Multiprotein-bridging factor 1 regulates vegetative growth, osmotic stress, and virulence in Magnaporthe oryzae.
Multiprotein bridging factor 1 (MBF1) is a transcriptional co-activator that mediates transcriptional activation by bridging sequence-specific activator like proteins and the TATA-box binding protein (TBP). MBF1 has been well-studied in Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens, but it is not well understood in filamentous fungi. In this study, we report the identification and characterization of a MBF1 ortholog (MoMBF1) in the rice blast fungus Magnaporthe oryzae), which causes the devastating rice blast disease and is an ideal model for studying the growth, development and pathogenic mechanisms of filamentous fungi. MoMBF1 encodes a 161 amino acid protein with a typical MBF1 domain and HTH domain. Bioinformatics were used to analyze the structural domains in MoMBF1 and its phylogenetic relationship to other homologs from different organisms. We have generated MoMBF1 deletion mutants (ΔMoMBF1) and functional complementation transformants, and found that the deletion mutants showed significant defects in vegetative growth and tolerance to exogenous stresses, such as 1 M sorbitol, 0.5 M NaCl, and 5 mM H2O2. Moreover, ΔMoMBF1 showed reduced pathogenicity with smaller infection lesions than wild type and the complementation strain, and decreased response to the accumulation of ROS (reactive oxygen species) in planta at the initial infection stage. Taken together, our data indicate that MoMBF1 is required for vegetative growth, pathogenicity and stress response in M. oryzae.


Gout affecting the hand and wrist.
Tophaceous gout in the hand and wrist often presents de novo as the first sign of the disease process in the elderly. Tophaceous material may present in a liquid, pasty, or chalky/granular state. Treatment may be as simple as aspirating the liquid or squeezing out pasty tophaceous material. Other nonsurgical treatment options include lifestyle and dietary modifications and drug therapy. Surgery is often indicated for the patient with significant tendon and joint compromise as well as skin breakdown and for decompression of compressive peripheral neuropathy.


Knee extension moment arm variations relate to mechanical function in walking and running.
The patellofemoral joint plays a crucial mechanical role during walking and running. It increases the knee extensor mechanism's moment arm and reduces the knee extension muscle forces required to generate the extension moment that supports body weight, prevents knee buckling and propels the centre of mass. However, the mechanical implications of moment arm variation caused by patellofemoral and tibiofemoral motion remain unclear. We used a data-driven musculoskeletal model with a 12-degree-of-freedom knee to simulate the knee extension moment arm during walking and running. Using a geometric method to calculate the moment arm, we found smaller moment arms during running than during walking in the swing phase. Overall, knee flexion causes differences between running and walking moment arms as increased flexion causes a posterior shift in the tibiofemoral rotation axis and patella articulation with the distal femur. Moment arms were also affected by knee motion direction and best predicted by separating by direction instead of across the entire gait cycle. Furthermore, we found high inter-subject variation in the moment arm that was largely explained by out-of-plane motion. Our results are consistent with the concept that shorter moment arms increase the effective mechanical advantage of the knee and may contribute to increased running velocity.


Decreased Gray Matter Volume in the Frontal Cortex of Migraine Patients with Associated Functional Connectivity Alterations: A VBM and rs-FC Study.
Resting-state functional MRI is widely used in migraine research. However, the pathophysiology and imaging markers specific for migraine pathologies are not well understood. In this study, we combined both structural and functional images to explore the concurrence and process of migraines. Thirty-four patients with a history of migraine without aura presenting during the interictal period (MwoA-DI), 10 patients with migraine without aura presenting during the acute attack (MwoA-DA), and 32 healthy controls (HCs) were recruited in this study. All participants underwent scanning via MRI. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to detect the brain structural and associated brain functional connectivity. In VBM analysis, a decrease of gray matter volume (GMV) in the middle frontal cortex was found in MwoA patients compared with HCs. The GMV of the middle frontal cortex had a negative correction with the duration of disease. In rs-FC analysis, the left middle frontal cortex (lower, VBM result) in both the MwoA-DA and the HC groups showed significantly increased functional connectivity with the left middle frontal cortex (upper) and left superior frontal cortex compared with MwoA-DI. The left middle frontal cortex (lower) in the MwoA-DI group also showed decreased functional connectivity in the left posterior cingulate cortex (PCC) compared with the HC group. The left middle frontal cortex (lower) in the MwoA-DA group demonstrated significantly increased functional connectivity in the left cerebellum lobule VI compared with the HC group. Our results demonstrated that the middle frontal cortex may serve as an important target in the frequency and severity of migraines due to its role in pain regulation through the default mode network, especially in the PCC. In addition, the cerebellum may modulate the pathophysiology of migraines by serving as a communication point between the cortex and the brainstem.


Scaling of human behavior during portal browsing.
We investigated flows of visitors migrating between different portal subpages. Two various portals were studied as weighted networks where nodes are portal subpages and edge weights are numbers of user transitions. Such networks differ from networks of portal subpages connected by hyperlinks prepared by portal designers. Distributions of link weights, node strengths, and times spent by visitors at one subpage follow power laws over several decades for data collected during two different days and for weekly data. The distribution of numbers P(z) of unique subpages visited during one session is exponential and there is a square-root dependence between the total number of transitions n during a single visit and the average z . A model of portal surfing is developed where the browsing process corresponds to a self-attracting walk on the weighted network with a short memory. Results of numerical simulation are in agreement with weekly and daily portal data, and our analytical approach fits empirical data in the center part of scaling regime.


Maturity, size at age and predator-prey relationships of winter skate Leucoraja ocellata in the southern Gulf of St Lawrence: potentially an undescribed endemic facing extirpation.
The goals of this study were to document the size and age structure, size at maturity, ovarian fecundity and diet of the endangered population of winter skate Leucoraja ocellata that resides in the southern Gulf of St Lawrence (SGSL). The maximum size observed for SGSL L. ocellata was 68 cm total length (LT ) but >99% of animals caught were <60 cm LT . Fifty per cent of male and female L. ocellata were fully mature at 40 and 42 cm LT , respectively, age c. 5 years. The oldest individual caught was age 11 years, but 98% of the 561 individuals examined were ≤age 8 years, indicating a short reproductive life span. Ovarian fecundity was low; no more than 29 ova >10 mm diameter were ever observed. At 40 cm LT , the diet changed from one dominated by shrimp Crangon septemspinosa and gammarid amphipods to one dominated by fishes (mainly sand lance Ammodytes spp. and rainbow smelt Osmerus mordax) and Atlantic rock crab Cancer irroratus. Sufficient differences were observed between SGSL L. ocellata and other populations in their size-at-maturity pattern and maximum size to propose the taxonomic re-evaluation of the population.


Artificial microRNAs for plant virus resistance.
RNA silencing is a natural plant defense system against foreign genetic elements including viruses. This natural antiviral mechanism has been adopted to develop virus-resistant plants by the expression of long stretches of viral sequences in perfectly paired double-stranded or stem-loop forms which, in turn, are processed into virus-specific small interfering RNAs (vsiRNAs) by the host's RNA silencing machinery. Recently, another set of RNA silencing-related small RNAs, microRNAs (miRNAs), have been exploited to engineer virus resistance in plants. Expression of modified miRNA precursors results in the production of artificial miRNAs (amiRNAs) targeting viral RNA sequences. The amiRNA-mediated virus resistance is efficient and superior to the long viral RNA-based antiviral approaches in that properly selected amiRNA sequences would have little chance to target the host plant genes or to complement or recombine with other invading viruses.


