DFT studies of the degradation mechanism of methyl mercury activated by a sulfur-rich ligand.
We describe theoretical insights into the mechanism of Hg-C bond protonolysis in methyl mercury coordinated by the tris(2-mercapto-1-tert-butylimidazolyl)hydroborato ligand, the structural and functional analogue of the organomercurial lyase MerB. Different cleavage pathways including both frontside and backside attack transition states were systematically studied by the hybrid density functional method B3LYP. Dependence of Hg-C bond activation on the primary sulfur coordination number of mercury was elaborated, and conceptual DFT indexes were suggested to be more appropriate than gross charge of atom sites in interpreting the dependence. Furthermore, absence of configurational inversion in MerB-catalyzed reactions was accounted for by examinations of the backside protonolysis pathways in the present system. Lastly, a rationalization was provided about the choice between different characteristics of transition states including both four-center and six-center ones.


Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections.
The occurrence of invasive fungal infections represents a substantial threat to human health that is particularly serious in immunocompromised patients. The limited number of antifungal agents, devoid of unwanted toxic effects, has resulted in an increased demand for new drugs. Herein, the chalcone framework was functionalized to develop new antifungal agents able to interfere with cell growth and with the infection process. Thus, a small library of chalcone-based analogues was evaluated in vitro against C. albicans ATCC 10231 and a number of compounds strongly inhibited yeast growth at non-cytotoxic concentrations. Among these, 5 and 7 interfered with the expression of two key virulence factors in C. albicans pathogenesis, namely, hyphae and biofilm formation, while 28 emerged as a potent and broad spectrum antifungal agent, enabling the inhibition of the tested Candida spp. and non-Candida species. Indeed, these compounds combine two modes of action by selectively interfering with growth and, as an added value, weakening microbial virulence. Overall, these compounds could be regarded as promising antifungal candidates worthy of deeper investigation. They also provide a chemical platform through which to perform an optimization process, addressed at improving potency and correcting liabilities.


THE EFFECTS OF HOST GENOTYPE AND SPATIAL DISTRIBUTION ON TREMATODE PARASITISM IN A BIVALVE POPULATION.
A basic assumption underlying models of host-parasite coevolution is the existence of additive genetic variation among hosts for resistance to parasites. However, estimates of additive genetic variation are lacking for natural populations of invertebrates. Testing this assumption is especially important in view of current models that suggest parasites may be responsible for the evolution of sex, such as the Red Queen hypothesis. This hypothesis suggests that the twofold reproductive disadvantage of sex relative to parthenogenesis can be overcome by the more rapid production of rare genotypes resistant to parasites. Here I present evidence of significant levels of additive genetic variance in parasite resistance for an invertebrate host-parasite system in nature. Using families of the bivalve mollusc, Transennella tantilla, cultured in the laboratory, then exposed to parasites in the field, I quantified heritable variation in parasite resistance under natural conditions. The spatial distribution of outplanted hosts was also varied to determine environmental contributions to levels of parasite infection and to estimate potential interactions of host genotype with environment. The results show moderate but significant levels of heritability for resistance to parasites (h2 = 0.36). The spatial distribution of hosts also significantly influenced parasite prevalence such that increased host aggregation resulted in decreased levels of parasite infection. Family mean correlations across environments were positive, indicating no genotype-environment interaction. Therefore, these results provide support for important assumptions underlying coevolutionary models of host-parasite systems.


Comparison of thyroid fine needle aspiration biopsy results before and after implementation of Bethesda classification.
The Bethesda classification was introduced in 2008 to provide standardisation in the evaluation of thyroid fine needle aspiration cytology (FNAC). We compared the diagnostic value of pre-Bethesda and Bethesda classification systems in the differentiation of benign and malignant thyroid nodules. Medical records of patients who underwent a thyroidectomy between June 2007 and June 2014 were reviewed retrospectively. Nodules evaluated with FNAC before March 2010 were classified as pre-Bethesda (non-diagnostic, benign, indeterminate, suspicious for malignancy and malignant), and those evaluated after March 2010 were considered Bethesda (non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasia/suspicious for follicular neoplasia, suspicious for malignancy and malignant). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the two classification systems were calculated. There were 1810 nodules in the pre-Bethesda and 5115 nodules in the Bethesda group. The non-diagnostic rate was significantly higher, and benign and suspicious for malignancy rates were lower in Bethesda compared with the pre-Bethesda group (P<.001 for each). When benign cytology was considered negative, and indeterminate, follicular neoplasia/suspicious for follicular neoplasia, suspicious for malignancy and malignant cytologies were considered positive, results for pre-Bethesda and Bethesda were as follows: sensitivity, 78.9% and 78.5%; specificity, 86.6% and 97.0%; PPV, 42.8% and 72.6%; NPV, 97% and 97.8%; and accuracy, 85.7% and 95.3%, respectively. Among operated nodules, percentages of benign and suspicious for malignancy cytologies decreased, and percentages of non-diagnostic and uncertain cytologies increased with the implementation of Bethesda. The diagnostic value of FNAC seems to have increased with the use of Bethesda classification.


Bone Marrow Suppression during Postoperative Radiation for Bladder Cancer and Comparative Benefit of Proton Therapy-Phase 2 Trial Secondary Analysis.
For patients with high-risk bladder cancer (pT3+ or N+), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose. All enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC). Eighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P < .001), and platelets (P = .03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC -0.593, P = .02), ANC (Pearson CC -0.597, P = .02), and hemoglobin (Pearson CC -0.506, P = .046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC -0.512 to -0.618, P < .05), and V20 to V30 correlated with lower ANC (Pearson CC -0.569 to -0.598, P < .04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P < .001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P < .001). Increased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.


Sleep and biological parameters in professional burnout: A psychophysiological characterization.
Professional burnout syndrome has been described in association with insomnia and metabolic, inflammatory and immune correlates. We investigated the interest of exploring biological parameters and sleep disturbances in relation to burnout symptoms among white-collar workers. Fifty-four participants with burnout were compared to 86 healthy control participants in terms of professional rank level, sleep, job strain (Karasek questionnaire), social support, anxiety and depression (HAD scale). Fasting concentrations of glycaemia, glycosylated hemoglobin (HbA1C), total-cholesterol, triglycerides, C-reactive protein (CRP), thyroid stimulating hormone (TSH), 25-hydroxyvitamin D (25[OH]D), and white blood cell (WBC) counts were assessed. Analysis of variance and a forward Stepwise Multiple Logistic Regression were made to identify predictive factors of burnout. Besides reporting more job strain (in particular job control p = 0.02), higher levels of anxiety (p<0.001), and sleep disorders related to insomnia (OR = 21.5, 95%CI = 8.8-52.3), participants with burnout presented higher levels of HbA1C, glycaemia, CRP, lower levels of 25(OH)D, higher number of leukocytes, neutrophils and monocytes (P<0.001 for all) and higher total-cholesterol (P = 0.01). In particular, when HbA1c is > 3.5%, the prevalence of burnout increases from 16.6% to 60.0% (OR = 4.3, 95%CI = 2.8-6.9). Strong significant positive correlation existed between HbA1C and the two dimensions (emotional exhaustion and depersonalization (r = 0.79 and r = 0.71, p<0.01)) of burnout. Models including job strain, job satisfaction, anxiety and insomnia did not predict burnout (p = 0.30 and p = 0.50). However, when HbA1C levels is included, the prediction of burnout became significant (P = 0.03). Our findings demonstrated the interest of sleep and biological parameters, in particular HbA1C levels, in the characterization of professional burnout.


Effect of home-use bleaching gels on fluoride releasing restorative materials.
To evaluate the effects of two home-use bleaching gels (Nite-White and Contrast PM) on the surface roughness of one high-viscosity glass ionomer cement (Fuji IX GP), four polyacid-modified resin-based composites (Dyract AP, F2000, Elan and Compoglass F), two resin-modified glass-ionomer cements (Vitremer and Fuji II LC), a microfilled fluoride-releasing resin-based composite (Tetric) and a microfilled non-fluoridated resin-based composite (Valux) were used as controls. The null hypotheses tested were: (1) the use of bleaching gels would not result in surface roughness values different from those obtained at baseline; (2) differences in the amount of carbamide peroxide present in the gels would not influence surface roughness. Thirty specimen disks (the first 10 used for controls and the balance divided randomly into two groups) were made for each material according to the manufacturers' instructions. Finishing and polishing of the test and control specimens was performed after 24 hours using a sequential series of three (medium, fine and superfine) Sof-Lex disks, keeping the restoration surface wet. For every sequence, 10 strokes were made in one direction using a low-speed handpiece. Ultrasonic cleaning of the polished specimens was performed for two minutes in distilled water to remove any surface debris. Prior to bleaching treatment, the specimens were stored in 37 degrees C deionized water for 24 hours. The specimens were exposed to the bleaching gels for a period that simulated the equivalent of 15 days (eight hours/day) under bleaching treatment. The average surface roughness (Ra) of the control and treated specimens was measured. Three separate Ra measurements along the direction of rotation of the finishing and perpendicular to the finishing direction and edge of the mold were made for each specimen surface. After treatment with bleaching gels, there was an increase in surface roughness for F2000, Dyract AP, Elan, Valux and Tetric, while Fuji IX, Fuji II LC, Vitremer and Compoglass F displayed decreased surface roughness values, suggesting that the effects of the gels appear to be material-dependent. Although Contrast PM contains 5% more carbamide peroxide as the active ingredient, the second null hypothesis was rejected for Fuji IX, Vitremer, Dyract AP, Compoglass F, Elan and Valux.


