitions of oral leukoplakia have been proposed, the last one, being authorized by the World Health Organization (WHO), dating from 2005. In the present treatise an adjustment of that definition and the 1978 WHO definition is suggested, being : "A predominantly white patch or plaque that cannot be characterized clinically or pathologically as any other disorder; oral leukoplakia carries an increased risk of cancer development either in or close to the area of the leukoplakia or elsewhere in the oral cavity or the head-and-neck region". Furthermore, the use of strict diagnostic criteria is recommended for predominantly white lesions for which a causative factor has been identified, e.g. smokers' lesion, frictional lesion and dental restoration associated lesion. A final diagnosis of such leukoplakic lesions can only be made in retrospect after successful elimination of the causative factor within a somewhat arbitrarily chosen period of 4-8 weeks. It seems questionable to exclude "frictional keratosis" and "alveolar ridge keratosis" from the category of leukoplakia as has been suggested in the literature. Finally, brief attention has been paid to some histopathological issues that may cause confusion in establishing a final diagnosis of leukoplakia.


Climate change adaptation networks for small and medium-sized cities.
Cities are particularly vulnerable to the impacts of climate change. Many larger cities have identified the potential impacts of different climate change adaptation scenarios. However, their smaller and medium-sized counterparts are often not able to address climate risks effectively due to a lack of necessary resources. Since a large number of cities worldwide are indeed small and medium-sized, this lack of preparedness represents a crucial weakness in global response systems. A promising approach to tackling this issue is to establish regional municipal networks. Yet, how might a regional network for small and medium-sized cities be systematically designed and further developed? Focussing on the German federal state of Baden-Wuerttemberg, we have explored this question by applying a participatory action research approach. As part of our research, we established a regional network framework for small and medium-sized cities. The framework supports small and medium-sized cities in identifying key regional actors, while taking local and regional contextual factors into account. Based on our findings, we suggest that other small and medium sized cities follow these steps: develop the knowledge base; build the network; and transfer and consolidate knowledge.


[Morphology of pulmonary atelectasis in patients operated on and not operated on taking into account pulmonary surfactant state].
The results of clinico-anatomical analysis and of histological examinations of 210 cases of atelectasis with simultaneous study of lung surfactant (126 cases) are described. Electron microscopic examinations of lung tissues were conducted in 8 cases of early autopsy. The postoperative atelectases were compared with those in nonoperated patients. The postoperative atelectases were characterized by substantially larger lesions and prevalence of reflectory, aspiratory, and polyetiological types of lesions. A certain dynamics of changes in the lung surfactant activity was established: a substantial increase of the activity during in the acutest phase of atelectasis and its significant decline towards the end of the first week of the disease. The changes of the surfactant indices directly depend on the synthesizing activity of type II pneumocytes. The decrease of the surfactant occurs secondarily as atelectasis advances.


The allocation and interaction model: A new model for predicting total energy expenditure of highly active humans in natural environments.
The purpose of this study was to develop a new model, the Allocation and Interaction Model (AIM), to better predict human total energy expenditure (TEE) among a group of highly active humans living in a variety of natural environments. AIM estimates were tested to determine if it produces more accurate TEE predictions than the Factorial Method. AIM includes metabolic cost terms for basal metabolic rate, thermoregulation, and the thermic effect of food, as well as more accurate activity cost estimations. AIM was tested using doubly labeled water and Flex-Heart Rate (Flex-HR)-measured TEEs of healthy, highly active adults (N = 59) participating in National Outdoor Leadership School semester-long courses. Data from a month-long pilot study (N = 6) were also included. AIM produced TEE estimates that were not significantly different from measured energy expenditure values. Overall, AIM came within 4.1% of measured values; the Factorial Method underestimated by over 25%. At TEEs greater than 3,000 kcal day(-1) , AIM underestimated TEE by 11% compared to 31.6% by the Factorial Method. Also, at TEEs greater than 3,000 kcal day(-1) , the Flex-HR method overestimated TEE by 17%. This analysis demonstrated that AIM is more accurate than the Factorial Method for predicting TEE across a range of climates and physical activity levels. This suggests that AIM should be used in place of the Factorial Method for estimating human TEE. Am. J. Hum. Biol. 28:372-380, 2016. © 2015 Wiley Periodicals, Inc.


Molecular tools unveil distinct waves of ADP-ribosylation during DNA repair.
ADP-ribosylation is a complex post-translation modification involved in DNA repair. In a recent Molecular Cell publication, Longarini and colleagues measured ADP-ribosylation dynamics with unprecedented specificity, revealing how the monomeric and polymeric forms of ADP-ribosylation regulate the timing of DNA repair events following strand breaks.


Pulmonary alveolar and vascular morphometry after gel plug occlusion of the trachea in a fetal rabbit model of CDH.
Tracheal occlusion (TO) induces lung growth in congenital diaphragmatic hernia (CDH) but is also associated with drawbacks. We devised a temporary gel plug that induced lung growth when placed in the fetal trachea. This study evaluates the effects of temporary versus permanent TO on histologic radial alveolar count (RAC) and vascular morphometrics. Experimental CDH was created surgically in 64 New Zealand White rabbit fetuses on gestational day (GD) 24. On GD 27, these fetuses were randomized to intratracheal instillation of a fibrin gel plug (GP), tracheal suture ligation (SL), intratracheal instillation of normal saline (NS), or sham amniotomy (SH). Non-manipulated fetuses served as controls (NM). Histologic lung sections were assessed blindly for RAC and relative arterial adventitial thickness (%AT) as a variable for vascular remodelling. Results were statistically compared. RAC was significantly lower in the ipsilateral lung of SH fetuses than in the contralateral lung (p = 0.011). Mean RAC was higher after SL (p < 0.001) and GP (p = 0.03) compared to SH. Furthermore, %AT was higher in GP (50 ± 28, p < 0.001) and SL (45 ±2 6, p = 0.003) fetuses than in controls (36 ± 19). Temporary and permanent TO leads to increased RAC; this effect was more pronounced with permanent TO. Both interventions were associated with an increased %AT. These findings may explain the adverse clinical effects of TO, despite causing accelerated lung growth.


Multivariate analysis of determinants of postoperative wound infection in orthopaedic patients.
In a prospective study of 376 orthopaedic patients, the relative contribution of host factors and patient-care variables to the risk of postoperative wound infection was evaluated. Host factors studied were age, sex, ethnic origin and diagnosis. The number of operations, the insertion of an open drain, the use of prophylactic antibiotics and the length of the operation were the patient-care variables studied. Of the risk factors identified, the performance of more than one operation during an admission had the highest risk coefficient, followed by the presence of an open drain, internal fixation of a fracture, and spine fusion. Within the group of operations for internal fixation, those for fractures of the femur had the highest risk of infection. In spine fusions those operations lasting 5 or more hours were associated with a high risk of infection. The length of stay of infected patients was on average 17.9 days longer than that of their individually-matched non-infected controls.


Characterizing adrenocortical activity in zoo-housed southern three-banded armadillos (Tolypeutes matacus).
Improving the husbandry in the southern three-banded armadillo (Tolypeutes matacus) through gaining knowledge of its stress physiology is imperative to maintaining a healthy, zoo-housed population. Our objectives were to: 1) validate the use of fecal hormone analysis for monitoring adrenocortical activity using both an adrenocorticotropic hormone (ACTH) challenge and biological events; and 2) characterize longitudinal adrenocortical activity in male and female southern three-banded armadillos. An ACTH injection was given intra-muscularly to one male (4IU/kg; 5.6IU total) and one female (5.5IU/kg; 8IU total) southern three-banded armadillo. Fecal samples were collected 1 day pre- and continued 5 days post-ACTH to capture the physiological response measured by elevated fecal glucocorticoid metabolites (FGM) to validate these techniques. Additionally, natural and routine events, including pairing individuals for breeding and veterinary procedures/handling, were used to biologically validate these techniques. To characterize adrenocortical activity, fecal samples (∼3025 total; n=275/animal/yr) were collected from 11 (5 males; 6 females) southern three-banded armadillos 5-7 times a week for 1 year at Lincoln Park Zoo (Chicago, IL). A cortisol enzyme immunoassay was used for FGM analysis. The ACTH challenge in the male resulted in a twofold increase of FGM (1123.2±36.2 ng/g dry feces) above baseline (675.7±10.0 ng/g dry feces) at approximately 54-94h post- injection. The female exhibited a twofold increase (1635.4 ng/g dry feces) over baseline FGMs (608.5±12.3 ng/g dry feces) approximately 30h post-injection. Reproductive behaviors and veterinary procedures resulted in elevated FGM concentrations from all individuals except for one male. The longitudinal characterization demonstrated that sex and season did not influence (P<0.05) FGM concentrations. Individuals were highly variable with mean FGM concentration of 2010.1±862.4 ng/g dry feces (range, 816.3-7889.1 ng/g dry feces). Mean FGM baseline concentration was 878.5±201.8ng/g dry feces (range, 475.2-1955.5 ng/g dry feces) with a mean elevated FGM concentrations of 2694.3±1111.4 ng/g dry feces (range, 1110.3-10,683.3 ng/g dry feces). This study provides the foundation for future research on how the environment directly affects the adrenocortical activity in this species of armadillo.