A quantitative estimation of electric current due to myocardial injury.
Myocardial injury causes electric current at the border of injured muscle and the surrounding intact region. In order to determine the magnitude of the injury current, experiments were performed with the isolated canine heart perfused with Tyrode's solution. The anterior descending branch of the left coronary artery was perfused selectively with high potassium (K+) solution and the resulting injury current was reflected in the ST shift of the orthogonal electrocardiogram, derived from the surface of a cubic container in which the heart was placed. After measurement of the ST vector with different K+ concentrations, the heart has fixed with formalin and the injury zone was delineated with serial sections. The boundaries of the selectively perfused region were reconstructed. The algebraic sum of orthogonal components of boundary surfaces determined the average direction normal to the boundary, which was found to be parallel with the ST vector. With increasing K+ concentrations, the ST shift became more marked. However, it was saturated at about 30 mEq/L K+. The maximum injury current, calculated from the saturated value of the ST magnitude, amounted to 0.10 mA.cm per unit area of the boundary surface. Additional experiments were performed with right ventricular papillary muscle preparations. Injuries were caused by a cotton pad containing high K+ solution placed in two directions to make the border along and across the long axis of the papillary muscle. The results indicate that the injury current in an anisotropic structure was essentially directed along the fiber orientation.


The ratification of the Convention on Psychotropic Substances 1971 and its transposition into national legislation in the Federal Republic of Germany.
The Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol Amending the Single Convention on Narcotic Drugs, 1961, and the Convention on Psychotropic Substances 1971 have been implemented in the Federal Republic of Germany as follows: (a) No distinction is made between narcotic drugs and psychotropic substances; all substances which are controlled and non-exempted preparations containing such substances fall under the legal designation of "narcotic drugs"; (b) The same control measures as for narcotic drugs apply to all substances in Schedules II, III and IV of the 1971 Convention, i.e. control of manufacture, trade, import and distribution; (c) Under the new Narcotics Act of the Federal Republic of Germany, which entered into force on 1 January 1982, preparations containing substances listed in Schedules II and III of the 1971 Convention are subject to the same full control measures, including mandatory special prescriptions, with the exception of approximately 50 preparations from substances in Schedule III of the 1971 Convention. These 50 preparations are also subject to import, export and transit controls under the Narcotics Act; (d) The approximately 50 preparations containing substances in Schedule III of the 1971 Convention, as well as all preparations containing substances in Schedule IV of this Convention (about 340), are treated as "exempted preparations" under the Narcotics Act. These preparations, however, may only be dispensed under medical prescription which is in conformity with the provisions of article 9, paragraphs 1 and 2 of the 1971 Convention; (e) Within the meaning of the Narcotics Act, the term "exempted preparations" denotes that no mandatory special prescriptions are required for these preparations but only the normal medical prescriptions. A number of regulations of the Narcotics Act apply to these exempted preparations, including: (i) Licence of manufacture; (ii) Records of dispensing of exempted preparations by the manufacturer to the first acquirer; (iii) Import, export and transit regulations for the exempted preparations containing substances listed in Schedule III (Schedule III B in the Narcotics Act); (iv) Export bans for countries which have prohibited import.


Predictive modeling for classification of positive valence system symptom severity from initial psychiatric evaluation records.
In response to the challenges set forth by the CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing, we describe a framework to automatically classify initial psychiatric evaluation records to one of four positive valence system severities: absent, mild, moderate, or severe. We used a dataset provided by the event organizers to develop a framework comprised of natural language processing (NLP) modules and 3 predictive models (two decision tree models and one Bayesian network model) used in the competition. We also developed two additional predictive models for comparison purpose. To evaluate our framework, we employed a blind test dataset provided by the 2016 CEGS N-GRID. The predictive scores, measured by the macro averaged-inverse normalized mean absolute error score, from the two decision trees and Naïve Bayes models were 82.56%, 82.18%, and 80.56%, respectively. The proposed framework in this paper can potentially be applied to other predictive tasks for processing initial psychiatric evaluation records, such as predicting 30-day psychiatric readmissions.


p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix.
p38 MAPK has been shown to regulate osteoblast differentiation. Inhibition of this kinase with inhibitors or dominant-negative mutant impedes osteoblast differentiation. Yet the molecular mechanism behind this regulation is not well understood. Here we provide evidence that the effect of p38 MAPK on osteoblast differentiation can be mediated by osterix (Osx), a transcription factor necessary and sufficient for osteoblast differentiation. Inhibition of p38 MAPK had minimal effects on differentiation of p53-/- osteoblasts, which had sustained Osx expression. Inhibition of p38 MAPK down-regulated the expression of Osx at both protein and mRNA levels, but not other transcription factors involved in osteoblast differentiation. More importantly, this inhibitory effect could be significantly relieved in osteoblasts overexpressing Osx. Further experiments support that Osx expression is mainly controlled by bone morphogenetic proteins existing in the culture medium, secreted by osteoblasts or provided by serum, and p38 MAPK plays a positive role in bone morphogenetic proteins-induced Osx expression. These findings identify a novel mechanism by which p38 MAPK regulates osteoblast differentiation.


Effect of local heat application during exercise on gene expression related to mitochondrial homeostasis.
The aim of this study was to determine the impact of local muscle heating during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (25 ± 6 yr, 177 ± 8 cm, 78 ± 16 kg, and peak aerobic capacity 45 ± 8 mL·kg-1·min-1) cycled with one leg heated (HOT) and the other serving as a control (CON). Skin and intramuscular temperatures were taken before temperature intervention (Pre), after 30 minutes (Pre30), after exercise (Post) and four hours after exercise (4Post). Muscle biopsies were taken from each leg at Pre and 4Post. Intramuscular temperature increased within HOT (34.4 ± 0.7 °C to 36.1 ± 0.5 °C, p < 0.001) and was higher than CON at Pre30 (34.0 ± 0.7 °C, p < 0.001). However, temperatures at POST were similar (HOT 38.4 ± 0.7 °C, CON 38.3 ± 0.5 °C, p = 0.661). Skin temperature was higher than CON at Post30 (30.3 ± 1.0 °C, p < 0.001) and Post (HOT 34.6 ± 0.9 °C, CON 32.3 ± 1.6 °C, p < 0.001). PGC-1α, VEGF and NRF2 mRNA increased with exercise (p < 0.05) but was not altered with heating (p > 0.05). TFAM increased after exercise with heat application (HOT, p = 0.019) but not with exercise alone (CON, p = 0.422). There was no difference in NRF1, ESRRα, or any of the mitophagy related genes in response to exercise or temperature (p > 0.05). In conclusion, TFAM is enhanced by local heat application during endurance exercise, whereas other genes related to mitochondrial homeostasis are unaffected. Novelty: The main finding of this study is that localized heating increased TFAM mRNA expression. The normal exercise-induced increased PGC-1α gene expression was unaltered by local muscle heating.