Clinical pitfalls in diagnosis of nonmuscle-invasive bladder cancer.
Current global economic crisis imposes healthcare system to reduce unnecessary investigations and increase early detection of tumors, to decrease the costs of an advanced disease. Several diagnostic pitfalls may occur dealing with bladder cancer (BC), particularly in nonmuscle-invasive (NMIBC) one. Hematuria, the commonest sign in NMIBC, is often underestimated. Urinary cytology is highly specific for high-grade tumors, but has a low sensitivity for low-grade BC, is operator dependent, and not always obtainable in clinical practice. Numerous urinary tests are available to ameliorate the accuracy of cytology, but none of them is routinly used in urological practice. Ultrasound could hardly detect a small bladder tumor, especially if located in the bladder neck or in the anterior wall. Computed tomography (CT) is widely adopted as an alternative to conventional urography, but its usefulness in patients with hematuria is still debated. MRI has a higher accuracy than CT for staging BC and evaluate the bladder-wall invasion. A negative cystoscopy cannot exclude Tis and should be accompanied by urinary cytology in patients with suspected Tis or high-risk NMIBC; however, new techniques such as narrow band imaging (NBI) and photodynamic (PDD) increase the detection rate of BC and flat lesions. Nearly half of all diagnostic resections present omission of muscle in the specimen or its mention in the pathology report, which is associated with an increased mortality. An adequate muscle sampling during endoscopic resection is mandatory, particularly in patients with high-grade disease. Recognition of pitfalls in diagnosis and management of BC represents the first step for a correct approach.


Interpolated testing and content pretesting as interventions to reduce task-unrelated thoughts during a video lecture.
Considerable research has examined the prevalence and apparent consequences of task-unrelated thoughts (TUTs) in both laboratory and authentic educational settings. Few studies, however, have explored methods to reduce TUTs during learning; those few studies tested small samples or used unvalidated TUT assessments. The present experimental study attempted to conceptually replicate or extend previous findings of interpolated testing and pretesting effects on TUT and learning. In a study of 195 U.S. undergraduates, we investigated whether interpolated testing (compared to interpolated restudy) and pretesting on lecture-relevant materials (compared to pretesting on conceptually related but lecture-irrelevant materials) would reduce TUTs during a video lecture on introductory statistics. Subjects completed either a content-matched or content-mismatched pretest on statistics concepts and then watched a narrated lecture slideshow. During the lecture, half of the sample completed interpolated tests on the lecture material and half completed interpolated restudy of that material. All subjects responded to unpredictably presented thought probes during the video to assess their immediately preceding thoughts, including TUTs. Following the lecture, students reported on their situational interest elicited by the lecture and then completed a posttest. Interpolated testing significantly reduced TUT rates during the lecture compared to restudying, conceptually replicating previous findings-but with a small effect size and no supporting Bayes-factor evidence. We found statistical evidence for neither an interpolated testing effect on learning, nor an effect of matched-content pretesting on TUT rates or learning. Interpolated testing might have limited utility to support students' attention, but varying effect sizes across studies warrants further work.


Health impacts of frequent heavy automobile traffic on children and adolescents.
This paper assesses the extent to which particulate, elemental and organic carbon emissions from heavy traffic in urban city roads affect the health of children and the adolescent health. Although the health effects of exposures may be cumulative, it is in the adolescence that the manifestations are realized. This paper therefore, assesses the best way forward for monitoring and preventing the environmental health impacts of heavy traffic on children and adolescents who live within the vicinity of urban city transportation systems. Major urban cities such as Houston, New York, and California are cited as examples of cities where health-related problems have already been reported. The particulate, elemental and organic carbon emissions are reviewed as the sources by which heavy traffic and the hazardous chemical emissions affect the health of the populace. The role of accessory loading and engine speed on idling emissions in direct health risks of children and adolescents is evaluated. The association of particulate, elemental, and organic carbon emission with respiratory effects (including, allergies and asthma), and the related behavior problems in children and the adolescents are discussed. The best strategies in preventing the effects of heavy traffic in the urban cities are suggested by introducing new effective monitoring techniques and exposure assessment methods. It is visualized that a more comprehensive research is needed to develop robust regulatory systems that would control the efficiency of automobiles and prevent the adverse health effects relating to heavy traffics in urban city roads. Strong city environmental health authorities-community partnerships relevant to exposure information should be encouraged.


Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway.
Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia- associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITFsiRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies.


EFFECTIVE POPULATION SIZE AND GENETIC DRIFT IN TRISTYLOUS EICHHORNIA PANICULATA (PONTEDERIACEAE).
Populations of the tristylous, annual Eichhornia paniculata are markedly differentiated with respect to frequency of mating types. This variation is associated with evolutionary changes in mating system, from predominant outcrossing to high self-fertilization. To assess the potential influence of genetic drift acting on this variation, we estimated effective population size in 10 populations from northeastern Brazil using genetic and demographic methods. Effective size (Ne ) was inferred from temporal changes in allele frequency at two to eight isozyme loci and also calculated using five demographic variables: 1) the number of flowering individuals (N); 2) temporal fluctuations in N; 3) variance in flower number; 4) frequency of mating types; and 5) selfing rate. Average Ne based on isozyme data was 15.8, range 3.4-70.6, and represented a fraction (mean Ne /N = 0.106) of the census number of individuals (mean N = 762.8; range: 30.5-5,040). Temporal variation in N and variance in flower number each reduced Ne to about a half of N whereas mating type frequencies and selfing rate caused only small reductions in Ne relative to N. All estimates of Ne based on demographic variables were considerably larger than those obtained from genetic data. The two kinds of estimates were in general agreement, however, when all demographic variables were combined into a single measure. Monte Carlo simulations indicated that effective size must be fewer than about 40 for drift to overcome the frequency-dependent selection that maintains the polymorphism for mating type. Applying the average Ne /N value to 167 populations censused in northeastern Brazil indicated that 72% had effective sizes below this number. This suggests that genetic drift is likely to play a dominant role in natural populations of E. paniculata.


Anesthesia methods for full-endoscopic lumbar discectomy: a review.
Full-endoscopic lumbar discectomy under local anesthesia is major trends for the treatment of lumbar disc herniation in spine minimally invasive surgery. However, sometimes local anesthesia is not enough for analgesic in surgery especially in interlaminar approach. This study summarizes the current study of anesthesia methods in full-endoscopic lumbar discectomy. Local anesthesia is still the most common anesthesia method in full-endoscopic lumbar discectomy and the comparison group for other anesthesia methods due to high safety. Compared to local anesthesia, Epidural anesthesia is less applied in full-endoscopic lumbar discectomy but reports better intraoperative pain control and equivalent safety due to the motor preservation and pain block characteristic of ropivacaine. General anesthesia can achieve totally pain block during surgery but nerve injury can not be ignored, and intraoperative neuromonitoring can assist. Regional anesthesia application is rare but also reports better anesthesia effects during surgery and equivalent safety. Anesthesia methods for full-endoscopic lumbar discectomy should be based on patient factors, surgical factors, and anesthesiologist factors to achieve satisfactory anesthesia experience and successful surgery.


MIR210HG promotes breast cancer progression by IGF2BP1 mediated m6A modification.
Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2'-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer. High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN. In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression.


Alpha-ketoadipic aciduria: a description of a new metabolic error in lysine-tryptophan degradation.
Our studies of a mentally retarded male with extremely elevated levels of alpha-aminoadipic acid and alpha-ketoadipic acid in his urine have led to the description of a new metabolic defect, alpha-ketoadipic aciduria. Analysis of the urine and serum from the patient's family revealed that the patient (KW) had a mentally and physically normal sister (CW) with the same metabolites elevated, but the rest of the family appeared normal.