Red Breast Syndrome: Complete Resolution Following Replacement of Acellular Dermal Matrices With Acellular Collagen Matrices.
What is red breast syndrome (RBS)?What causes RBS?How often do patients present with RBS?What are effective treatments for RBS?


Causes of Vitamin D Deficiency and Effect of Vitamin D Supplementation on Metabolic Complications in Obesity: a Review.
Obese subjects are often characterized by low plasma 25-hydroxy-vitamin D (25OHD) levels. Many explanations for this association have been proposed. Low plasma 25OHD is associated with obesity-related comorbidities such as insulin resistance, type 2 diabetes mellitus, and low-grade inflammation. In this review, we discuss the proposed mechanisms for low 25OHD in obesity and explore the results of recent RCTs on vitamin D (VD) supplementation on obesity and its metabolic complications such as insulin resistance and type 2 diabetes. Although the results from these clinical randomized controlled trials vary, the general picture is that VD treatment of obese individuals does not seem to be an effective treatment of obesity-related metabolic complications.


Perinatal HIV-1 transmission: Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility.
Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (FcγR) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of FcγR-mediated effector functions in modulating perinatal HIV-1 transmission risk. In this study, genotypic data from 79 HIV-1 infected mothers and 78 HIV-1 infected infants (transmitting cases) were compared to 234 HIV-1 infected mothers and 235 HIV-1 exposed-uninfected infants (non-transmitting controls). Associations, unadjusted and adjusted for multiple comparisons, were assessed for overall transmission and according to mode of transmission-intrapartum (n = 31), in utero (n = 20), in utero-enriched (n = 48). The maternal FcγRIIIa-158V allele that confers enhanced antibody binding affinity and antibody-dependent cellular cytotoxicity capacity significantly associated with reduced HIV-1 transmission [odds ratio (OR) 0.47, 95 % confidence interval (CI) 0.28-0.79, P = 0.004; PBonf > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; PBonf > 0.05) and in utero-enriched transmitting groups (P = 0.0001; PBonf < 0.01). In both mother and infant, possession of an FcγRIIIb-HNA1b allotype that reduces neutrophil-mediated effector functions associated with increased transmission (OR 1.87, 95 % CI 1.08-3.21, P = 0.025; PBonf > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; PBonf > 0.05), respectively. Conversely, the infant FcγRIIIb-HNA1a|1a genotype was significantly protective of perinatal HIV-1 acquisition (OR 0.42, 95 % CI 0.18-0.96, P = 0.040; PBonf > 0.05). The findings of this study suggest a potential role for FcγR-mediated effector functions in perinatal HIV-1 transmission. However, future studies are required to validate the findings of this study, in particular associations that did not retain significance after adjustment for multiple comparisons.


Modelling and optimisation of enzymatic separating micro-reactor.
A mathematical model of an enzymatic separating microreactor with the electro-osmotic control of reaction component transport rates is analysed. The micro-reactor is considered in a form of a thin channel filled with a gel containing an immobilised enzyme and an adsorbent where the enzyme reaction, the molecular diffusion, the electro-osmotic flux and the adsorption take place. The substrate inhibited enzyme reaction splitting a non-ionic substrate to two non-ionic products is considered. The reactor operates in a periodic regime, when the channel entry is exposed to the periodic substrate concentration pulses. A chromatographic separation of reaction components, therefore, proceeds in the channel. Effects of principal operational parameters of the reactor system-the reaction channel length, the electric current density, the substrate inlet concentration, the rate of adsorption, and the enzyme activity--on resolution of the products at reactor outlet are analysed. The existence of optimum parameter values (maximising the resolution of reaction products) is shown and a multiparametric optimisation of the reactor performance is accomplished.


Body mass index and screening for colorectal cancer: gender and attitudinal factors.
Overweight/obese women and men are at increased risk for colorectal cancer (CRC) incidence and mortality. Research examining body mass index (BMI) and CRC screening has had mixed results. A clearer understanding of the extent to which high-BMI subgroups are screened for CRC is needed to inform planning for CRC screening promotions targeting BMI. Data were obtained from a random, population-based sample of women and men at average-risk for CRC (aged 50-75 years) during 2004 (n = 1098). Multiple logistic regression analyses were conducted to evaluate whether BMI category was significantly associated with the probability of reporting recent CRC screening and with the probability of agreeing with statements denoting attitudes/perceptions about CRC and screening. Attitudes/perceptions about CRC and screening were evaluated as potential mediators and moderators of the association between BMI category and CRC screening. After controlling for characteristics associated with CRC screening, overweight and obese women were each 40% less likely to have CRC screening than women with normal-BMI (OR = 0.6, 95% CI:0.4-0.9 and OR = 0.6, 95% CI:0.3-0.9). BMI category was unrelated to screening among men. Obese women (but not men) were less aware than normal-BMI women that obesity increased risk for CRC (OR = 0.5, 95% CI:0.3-0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3-0.8). However, findings suggest that attitudes/perceptions about CRC and screening did not mediate or moderate the association between BMI category and CRC screening. Overweight/obese women are at increased risk for CRC because of their greater BMI and their propensity not to screen for CRC. Study findings suggest that potentially modifiable perceptions, e.g., lack of awareness of risk for CRC and less worry about CRC, in this subgroup may not explain the relationship between BMI category and reduced screening.


Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.
Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.


Writing-Speed Dependent Thresholds of Ferroelectric Domain Switching in Monolayer α-In2 Se3.
An electrical-biased or mechanical-loaded scanning probe written on the ferroelectric surface can generate programmable domain nanopatterns for ultra-scaled and reconfigurable nanoscale electronics. Fabricating ferroelectric domain patterns by direct-writing as quickly as possible is highly desirable for high response rate devices. Using monolayer α-In2 Se3 ferroelectric with ≈1.2 nm thickness and intrinsic out-of-plane polarization as an example, a writing-speed dependent effect on ferroelectric domain switching is discovered. The results indicate that the threshold voltages and threshold forces for domain switching can be increased from -4.2 to -5 V and from 365 to 1216 nN, respectively, as the writing-speed increases from 2.2 to 10.6 µm s-1 . The writing-speed dependent threshold voltages can be attributed to the nucleations of reoriented ferroelectric domains, in which sufficient time is needed for subsequent domain growth. The writing-speed dependent threshold forces can be attributed to the flexoelectric effect. Furthermore, the electrical-mechanical coupling can be employed to decrease the threshold force, achieving as low as ≈189±41 nN, a value smaller than those of perovskite ferroelectric films. Such findings reveal a critical issue of ferroelectric domain pattern engineering that should be carefully addressed for programmable direct-writing electronics applications.