Respiratory Complications Among Living Liver Donors: A Single-Center Retrospective Observational Study.
The safety of living liver donors is considered a high priority. In this study, we aimed to highlight the incidence and risk factors of respiratory complications among living liver transplant donors at our institute. We evaluated data of 178 related living liver donors who were seen from January 2014 to December 2018. We recorded significant respiratory complications, such as pulmonary embolism, pleural effusion, pneumothorax, pneumonia, acute lung injury, acute respiratory distress syndrome, and transfusion-related acute lung injury. Complications were noted as clinically evident and/or needing intervention. We also recorded the frequency of nonrespiratory complications and duration of intensive care unit and hospital stays. Ten donors (5.6%) developed significant respiratory complications: 2 (1.1%) had pulmonary embolisms, 3 (1.7%) developed symptomatic pleural effusion that required thoracentesis, and 4 (2.25%) had chest infections. The remaining donor (0.6%) had unexplained respiratory insufficiency. Logistic regression analyses identified age ≥ 35 years and previous surgery as the main risk factors of significant respiratory complications. There were no recorded cases of pneumothorax, acute lung injury, acute respiratory distress syndrome, and transfusion-related acute lung injury. Raw surface collection (14.6%) and biliary leakage (7.9%) were the most frequent nonrespiratory complications. There was no significant difference between patients with and without significant respiratory complications with regard to intensive care unit and hospital stays. Despite the low incidence of significant respiratory complications among our living liver donor cohort, close monitoring and early management are essential to achieve better prognosis, especially in donors older than 35 years or those with previous surgery.


Electron transfer from axial ligand to S1- and S2-excited phosphorus tetraphenylporphyrin.
Photoinduced processes of a series of phosphorus tetraphenylporphyrin (PTPP) derivatives ([PTPP-(NHC6H4X)2]+Cl-, X = OCH3, CH3, H, Cl, CF3, and CN) have been investigated by using femtosecond laser flash photolysis mainly. PTPP with OH as an axial ligand showed S2 fluorescence upon excitation of the Soret band. The S2 fluorescence lifetime was estimated to be 1.5 ps. On the other hand, both S2 and S1 fluorescence bands of PTPP-(NHC6H4X)2 were difficult to observe, indicating the existence of an additional deactivation process such as charge separation (CS). From MO calculation and cyclic voltammetry, PTPP and the axial ligand are expected to act as an acceptor and a donor, respectively, upon excitation of PTPP. CS via the S2 state was confirmed during the femtosecond laser flash photolysis by observing the transient absorption of radical anion of PTPP. Furthermore, CS via the S1 state of PTPP was also observed. The CS rate via the S1 state was faster than that from the S2 state. The free energy dependence of the electron-transfer rates was discussed on the basis of Marcus theory.


H pylori and gastric cancer: shifting the global burden.
Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people (< 10%); and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA+ strains and in persons harboring genetic polymorphism of the IL-1B promoter (-511T/T) and the corresponding IL-1 receptor antagonist (IL-1RN*2). Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA+ strains and IL-1 genetic polymorphisms should be identified and treated.


Peripheral modifications of [Ψ[CH2NH]Tpg4]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics.
Subsequent to binding pocket modifications designed to provide dual d-Ala-d-Ala/d-Ala-d-Lac binding that directly overcome the molecular basis of vancomycin resistance, peripheral structural changes have been explored to improve antimicrobial potency and provide additional synergistic mechanisms of action. A C-terminal peripheral modification, introducing a quaternary ammonium salt, is reported and was found to provide a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of d-Ala-d-Ala/d-Ala-d-Lac binding. This modification, which induces cell wall permeability and is complementary to the glycopeptide inhibition of cell wall synthesis, was found to provide improvements in antimicrobial potency (200-fold) against vancomycin-resistant Enterococci (VRE). Furthermore, it is shown that this type of C-terminal modification may be combined with a second peripheral (4-chlorobiphenyl)methyl (CBP) addition to the vancomycin disaccharide to provide even more potent antimicrobial agents [VRE minimum inhibitory concentration (MIC) = 0.01-0.005 μg/mL] with activity that can be attributed to three independent and synergistic mechanisms of action, only one of which requires d-Ala-d-Ala/d-Ala-d-Lac binding. Finally, it is shown that such peripherally and binding pocket-modified vancomycin analogs display little propensity for acquired resistance by VRE and that their durability against such challenges as well as their antimicrobial potency follow now predictable trends (three > two > one mechanisms of action). Such antibiotics are expected to display durable antimicrobial activity not prone to rapidly acquired clinical resistance.


Dietary exposure to acrylamide from cafeteria foods in Jeddah schools and associated risk assessment.
Acrylamide (AA) is a carcinogenic and genotoxic food contaminant produced at high temperatures in foods that are rich in carbohydrates. Foods sold in schools in Jeddah, Saudi Arabia, are among such carbohydrate-rich foods produced at high cooking temperatures. It is crucial to determine the importance of AA exposure with respect to cafeteria foods and assess the associated risks. The highest mean AA level was measured in chocolate pies (439 µg kg-1 ), followed by custard pies (435 µg kg-1 ) and cheese pies (432 µg kg-1 ). The average and 95th percentile values of AA exposure were 0.51 and 1.17 [µg kg-1 body weight (BW) school day-1 ]. The average exposure significantly decreased with an increase in age, from 0.65 (µg kg-1 BW school day-1 ) in primary school students to 0.37 in secondary school students. Cheese and chocolate pies are the main contributors in AA intake. The contributions of cheese and chocolate pies to the average exposure among primary, middle and secondary school students were 23.1%, 24.7% and 29.4% and 16.9%, 12.1% and 11.9%, respectively. Other products with significant contributions included cheese sandwiches (10.8%, 8.9% and 12.7%), plain cookies (7.7%, 5.6% and 6.7%) and custard pies (7.7%, 4.8% and 8.9%). Other cafeteria products contributed to AA exposure at much lower percentages. The calculated margins of exposure (MOEs) for the average [356 and 614 for both benchmark dose lower confidence limit (BMDL) 0.18 and 0.31 mg kg-1 BW day-1 ] and 95th percentile AA exposure values (154 and 265 for both BMDL 0.18 and 0.31 mg kg-1 BW day-1 ) suggest that there is a health concern with respect to school-aged students. © 2017 Society of Chemical Industry.


Integration mechanisms and hospital efficiency in integrated health care delivery systems.
This study analyzes integration mechanisms that affect system performances measured by indicators of efficiency in integrated delivery systems (IDSs) in the United States. The research question is, do integration mechanisms improve IDSs' efficiency in hospital care? American Hospital Association's Annual Survey (1998) and Dorenfest's Survey on Information Systems in Integrated Healthcare Delivery Systems (1998) were used to conduct the study, using IDS as the unit of analysis. A covariance structure equation model of the effects of system integration mechanisms on IDS performance was formulated and validated by an empirical examination of IDSs. The study sample includes 973 hospital-based integrated health care delivery systems operating in the United States, carried in the list of Dorenfests Survey on Information Systems in Integrated Health care Delivery Systems. The measurement indicators of system integration mechanisms are categorized into six related domains: informatic integration, case management, hybrid physician-hospital integration, forward integration, backward integration, and high tech medical services. The multivariate analysis reveals that integration mechanisms in system operation are positively correlated and positively affect IDSs' efficiency. The six domains of integration mechanisms account for 58.9% of the total variance in hospital performance. The service differentiation strategy such as having more high tech medical services have much stronger influences on efficiency than other integration mechanisms do. The beneficial effects of integration mechanisms have been realized in IDS performance. High efficiency in hospital care can be achieved by employing proper integration strategies in operations.