TriGlycerides and high-density lipoprotein cholesterol ratio compared with homeostasis model assessment insulin resistance indexes in screening for metabolic syndrome in the chinese obese children: a cross section study.
Metabolic Syndrome (MS) is prevalant in China, especially according to the pediatric obesity group. Based on the MS-CHN2012 definition for Chinese children and adolescents the need to explore and establish a convienent MS screening become imminent. This study aims to investigate the optimal cut-off values, compare the accuracy for the (TriGlycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C)) (TG/HDL-C) ratio and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) indexs to identify Metabolic Syndrome in obese pediatric population in China. A total sample of 976 children (female 286 male 690, BMI > = 95 percentile) aged from 6-16 years underwent a medical assessment including a physical examination and investigations of total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, insulin, glucose, and oral glucose tolerance test to identify the components of Metabolic Syndrome. The validity and accuracy between TG/HDL-C ratio and HOMA-IR were compared by Receiver Operating Characteristics analysis (ROC). TG/HDL-C ratio achieved a larger ROC Area under Curve (AUC = 0.843) than HOMA-IR indexes (0.640, 0.625 for HOMA1-IR, HOMA2-IR respectively) to screen for Metabolic Syndrome. The cut-off values for MS were: TG/HDL-C ratio > 1.25 (sensitivity: 80%; specificity: 75%), HOMA1-IR > 4.59 (sensitivity: 58.7%; specificity: 65.5%) and HOMA2-IR > 2.76 (sensitivity: 53.2%; specificity: 69.5%). The results kept robust after stratified by gender, age group and pubertal stage. TG/HDL-C ratio was a better indicator than the HOMA-IR to screen for a positive diagnosis for MS. Furthermore, the TG/HDL-C ratio was superior to the HOMA-IR indexes even after the control of possible confusions from the gender, age group and puberty stage. TG/HDL-C ratio proved a better index than HOMA-IR in screening for MS in obese children and adolescents. TG/HDL-C ratio has a discriminatory power in detecting potential MS in the Chinese obese pediatric population.


Levinsonian studies of women's adult development.
We reviewed four unpublished dissertations that used Levinson's theory to study women's adult development. The 39 biographies presented in these studies suggested that the women progressed through the same developmental periods as had men in Levinson's study and at roughly the same ages. Although the timing of the periods and the nature of the developmental tasks appeared to be similar, the ways of working on these tasks as well as the outcomes achieved were different. These differences are understood in part as consequences of the greater complexity of women's dreams and the problems encountered in living them out.


The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols.
The use of inhaled antibiotics in the treatment of cystic fibrosis has become widespread despite controversy in the literature as to the appropriate dosing regimen and its effectiveness. This study compared two tobramycin (T) preparations (one with and one without the addition of albuterol) using two different jet nebulizers in order to determine if drug output would be affected. Using calibrated flows from a dry compressed gas source of 6 and 8 L/min as well as a specific compressor (Pulmo-Aide), the Hudson 1720 nebulizer was compared with the newer disposable Hudson 1730. The albuterol preparation used in this study was the Ventolin (albuterol) Respirator Solution (VRS). The nebulizers were charged with (1) 2 mL T (80 mg/2 mL) with 0.5 mL VRS (5 mg/mL) and normal saline solution to make the total nebulizer charge of 3 or 4 mL, or (2) 2 mL T and either 1 or 2 mL normal saline solution. A laser diffraction analyzer (Malvern 2600) was used to determine the aerosol particle size distribution. From the distribution, the respirable fraction, which is the fraction of aerosol that could enter and remain in the lungs, was calculated. For all solutions and each particular flow, the Hudson 1730 had a larger respirable fraction of T. The addition of VRS lowered the surface tension of the solution in the nebulizer and resulted in a greater output of T. This effect was most apparent for the 3-mL volume fills of the Hudson 1720. The greatest differences were between the 3-mL nebulizer charges of T using the Hudson 1720 driven by a flow of 6 L/min, which produced 8 mg of T in the respirable fraction, compared with 35 mg produced by the Hudson 1730 driven by a flow of 8 L/min. These results suggest that different nebulizers, different nebulizer solutions, and different techniques of nebulization may result in very different amounts of T aerosol output in the respirable fraction.


[Birth asphyxia and hypoxic ischemic encephalopathy, incidence and obstetric risk factors].
Modern medical practice has changed dramatically during the past decades because of improved technology. Still, fetal surveillance during labor is relatively unchanged since 1960 s when fetal heart rate monitoring (FHR) became standard practice. Newborn infants are still suffering from birth asphyxia and in severe cases leading to hypoxic ischemic encephalopathy (HIE) which sometimes results in permanent neurological damage. The incidence of birth asphyxia and HIE in Iceland is unknown and so are the risk factors for severe asphyxia. The objective of this study was to assess the incidence, obstetric risk factors and the sequela of severe asphyxia at Landspitali university hospital (LSH). All term infants born at LSH from 1.1.1997- 31.12.2001 with birth asphyxia, defined as five minute Apgar score %lt;6, were included in the study (n=127). Clinical information were collected retrospectively from maternal records on maternal diseases during pregnancy, cardiotocogram (CTG), type of birth, the presence of meconium and operative delivery rates. Information was also collected regarding birth asphyxia and HIE in the neonatal period. The incidence of birth asphyxia was 9.4/1000 live term births during the study period, with increasing incidence during the three last years. The incidence of HIE was 1.4/ 1,000 live term births. Severe maternal diseases during pregnancy were not a significant risk factor for asphyxia. The amniotic fluid was meconium stained in fifty percent of cases and the umbilical cord was wrapped around the fetal neck in 41% of cases. Abnormal CTG tracing was observed in 66% of cases in the study group and in 79% of the HIE cases. Operative deliveries were significantly more common in the study cohort compared with other deliveries at LSH at the same time: ventouse delivery 22% vs 6.8% (p<0,001), forceps delivery 6.3% vs 1,03% (p<0,001), emergency cesarean section 19.7% vs 11.4% ( p=0,008). The incidence of birth asphyxia is higher in LSH compared with the incidence found in other studies. Signs of fetal distress on CTG and delivery with operative interventions are common. With current available methods to detect intrapartum asphyxia there is a poor correlation with CTG and the development of HIE after severe asphyxia. The presence of severe maternal diseases does not correlate with increased incidence of asphyxia, presumably due to increased surveillance of these pregnancies and a lower treshold for intervention during delivery. In low risk pregnancies there is a lack of appropriate methods with high sensitivity and specificity to detect intrapartum asphyxia.


Role of metastasis-associated protein 1 in prognosis of patients with digestive tract cancers: A meta-analysis.
Metastasis-associated protein 1 (MTA1) is a transcriptional regulator and significantly associated with prognosis of patients with cancer. However, its role as a potential prognostic marker in digestive tract cancer (DTC) is controversial. In this study, a meta-analysis was conducted to evaluate the MTA1 expression as a predictor of clinicopathology and survival of patients with DTC. We searched PubMed, Ovid, Web of Science and Cochrane databases using multiple search strategies for eligible studies. STATA 11.0 software was used to pool the data and analyze the association, odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the strength of the association. Furthermore, the Newcastle-Ottawa scale was used to evaluate the quality of eligible studies. MTA1 overexpression was strongly associated with depth of invasion (OR = 1.88, 95%CI: 1.05-3.37, P = 0.03), lymph node metastasis (OR = 2.30, 95%CI: 1.76-3.01, P<0.001), vascular invasion (OR = 2.02, 95%CI: 1.40-2.91, P<0.001) and TNM stage (OR = 2.78, 95%CI: 1.63-4.74, P<0.001), and was related to 1- (RR = 1.84, 95%CI: 1.18-2.89, P = 0.008), 3- (RR = 1.74, 95%CI: 1.32-2.30, P<0.001) and 5-year (RR = 1.64, 95%CI: 1.18-2.27, P = 0.003) OS. Further, MTA1 was associated with 1- (RR = 4.16, 95%CI: 1.35-12.81, P = 0.01), 3- (RR = 1.90, 95%CI: 1.02-3.53, P = 0.04) and 5- (RR = 2.17, 95%CI: 1.41-3.32, P<0.001) year DFS. In subgroup analyses based on study quality and tumor type, MTA1 overexpression was obviously related to clinical parameters, such as lymph node metastasis and TNM stage, and was also associated with prognosis of patients with gastrointestinal or esophageal cancer. MTA1 expression is strongly correlated with metastasis-related variables, and represents a promising prognostic factor in DTC.


Perfect coupling of light to surface plasmons by coherent absorption.
We show theoretically that coherent light can be completely absorbed and transferred to surface plasmons in a two- or three-dimensional metallic nanostructure by exciting it with the time-reversed mode of the corresponding surface plasmon laser ("spaser"). The narrow-band perfect absorption is a generalization and application of the concept of critical coupling to a nanocavity with surface plasmon resonances. Perfect coupling of light to nanostructures has potential applications to nanoscale probing as well as background-free spectroscopy and ultrasensitive detection or sensing.