Buyang Huanwu Decoction ameliorates atherosclerosis by regulating TGF-β/Smad2 pathway to promote the differentiation of regulatory T cells.
As a classic prescription of Traditional Chinese Medicine in Correction on the Errors of Medical Works, Buyang Huanwu Decoction (BYHWD) has a good curative effect on prevention of atherosclerosis (AS). This study aims to elucidate the anti-atherosclerosis mechanism of BYHWD, which may promote the differentiation of regulatory T cells by regulating the TGF-β/Smad2 pathway. ApoE-/- mice were fed a high-fat diet for 12 weeks, then drugs group were given BYHWD with intragastric administration once a day for 4 weeks. The effect of BYHWD on lipid content in peripheral blood and plaque was evaluated by blood lipid test and oil red O staining. The number of Tregs in peripheral blood was tested by flow cytometry, and that in the spleen was evaluated by immunohistochemistry methods. Gene and protein expression relating with Tregs differentiation pathway in mice were checked by RT-PCR and Western blot experiments. CD4+T cells were isolated and interfered by BYHWD drug-loaded serum. The proportion of Tregs was evaluated by flow cytometry. The chemical compositions of BYHWD and rat drug-loaded serum were analyzed by ultra-high performance liquid chromatograph and liquid chromatography-tandem mass spectrometry. BYHWD significantly reduced plaque area and cholesterol accumulation, increased the number of Tregs in spleen and peripheral blood of ApoE-/- AS mice, raised the proportion of Tregs in CD4+T cells, and regulated the levels of inflammatory factors. It also increased the TGF-β and Smad2 mRNA and protein levels relating with Tregs differentiation pathway in vivo. The mRNA levels of Foxp3/TGF-β/Smad2 were enhanced via BYHWD in vitro. BYHWD regulates TGF-β/Smad2 signaling pathway to promotes the peripheral differentiation of Tregs, increases the number of Tregs, restores the immune balance between CD4+T cells, regulates lipid metabolism, inhibits inflammatory reaction and possesses the potential of enhancing plaque stability.


Placental characteristics in monochorionic twins with selective intrauterine growth restriction assessed by gradient angiography and three-dimensional reconstruction.
To investigate the placental characteristics in selective intrauterine growth restriction (sIUGR) using gradient angiography and three-dimensional (3D) reconstruction from computed tomography (CT) scan data. This study included 23 sIUGR cases and 16 monochorionic twin-pregnancies without sIUGR. We injected nonionic iodinated contrast agents into the umbilical arteries and veins. Placental characteristics were analyzed after CT scanning and 3D reconstruction. 73.9% of smaller twins in sIUGR cases had marginal or velamentous cord insertions and less placental sharing. The terminal branch of the arterial tree was scored III-IV in smaller sIUGR twins, while it was scored V-VII in normal monochorionic twins and larger sIUGR twins. Arterio-arterial (A-A) anastomoses presented in all monochorionic placentas. Veno-venous (V-V) anastomoses present in 83.3% (5/6) of Type III sIUGR cases, which was higher than observed in Type I-II cases. The mean diameters of A-A and V-V anastomoses were larger in Type III sIUGR cases. Gradient angiography and 3D placental models displayed different placental angioarchitectures and voluminal placental sharing among three types of sIUGR cases. Placental dysplasia in the smaller twin may cause abnormal cord insertion and unequal placental sharing. The inter-twin anatomoses influence the umbilical cord artery (UA) Doppler and natural pathogenesis of sIUGR.


Prognostic value of the flow cytometric DNA index in human ovarian carcinoma.
Flow cytometric measurements were done on 51 ovarian carcinoma specimens collected from consecutive patients in a prospective study. The ploidy status was related to the course of the disease. The tumors from 26 (52%) of 50 evaluable patients had DNA aneuploidy. Patients with diploid tumors were more often considered disease-free after initial operation (P less than 0.01). Patients with aneuploid tumors had a more aggressive course of the disease in all respects of comparison. The median survival of patients with diploid tumors was 18 months as compared to 8 months for those with aneuploid tumors (P less than 0.0005). Flow cytometric DNA measurements give important prognostic information and such analyses should be included in future clinical trials. Through the development of high-speed instrumentation they also may become feasible in routine clinical work.


Biological assay for zinc availability in wheat germ.
Our objective was to develop a method to determine the bioavailability of zinc in wheat germ. Weanling rats were fed for 10 days a Zn-free diet supplemented with different levels of Zn, with or without 2% wheat germ. Zinc concentrations of either tibia or femurs were plotted directly against Zn added to the diet, giving two lines that were essentially parallel. A multiple regression model was used to obtain a common slope but different intercepts for the lines. The amount of available Zn was calculated by taking the ratio of the difference in intercepts to the common slope. The result showed that wheat germ contained 163.7 micrograms Zn/g, of which 86.7% was bioavailable to the rat.


Use of the saline infusion electrode catheter for improved energy delivery and increased lesion size in radiofrequency catheter ablation.
Although radiofrequency catheter ablation has undergone explosive growth as the treatment for a variety of arrhythmias, a limiting factor with the existing catheter delivery system has been the relatively small size of the lesions, which appears to be in part due to coagulum formation around the catheter tip, producing a rise in impedance and limiting energy delivery. In order to test the hypothesis that infusion of saline during radiofrequency current application can increase the lesion size and decrease the incidence of impedance rise, ten dogs were each given two radiofrequency ablation lesions to the left ventricular endocardium. One of these lesions was delivered with a standard 7 French quadripolar catheter with a 2-mm tip, and the second was done with a 7 French luminal electrode catheter (also with a 2-mm tip) for the infusion of normal saline during the delivery of radiofrequency energy. Energy was delivered for 60 seconds at either 10 or 20 watts at two distinct sites in the left ventricle for each animal. Four to 7 days following ablation, the animals were sacrificed for pathological examination. The lesions created with the saline infusion catheter were significantly bigger than those produced with a standard catheter (7.3 x 7.0 x 5.1 vs 5.2 x 4.9 x 3.5 mm, respectively, P < 0.001). At the lower energy level (10 W), none of the animals with the saline infusion catheter experienced an impedance rise versus 3 of 5 of the animals in whom the standard catheter was used.(ABSTRACT TRUNCATED AT 250 WORDS)


Anemia in African malnourished pre-school children: A systematic review and meta-analysis.
Generating accurate epidemiological data on the magnitude of anemia in malnourished children is a vital step for health policymakers. Therefore, this study is aimed to synthesize the overall magnitude of anemia in African malnourished pre-school children. We have searched the databases PubMed/MEDLINE, Embase, Scopus, Web of Science, Google Scholar, and Google to identify relevant articles. Joana Brigg's Institute critical appraisal tool was used to assess the quality of articles. A random-effects model was applied to estimate the pooled prevalence of anemia in malnourished children. The I2 statistics were used to examine heterogeneity among the included studies. In the presence of heterogeneity, a subgroup analysis has been used. The funnel plot analysis and Egger's tests were used to investigate the presence of publication bias. A total of 15 articles with 12,211 study participants were included in this study. Anemia was observed in 57.53% (95% CI: 47.05, 68.01) of African malnourished pre-school children. Moreover, the prevalence of anemia was 58.52% (95% CI: 43.04, 73.81) and 56.18% (95% CI: 40.24, 72.13) in HemoCue and auto-machine diagnosis method of anemia, respectively. This review showed that the magnitude of anemia was high among African malnourished pre-school children. Therefore, planning preventive measures to decrease anemia and its complications in malnourished children in Africa is an important step.


Synthesis of sorbicillinoid analogues with anti-inflammation activities.
Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.


Timing of surgery for cerebral aneurysms: a plea for early referral.
Two groups of patients with aneurysmal subarachnoid haemorrhages--111 patients who underwent surgery within three days of haemorrhage, and 203 patients who underwent operations four or more days after the haemorrhage--were compared. No significant differences were found in outcome between the two groups. This indicates that early operation, which has the advantage of minimizing the risk of recurrent haemorrhage, is safe. The importance of the early diagnosis of subarachnoid haemorrhage and of an urgent referral for neurosurgical management is stressed.