Health inequalities among British civil servants: the Whitehall II study.
The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality.


HPLC determination of ITF 188 and its metabolite ITF 1078 in urine after intranasal administration of new heparin salt ITF 1300 to dogs.
Heparin salt ITF 1300 in which low molecular weight heparin is salified with a new counterion, di-[3-(N,N-dibutylamino)]propyl carbonate (ITF 188), was selected for the pharmacological development. A specific, sensitive and reproducible HPLC method for the determination of ITF 188 and its alcoholic metabolite ITF 1078 in urine was developed. The method was employed for the study of urinary excretion of the counterion after intranasal administration of ITF 1300 to dogs. The total amount of ITF 188 and ITF 1078 found in urine within 72 hours after the nasal instillation of ITF 1300 accounts for about 5% of the administered dose.


Perioperative management of patients with paroxysmal nocturnal hemoglobinuria.
During the past two decades, we have had the opportunity to study a large number of patients with the rare hemolytic anemia, paroxysmal nocturnal hemoglobinuria. Sixteen surgical procedures have been performed upon ten patients with paroxysmal nocturnal hemoglobinuria. From this experience, we have developed certain recommendations for preoperative evaluation and preparation, intraoperative management and post-operative care. Any proposed surgical procedure for a patient with paroxysmal nocturnal hemoglobinuria should be closely managed by a team consisting of a surgeon, hematologist and anesthesiologist. In the preoperative evaluation, particular attention should be paid to the hematologic, renal and hepatic status. Transfusion requirements, whether precipitated by hemolytic episodes or surgical blood loss, should be met with either washed or perviously frozen erythrocytes, with consideration of the use of dextran for volume replacement. Dextran is the treatment of choice for thrombotic epidsodes. Close attention should be given to avoiding hypoxia and dehydration. Anesthetic agents which may activate complement or may be hepatotoxic are to be avoided.


[Angiotensin I converting enzyme inhibitor enalapril in treatment of progressive chronic nephropathy. An open randomized controlled trial].
In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomised in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least two years or until they needed dialysis. The therapeutic goal, was a blood pressure of 120 ti 140/80 to 90 mmHg. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month, and in the control group, it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (p < 0.05). There was no significant difference in blood pressure between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.


Collateral benefits on other respiratory infections during fighting COVID-19.
Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. A downturn trend of severe influenza, invasive S. pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive S. pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.


Substance P antibody reveals homologous neurons with axon terminals among somata in the crayfish and crab brain.
In the search for particular neurons that stain selectively and can be identified, the cerebral ganglia (brains) of the crayfish Cherax destructor and the crab Leptograpsus variegatus were immunocytochemically treated with a monoclonal antibody raised against substance P. Four large neurons in the cerebral ganglion of the crayfish and crab label selectively with a monoclonal antibody raised against substance P. Two of the large neurons have their cell bodies in the protocerebrum and two in the deutocerebrum in both animals. Each protocerebral cell in both animals projects through the ipsilateral and contralateral olfactory lobes to end among the lateral cell somata of the olfactory lobe and not in the neuropile. Electron micrographs show the presence of synapses within the cell somata area and on the cell somata themselves. Each deutocerebral cell in both animals projects only ipsilaterally and ends within the neuropile of the olfactory lobes. The immunoreactivity to substance P antibody and the shapes and the unique projections of the four cells suggest that they are homologous in the two species. Synaptic connections between axons and cell somata are rare in the arthropods but have been found on the Kenyon cells of the mushroom bodies of Limulus. This raises questions about homologies between the crustacean olfactory lobe and the mushroom bodies of Limulus and insects.


Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities.
Chromosomal translocations involving 11q23 are frequent in infant acute leukemia and give rise to the formation of MLL fusion genes. The mechanism of leukemic transformation by these fusions has been the subject of numerous investigations. However, the dependence of acute leukemia on MLL fusion activity in vivo and the efficacy of targeting this activity to eliminate disease have not been established. We have developed a model for conditional expression of MLL-ENL in hematopoietic progenitor cells, in which expression of the fusion oncogene is turned off by doxycycline. Conditionally immortalized myeloblast cells derived from these progenitors were found to induce leukemia in vivo. Leukemic cells isolated from primary recipient mice were shown to have acquired additional genetic abnormalities and, when transplanted into secondary recipients, induced leukemia with shortened latencies. However, the leukemic cells remained dependent on MLL-ENL expression in vitro and in vivo, and its ablation resulted in regression of established leukemias. This study demonstrates that even genetically complex leukemias can be reversed on inactivation of the initiating MLL fusion and has important implications for the design of novel leukemia therapies.


WAIS performance in young normal, young alcoholic, and elderly normal groups: an evaluation of organicity and mental aging indices.
Investigated the effects of alcoholism and advanced age on Wechsler Adult Intelligence Scale (WAIS) performance and tested the validity of indices of "organicity" and "mental aging" derived from WAIS scores. The WAIS was administered to three groups of 20 males each: young normal (mean age 31 years), young alcoholic (mean age 33 years), and elderly normal (mean age 71 years. In terms of scaled scores, the young normal group was generally superior to the other groups on Verbal and Performance subtests, and the alcoholic and elderly groups resembled each other more on the Verbal than the Performance subtests. In view of an almost 40-year difference in age between the young alcoholic and the elderly normal Ss, similarities in pattern of performance provided some evidence for the hypothesis of "premature aging" in alcholics.


Pyrimidine biosynthetic enzymes of Salmonella typhimurium, repressed specifically by growth in the presence of cytidine.
The repressive effects of exogenous cytidine on growing cells was examined in a specially constructed strain in which the pool sizes of endogenous uridine 5'-diphosphate and uridine 5'-triphosphate cannot be varied by the addition of uracil and/or uridine to the medium. Five enzymes of the pyrimidine biosynthetic pathway and one enzyme of the arginine biosynthetic pathway were assayed from cells grown under a variety of conditions. Cytidine repressed the synthesis of dihydroorotase (encoded by pyrC), dihydroorotate dehydrogenase (encoded by pyrD), and ornithine transcarbamylase (encoded by argI). Moreover, aspartate transcarbamylase (encoded by pyrB) became further derepressed upon cytidine addition, whereas no change occurred in the levels of the last two enzymes (encoded by pyrE and pyrF) of the pyrimidine pathway. Quantitative nucleotide pool determinations have provided evidence that any individual ribo- or deoxyribonucleoside mono-, di-, or triphosphate of cytosine or uracil is not a repressing metabolite for the pyrimidine biosynthetic enzymes. Other nucleotide derivatives or ratios must be considered.