Reproducibility of laboratory assays for steroid hormones and sex hormone-binding globulin.
The relationship of serum hormones to cancer risk has recently been pursued in epidemiological studies, but few have reported on the reproducibility of laboratory findings. Prior to conducting a study of endogenous hormones and endometrial cancer, we evaluated the reproducibility of measurements for several hormones (estrone, estradiol, free estradiol, albumin-bound estradiol, and androstenedione) and sex hormone-binding globulin. We obtained a single unit of blood from each of six women and prepared aliquots of serum for repeated testing. Three laboratories analyzed multiple samples on consecutive working days from which estimates of intraassay and interassay measurement variability were obtained. For estrone and estradiol, a log transformation of the data produced distributions which were nearly normal and permitted the use of parametric statistical tests. In general, we found measurements for most hormones varied considerably between assays. Moreover, differences were observed in the absolute values of sex hormone-binding globulin and of the hormones, particularly for estrone and estradiol, from one laboratory to the next. Our findings suggest that variability of current laboratory procedures may hamper efforts to study the association between disease and endogenous hormones in epidemiological studies. In addition, validation of hormone assays is essential in order to assure standardized results and enable comparisons of data across studies.


Content Validity of a Novel Scar Assessment Tool Evaluating the Career and Sexual Well-being Impact of Scars.
Currently, patient reported outcome scales used to assess scar impact focus solely on psychosocial well-being, symptoms, and appearance. There remains a need to develop a broadened measure of scar impact on patients, focusing on sexual and career aspects. This study investigates the content validity of the novel Career and Sexual Well-being (CS) Scar Impact Scale. The CS scale contains five questions and was developed from previous patient thematic analysis interviews describing scar impact, and covers self-conscious behavior, new partners, hiding of the scar, being hindered in the workplace, and concerns regarding unprofessional appearance. Cognitive interviews and established guidelines were used to ensure that the scale was comprehensive, reproducible, and easily understandable. In total, 86 patients completed cognitive interviews. Patients had a clear understanding of the questions and elicited their intent in the interviews. An estimated 86% of patients rated the CS scale coverage of scar impact on career and sexual health at a three or above out of four; 95% said the specific instructions were clear, and 92% stated it took them less than 4 minutes to complete the scale. After the first round of interviews, a question about "perception/self-consciousness in a professional environment" was added based on patient suggestions. The CS scar scale demonstrated face validity, acceptability, and field-readiness through cognitive interviewing of patients at our institution. Sexual well-being and career performance are important yet often neglected themes with which scars should be assessed. Usage of these tools would serve to improve current scar scales.


Modular assembly of microswimmers with liquid compartments.
Artificial microswimmers, i.e. colloidal scale objects capable of self-propulsion, have garnered significant attention due to their central role as models for out of equilibrium systems. Moreover, their potential applications in diverse fields such as biomedicine, environmental remediation, and materials science have long been hypothesized, often in conjunction with their ability to deliver cargoes to overcome mass transport limitations. A very efficient way to load molecular cargoes is to disperse them in a liquid compartment, however, fabricating microswimmers with multiple liquid compartments remains a significant challenge. To address this challenge, we present a modular fabrication platform that combines microfluidic synthesis and sequential capillarity-assisted particle assembly (sCAPA) for microswimmers with various liquid compartments. We demonstrate the synthesis of monodisperse, small polymer-based microcapsules (Ø = 3-6μm) with different liquid cargoes using a flow-focusing microfluidic device. By employing the sCAPA technique, we assemble multiple microcapsules into microswimmers with high precision, resulting in versatile microswimmers with multiple liquid compartments and programmable functionalities. Our work provides a flexible approach for the fabrication of modular microswimmers, which could potentially actively transport cargoes and release them on demand in the future.


Topical application of autologous blood products during surgical closure following a coronary artery bypass graft.
Surgical site wound complications are associated with increased cost, morbidity, and mortality following cardiothoracic surgery. Recent publications have advocated the application of autologous blood components as an adjunctive tool to surgical closure during various surgical procedures. The current study was intended to assess the safety and efficacy of the application of autologous platelet rich and platelet poor plasma to the sternal closure and saphenous vein harvest site during closure following a coronary artery bypass graft. A retrospective analysis was performed on 1446 consecutive coronary artery bypass grafting procedures from two surgeons. A patient group receiving topical application of platelet rich and platelet poor plasma during closure of their chest and leg surgical incisions was compared to a patient population receiving standard treatment of care. Forty covariates were collected for each patient included in the study. Propensity scoring was used to adjust for baseline imbalance. Asymptotic logistic regression and exact statistical methods were used to determine the effect of the autologous blood application on infection and drainage of the sternal and leg wounds. One thousand, one hundred and twenty-eight patients had sufficient data to be included in the final analysis, with 571 of these patients receiving the treatment compared to 557 control patients. No treatment-related adverse events were noted and the application process did not significantly affect the operative time. This retrospective analysis of a consecutive series of patients receiving a coronary artery bypass grafting procedure concluded that application of platelet rich and platelet poor plasma significantly reduced occurrences of chest wound infection, chest drainage, and leg wound drainage. This novel therapy merits further investigation.


Phase II trials of Baker's antifol, bleomycin, CCNU, streptozotocin, tilorone, and 5-fluorodeoxyuridine plus arabinosyl cytosine in metastatic breast cancer.
A total of 202 patients with advanced breast cancer were entered into two prospectively randomized Phase II trials conducted by the Eastern Cooperative Oncology Group, in an effort to identify promising agents and combinations for previously treated cases. Patients in Study 1 received bleomycin, CCNU, or streptozotocin and those in Study 2 received tilorone, Baker's antifol, or a combination of 5-fluorodeoxyuridine plus arabinosyl cytosine. Partial responses were seen only with bleomycin, Baker's antifol, and 5-fluorodeoxyuridine plus arabinosyl cytosine. The median times to treatment failure ranged from 3.6 weeks to 5.7 weeks, and the median survival times, from 8 weeks to 25 weeks for tilorone and bleomycin, respectively. Toxic reactions was primarily hematologic and gastrointestinal, but skin, neurologic, respiratory, and renal abnormalities were noted in some treatment arms. The treatment schedules outlined and the toxic effects noted provide background information that might prove useful in designing complex new chemotherapeutic programs, since there is pharmacological rationale for incorporating some of the agents tested into present standard combination chemotherapy regimens.


Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell.
The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules.


Integrative Approach for Precise Genotyping and Transcriptomics of Salt Tolerant Introgression Rice Lines.
Rice is the most salt sensitive cereal crop and its cultivation is particularly threatened by salt stress, which is currently worsened due to climate change. This study reports the development of salt tolerant introgression lines (ILs) derived from crosses between the salt tolerant indica rice variety FL478, which harbors the Saltol quantitative trait loci (QTL), and the salt-sensitive japonica elite cultivar OLESA. Genotyping-by-sequencing (GBS) and Kompetitive allele specific PCR (KASPar) genotyping, in combination with step-wise phenotypic selection in hydroponic culture, were used for the identification of salt-tolerant ILs. Transcriptome-based genotyping allowed the fine mapping of indica genetic introgressions in the best performing IL (IL22). A total of 1,595 genes were identified in indica regions of IL22, which mainly located in large introgressions at Chromosomes 1 and 3. In addition to OsHKT1;5, an important number of genes were identified in the introgressed indica segments of IL22 whose expression was confirmed [e.g., genes involved in ion transport, callose synthesis, transcriptional regulation of gene expression, hormone signaling and reactive oxygen species (ROS) accumulation]. These genes might well contribute to salt stress tolerance in IL22 plants. Furthermore, comparative transcript profiling revealed that indica introgressions caused important alterations in the background gene expression of IL22 plants (japonica cultivar) compared with its salt-sensitive parent, both under non-stress and salt-stress conditions. In response to salt treatment, only 8.6% of the salt-responsive genes were found to be commonly up- or down-regulated in IL22 and OLESA plants, supporting massive transcriptional reprogramming of gene expression caused by indica introgressions into the recipient genome. Interactions among indica and japonica genes might provide novel regulatory networks contributing to salt stress tolerance in introgression rice lines. Collectively, this study illustrates the usefulness of transcriptomics in the characterization of new rice lines obtained in breeding programs in rice.