Alcohol preference in AXB/BXA recombinant inbred mice: gender differences and gender-specific quantitative trait loci.
The purpose of the present study was to characterize the C57BL/6J, A/J, and AXB/BXA Recombinant Inbred (RI) strains of mice for voluntary alcohol consumption. Quantitative Trait Locus (QTL) analysis was used to provide provisional location of QTLs for alcohol consumption. The inbred strains were screened for levels of alcohol intake (calculated as alcohol preference and absolute alcohol consumption) by receiving 4 days of forced exposure to a 10% (wt/vol) solution of alcohol, followed by 3 weeks of free choice between water and 10% alcohol. A wide and continuous distribution of values for alcohol consumption and preference was obtained in the AXB/BXA RI strains, confirming polygenic influences on alcohol-related behaviors. Significant gender differences were found for both alcohol preference [F28,651 = 2.12, p < 0.001] and absolute alcohol consumption [F28,647 = 2.57, p < 0.001]. In males, putative QTLs were mapped to chromosomes (Chrs) 2, 5, 7, 10, 11, and 16. Multiple regression analysis indicated that approximately 75% of the genetic variance in alcohol preference in males could be accounted for by three of the QTL regions. Several of the putative QTLs appeared to be male-specific (Tyr on Chr 7; D10Mit126 on Chr 10; D11Mit61 on Chr 11). In females, seven putative QTLs were mapped to Chrs 2, 4, 5, 7, 11, 16, and 19. Approximately 90% of the genetic variance in alcohol preference in females could be accounted for by four QTL regions, as determined by multiple regression. The QTL on Chr 11 near D11Mit35 appeared to be female-specific. This site was close to a female-specific QTL (Alcp2) previously mapped in C57BL/6J x DBA/2J backcrosses by Melo and coworkers (Nat Genet 13, 147, 1996). The QTLs mapped for alcohol preference in the present study must be considered suggestive at the present time, since only D2Mit74 met very strict statistical criteria for significance. However, the concordance across several studies for the loci on Chrs 2, 4, 7, 9, and 11 suggest that some common QTLs influencing alcohol preference have been identified. Confirmation of QTLs mapped in the present study is currently being conducted in a new series of recombinant congenic (RC) strains developed from reciprocal backcrosses between the A/J and C57BL/6J progenitors. The concomitant use of both RI and RC strains developed from the same progenitors should provide a powerful means of detecting, confirming, and mapping QTLs for alcohol-related traits.


Radiostrontium and radium analysis in low-level environmental samples following a multi-stage semi-automated chromatographic sequential separation.
Strontium isotopes, (89)Sr and (90)Sr, and (226)Ra being radiotoxic when ingested, are routinely monitored in milk and drinking water samples collected from different regions in Canada. In order to monitor environmental levels of activity, a novel semi-automated sensitive method has been developed at the Radiation Protection Bureau of Health Canada (Ottawa, Canada). This method allows the separation and quantification of both (89)Sr and (90)Sr and has also been adapted to quantify (226)Ra during the same sample preparation procedure. The method uses a 2-stage purification process during which matrix constituents, such as magnesium and calcium that are rich in milk, are removed as well as the main beta-interferences (e.g., (40)K, (87)Rb, (134)Cs, (137)Cs, and (140)Ba). The first purification step uses strong cation exchange (SCX) chromatography with commercially available resins. In a second step, fractions containing the radiostrontium analytes are further purified using high-performance ion chromatography (HPIC). While (89)Sr is quantified by Cerenkov counting immediately after the second purification stage, the same vial is counted again after a latent period of 10-14 days to quantify the (90)Sr activity based on (90)Y ingrowth. Similarly, the activity of (226)Ra, which is separated by SCX only, is determined via the emanation of (222)Rn in a 2-phase aqueous/cocktail system using liquid scintillation counting. The minimum detectable concentration (MDC) for (89)Sr and (90)Sr for a 200 min count time at 95% confidence interval is 0.03 and 0.02 Bq/L, respectively. The MDC for (226)Ra for a 100 min count time is 0.002 Bq/L. Semi-annual intercomparison samples from the USA Department of Energy Mixed Analyte Performance Evaluation Program (MAPEP) were used to validate the method for (89)Sr and (90)Sr. Spiked water samples prepared in-house and from International Atomic Energy Agency (IAEA) were used to validate the (226)Ra assay.


Ablation of nucleus isthmi leads to loss of specific visually elicited behaviors in the frog Rana pipiens.
Ablation of the frog's nucleus isthmi results in a visual scotoma contralateral to the lesion. Within the scotoma, animals do not respond to visually presented prey or threats. The locus of visual loss is related to the area of isthmal tissue ablated. With complete unilateral ablation, a frog displays no visually elicited prey-catching or threat-avoidance behaviors in the entire monocular field.


Enhanced analysis of weathered crude oils by gas chromatography-flame ionization detection, gas chromatography-mass spectrometry diagnostic ratios, and multivariate statistics.
Artificially weathered crude oil "spill" samples were matched to unweathered suspect "source" oils through a three-tiered approach as follows: Tier 1 gas chromatography-flame ionization detection (GC/FID), Tier 2 gas chromatography-mass spectrometry (GC/MS) diagnostic ratios, and Tier 3 multivariate statistics. This study served as proof of concept for a promising and new method of crude oil forensics that applies principal component analysis (PCA) and partial least squares discriminant analysis (PLSDA) in tandem with traditional forensic oil fingerprinting tools to confer additional confidence in challenging oil spill cases. In this study, weathering resulted in physical and chemical changes to the spilled oils, thereby decreasing the reliability of GC/FID and GC/MS diagnostic ratios in source attribution. The shortcomings of these traditional methods were overcome by applying multivariate statistical tools that enabled accurate characterization of the crude oil spill samples in an efficient and defensible manner.


An implantable pulse generator indicating asystole or extreme bradycardia.
The design of a pacemaker which indicates the occurrence of significant bradyarrhythmia is described. Significant bradyarrhythmia is defined as either asystole for 6 seconds, bradycardia with three successive RR-intervals greater than 2 seconds each, or five or more RR-intervals of 2 seconds or more over a period of 25 seconds, but without three such intervals in succession. During bradyarrhythmia the generator initially stimulates at an interval of 2 seconds (30 per minute) and when the described criteria have been fullfilled the pacemaker automatically converts to a conventional ventricular inhibited pulse generator stimulating at a rate of 70 per minute.


Cyperane and eudesmane-type sesquiterpenoids from Chinese liverwort and their anti-diabetic nephropathy potential.
Six new sesquiterpenoids, including cyperane (1 and 2) and eudesmane (3-6) types, and one known eudesmane derivative (7), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis (Schrad.) Nees. The structures of 1-7 were determined based on a combination of their spectroscopic data (NMR, HRESIMS and IR), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Preliminary anti-diabetic nephropathy activity testing showed that the cyperane-type sesquiterpenoids could inhibit cell proliferation and extracellular matrix accumulation in high glucose cultured mesangial cells in a dose-dependent manner.


Impact of air pollution exposure during various periods of pregnancy on term birth weight: a large-sample, retrospective population-based cohort study.
Previous studies have suggested that maternal exposure to air pollution might affect term birth weight. However, the conclusions are controversial. Birth data of all term newborns born in Xi'an city of Shaanxi, China, from 2015 to 2018 and whose mother lived in Xi'an during pregnancy were selected form the Birth Registry Database. And the daily air quality data of Xi'an city was collected from Chinese Air Quality Online Monitoring and Analysis Platform. Generalized additive models (GAM) and 2-level binary logistic regression models were used to estimate the effects of air pollution exposure on term birth weight, the risk term low birth weight (TLBW), and macrosomia. Finally, 321521 term newborns were selected, including 4369(1.36%) TLBW infants and 24,960 (7.76%) macrosomia. The average pollution levels of PM2.5, PM10, and NO2 in Xi'an city from 2015 to 2018 were higher than national limits. During the whole pregnancy, maternal exposure to PM2.5, PM10, SO2, and CO all significantly reduced the term birth weight and increased the risk of TLBW. However, NO2 and O3 exposure have significantly increased the term birth weight, and O3 even increased the risk of macrosomia significantly. Those effects were also observed in the first and second trimesters of pregnancy. But during the third trimester, high level of air quality index (AQI) and maternal exposure to PM2.5, PM10, SO2, NO2, and CO increased the term birth weight and the risk of macrosomia, while O3 exposure was contrary to this effect. The findings suggested that prenatal exposure to air pollution might cause adverse impacts on term birth weight, and the effects varied with trimesters and pollutants, which provides further pieces of evidence for the adverse effects of air pollution exposure in heavy polluted-area on term birth weight.