[Identification of occult disseminated tumor cells by recombinant herpes simplex virus expressing GFP (HSV(GFP))].
To develop a novel rapid protocol for the detection of occult disseminated tumor cells by a recombinant herpes simplex virus expressing GFP (HSV(GFP)). Tumor cells of seven cell lines were exposed to HSV(GFP) and then examined for GFP expression by fluorescence microscopy. Various numbers of tumor cells (10, 100, 1000, 10 000) were mixed into 2 ml human whole blood, separated with lymphocytes separation medium, exposed to HSV(GFP), incubated at 37°C for 6 - 24 h and then counted for the number of green cells under the fluorescence microscope. Some clinical samples including peripheral blood, pleural effusion, ascites, spinal fluid from tumor-bearing patients were screened using this protocol in parallel with routine cytological examination. HSV(GFP) was able to infect all 7 tumor cell lines indicating that the HSV(GFP) can be used to detect different types of tumor cells. The detection sensitivity was 10 cancer cells in 2 ml whole blood. In the clinical samples, there were 4/15 positive by routine cytological examination but 11/15 positive by HSV(GFP), indicating a higher sensitivity of this new protocol. Recombinant herpes simplex virus-mediated green fluorescence is a simple and sensitive technique for the identification of occult disseminated cancer cells including circulating tumor cells (CTCs).


Modelling multi-rotor UAVs swarm deployment using virtual pheromones.
In this work, a swarm behaviour for multi-rotor Unmanned Aerial Vehicles (UAVs) deployment will be presented. The main contribution of this behaviour is the use of a virtual device for quantitative sematectonic stigmergy providing more adaptable behaviours in complex environments. It is a fault tolerant highly robust behaviour that does not require prior information of the area to be covered, or to assume the existence of any kind of information signals (GPS, mobile communication networks …), taking into account the specific features of UAVs. This behaviour will be oriented towards emergency tasks. Their main goal will be to cover an area of the environment for later creating an ad-hoc communication network, that can be used to establish communications inside this zone. Although there are several papers on robotic deployment it is more difficult to find applications with UAV systems, mainly because of the existence of various problems that must be overcome including limitations in available sensory and on-board processing capabilities and low flight endurance. In addition, those behaviours designed for UAVs often have significant limitations on their ability to be used in real tasks, because they assume specific features, not easily applicable in a general way. Firstly, in this article the characteristics of the simulation environment will be presented. Secondly, a microscopic model for deployment and creation of ad-hoc networks, that implicitly includes stigmergy features, will be shown. Then, the overall swarm behaviour will be modeled, providing a macroscopic model of this behaviour. This model can accurately predict the number of agents needed to cover an area as well as the time required for the deployment process. An experimental analysis through simulation will be carried out in order to verify our models. In this analysis the influence of both the complexity of the environment and the stigmergy system will be discussed, given the data obtained in the simulation. In addition, the macroscopic and microscopic models will be compared verifying the number of predicted individuals for each state regarding the simulation.


Imaging of hip injuries in dancers.
Dancers are quite prone to injuries in the hip region. Imaging plays a key role in evaluation of the pain resulting from such injuries, as proximity of structures and cross-innervation can result in a clinical dilemma regarding the specific injury, and thus origin of the pain generator. Advanced imaging techniques, including MRI, ultrasound, and multidetector CT, are becoming increasingly important in the workup of injuries in athletes, yet radiographs remain an essential component. This article presents a variety of injuries in the hip and groin region that may be seen in dancers and discusses the utility of basic and advanced imaging modalities.


COVID-19 pandemic and lacrimal practice: Multipronged resumption strategies and getting back on our feet.
The aim of this review was to propose multi-pronged resumption strategies for lacrimal practice in an effort to plan a sustainable recommencement of elective surgeries after we emerge from the peak of COVID-19 pandemic. The strategies for lacrimal practice were classified into 7 subtypes, and each of the blueprints were reassessed based on existing information on resumption strategies of elective surgeries from other specialties in COVID-19 era. The specific needs of lacrimal practice were then added to construct algorithms summarizing the resumption strategies. The basic principle of 'primum non nocere' needs to be followed. The overall proposed plan advocates the transition to a more sustainable health care reality in a world where we would still co-exist with COVID-19. A comprehensive effort involving screening, laboratory testing, appropriate triage, effective personal protection and specific precautionary measures for lacrimal clinics and operating room are needed to be able to safely resume elective surgery when the pandemic peak declines. To predict the timing of the resumption of elective surgeries is quite complex and influenced by several geographic, political and economic factors. It is equally important to remember that COVID-19 crisis is a dynamic situation and constantly evolving, hence the strategies provided are subject to change. Strict adherence to standard COVID-19 guidelines combined with effective testing and personal protection strategies can ensure slow yet smooth and safe return to full lacrimal practice after the COVID-19 pandemic calms down. The local government directives, individual and institutional discretion are advised.


Crystal growth in deeply undercooled Ni50Al50: Signature of the ordering sequence at the interface.
Crystal growth of the intermetallic alloy, Ni50Al50, is investigated by molecular dynamics simulations with two different interatomic potentials. The calculated growth rate can be captured by the Wilson-Frenkel or Broughton-Gilmer-Jackson model at small undercoolings but deviates from the theory at deep undercoolings. Failure of the theory is found to be correlated with the dynamic processes that emerged at the interface, but not apparently with the static interface structure. The chemical segregation of Ni and Al atoms occurs before the geometrical ordering upon crystallization at small undercoolings. In contrast, the geometrical ordering precedes the chemical one at deep undercoolings. These two ordering processes show a collapsed time evolution at the crossover temperature consistent with the onset of the theoretical deviation. We rationalize the delayed chemical segregation behavior by the collective atomic motion, which is characterized by the super-Arrhenius transition of the temperature-dependent diffusivity and structural relaxation time at the crossover point.


Quality of Dying in the Medical Intensive Care Unit: Comparison between Thai Buddhists and Thai Muslims.
Religious belief is an important aspect that influences the life of a patient, especially in Asia. We aim to compare the quality of death in an Intensive Care Unit (ICU) between Buddhists and Muslims from the perspectives of the relatives of the patients and the nurses and physicians. This was a cohort study of critically ill patients who died after admission to a medical ICU in Songklanagarind Hospital in Thailand between 2015 and 2016. We interviewed by telephone the relatives of patients. The nurses and physicians who cared for the patients responded to a self-questionnaire. A total of 112 patients were enrolled in the study. The quality of death and dying-1 scores in Thai Buddhists and Muslim patients rated by the relatives (8 vs. 8, P = 0.55), nurses (8 vs. 8, P = 0.28), and physicians (7 vs. 7, P = 0.74) were not different. The ratings by the nurses correlated with the relatives (rs = 0.41, P < 0.001) but did not correlate with the physicians (rs = 0.15, P = 0.12). Compared with Buddhist patients, Muslim patients were more likely to have documentation in place at the time of the death of do not resuscitate (100% vs. 80.2%, P = 0.02) and withholding and withdrawing life support (100% vs. 80.2%, P = 0.02). There was no difference in the quality of dying and death between Thai Buddhists and Muslims. However, some elements of palliative care were not similar.