Relationship between deep medullary veins in susceptibility-weighted imaging and ipsilateral cerebrovascular reactivity of middle cerebral artery in patients with ischemic stroke.
Deep cerebral veins have been recently associated with the severity of hemodynamic impairment in moyamoya disease. The aim of the current study was to determine the correlation of deep medullary veins (DMVs) in susceptibility-weighted imaging (SWI) with ipsilateral cerebrovascular reactivity (CVR) of and anterior cecebrocervical artery stenosis in patients with ischemic stroke. Patients with unilateral TIA or infarction who underwent 3.0 T magnetic resonance imaging SWI, digital subtraction angiography and transcranial Doppler with CO2 stimulation within the first 7 days of hospitalization were retrospectively selected. CVR and stenosis of anterior cerebrocervical arteries were compared between different DMVs stages in symptomatic hemispheres (SHs) and asymptomatic hemispheres (AHs). A total of 61 patients were subsequently included in the present study. A univariate analysis was conducted and results for age (PAHs=0.004, PSHs=0.006), hypertension (PAHs=0.008, PSHs=0.020), current smoking (PAHs=0.006, PSHs=0.021), CVR (PAHs=0.000, PSHs=0.000), and artery stenosis (PAHs=0.000, PSHs=0.000) were obtained. The results suggested statistically significant differences between DMVs grades in SHs and AHs. A subsequent multivariate analysis revealed that CVR (ORAHs=0.925, 95% CIAHs: 0.873-0.981; ORSHs=0.945, 95% CISHs: 0.896-0.996), and artery stenosis (ORAH=3.147, 95% CIAH: 1.010-9.806; ORSHs=2.882, 95% CISHs: 1.017-8.166) were independent risk factors of DMVs. In conclusion, 3.0 T SWI was useful in detecting the DMVs around the lateral ventricle in patients with atherosclerotic ischemic stroke. CVR and stenosis of anterior cerebrocervical arteries were independent risk factors for ipsilateral DMVs in SHs and AHs.


Synthesis of a novel glucose capped gold nanoparticle as a better theranostic candidate.
Gold nanoparticles are predominantly used in diagnostics, therapeutics and biomedical applications. The present study has been designed to synthesize differently capped gold nanoparticles (AuNps) by a simple, one-step, room temperature procedure and to evaluate the potential of these AuNps for biomedical applications. The AuNps are capped with glucose, 2-deoxy-D-glucose (2DG) and citrate using different reducing agents. This is the first report of synthesis of 2DG-AuNp by the simple room temperature method. The synthesized gold nanoparticles are characterized with UV-Visible Spectroscopy, Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM) and selected area electron diffraction (SAED), Dynamic light scattering (DLS), and Energy-dispersive X-ray spectroscopy (SEM-EDS). Surface-enhanced Raman scattering (SERS) study of the synthesized AuNps shows increase in Raman signals up to 50 times using 2DG. 3-(4, 5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay has been performed using all the three differently capped AuNps in different cell lines to assess cytotoxcity if any, of the nanoparticles. The study shows that 2DG-AuNps is a better candidate for theranostic application.


Phenomenology of Non-Ordinary Logics in Brief Strategic Therapy.
Brief Strategic Therapy (BST) is a psychosocial treatment for mental disorders based on a unique theory of psychological dysfunction that differs from major psychotherapy approaches in that psychological dysfunction follows non-ordinary logics rather than classic logical principles. BST contends that there are three different kinds of non-ordinary logics that underpin psychological dysfunction: the logic of contradiction, the logic of paradox, and the logic of belief. BST therapeutic strategies are based on these non-ordinary logics processes. Unfortunately, descriptions and case examples of these non-ordinary logics are scattered among a myriad of books so that it is difficult for the clinician to get acquainted with them. Additionally, BST literature has described these non-ordinary logics with a somewhat obscure and metaphorical language that might be difficult for the clinician to grasp. Herein, we condensate descriptions and case examples of the three non-ordinary logics, clarify the phenomenological processes of each of the classes of non-ordinary logics, and highlight research findings from different theoretical orientations that are coherent and consistent with our phenomenological accounts of non-ordinary logics. Based on our clinical observations, non-ordinary logics can be distinguished by three variables: (a) the immediate effect of the dysfunctional attempted solution (DAS), (b) the long-term effect of the DAS, and (c) the most salient mental phenomenon associated with the DAS that maintains a psychological problem. This advancement could foster clinicians' ability to identify non-ordinary logics and their ability to devise appropriate strategies to solve psychological problems.


[Reconstruction of the lower third of the face--microsurgical monobloc transfer with vascularized bone].
The authors present two microsurgical options of the reconstruction of the lower third of the face. They outline a systematisation of indications and techniques and emphasise versatility and flexibility of free flaps compared to pedicled flaps, and describe the advantages of the vascularisation and the techniques of the iliac crest osteocutaneous flap and the parascapular cutaneous-latissimus dorsi osteomyocutaneous flap which was developed by Nassif.


Targeted transgene expression in neuronal precursors: watching young neurons in the old brain.
Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age-related neuronal loss and cognitive declines.


Establishment of Mouse Primed Stem Cells by Combination of Activin and LIF Signaling.
In mice, embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are established from pre- and post-implantation embryos and represent the naive and primed state, respectively. Herein we used mouse leukemia inhibitory factor (LIF), which supports ESCs self-renewal and Activin A (Act A), which is the main factor in maintaining EpiSCs in post-implantation epiblast cultures, to derive a primed stem cell line named ALSCs. Like EpiSCs, ALSCs express key pluripotent genes Oct4, Sox2, and Nanog; one X chromosome was inactivated; and the cells failed to contribute to chimera formation in vivo. Notably, compared to EpiSCs, ALSCs efficiently reversed to ESCs (rESCs) on activation of Wnt signaling. Moreover, we also discovered that culturing EpiSCs in AL medium for several passages favored Wnt signaling-driven naive pluripotency. Our results show that ALSCs is a primed state stem cell and represents a simple model to study the control of pluripotency fate and conversion from the primed to the naive state.


Comparing the antibacterial activity of chitin nanocrystals with chitin: exploring the feasibility of chitin nanocrystals as novel pesticide nanocarriers in agriculture.
In recent years, nanomaterials-based pesticide carriers have garnered significant attention and sparked extensive research. However, most studies have primarily focused on investigating the impact of physical properties of nanomaterials, such as size and modifiable sites, on drug delivery efficiency of nano-pesticides. The limited exploration of biologically active nanomaterials poses a significant obstacle to the advancement and widespread adoption of nano-pesticides. In this study, we prepared chitin nanocrystals (ChNC) based on acid hydrolysis and systematically investigated the differences between nano- and normal chitin against plant bacteria (Pseudomonas syringae pv. tabaci). The primary objective was to seek out nanocarriers with heightened biological activity for the synthesis of nano-pesticides. Zeta potential analysis, Fourier Transform infrared spectrometry (FTIR), X-Ray diffraction (XRD), Atomic force microscopy (AFM) and Transmission electron microscopy (TEM) identified the successful synthesis of ChNC. ChNC showcased remarkable bactericidal activity at comparable concentrations, surpassing that of chitin, particularly in its ability to inhibit bacterial biofilm formation. Furthermore, ChNC displayed heightened effectiveness in disrupting bacterial cell membranes, resulting in the leakage of bacterial cell contents, structural DNA damage, and impairment of DNA replication. Lastly, potting experiments revealed that ChNC is notably more effective in inhibiting the spread and propagation of bacteria on plant leaves. ChNC exhibited higher antibacterial activity compared to chitin, enabling efficient control of plant bacterial diseases through enhanced interaction with bacteria. These findings offer compelling evidence of ChNC's superior bacterial inhibition capabilities, underscoring its potential as a promising nanocarrier for nano-pesticide research. © 2023 Society of Chemical Industry.


Toxicity and Biodistribution of Activated and Non-activated Intravenous Iron Oxide Nanoparticles.
The use of nanoparticles in medical treatment has prompted the question of their safety. In this study, the pathophysiology and biodistribution of three different concentrations of intravenously-delivered dextran-coated Fe3O4 iron oxide nanoparticles (IONP) were evaluated in mice. Some groups of mice were exposed to an AC magnetic field (AMF) at levels comparable with those proposed for cancer treatments. Iron biodistribution analysis for both AMF and non-AMF treated mice was performed for all three concentrations used (.6 mg Fe/mouse, 1.8 mg Fe/mouse, and 5.6 mg Fe/mouse). Blood urea nitrogen, alanine transaminase, alkaline phosphatase, total serum protein, and creatinine were also assessed at 4 hours, 7 days, and 14 days post-injection. Histological analysis of lung, spleen, heart, liver, and kidney tissue was conducted at 7 and 14 days post-injection. Prussian blue and H&E stains were used to histomorphometrically assess iron content in the tissues studied. Preliminary results demonstrate small temporary elevation in liver enzymes and hepatocyte vacuolization at all iron concentrations studied. Liver and spleen were the primary sites of IONP deposition. None of the animals demonstrated systemic or local toxicity or illness, with or without AMF activation.


Bouts of responding on variable-interval schedules: effects of deprivation level.
Rats obtained food pellets on a variable-interval schedule of reinforcement by nose poking a lighted key. After training to establish baseline performance (with the mean variable interval set at either 60, 120, or 240 s), the rats were given free access to food during the hour just before their daily session. This satiation operation reduced the rate of key poking. Analysis of the interresponse time distributions (log survivor plots) indicated that key poking occurred in bouts. Prefeeding lengthened the pauses between bouts, shortened the length of bouts (less reliably), and had a relatively small decremental effect on the response rate within bouts. That deprivation level affects mainly between-bout pauses has been reported previously with fixed-ratio schedules. Thus, when the focus is on bouts, the performances maintained by variable-interval schedules and fixed-ratio schedules are similarly affected by deprivation.