Approach to chronic abdominal pain in Cystic Fibrosis.
Abdominal pain in individuals with CF is challenging for the patient as well as the physician, as the differential diagnosis can be complex. Most gastrointestinal manifestations of CF present with regional abdominal pain. Pain localization, which requires knowledge of gut development and innervation, is crucial to understanding the pathophysiology of abdominal pain in CF. The location of the pain, together with the clinical presentation, shapes the differential diagnosis and thus guides the evaluation and management.


Effect of leaflet-based intervention on family members of terminally ill patients with cancer having delirium: historical control study.
We aimed to assess leaflet-based intervention effects on family-perceived distress, the need for improvements in professional care for delirium, and family knowledge of delirium causes. Leaflet-based intervention effects were assessed by comparing responses of family members given in the leaflet with those of a historical control group not receiving it. Knowledge of delirium causes was significantly more likely to be correct in the intervention group, while there were no significant differences in family-perceived distress or need for improvements in professional care for delirium between the 2 groups. The leaflet providing information about delirium improved family knowledge of cancer delirium. To relieve family distress, a comprehensive program focused mainly on psychological aspects, in addition to educational intervention with this leaflet, is a promising strategy.


Chinese midwives' views on a proposed midwife-led normal birth unit.
to investigate and assess Chinese midwives' views of their roles and ability to practice in a proposed midwife-led normal birth unit (MNBU). a self-completed questionnaire supplemented with semi-structured telephone interviews. Memos, diaries, correspondence and comments of Chinese collaborators were also accessed. six hospitals in Hangzhou, the capital of Zhejiang province. 143 midwives were contacted and completed the questionnaire survey. Three midwives were subsequently interviewed. the response rate was 100%; 86% of midwives supported the development of an MNBU, and 94.4% expressed confidence that they would be able to practice in an MNBU. The study shed new light on: (1) the meaning of an MNBU in the Chinese context; (2) the need for development of an MNBU; (3) role conflicts among midwives, doulas, nurses and obstetricians; (4) professional expertise and tension; and (5) the low status of Chinese midwives. the proposed MNBU is welcomed by Chinese midwives. Their consensus and confidence show that there is enthusiasm for this project to proceed. However, the Chinese have never thought of MNBU services before. There is a need to develop well-structured philosophy, policy, procedures and outcome measures. the findings highlight the importance of an MNBU to re-establish Chinese midwives' support of physiological childbirth. The extent to which Chinese midwives understand an MNBU could be further explored. The result may provide a possible route to the continuity of midwifery care and support.


Integrative systems biology characterizes immune-mediated neurodevelopmental changes in murine Zika virus microcephaly.
Characterizing perturbation of molecular pathways in congenital Zika virus (ZIKV) infection is critical for improved therapeutic approaches. Leveraging integrative systems biology, proteomics, and RNA-seq, we analyzed embryonic brain tissues from an immunocompetent, wild-type congenital ZIKV infection mouse model. ZIKV induced a robust immune response accompanied by the downregulation of critical neurodevelopmental gene programs. We identified a negative correlation between ZIKV polyprotein abundance and host cell cycle-inducing proteins. We further captured the downregulation of genes/proteins, many of which are known to be causative for human microcephaly, including Eomesodermin/T-box Brain Protein 2 (EOMES/TBR2) and Neuronal Differentiation 2 (NEUROD2). Disturbances of distinct molecular pathways in neural progenitors and post-mitotic neurons may contribute to complex brain phenotype of congenital ZIKV infection. Overall, this report on protein- and transcript-level dynamics enhances understanding of the ZIKV immunopathological landscape through characterization of fetal immune response in the developing brain.


Vascular tufts of pupillary margin of iris.
A 71-year-old woman complained of "smoky" vision, which was found to be caused by a hyphema with blood dripping from a vascular tuft located in the 12 o'clock meridian of the iris. Fluorescein angiography delineated vascular tufts and argon laser photocoagulation eradicated one of the tufts that bled. Histopathologic studies of iris obtained at the time of cataract extraction showed an aggregate of small vessels at the pupillary margin. Most patients with vascular tufts of the pupillary margin have no systemic disease but they are also observed in diabetes mellitus and myotonic dystrophy.


Isolation and characterization of transcription fidelity mutants.
Accurate transcription is an essential step in maintaining genetic information. Error-prone transcription has been proposed to contribute to cancer, aging, adaptive mutagenesis, and mutagenic evolution of retroviruses and retrotransposons. The mechanisms controlling transcription fidelity and the biological consequences of transcription errors are poorly understood. Because of the transient nature of mRNAs and the lack of reliable experimental systems, the identification and characterization of defects that increase transcription errors have been particularly challenging. In this review we describe novel genetic screens for the isolation of fidelity mutants in both Saccharomyces cerevisiae and Escherichia coli RNA polymerases. We obtained and characterized two distinct classes of mutants altering NTP misincorporation and transcription slippage both in vivo and in vitro. Our study not only validates the genetic schemes for the isolation of RNA polymerase mutants that alter fidelity, but also sheds light on the mechanism of transcription accuracy. This article is part of a Special Issue entitled: Chromatin in time and space.


Experimental design approach to the optimization of ultrasonic degradation of alachlor and enhancement of treated water biodegradability.
This work presents the application of experimental design for the ultrasonic degradation of alachlor which is pesticide classified as priority substance by the European Commission within the scope of the Water Framework Directive. The effect of electrical power (20-80W), pH (3-10) and substrate concentration (10-50mgL(-1)) was evaluated. For a confidential level of 90%, pH showed a low effect on the initial degradation rate of alachlor; whereas electrical power, pollutant concentration and the interaction of these two parameters were significant. A reduced model taking into account the significant variables and interactions between variables has shown a good correlation with the experimental results. Additional experiments conducted in natural and deionised water indicated that the alachlor degradation by ultrasound is practically unaffected by the presence of potential *OH radical scavengers: bicarbonate, sulphate, chloride and oxalic acid. In both cases, alachlor was readily eliminated ( approximately 75min). However, after 4h of treatment only 20% of the initial TOC was removed, showing that alachlor by-products are recalcitrant to the ultrasonic action. Biodegradability test (BOD5/COD) carried out during the course of the treatment indicated that the ultrasonic system noticeably increases the biodegradability of the initial solution.


The financial toll of career-ending concussions in professional hockey.
Several high-profile professional hockey players have retired due to career-ending concussions sustained in the National Hockey League (NHL). We sought to determine the salary cost of career-ending concussions in the NHL. Concussion-induced retirements from 1995 to 2015 were identified using public media sources. The number of missed games due to a player's final concussion was multiplied by per game salary to determine cost. In total, 35 players were identified: the total cost to teams and insurers of career-ending concussions was US$135,476,777. Half of the total consisted of salaries owing three players with contracts still active in 2015. The financial impact of concussion-induced retirements provides another reason for professional leagues to take measures to better protect their players from concussion.


Refractory hepatic lymphorrhea after total pancreatectomy. Case report and literature review of this uncommon complication.
After extended abdominal lymphoadenectomy, lymphatic vessel injury may cause lymphorrhea that usually disappears spontaneously. However, intractable ascites sometimes develops. Although there are many reports describing persistent chylous ascites from intestinal lymphorrhea, little is known about hepatic lymphorrhea, not containing chyle. It is caused by injury of the lymphatic vessels during hepatoduodenal ligament lymphadenectomy. We present a case of massive ascites due to hepatic lymphorrhea after total pancreatectomy and extended lymhoadenectomy for Ampullar adenocarcinoma. We successfully treated it with prolonged medical therapy after surgical relaparotomy. A 65-year old man underwent total pancreatectomy with extended nodal dissection. Massive clear-colored ascites (2000-9000mL per day) developed since the second postoperative day and persisted despite conservative therapy. At re-laparotomy no lymphatic leakage was found. Similarly lymphangiography was showed no contrast spreading. We treated this hepatic lymphorrea with intermittent opening of the abdominal drainage until spontaneous resolution. The standard treatment of hepatic lymphorrhea is an aggressive medical treatment. After such approach the most effective therapy seems to be surgical exploration. Other option are peritoneovenous shunt or intraperitoneal administration of OK-432. In our experience the intermittent abdominal drainage until spontaneous resolution is an useful approach to hepatic lymphorrhea.