[Value of serum miR-17-92 cluster in diagnosis of retinoblastoma].
To investigate the value of serum miR-17-92 cluster in the diagnosis of retinoblastoma (RB). Serum samples were collected from 20 children with RB and 20 healthy controls. Quantitative real-time PCR was used to measure the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was compared between children with different stages of RB and the changes in the expression of miR-17-92 cluster after multimodality therapy were analyzed. The receiver operating characteristic (ROC) curve was used to investigate the value of serum miR-17-92 cluster in the diagnosis of RB. Compared with the healthy controls, the children with RB had significantly higher relative expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P<0.05), and miR-18a showed the greatest increase. There were no significant differences in the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children with RB and healthy controls (P>0.05). There were no significant differences in the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children with early-to-moderate stage of RB and those with advanced stage of RB (P>0.05), but there were significant reductions after multimodality therapy (P<0.05). In the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P, miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively, and miR-18a had the largest AUC, with a sensitivity of 90% and a specificity of 65%. miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with RB, and miR-18a may be used as a new marker for the diagnosis of RB.


Development, Implementation and Evaluation of an M3 Community Health Curriculum.
This paper describes the development, implementation and evaluation of an M3 community health curriculum that responds to recent changes within the health care finance and delivery system. The new curriculum was developed based on AAMC recommendations, LCME requirements, a national review of undergraduate community health curricula, and an internal review of the integration of community health concepts in M3 clerkships. The M3 curriculum teaches: 1) the importance of being a community responsive physician; 2) SES factors that influence health; 3) cultural competency; and 4) the role of physicians as health educators. Student evaluations for the first twelve months of implementation indicate that students are most satisfied with presentations and less satisfied with required readings and a patient interview project. Most students agree that at the completion of the course they understand what it means to be a community-responsive physician, and they have developed skills to help them become more community responsive. Evaluation tools need to be developed to assess if students' behavior has changed due to course participation.


Suboptimal Anticoagulant Management in Japanese Patients with Nonvalvular Atrial Fibrillation Receiving Warfarin for Stroke Prevention.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers). Patients with NVAF receiving oral anticoagulants between February 2013 and June 2015 were identified using a nationwide electronic medical record (EMR) database from 69 hospitals in Japan. Demographics and characteristics of patients, PT-INR, time in therapeutic range (TTR), and frequency in range (FIR) of PT-INR between warfarin maintainers and warfarin switchers were assessed. A total of 1705 patients met inclusion criteria and were examined (1501 warfarin maintainers versus 204 warfarin switchers). CHADS2, CHA2DS2-VASc, and HAS-BLED scores were comparable between groups. However, these scores were significantly higher among warfarin switchers at the time of switching than at the time of warfarin initiation. Furthermore, TTR and FIR of PT-INR were lower in warfarin switchers than in maintainers. Nevertheless, TTR and FIR were below 50% (PT-INR, 1.6-2.6) in both patient groups. In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke.


Spin-Blocking Effect in CO and H2 Binding Reactions to Molybdenocene and Tungstenocene: A Theoretical Study on the Reaction Mechanism via the Minimum Energy Intersystem Crossing Point.
Potential energy profiles and electronic structural interpretation of the CO and H2 binding reactions to molybdenocene and tungstenocene complexes [MCp2] (M = Mo and W, Cp = cycropentadienyl) were studied using density functional theory calculations and ab initio multiconfigurational electronic structure calculations. Experimentally observed slow H2 binding was reasonably explained in terms of the spin-blocking effect. Electronic structural analysis at the minimum-energy intersystem crossing point (MEISCP) revealed that the singly occupied molecular orbital's π-bonding/σ-antibonding character in the M-CO/H2 moiety determines the energy levels of the MEISCP. Analysis of the reaction coordinate showed that the singlet-triplet gap significantly depends on the Cp-M-Cp angle. Therefore, not only the metal-ligand distance but also the Cp-M-Cp angle is an important reaction coordinate to reach the MEISCP, the transition state of H2 binding. The role of spin-orbit coupling is also discussed.


IL-1R Regulates Disease Tolerance and Cachexia in Toxoplasma gondii Infection.
Toxoplasma gondii is an obligate intracellular parasite that establishes life-long infection in a wide range of hosts, including humans and rodents. To establish a chronic infection, pathogens often exploit the trade-off between resistance mechanisms, which promote inflammation and kill microbes, and tolerance mechanisms, which mitigate inflammatory stress. Signaling through the type I IL-1R has recently been shown to control disease tolerance pathways in endotoxemia and Salmonella infection. However, the role of the IL-1 axis in T. gondii infection is unclear. In this study we show that IL-1R-/- mice can control T. gondii burden throughout infection. Compared with wild-type mice, IL-1R-/- mice have more severe liver and adipose tissue pathology during acute infection, consistent with a role in acute disease tolerance. Surprisingly, IL-1R-/- mice had better long-term survival than wild-type mice during chronic infection. This was due to the ability of IL-1R-/- mice to recover from cachexia, an immune-metabolic disease of muscle wasting that impairs fitness of wild-type mice. Together, our data indicate a role for IL-1R as a regulator of host homeostasis and point to cachexia as a cost of long-term reliance on IL-1-mediated tolerance mechanisms.


Association-dissociation equilibrium of loop structures in single-chain folding into a toroidal condensate.
Recently, it has been revealed that a semiflexible polyelectrolyte chain can form a partially folded conformation stably as a result of an electrostatic interaction. Interestingly, there are cases where the appearance of this structure requires a high-salt condition of a solution. In order to solve this problem, we consider the double equilibrium of the formation of loops and their aggregation on a single-chain polymer. First, an aggregate with a typical surface energy is examined as a test case. The basic nature of the folding transition is discussed with regard to the chemical potential of loop structures. Next, we consider a charged aggregate for which the interior is completely neutralized by counter ions. In this model, a partially folded chain appears with a high-salt condition. Based on this model, screened interactions between surface charges and a toroidal shape of a folded structure are considered essential factors bihind this phenomenon.


Acquired aortopulmonary fistula.
An acquired aortopulmonary artery fistula is rare. We describe a case with an aortic arch aneurysm communicating with the main pulmonary artery. The diagnosis was made on the basis of transthoracic echocardiography and confirmed by transesophageal echocardiography. A post-mortem examination revealed the complete anatomy of the aneurysm and the aortopulmonary communication.


Synthesis and evaluation of molecular rotors with large and bulky tert-butyldiphenylsilyloxy-substituted trityl stators.
The search for voluminous stators that may accommodate large rotator units and speed rotational dynamics in the solid state led us to investigate a simple and efficient method for the synthesis of molecular rotors with tert-butyldiphenylsilyl-protected (TBDPS) triphenylmethyl stators. Additionally, solid state characterization of these systems with two-, four-, and six-TBDPS groups provided us with a description of their crystallinity and thermal stability. Among them, molecular rotor 7c with the largest and most symmetric stator resulting from six peripheral silyl groups showed the best tendency to crystallize, and the study of its isotopologue 7c-d(4) by solid state (2)H NMR revealed a 2-fold motion of the 1,4-diethynylphenylene-d(4) rotator in the kHz regime.