[Conductive hearing loss caused by eustachian tube dysfunction according to the data of functional computed tomography].
The paper deals with computed tomography (CT) diagnosis of Eustachian tube dysfunction. A functional multislice spiral (MS) CT protocol has been first elaborated for the Eustachian tube. Twenty-three patients with unilateral conductive hearing loss and Eustachian tube dysfunction were examined. The normal functional anatomy of the Eustachian tube was evaluated on the side without evidence of pathology in 23 patients. Functional MSCT showed that the cartilaginous portion of the Eustachian tube opened partially and closed completely in 9 patients. Ten patients were found to have steady changes in the cartilaginous portion of the Eustachian tube. The developed method could confirm the cause of conductive hearing loss and optimally define a treatment policy.


Demographic characteristics and antisocial personality disorder of early and late onset alcoholics identified in a primary care clinic.
A total of 1,734 persons were prospectively screened in a primary care clinic to examine the demographic characteristics and presence or absence of antisocial personality disorder among early onset alcoholics (EOA) and late onset alcoholics (LOA). A total of 76 EOA (male = 58 and female = 18) and 80 LOA (male = 56 and female = 24), as determined by the Comprehensive Drinking Profile Scale, participated in the study. EOA tended to be single and were younger, in a lower socioeconomic class, raised by non-biological parents, more likely to have antisocial personality disorder, and more likely to commit certain convicted offenses compared to LOA (p <or= .05). This study found that EOA identified in a primary care clinic have a different demographic profile and are more likely to have antisocial personality disorder compared to LOA.


Biochemical Fingerprinting of Methicillin-Resistant Staphylococcus aureus Isolated From Sewage and Hospital in Iran.
Methicillin-resistant Staphylococcus aureus (MRSA) is known as a common pathogen in nosocomial and community-acquired infections. Sewage acts as an environmental reservoir and may have a significant role in development and dissemination of antibiotic resistance. This study was undertaken to determine the epidemiological relatedness between the MRSA isolated from sewage and human infections. Samples were collected from a referral hospital and also a sewage treatment plant in Tehran, Iran, during 2010. All the MRSA isolates were identified at the species level and typed using Phene plate (PhP) system and SCCmec typing. Antibiotic susceptibility tests were also performed. Of the 1142 isolates, 200 MRSA strains from the sewage (n = 100) and the clinic (n = 100) were isolated. Distinct PhP types, consisting of 16 common types and 13 single types, and also 3 different staphylococcal cassette chromosome mec (SCCmec) types (III, IVa and IVc) were found amongst the MRSA isolated from the two different sources. The results of antibiotic susceptibility testing showed an increased resistance to penicillin, ciprofloxacin, erythromycin, clindamycin and tetracycline. In addition, none of the isolates showed resistance to vancomycin, quinupristin -dalfopristin and linezolid. The presence of common PhP types and also SCCmec type III, as an indicator for hospital strains, among the isolates, may indicate an epidemiological link between clinical and sewage MRSA isolates in Tehran.


Bisphosphonates and atherosclerosis: why?
The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget's disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.


[Study of condyle movement in Angle Class Ⅲ malocclusion with temporomandibular dysfunctions].
Subjects with normal occlusion, Angle Class Ⅲ malocclusion and Angle Class Ⅲ malocclusion with temporomandibular dysfunctions(TMD) were included, and their protraction and retraction, opening and closing mouth were recorded and compared to determine the condyle movement characteristics of Angle Class Ⅲ malocclusion patients with TMD. Thirty cases of Angle Class Ⅲ malocclusion with TMD (experimental group), 30 cases of simple Angle Class Ⅲ malocclusion (control group 1) and 30 cases of normal occlusion (control group 2) were chosen, the condyle movement of mouth opening and closing, protraction and retraction were recorded and analyzed by computer aided axiography (CADIAX Ⅲ) , the measurements were compared and qualitative analysis was performed. SPSS 10.0 software package was used for statistical analysis. The indexes of opening and closing mouth, forward, backward and lateral movement were higher in experimental group and control group 1 than in the control group 2, especially in the vertical direction. The maximum variation was on the Y axis between the experimental group and the control group 2, the lateral movement of working side was significantly higher than that of the normal group, while the movement ranges at other directions were significantly smaller than that of control group 2, especially in opening and closing mouth horizontally upward and the maximum space displacement at right, upward direction (P<0.01). The tracking of condyle movements has its own characteristics in three dimensions in the experimental group ,compared with control group 1 and 2.


Endoscopic ultrasound-guided needle confocal laser endomicroscopy in pancreatic masses.
Endoscopic ultrasound (EUS) is an established tool in diagnosing pancreatic masses and enables guided fine-needle aspiration (FNA). Confocal laser endomicroscopy (CLE) has allowed in vivo microscopic analysis during on-going endoscopy. Recently, CLE has gone beyond luminal indications with the development of a new microprobe (nCLE). The aim of this case series was to study the feasibility of EUS-guided nCLE and to correlate the findings with microscopy. A total of 25 patients with pancreatic masses were included. During the procedure, an nCLE fiber preloaded into a 19 gauge FNA needle was advanced into the lesion under EUS guidance. Fluorescein was administered intravenously and imaging performed. Afterwards EUS-FNA was performed in the same location. Safety and feasibility were evaluated and CLE structures were registered and correlated to the standard hematoxylin and eosin cytopathology specimens. Moreover, additional topical acriflavine-enhanced ex vivo examinations on fresh pancreatic specimens were conducted. EUS-guided nCLE procedures were accomplished in all patients. No adverse advents were registered. Furthermore, it was feasible to do nCLE inside pathological lesions and relatively easy to visualize organ specific tissue. Despite selecting predefined structures the diagnostic value was limited mainly due to the missing ability to elucidate the cell nuclei, In the ex vivo examinations, where acriflavine was administered topically on excised pancreatic tissue, the nuclei were clearly visualized, thus increasing the diagnostic value. EUS-guided nCLE procedures on focal pancreatic masses are feasible and safe, but the diagnostic value seems limited. Thus, further studies using different contrast agents are required to optimize the diagnostic accuracy.


When more is not merrier: Using wild population dynamics to understand the effect of density on ex situ seahorse mating behaviors.
Seahorses are considered one of the most iconic examples of a monogamous species in the animal kingdom. This study investigates the relationship between stocking density and mating and competitive behavior from the context of the field biology of the dwarf seahorse, Hippocampus zosterae (Jordan & Gilbert). Animals were housed in 38 liter tanks at a range of densities and sex ratios (from 2-8 animals per tank), and their reproductive and other social behaviors were monitored from tank introduction through copulation. At low tank densities and even sex ratios but comparatively high field densities, frequency of both mating and competitive behaviors was low in trials. A higher level of males in tanks across all densities increased competition, activity levels, and aggression leading to egg transfer errors and brood expulsion, resulting in lower reproductive success. Across seahorse species, mean and maximum wild densities were consistently lower than those used in ex situ breeding, with adult sex ratios that were significantly female biased. However, significant variation exists in wild seahorse densities across species, with higher densities detected in focal/mark recapture studies and on artificial habitat structures than reported with belt transect sampling techniques. Interchange of knowledge gained in both aquarium and wild contexts will allow us to better understand the biology of this genus, and improve reproduction in captivity. Interpreting ex situ reproductive behaviors of seahorses within various densities reported from natural populations will help us predict the impact of conservation efforts and increase the likelihood of long-term persistence of populations for this threatened genus.


Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS. These clinical features were accompanied by an early-onset and progressive loss of Purkinje cells, followed by gliosis. Additionally, the loss of Ankfy1 function resulted in an abnormal expression of neurotrophic factors (NTFs) in the Ankfy1/+ mouse cerebellum. Moreover, Purkinje cells cultured from neonatal Ankfy1/+ mice exhibited a shorter dendritic length and decreased numbers of dendritic spines. Importantly, cerebellar Purkinje cells from Ankfy1/+ mice and cells transfected with a lentiviral Ankfy1 shRNA underwent apoptosis. We propose that transgenic Ankfy1/+ mice are a useful model for studying the pathogenesis of ARSACS and for exploring the molecular mechanisms involved in this neurodegenerative disease.


Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.
The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.


Protein targeting to dense-core secretory granules.
Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans-Golgi network (TGN) prior to their aggregation to form the characteristic dense-core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules.