Testicular torsion: a 15-year single-centre clinical and histological analysis.
This study reviewed the demographic, epidemiological and clinical factors of boys seen at a single centre who underwent surgical exploration for testicular torsion. Retrospective single-centre review of boys with testicular torsion between 1996 and 2011 was made. Testicular torsion (right n = 43, left n = 60, bilateral n = 1) was identified in 104 boys between 0 and 18 years. Ten newborns presented with 11 intrauterine torsions. Nine torsions presented in undescended inguinal testes (one intrauterine). In 94 boys with descended testes, presentation included pain (76%), scrotal swelling (65%) and abdominal symptoms (22%). Ultrasonography was performed in 85 patients with false-negative results in 4 (4.7%). Orchiectomy was performed during initial exploration in 41, with significantly higher rates of orchiectomies in patients with late (>6 h) versus patients with early referrals (<6 h) (56% vs. 9.1%). Histological evaluation was carried out in 68 testes, with 43 resected testes demonstrating haemorrhagic necrosis. In 25 biopsied testes, histology revealed acute parenchymal bleeding (n = 14), onset of parenchymal infarction (n = 8), orchitis (n = 1) and normal tissue (n = 2). Eighty-two patients were followed up with pathological findings in four patients: testicular atrophies requiring orchiectomy (n = 2), testicular autolysis (n = 1) and small testicular vein thrombosis (n = 1). Chances of testicular salvage after torsion are higher if patients present early. The majority of patients presenting late (>6 h) require orchiectomy owing to testicular necrosis.


Sequences of smoothly correlated patterns in neural networks with random transmission delays.
A neural network with a broad distribution of transmission delays was used to study numerically the retrieval of sequences having several types of correlations between successive patterns. In the case of sequences consisting of patterns correlated for finite time, the quality of retrieval was found to be (more or less) independent of the pattern correlation width and the delay distribution. On the other hand the quality of retrieval is dependent on these factors in the case of sequences with pattern correlation functions with long time 'tails'. Finally we have studied to what extent the storage capacity depends on the pattern correlation function and the delay distribution.


Surgical Procedures in Hidradenitis Suppurativa.
Hidradenitis suppurativa is difficult to treat owing to its complex pathomechanism; beside the extensive inflammation with abscesses and inflammatory nodules, there is also an architectural loss with sinus tract formation and in severe cases with extensive scarring. Therefore, surgery is mandatory in moderate and severe HS.


Contrast-enhanced sonography of juxtapleural pulmonary tuberculoma.
The purpose of this study was to describe the findings of juxtapleural pulmonary tuberculoma on contrast-enhanced sonography and investigate their correlation with histologic findings. From April 2008 to April 2012, 21 patients with biopsy or clinically proven juxtapleural pulmonary tuberculomas underwent contrast-enhanced sonography with an intravenous bolus injection of 4.8 mL of a sulfur hexafluoride-filled microbubble contrast agent. Enhancement patterns and functional parameters (time to enhancement, time to peak enhancement, and peak signal intensity) derived from a time-intensity curve were evaluated. Enhancement patterns were correlated with their histologic findings. A rim enhancement pattern was presented in 12 (57.1%), a homogeneous enhancement pattern in 5 (23.8%), and a heterogeneous enhancement pattern in 4 (19.1%) of 21 tuberculomas. A pathologic study confirmed that the nonenhancing center of the rim enhancement pattern corresponded to caseous or liquefied necrosis, and homogeneously enhanced portions corresponded to granulomatous inflammation. The medians (25th-75th interquartile ranges) for the time to enhancement, time to peak enhancement, and peak signal intensity were 14 seconds (9-14 seconds), 22 seconds (21-26 seconds), and 83 dB (55-92 dB), respectively. Contrast-enhanced sonography of juxtapleural pulmonary tuberculoma is feasible. Juxtapleural pulmonary tuberculomas usually show rim, homogeneous, or heterogeneous enhancement. Enhancement patterns of juxtapleural pulmonary tuberculomas are well correlated with their pathologic features.


A case of chronic myelogenous leukemia with 11q- in blast crisis with monoblastic differentiation.
We report a case of chronic myeloid leukemia in monoblastic blast crisis in which a deletion of chromosome 11 (11q-) was detected. Such a finding seems to provide further support to a relationship between this chromosome anomaly and monocytic proliferation.


BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability.
Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia in chronic phase (CML-CP). Unfortunately, 25% of TKI-naive patients and 50-90% of patients developing TKI-resistance carry CML clones expressing TKI-resistant BCR-ABL1 kinase mutants. We reported that CML-CP leukemia stem and progenitor cell populations accumulate high amounts of reactive oxygen species, which may result in accumulation of uracil derivatives in genomic DNA. Unfaithful and/or inefficient repair of these lesions generates TKI-resistant point mutations in BCR-ABL1 kinase. Using an array of specific substrates and inhibitors/blocking antibodies we found that uracil DNA glycosylase UNG2 were inhibited in BCR-ABL1-transformed cell lines and CD34(+) CML cells. The inhibitory effect was not accompanied by downregulation of nuclear expression and/or chromatin association of UNG2. The effect was BCR-ABL1 kinase-specific because several other fusion tyrosine kinases did not reduce UNG2 activity. Using UNG2-specific inhibitor UGI, we found that reduction of UNG2 activity increased the number of uracil derivatives in genomic DNA detected by modified comet assay and facilitated accumulation of ouabain-resistant point mutations in reporter gene Na(+)/K(+)ATPase. In conclusion, we postulate that BCR-ABL1 kinase-mediated inhibition of UNG2 contributes to accumulation of point mutations responsible for TKI resistance causing the disease relapse, and perhaps also other point mutations facilitating malignant progression of CML.


I.V. glucose tolerance test: correlation between FFA, glucose and IRI in normal, obese and diabetic subjects.
Insulin response and FFA behavior have been evaluated during an IVGTT in 63 subjects of whom 18 were normal, 31 were obese (with varying degrees of carbohydrate tolerance) and 14 were mild non insulin-dependent diabetics. The extreme reduction of insulin secretion in the early phase (delta 0-15 min) and the less severe impairment of the late phase (delta 15-60 min) have been confirmed; obese subjects showed on the average an active insulin response to venous loading; this was more marked and more consistent in the late phase. Compared to controls, FFA concentration both in basal conditions and during IVGTT was progressively higher in obese and diabetic patients. When analyzing the interplay between IRI, KG and FFA in the course of IVGTT, it was observed that: (1) a close correlation exists between IG and early insulin response (r = 0.72); (2) a correlation between delta IRI 0-15 min and percentage decrease of FFA at 45 min is found only in normal subjects; (3) a negative highly significant correlation is found between KG and mean FFA plasma level 0-60 min. This last correlation is evidence of the important role played by FFA in carbohydrate tolerance. The conflicting results reported by others have been discussed.


Exploring the Potential of Metal-Based Candidate Drugs as Modulators of the Cytoskeleton.
During recent years, accumulating evidence suggested that metal-based candidate drugs are promising modulators of cytoskeletal and cytoskeleton-associated proteins. This was substantiated by the identification and validation of actin, vimentin and plectin as targets of distinct ruthenium(II)- and platinum(II)-based modulators. Despite this, structural information about molecular interaction is scarcely available. Here, we compile the scattered reports about metal-based candidate molecules that influence the cytoskeleton, its associated proteins and explore their potential to interfere in cancer-related processes, including proliferation, invasion and the epithelial-to-mesenchymal transition. Advances in this field depend crucially on determining binding sites and on gaining comprehensive insight into molecular drug-target interactions. These are key steps towards establishing yet elusive structure-activity relationships.