[Acute complications in sickle cell disease].
Sickle cell disease is an inherited disease characterised by the presence of an abnormal haemoglobin. Sickle cell disease can be complicated by acute vaso-occlusive crisis, which are the major clinical problem prompting admission to hospital and the major cause of death. It mainly manifests by osteo-articular pain and acute chest syndrome and can be complicated by multi-organ failure. The main treatment of severe acute vaso-occlusive crisis is based on transfusion.


Belfast. Working with girls.
Belfast has many of the social problems common in major British cities: soaring unemployment, teenage crime, joy-riding, high levels of teenage pregnancy, drug and alcohol abuse. In Belfast, these problems are further complicated by the political and religious divide which affects virtually every area of society. Maura Thompson reports on a unique health visitor-led initiative working with teenage girls.


Transjugular approach as a challenging access in PTMC: case report.
Advantage of transjugular approach in percutaneous mitral commissurotomy (PTMC) of severe mitral stenotic patients with venous drainage anomalies was obtained as the authors' first case experience. This approach should be considered whenever difficulties are encountered in the femoral approach in PTMC case before valve surgery.


Neurological symptoms in type A aortic dissections.
Aortic dissection typically presents with severe chest or back pain. Neurological symptoms may occur because of occlusion of supplying vessels or general hypotension. Especially in pain-free dissections diagnosis can be difficult and delayed. The purpose of this study is to analyze the association between type A aortic dissection and neurological symptoms. Clinical records of 102 consecutive patients with aortic dissection (63% male, median age 58 years) over 7.5 years were analyzed for medical history, preoperative clinical characteristics, treatment and outcome with main emphasis on neurological symptoms. Thirty patients showed initial neurological symptoms (29%). Only two-thirds of them reported chest pain, and most patients without initial neurological symptoms experienced pain (94%). Neurological symptoms were attributable to ischemic stroke (16%), spinal cord ischemia (1%), ischemic neuropathy (11%), and hypoxic encephalopathy (2%). Other frequent symptoms were syncopes (6%) and seizures (3%). In half of the patients, neurological symptoms were transient. Postoperatively, neurological symptoms were found in 48% of all patients encompassing ischemic stroke (14%), spinal cord ischemia (4%), ischemic neuropathy (3%), hypoxic encephalopathy (8%), nerve compression (7%), and postoperative delirium (15%). Overall mortality was 23% and did not significantly differ between patients with and without initial neurological symptoms or complications. Aortic dissections might be missed in patients with neurological symptoms but without pain. Neurological findings in elderly hypertensive patients with asymmetrical pulses or cardiac murmur suggest dissection. Especially in patients considered for thrombolytic therapy in acute stroke further diagnostics is essential. Neurological symptoms are not necessarily associated with increased mortality.


Treatment of localized gingival recessions. Part IV. Results after three years.
Twenty-six localized recessions treated with either a lateral sliding flap or a coronally repositioned flap procedure more than 3 years ago were reevaluated. Biometric measurements on the recipient and the donor of control teeth included: a) cementoenamel junction, gingival margin; b) sulcus depth; c) gingival margin, mucogingival line. These recordings were statistically compared to those taken 180 days after the surgical procedures were performed. Pairwise t tests were used to determine whether there were any changes between the 180 days and the 3 years postoperative control with either procedure. A two sample t test was run to see whether the changes obtained with the two procedures differed from each other. No significant changes were found. The values for gingival recession, sulcus depth and width of keratinized gingiva remained stable for both techniques throughout the observation period.


Low erythropoietin production in familial amyloidosis TTR V30M is not related with renal congophilic amyloid deposition. A clinicopathologic study of twelve cases.
Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid polyneuropathy (FAP). Low EPO production can be observed before clinical disease. Renal amyloidosis is observed in FAP, mainly in the medulla. Renal manifestations correlate with glomerular and vascular involvement, but not with tubulointerstitial deposition. To evaluate the potential role of renal amyloid deposits in the genesis of the EPO defect in FAP, we analyzed the renal biopsies of 12 patients (5 males, 7 females, aged from 29 to 54 years) with a clinical evolution varying from 3 to 12 (mean 5.4 +/- 2.8) years. Formalin-fixed, paraffin-embedded sections of renal biopsies were stained by Congo red. Amyloid deposits were assessed by a semiquantitative method based on the percentage of amyloid deposition in each renal structure. Hemoglobin, creatinine, urea, EPO and proteinuria were concomitantly evaluated and correlated with the pathological findings. Renal amyloid deposits were observed in all biopsies analyzed, independently of the neuropathy score. Low serum EPO levels were not related with either the amount of amyloid deposition or the renal clinical manifestations. Impairment of EPO production in FAP is not directly related to renal amyloid deposits and more studies are needed to clarify this question.


Novel water insoluble lipoparticulates for gene delivery.
The objective was to design and prepare water insoluble lipoparticulates (ISLPs) for efficient gene delivery to lung tissue. Nona[(ethylenimine)-co-[(2-aminoethyl)-N-choleseteryl-oxycarbonyl-ethylenimine]] (NEACE-T) was synthesized in both its free-base and chloride salt-forms using linear polyethylenimine (PEI, Mw 423) as a headgroup and cholesteryl chloroformate as a hydrophobic lipid anchor resulting in a T-shaped lipononamer. Semitelechelic N(alpha)-cholesteryloxycarbonyl nona(ethylenimine) (st-NCNEI-L) was synthesized similarly resulting in a linear lipononamer. As confirmed by 1H-NMR, the site of conjugation was either a primary amine resulting in a linear configuration (st-NCNEI-L) or a secondary amine resulting in a T-shaped configuration (NEACE-T). ISLPs were prepared by combining NEACE-T or st-NCNEI-L with a co-lipid, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) at 1/1, 1/2, and 2/1 molar ratios and the lipoparticulates were hydrated and filtered. ISLP/p2CMVmIL-12 complexes were characterized for particle size, zeta potential, surface morphology, cytotoxicity, and in vitro transfection efficiency. Transgene expression was dependent on the site of cholesterol conjugation, lipononamer:colipid molar ratio, and ISLP/ p2CMVmIL-12 charge ratios. ISLP/p2CMVmIL-12 complexes were nontoxic to murine colon adenocarcinoma (CT-26) cells at 9/1 (+/-) or lower, had a mean particle size of 330-400 nm while the zeta potential varied from 36-39 mV. Atomic force microscopy (AFM) showed the surface morphology to be that of an oblate spheroid with a size comparable to that determined by dynamic light scattering. ISLP/ p2CMVmIL-12 complexes prepared using free-base NEACE-T:DOPE (1/2) at charge ratios of 3/1 and 5/1 (+/-) provided the highest levels of transgene expression, 18 times more than the levels provided by the salt-form. Secreted levels of mIL-12 p70 were 75 times higher for ISLP/p2CMVmIL-12 complexes than naked p2CMVmIL-12 and nearly 4 times higher than PEI 25 kDa/p2CMVmIL-12 complexes. The transfection efficiency of the ISLPs was dependent on the site of cholesterol conjugation, amount of colipid, and charge ratio. The highest levels of transgene expression were provided by NEACE-T:DOPE (1/2)/p2CMVmIL-12 at a 3/1 (+/-) charge ratio.