Management of Diabetic Ketoacidosis in a Patient With Chronic Kidney Disease Under Maintenance Hemodialysis: A Case Report.
Diabetic ketoacidosis (DKA) is a potentially fatal metabolic complication seen in individuals with type 1 diabetes mellitus (DM) or type 2 DM under stress, such as infections and non-compliance with treatment. DKA in chronic kidney disease (CKD) patients undergoing maintenance hemodialysis (HD) presents challenges due to the unique pathophysiology and the absence of specific management guidelines. This case report highlights the importance of tailoring the treatment of DKA based on the specific requirements of CKD patients on HD. The presented case involves a 47-year-old female with type 2 DM and CKD who developed DKA in the context of a urinary tract infection (UTI). Management included insulin infusion, cautious fluid replacement therapy, electrolyte monitoring, and identifying precipitating factors, such as an infection. The case highlights the complexity of DKA management in CKD patients and the necessity of individualized approaches. More studies and guidelines are needed to optimize the proper management of DKA in CKD patients.


Cloning and characterization of a novel hepatitis B virus core binding protein C12.
To elucidate the biological function of HBV core antigen (HBcAg) on pathogenesis of hepatitis B, a novel gene C12 coding for protein with unknown function interacting with HBcAg in hepatocytes was identified and characterized. HBcAg bait plasmid pGBKT7-HBcAg was constructed and transformed into yeast AH109, then the transformed yeast was mated with yeast Y187 containing liver complementary DNA (cDNA) library plasmid in 2XYPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) and synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing X-alpha-gal for screening twice. After extracting and sequencing of plasmid from blue colonies, we isolated a cDNA clone encoding a novel protein designated as C12 that directly interacted with HBcAg. The interaction between HBcAg and C12 was verified again by re-mating. pEGFP-N1-C12 fluorescent protein fusion gene was transfected in 293 and L02 cell, and observed by fluorescent microscope. MTT reduction assay was used to study the action of C12 protein effect on metabolism of mammal cell. Yeast two-hybrid and cDNA microarray were performed to search binding protein and differential expression genes regulated by C12 protein. C12 gene was screened and identified by yeast two-hybrid system 3. The interaction between HBcAg and the novel protein coded by the new gene C12 was further confirmed by re-mating. After 48 h, fluorescence of fusion protein could be observed steadily in the 293 and L02 cell plasma. Under MTT assay, we found that the expression of C12 did not influence the growth of liver cells. Seventeen differential expression genes in HepG2 cells transfected with C12 protein expression plasmid by cDNA microarray, of which 16 genes were upregulated and 1 gene was downregulated by C12 protein. Twenty-one colonies containing 16 different genes coding for C12 protein binding proteins were isolated by yeast two-hybrid, there were 2 new genes with unknown function. The novel protein C12 is located in cell plasma, and its overexpression has no significant effect on the metabolism of liver cell. It interacts with many proteins in hepatocytes and may be involved in many processes of gene expression.


Evolution of male life histories and age-dependent sexual signals under female choice.
Sexual selection theory models evolution of sexual signals and preferences using simple life histories. However, life-history models predict that males benefit from increasing sexual investment approaching old age, producing age-dependent sexual traits. Age-dependent traits require time and energy to grow, and will not fully mature before individuals enter mating competition. Early evolutionary stages pose several problems for these traits. Age-dependent traits suffer from strong viability selection and gain little benefit from mate choice when rare. Few males will grow large traits, and they will rarely encounter choosy females. The evolutionary origins of age-dependent traits therefore remain unclear. I used numerical simulations to analyze evolution of preferences, condition (viability) and traits in an age-structured population. Traits in the model depended on age and condition ("good genes") in a population with no genetic drift. I asked (1) if age-dependent indicator traits and their preferences can originate depending on the strength of selection and the size of the trait; (2) which mode of development (age-dependent versus age-independent) eventually predominates when both modes occur in the population; and (3) if age-independent traits can invade a population with age-dependent traits. Age-dependent traits evolve under weaker selection and at smaller sizes than age-independent traits. This result held in isolation and when the types co-occur. Evolution of age-independent traits depends only on trait size, whereas evolution of age-dependent traits depends on both strength of selection and growth rate. Invasion of age-independence into populations with established traits followed a similar pattern with age-dependence predominating at small trait sizes. I suggest that reduced adult mortality facilitates sexual selection by favoring the evolution of age-dependent sexual signals under weak selection.


The complete mitochondrial genome of the fall webworm, Hyphantria cunea (Lepidoptera: Arctiidae).
The complete mitochondrial genome (mitogenome) of the fall webworm, Hyphantria cunea (Lepidoptera: Arctiidae) was determined. The genome is a circular molecule 15 481 bp long. It presents a typical gene organization and order for completely sequenced lepidopteran mitogenomes, but differs from the insect ancestral type for the placement of tRNA(Met). The nucleotide composition of the genome is also highly A + T biased, accounting for 80.38%, with a slightly positive AT skewness (0.010), indicating the occurrence of more As than Ts, as found in the Noctuoidea species. All protein-coding genes (PCGs) are initiated by ATN codons, except for COI, which is tentatively designated by the CGA codon as observed in other lepidopterans. Four of 13 PCGs harbor the incomplete termination codon, T or TA. All tRNAs have a typical clover-leaf structure of mitochondrial tRNAs, except for tRNA(Ser)(AGN), the DHU arm of which could not form a stable stem-loop structure. The intergenic spacer sequence between tRNA(Ser)(AGN) and ND1 also contains the ATACTAA motif, which is conserved across the Lepidoptera order. The H. cunea A+T-rich region of 357 bp is comprised of non-repetitive sequences, but harbors several features common to the Lepidoptera insects, including the motif ATAGA followed by an 18 bp poly-T stretch, a microsatellite-like (AT)(8) element preceded by the ATTTA motif, an 11 bp poly-A present immediately upstream tRNA(Met). The phylogenetic analyses support the view that the H. cunea is closerly related to the Lymantria dispar than Ochrogaster lunifer, and support the hypothesis that Noctuoidea (H. cunea, L. dispar, and O. lunifer) and Geometroidea (Phthonandria atrilineata) are monophyletic. However, in the phylogenetic trees based on mitogenome sequences among the lepidopteran superfamilies, Papillonoidea (Artogeia melete, Acraea issoria, and Coreana raphaelis) joined basally within the monophyly of Lepidoptera, which is different to the traditional classification.


Cardiovascular lifetime risk predicts incidence of coronary calcification in individuals with low short-term risk: the Dallas Heart Study.
The absence of coronary artery calcium (CAC) in middle age is associated with very low short-term risk for coronary events. However, the long-term implications of a CAC score of 0 are uncertain, particularly among individuals with high cardiovascular lifetime risk. We sought to characterize the association between predicted lifetime risk and incident CAC among individuals with low short-term risk. We included 754 Dallas Heart Study participants with serial CAC scans (6.9 years apart) and both low short-term risk and baseline CAC=0. Lifetime risk for cardiovascular disease was estimated according to risk factor burden. Among this group, 365 individuals (48.4%) were at low lifetime risk and 389 (51.6%) at high lifetime risk. High lifetime risk was associated with higher annualized CAC incidence (4.2% versus 2.7%; P < 0.001). Similarly, mean follow-up CAC scores were higher among participants with high lifetime risk (7.8 versus 2.4 Agatston units). After adjustment for age, sex, and race, high lifetime risk remained independently associated with incident CAC (OR 1.60; 95% CI 1.12 to 2.27; P=0.01). When assessing risk factor burden at the follow-up visit, 66.7% of CAC incidence observed in the low lifetime risk group occurred among individuals reclassified to a higher short- or long-term risk category. Among individuals with low short-term risk and CAC scores of 0, high lifetime risk is associated with a higher incidence of CAC. These findings highlight the importance of lifetime risk even among individuals with very low short-term risk.


Experience and lessons learned from sewage sludge pyrolysis in Australia.
Management of sewage sludge via "publicly acceptable" methods is becoming increasingly difficult, primarily due to health and environmental concerns with respect to reuse of the product in agriculture. Consequently thermal processes are gaining popularity with significantly increased interest being shown in pyrolysis and gasification processes, due to their "non-incineration status". One such process is the ENERSLUDGE technology which has been developed and commercialised by Environmental Solutions International Ltd (ESI). The world's first commercial ENERSLUDGE plant is located at the Subiaco Wastewater Treatment Plant (WWTP) that was handed over to the client, the Water Corporation of Western Australia in June 2001. Extensive design knowledge and operational experience has now been accumulated from this commercial pyrolysis facility and future applications of the technology will benefit immensely from the lessons learned and experience gained from this facility.


Left bundle branch pacing in alternating bundle branch block.
We present a case of symptomatic intermittent AV block showing during monitorization alternating bundle branch block. Presuming a high need of pacing, conduction system pacing was considered a more physiological alternative in this patient. Left bundle branch pacing restored a stable atrioventricular synchrony with a paced QRS complex similar to the native one and might be a good alternative in these cases.