Health care reform and air medical transport services.
American medical centers provide, at significant operating losses, air medical transport services to improve trauma care and interhospital transfers. These programs are cross subsidized by the publicity that encourages high-payer classification patients to seek out these facilities for their tertiary services. This article argues that as American health reform focuses more on constraining costs and as more belt tightening is needed, health managers and physicians will prefer giving up their "flying billboards" rather than their sophisticated tertiary services. It is proposed that, because of fiscal constraints, we might be forced to use the Australian or German Emergency Medical Services (EMS) model. This approach would require that we spin off the air medical transport and ground ambulance services from their present governance structures, and manage and fund these programs directly through statewide EMS-type governing boards with their own chief executive officers and staff.


Pain relieving and protective effects of Astragalus hydroalcoholic extract in rat arthritis models.
The evaluation of the pharmacological profile of the dried 50% hydroalcoholic extract (50%HA) of Astragali radix in two different animal models of articular damage resembling osteoarthritis and rheumatoid arthritis. Sodium monoiodoacetate (MIA) or complete Freund's adjuvant (CFA) was intra-articular injected (day 0) in the rat tibiotarsal joint to induce damages mimicking osteoarthritis or rheumatoid arthritis. Pain measurements (responses to non-noxious and noxious stimuli, spontaneous pain, articular pain) were assessed on days 7 and 14. On day 14, the tibiotarsal joints were explanted in order to measure the diameter and to assess histological evaluations. Furthermore, the plasmatic concentrations of inflammatory and anti-inflammatory cytokines were measured. A single administration of 50%HA (300 mg/kg per os) significantly reduced both MIA-induced pain and CFA-induced pain (78% and 96% pain relief, respectively). The repeated administration prevented the development of hypersensitivity on day 14. The haematoxylin/eosin staining revealed that 50% HA attenuated joint alterations in MIA-injected rats, and furthermore, the joint inflammatory infiltrate was reduced in both models (by about 50%). In CFA-treated rats, 50%HA lowered the plasmatic levels of the pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α as well as the joint diameter. The 50% hydroalcoholic extract of Astragali radix is a valuable candidate for the adjuvant treatment of articular diseases.


Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study.
The use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). We recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. Compared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. These findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.


Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry as a Platform for Characterizing Multimeric Membrane Protein Complexes.
Membrane protein characterization is consistently hampered by challenges with expression, purification, and solubilization. Among several biophysical techniques employed for their characterization, native-mass spectrometry (MS) has emerged as a powerful tool for the analysis of membrane proteins and complexes. Here, two MS platforms, the FT-ICR and Q-ToF, have been explored to analyze the homotetrameric water channel protein, AquaporinZ (AqpZ), under non-denaturing conditions. This 97 kDa membrane protein complex can be readily liberated from the octylglucoside (OG) detergent micelle under a range of instrument conditions on both MS platforms. Increasing the applied collision energy of the FT-ICR collision cell yielded varying degrees of tetramer (97 kDa) liberation from the OG micelles, as well as dissociation into the trimeric (72 kDa) and monomeric (24 kDa) substituents. Tandem-MS on the Q-ToF yielded higher intensity tetramer signal and, depending on the m/z region selected, the observed monomer signal varied in intensity. Precursor ion selection of an m/z range above the expected protein signal distribution, followed by mild collisional activation, is able to efficiently liberate AqpZ with a high S/N ratio. The tetrameric charge state distribution obtained on both instruments demonstrated superpositioning of multiple proteoforms due to varying degrees of N-terminal formylation. Graphical Abstract .


A binning tool to reconstruct viral haplotypes from assembled contigs.
Infections by RNA viruses such as Influenza, HIV still pose a serious threat to human health despite extensive research on viral diseases. One challenge for producing effective prevention and treatment strategies is high intra-species genetic diversity. As different strains may have different biological properties, characterizing the genetic diversity is thus important to vaccine and drug design. Next-generation sequencing technology enables comprehensive characterization of both known and novel strains and has been widely adopted for sequencing viral populations. However, genome-scale reconstruction of haplotypes is still a challenging problem. In particular, haplotype assembly programs often produce contigs rather than full genomes. As a mutation in one gene can mask the phenotypic effects of a mutation at another locus, clustering these contigs into genome-scale haplotypes is still needed. We developed a contig binning tool, VirBin, which clusters contigs into different groups so that each group represents a haplotype. Commonly used features based on sequence composition and contig coverage cannot effectively distinguish viral haplotypes because of their high sequence similarity and heterogeneous sequencing coverage for RNA viruses. VirBin applied prototype-based clustering to cluster regions that are more likely to contain mutations specific to a haplotype. The tool was tested on multiple simulated sequencing data with different haplotype abundance distributions and contig sizes, and also on mock quasispecies sequencing data. The benchmark results with other contig binning tools demonstrated the superior sensitivity and precision of VirBin in contig binning for viral haplotype reconstruction. In this work, we presented VirBin, a new contig binning tool for distinguishing contigs from different viral haplotypes with high sequence similarity. It competes favorably with other tools on viral contig binning. The source codes are available at: https://github.com/chjiao/VirBin .


New chiral zwitterionic phosphorus heterocycles: synthesis, structure, properties and application as chiral solvating agents.
A family of new chiral zwitterionic phosphorus-containing heterocycles (zPHC) have been derived from methylene-bridged bis(imidazolines). These structures were unambiguously determined, including single-crystal XRD analysis for two compounds. The stability, acid/base and electronic properties of these dipolar phosphorus heterocycles were subsequently investigated. zPHCs can be successfully employed as a new class of chiral solvating agents for the enantiodifferentiation of chiral carboxylic and sulfonic acids by NMR spectroscopy. The stoichiometry and binding constants for the donor-acceptor complexes formed were established by NMR titration methods.


TmDorX2 positively regulates antimicrobial peptides in Tenebrio molitor gut, fat body, and hemocytes in response to bacterial and fungal infection.
Dorsal, a member of the nuclear factor-kappa B (NF-κB) family of transcription factors, is a critical downstream component of the Toll pathway that regulates the expression of antimicrobial peptides (AMPs) against pathogen invasion. In this study, the full-length ORF of Dorsal was identified from the RNA-seq database of the mealworm beetle Tenebrio molitor (TmDorX2). The ORF of TmDorX2 was 1,482 bp in length, encoding a polypeptide of 493 amino acid residues. TmDorX2 contains a conserved Rel homology domain (RHD) and an immunoglobulin-like, plexins, and transcription factors (IPT) domain. TmDorX2 mRNA was detected in all developmental stages, with the highest levels observed in 3-day-old adults. TmDorX2 transcripts were highly expressed in the adult Malpighian tubules (MT) and the larval fat body and MT tissues. After challenging the larvae with Staphylococcus aureus and Escherichia coli, the TmDorX2 mRNA levels were upregulated 6 and 9 h post infection in the whole body, fat body, and hemocytes. Upon Candida albicans challenge, the TmDorX2 mRNA expression were found highest at 9 h post-infection in the fat body. In addition, TmDorX2-knockdown larvae exposed to E. coli, S. aureus, or C. albicans challenge showed a significantly increased mortality rate. Furthermore, the expression of 11 AMP genes was downregulated in the gut and fat body of dsTmDorX2-injected larvae upon E. coli challenge. After C. albicans and S. aureus challenge of dsTmDorX2-injected larvae, the expression of 11 and 10 AMPs was downregulated in the gut and fat body, respectively. Intriguingly, the expression of antifungal transcripts TmTenecin-3 and TmThaumatin-like protein-1 and -2 was greatly decreased in TmDorX2-silenced larvae in response to C. albicans challenge, suggesting that TmDorX2 regulates antifungal AMPs in the gut in response to C. albicans infection. The AMP expression profiles in the fat body, hemocytes, gut, and MTs suggest that TmDorX2 might have an important role in promoting the survival of T. molitor larvae against all mentioned pathogens.


Accuracy and postoperative assessment of pedicle screw placement during scoliosis surgery with computer-assisted navigation: a meta-analysis.
Accurate insertion of pedicle screws in scoliosis patients is a challenge for surgeons. Computer-assisted navigation techniques might help improve the accuracy of screw placement, thereby avoiding complications. Thus, the objective of this present work is to compare the accuracy and postoperative assessment of pedicle screw placement in scoliosis patients using a computer-assisted navigation technique and using a conventional free-hand method. A search of the PubMed, Cochrane, and Web of Science databases was executed. In vivo comparative studies that assessed the accuracy and postoperative evaluation of pedicle screw placement in scoliosis patients with or without navigation techniques were chosen and analyzed. The accuracy of pedicle screw insertion was significantly increased when using the navigation system, although the average operative time and correction rate was not significantly different from that with non-navigated surgery. The navigation technique improves the accuracy of pedicle screw placement during scoliosis surgery without prolonging the operative time or decreasing the deformity correction effect. Copyright © 2016 John Wiley & Sons, Ltd.


Inferior Vena Cava Filter Thrombus: a Possible Cause of an Unanticipated Finding of (99m)Tc-labeled Red Blood Cell Scintigraphy.
(99m)Tc-labeled red blood cell scintigraphy, a sensitive and specific diagnostic test, is useful for patients suspected of suffering from active gastrointestinal bleeding. This study follows a case of a patient who was suspected of gastrointestinal bleeding after an inferior vena cava filter was inserted due to a deep vein thrombosis of the femoral vein. To evaluate an exact focus of bleeding, (99m)Tc-labeled red blood cell scintigraphy was executed. Herein, an unanticipated finding of (99m)Tc-labeled red blood cell scintigraphy probably due to a thrombus on the inferior vena cava filter is reported.


Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/β-TrCP.
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular homeostasis that controls the expression of more than 1% of human genes related to biotransformation reactions, redox homeostasis, energetic metabolism, DNA repair, and proteostasis. Its activity has a tremendous impact on physiology and pathology and therefore it is very tightly regulated, mainly at the level of protein stability. In addition to the very well established regulation by the ubiquitin E3 ligase adapter Keap1, recent advances have identified a novel mechanism based on signaling pathways that regulate glycogen synthase kinse-3 (GSK-3). This kinase phosphorylates specific serine residues in the Neh6 domain of Nrf2 to create a degradation domain that is then recognized by the ubiquitin ligase adapter β-TrCP and tagged for proteasome degradation by a Cullin1/Rbx1 complex. Here we review the mechanistic elements and the signaling pathways that participate in this regulation by GSK-3/β-TrCP. These pathways include those activated by ligands of tyrosine kinase, G protein-coupled, metabotropic, and ionotropic receptors that activate phosphatidyl inositol 3-kinase (PI3K)/ATK and by the canonical WNT signaling pathway, where a fraction of Nrf2 interacts with Axin1/GSK-3. Considering that free Nrf2 protein is localized in the nucleus, we propose a model termed "double flux controller" to explain how Keap1 and β-TrCP coordinate the stability of Nrf2 in several scenarios. The GSK-3/β-TrCP axis provides a novel therapeutic strategy to modulate Nrf2 activity.


Spatial-temporal profiling of antibiotic metabolites using graphite dots-assisted laser desorption ionization mass spectrometry.
Appropriate prescription of antibiotics requires the pharmacokinetic knowledge of the drugs and their metabolites in blood, and their distribution/retention in organ tissues. Here we report that highly crystalline graphite dots (GDs) allow for quantitative profiling of antibiotic metabolites in a spatial-temporal manner, in combination with matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). GDs matrix features an ultra-clean background base line and high efficiency in ionization of small molecules, thus enabling quantification of sulfamethoxazole (SMZ) and its metabolites with limit of detection (LOD) in the femtomole range. Distinctly different from the other MS techniques, our approach is tolerant to high levels of salt contaminants in the complexed biological samples, thus minimizing the sample purification requirements and allowing for tests in small volumes. We have demonstrated quantitative measurements of the dynamic concentration changes of SMZ (m/z 276.27) and two metabolites, N4-hydroxy-SMZ (m/z 292.28) and N4-acetyl-SMZ (m/z 318.31) with only 1 μL mouse blood sample for each test. High-resolution distribution patterns of SMZ metabolites have directly been visualized a on the liver subsegments. Therefore, it allows for simultaneously acquisition of pharmacokinetic data in the blood combined with detailed hepatic zonation of SMZ metabolites for the first time. As a rapid, high-throughput platform to monitor small molecules in vivo, our approach of GDs-assisted MADLI MSI will foster the medical research on the antibiotic usage and drug development.


Antibiotic sensitivity testing by flow microcalorimetry.
The proposed flow microcalorimetric method for the diagnosis of bacteriuria has been extended to include antibiotic sensitivity testing. Sensitive organisms rapidly (4-8 min) show thermal responses to the added antibiotics over the normal range of concentrations (1 x, 2x, MIC value).


[Disability and occupational medicine: definitions, scope, and operative examples].
2003 is the year of disability. This paper briefly illustrates the multiform relationships between occupational medicine and disability, discussing the complex legislation on this matter. A historiographic account is presented of the image of the disabled individual through the centuries. The main terms regarding disability are defined according to current legislation. Current Italian laws are difficult to interpret and to be put into effect. In this process, the occupational physician may be asked to perform several duties, including diagnosis and certification, fitting the disabled to work, safeguarding his/her moral and legislative rights, prevention and sanitary surveillance. Some professional experiences of the authors (regarding certification of the working capability, medico-legal recognition, and adaptation to work) are finally presented.


Human monoclonal antibodies to myelin-associated glycoprotein are directed against the polypeptide and not the carbohydrate moiety.
We have used an approach which combines the technique of electrophoretic blotting of polyacrylamide gels with methods for the degradation of carbohydrates, to study the myelin-associated glycoprotein (MAG)-specific antibodies found in 5 patients with demyelinating neuropathy. Our results show that it is possible to deglycosylate proteins on nitrocellulose blots and then to examine their antigenicity and lectin-binding properties. With MAG, our findings suggest that the monoclonal IgM antibodies from all the patients studied have specificity for the polypeptide and not the carbohydrate moiety.


Cytostatic effects of bleomycin and cis-platinum in A549 human lung tumour cells using autofeeder conditions.
Residual colony forming ability (CFA) of cells from a human alveolar carcinoma (A549) was determined after 48 hours of contact with bleomycin (BLM) or cisdichlorodiammineplatinum (II) (DDP) using feeder cells arising from parallel cultures left in contact with sublethal BLM or DDP concentrations. The CFA of untreated cells was 60 to 80% (45% with X-irradiated feeder cells). Growing cultures were more resistant to DDP and more sensitive to BLM than plateau phase cultures. Subclones arising from a first treatment were resistant to a second BLM or X-ray treatment, but more sensitive to a second DDP treatment.


Efficient removal of electroneutral carbonyls by combined vacuum-UV oxidation and anion-exchange resin adsorption: mechanism, model simulation, and optimization.
Electroneutral carbonyls (ENCs) with low molecular weights (e.g., aldehydes and ketones) are recalcitrant to single water treatment process to achieve ultralow concentration. Residual ENCs are present in reverse osmosis permeate and pose risks to human health during potable use or industrial application in manufacturing processes. Herein, a combined vacuum-UV (VUV) oxidation and anion-exchange resin (AER) adsorption method was developed to treat the ENCs and reduce total organic carbon (TOC) to an ultralow concentration (< 5 μg/L) with high efficiency and at low cost. VUV-AER was 2.1-2.4 times more efficient than VUV alone for the removal of TOC. VUV oxidized the ENCs to electronegative carboxylic acids, which were adsorbed by the AER through electrostatic interactions and hydrogen bonding. When the VUV fluence was lower than 643 mJ cm-2, the AER could not achieve ultralow TOC removal of ENCs. The treat capacity of 1500-2900 valid bed volume (BVs) was achieved after increasing the VUV fluence to 1929 mJ cm-2. The AER could more efficiently adsorb carboxylic acids that contained more carboxylic groups or shorter carbon chain. Acetate was identified as the primary breakthrough product at relatively low VUV fluence, and oxalate was the main byproduct at relatively high VUV fluence. A mathematical model to predict TOC breakthrough was developed considering the VUV-oxidation kinetics and the AER breakthrough curve. The model was used to optimize the method to maximize TOC removal and minimize energy consumption. These results imply that VUV-AER is technically feasible and economically applicable to eliminate recalcitrant ENCs to ultralow concentration for the production of water requires high quality (e.g., potable water or electronic-grade ultrapure water).