Divalent ion binding properties of the timothy grass allergen, Phl p 7.
The timothy grass allergen, Phl p 7, was studied by calorimetry, spectroscopy, and analytical ultracentrifugation. As judged by isothermal titration calorimetry (ITC), the protein binds Ca (2+) cooperatively with stepwise macroscopic association constants of 1.73 x 10 (6) and 8.06 x 10 (6) M (-1). By contrast, Mg (2+) binding is sequential with apparent macroscopic association constants of 2.78 x 10 (4) and 170 M (-1). Circular dichroism and ANS fluorescence data suggest that Ca (2+) binding provokes a major conformational change that does not occur upon Mg (2+) binding. Conformational stability was assessed by differential scanning calorimetry (DSC). In phosphate-buffered saline (PBS) containing EDTA, the apoprotein undergoes two-state denaturation with a T m of 78.4 degrees C. In the presence of 0.02 mM Ca (2+), the T m exceeds 120 degrees C. Phl p 7 is known to crystallize as a domain-swapped dimer at low pH. However, analytical ultracentrifugation data indicate that the protein is monomeric in neutral solution at concentrations exceeding 1.0 mM, in both the apo and Ca (2+)-bound states.


Theiler's virus-mediated autoimmunity: local presentation of CNS antigens and epitope spreading.
Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a neurotropic picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to those of chronic-progressive multiple sclerosis. Upon infection, TMEV-specific CD4+ T cells target persistent viral antigens in the CNS and initiate myelin damage. Later in the disease, myelin-specific CD4+ T cells are primed by epitope spreading, and these autoimmune T cells contribute to the pathogenesis of the chronic-progressive disease. This review focuses upon aspects of the initiation of a virally induced CD4+ T cell-mediated autoimmune response. First, the steps involved in the hierarchical activation of non-cross-reactive myelin-specific T cells in the SJL/J mouse after CNS infection with TMEV and the role of these autoreactive T cells in chronic myelin damage are discussed. Second, the process of epitope spreading and the role of CNS antigen presenting cells in the temporal presentation of self-antigens is considered. Finally, we will discuss aspects of T cell activation and antigen presentation, and how they can impact autoimmune disease.


Prognostic value of a new clinically-based classification system in patients with CMML undergoing allogeneic HCT: a retrospective analysis of the EBMT-CMWP.
Recently a new three-group clinical classification was reported by an International Consortium to stratify CMML patients with regard to prognosis. The groups were defined as follows: (1) Myelodysplastic (MD)-CMML: WBC ≤ 10 × 109/l, circulating immature myeloid cells (IMC) = 0, no splenomegaly; (2) MD/MP (overlap)-CMML: WBC 10-20 × 109/l or WBC ≤ 10 × 109/l but IMC > 0 and/or splenomegaly; (3) Myeloproliferative (MP)-CMML: WBC > 20 × 109/l. By analysing EBMT Registry patients who underwent allo-HCT for CMML between 1997 and 2016, we aimed to determine the impact of this classification on transplantation outcome and to make a comparison with the conventional WHO classification (CMML-0/CMML-1/CMML-2). Patient grouping was based on the data registered at time of transplantation, with IMC replaced by peripheral blasts. Among 151 patients included in the analysis, 38% were classified as MD-CMML, 42% as MD/MP-CMML and 20% as MP-CMML. With a median survival of 17 months in the whole series, MD-CMML patients were distinguished as a low-risk group with higher CR rate at transplant and a longer post-transplant 2-year progression-free survival in comparison to others (44.5% vs 33.5%, respectively), whereas the WHO classification was superior in identifying high-risk patients (CMML-2) with inferior survival outcomes.


GigA and GigB are Master Regulators of Antibiotic Resistance, Stress Responses, and Virulence in Acinetobacter baumannii.
A critical component of bacterial pathogenesis is the ability of an invading organism to sense and adapt to the harsh environment imposed by the host's immune system. This is especially important for opportunistic pathogens, such as Acinetobacter baumannii, a nutritionally versatile environmental organism that has recently gained attention as a life-threatening human pathogen. The emergence of A. baumannii is closely linked to antibiotic resistance, and many contemporary isolates are multidrug resistant (MDR). Unlike many other MDR pathogens, the molecular mechanisms underlying A. baumannii pathogenesis remain largely unknown. We report here the characterization of two recently identified virulence determinants, GigA and GigB, which comprise a signal transduction pathway required for surviving environmental stresses, causing infection and antibiotic resistance. Through transcriptome analysis, we show that GigA and GigB coordinately regulate the expression of many genes and are required for generating an appropriate transcriptional response during antibiotic exposure. Genetic and biochemical data demonstrate a direct link between GigA and GigB and the nitrogen phosphotransferase system (PTSNtr), establishing a novel connection between a novel stress response module and a well-conserved metabolic-sensing pathway. Based on the results presented here, we propose that GigA and GigB are master regulators of a global stress response in A. baumannii, and coupling this pathway with the PTSNtr allows A. baumannii to integrate cellular metabolic status with external environmental cues.IMPORTANCE Opportunistic pathogens, including Acinetobacter baumannii, encounter many harsh environments during the infection cycle, including antibiotic exposure and the hostile environment within a host. While the development of antibiotic resistance in A. baumannii has been well studied, how this organism senses and responds to environmental cues remain largely unknown. Herein, we investigate two previously identified virulence determinants, GigA and GigB, and report that they are required for in vitro stress resistance, likely comprising upstream elements of a global stress response pathway. Additional experiments identify a connection between GigA/GigB and a widely conserved metabolic-sensing pathway, the nitrogen phosphotransferase system. We propose that coordination of these two pathways allows A. baumannii to respond appropriately to changing environmental conditions, including those encountered during infection.


Star formation inside a galactic outflow.
Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.


Imprinted NanoVelcro Microchips for Isolation and Characterization of Circulating Fetal Trophoblasts: Toward Noninvasive Prenatal Diagnostics.
Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to prepare the LCM-compatible nanoVelcro substrates. Using an optimized cTB-capture condition and an immunocytochemistry protocol, we were able to identify and isolate single cTBs (Hoechst+/CK7+/HLA-G+/CD45-, 20 μm > sizes > 12 μm) on the imprinted nanoVelcro microchips. Three cTBs were polled to ensure reproducible whole genome amplification on the cTB-derived DNA, paving the way for cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis. Using maternal blood samples collected from expectant mothers carrying a single fetus, the cTB-derived aCGH data were able to detect fetal genders and chromosomal aberrations, which had been confirmed by standard clinical practice. Our results support the use of nanoVelcro microchips for cTB-based noninvasive prenatal genetic testing, which holds potential for further development toward future NIPD solution.


Impact of new guidelines on physicians' ordering of preoperative tests.
To compare the number of preoperative tests ordered for elective ambulatory surgery patients during the 2 years before and the 2 years after the establishment of new hospital testing guidelines. The patterns of preoperative testing by surgeons and a medical consultant during the 2 years before and the 2 years after the establishment of new guidelines at one orthopedic hospital were reviewed. All tests ordered preoperatively were determined by review of medical records. Preoperative medical histories, physical examinations, and comorbidities were obtained according to a protocol by the medical consultant (author). Perioperative complications were determined by review of intraoperative and postoperative events, which also were recorded according to a protocol. A total of 640 patients were enrolled, 361 before and 279 after the new guidelines. The mean number of tests decreased from 8.0 before to 5.6 after the new guidelines ( p =.0001) and the percentage decrease for individual tests varied from 23% to 44%. Except for patients with more comorbidity and patients receiving general anesthesia, there were decreases across all patient groups. In multivariate analyses only time of surgery (before or after new guidelines), age, and type of surgery remained statistically significant ( p =.0001 for all comparisons). Despite decreases in surgeons' ordering of tests, the medical consultant did not order more tests after the new guidelines ( p =.60) The majority of patients had no untoward events intraoperatively and postoperatively throughout the study period, with only 6% overall requiring admission to the hospital after surgery, mainly for reasons not related to abnormal tests. Savings from charges totaled $34,000 for the patients in the study. Although there was variable compliance among physicians, new hospital guidelines were effective in reducing preoperative testing and did not result in increases in untoward perioperative events or in test ordering by the medical consultant.


Reliability of modified functional reach test in the assessment of balance function in people with spinal cord injury: A systematic review.
To systematically review studies reporting reliability of modified functional reach test for the assessment of sitting balance function in people with spinal cord injury. The systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and comprised research studies published in English language from the earliest record till October 2019 on the subject of reliability of modified functional reach test in assessing balance function in adult spinal cord injury patients.. Prominent databases were searched with relevant key words to shortlist the targeted studies. Of the 108 studies retrieved initially, 6(5.55%) were included in the current systematic review. All the 6(100%) studies reported only test-retest reliability of modified functional reach test. Of them, 4(66.6%) studies measured only forward reach, while 2(33.3%) measured reach in different directions. All 6(100%) studies reported good to excellent reliability of modified functional reach test with interclass coefficient values ranging from 0.78 to 0.99. Modified functional reach test was found to be a reliable tool for assessing sitting balance function in individuals with spinal cord injury.