Mechanisms of dopamine and dobutamine interference in biochemical tests that use peroxide and peroxidase to generate chromophore.
Dopamine and dobutamine have recently been shown to produce a negative interference in several biochemical tests that use peroxide and peroxidase to generate a chromophore. To define the chemical mechanism of this interference, we examined the effects of dopamine and dobutamine in various peroxidase-based biochemical tests. Dopamine interfered stoichiometrically with peroxidase-based tests that use 4-aminophenazone to form chromophore but interfered little in those that use other compounds to generate chromophore. Dopamine reacts with 4-aminophenazone in the presence of peroxide and peroxidase to form a novel quinone-imine dye, with a smaller absorptivity than the chromophore formed in the absence of dopamine. The smaller absorptivity of this novel chromophore results in negative interference by reducing the total absorbance at the wavelength used to measure analyte. In contrast, dobutamine interfered stoichiometrically with all peroxidase-based tests studied, regardless of whether 4-aminophenazone was used to form the chromophore. Dobutamine was rapidly oxidized by peroxide in the presence of peroxidase, thus depleting the peroxide necessary to generate chromophore. Dopamine and dobutamine demonstrate two distinct general mechanisms of interference in peroxidase-based biochemical tests.


Theileria annulata and T. parva infect and transform different bovine mononuclear cells.
Bovine peripheral blood mononuclear cells (PBMC) were labelled with monoclonal antibodies recognizing bovine MHC class II, sIgM, monocyte, T-helper and T-cytotoxic cell phenotypes. They were sorted into positive and negative populations with a fluorescence-activated cell sorter (FACS). The cell populations were infected in vitro with sporozoites of either Theileria annulata or T. parva, and the degree of infection and transformation determined. The results showed that despite the many similarities between these two parasites, they infected different cells of the immune system. T. annulata preferentially infected MHC class II-positive cells but did not infect T cells. Monocytes were infected very efficiently by T. annulata but were uninfectable with T. parva. B cells were infected much more efficiently by T. annulata than T. parva. Cell lines derived from infections with T. annulata were analysed phenotypically. Virtually all reactivity was lost for the anti-sIgM and the anti-monocyte monoclonal antibodies post-infection and no T-cell markers were detected.


Morphologic Features Suggestive of Endometriosis in Nondiagnostic Peritoneal Biopsies.
Endometriosis is a common disorder that causes significant morbidity from dysmenorrhea, pelvic pain, and subfertility. Establishment of a definitive diagnosis has important therapeutic implications; however, only approximately 50% of biopsies of laparoscopically suspicious areas provide a diagnosis of endometriosis. Histologic criteria for diagnosis require the presence of endometrial glands or endometrial-type stroma. We hypothesize that other frequently present, but nondiagnostic, histologic features of endometriosis suggest its presence in patients with nondiagnostic peritoneal biopsies. We performed a retrospective clinicopathologic study of morphologic and immunohistochemical features that may improve the histologic diagnosis of endometriosis on laparoscopic peritoneal biopsies. We compared diagnostic (n=88) and nondiagnostic (n=54) peritoneal biopsies from pathologically confirmed endometriosis cases with negative peritoneal biopsies (n=84) from early-stage gynecologic cancer cases. Statistical analysis utilized the Fisher exact test. Multiple morphologic features were significantly increased in nondiagnostic biopsies from patients with endometriosis in comparison with those from negative controls, including foamy macrophages (P=0.0001) and submesothelial stromal clusters (SSCs) (P=0.0008). SSCs ranged from subtle aggregates of spindle cells to nodules of whorled spindle cells with small vessels and extravasated red blood cells resembling stromal endometriosis. Immunohistochemical studies confirmed that ER and CD10-positive SSCs were present in a greater proportion of both nondiagnostic and diagnostic peritoneal biopsies and at a greater number of lesions per biopsy. The overall histologic detection rate of peritoneal biopsies for endometriosis was 62.0%, and inclusion of SSCs with or without foamy macrophages in the diagnostic criteria appreciably increased this rate to between 72.5% and 76.8%. We describe SSCs, which appear to be an early or less developed form of stromal endometriosis, and, when included in the diagnostic criteria, improve the histologic detection rate of endometriosis in peritoneal biopsies.


Qualitative study exploring factors affecting the implementation of a vocational rehabilitation intervention in the UK major trauma pathway.
This study aimed to: (1) understand the context for delivering a trauma vocational rehabilitation (VR) intervention; (2) identify potential barriers and enablers to the implementation of a VR intervention post-trauma. Qualitative study. Data were collected in person or via phone using different methods: 38 semistructured interviews, 11 informal 'walk-through care pathways' interviews, 5 focus groups (n=25), 5 codesign workshops (n=43). Data were thematically analysed using the framework approach, informed by the Consolidated Framework for Implementation Research. Stakeholders recruited across five UK major trauma networks. A variety of stakeholders were recruited (n=117) including trauma survivors, rehabilitation physicians, therapists, psychologists, trauma coordinators and general practitioners. We recruited 32 service users (trauma survivors or carers) and 85 service providers. There were several issues associated with implementing a trauma VR intervention including: culture within healthcare/employing organisations; extent to which healthcare systems were networked with other organisations; poor transition between different organisations; failure to recognise VR as a priority; external policies and funding. Some barriers were typical implementation issues (eg, funding, policies, openness to change). This study further highlighted the challenges associated with implementing a complex intervention like VR (eg, inadequate networking/communication, poor service provision, perceived VR priority). Our intervention was developed to overcome these barriers through adapting a therapist training package, and by providing early contact with patient/employer, a psychological component alongside occupational therapy, case coordination/central point of contact, and support crossing sector boundaries (eg, between health/employment/welfare). Findings informed the implementation of our VR intervention within the complex trauma pathway. Although we understand how to embed it within this context, the success of its implementation needs to be measured as part of a process evaluation in a future trial.


A functional variant in the 3'-UTR of angiopoietin-1 might reduce stroke risk by interfering with the binding efficiency of microRNA 211.
Angiopoietin-1 is a vascular strengthening factor during vascular development and a protective factor for pathological vascular inflammation and leakage. Brain vascular leaking and inflammation are two important pathological processes of stroke; therefore, we hypothesized that variants of the microRNA-binding site in angiopoietin-1 would affect its expression and confer a risk of stroke. To test our hypothesis, a predicted microRNA-binding site was found in the 3'-UTR of angiopoietin-1 using bioinformatics; variant rs2507800 was identified to be located in the miR-211-binding site of angiopoietin-1. Secondly, the effects of the identified variant on angiopoietin-1 translation were assessed using a luciferase reporter assay and ELISA. We found that the A allele of rs2507800 suppressed angiopoietin-1 translation by facilitating miR-211 binding, but not the T allele. Subjects carrying the TT genotype had higher plasma angiopoietin-1 levels than those with the A allele. Finally, the association of the variant with stroke was tested in 438 stroke patients and 890 controls, and replicated in an independent population of 1791 stroke patients and 1843 controls. The TT genotype resulted in a significant reduction in overall stroke risk {OR, 0.51 [95% confidence interval (CI), 0.36-0.74], P = 0.0003}, ischemic stroke [OR, 0.56 (95% CI, 0.36-0.85), P = 0.007] and hemorrhagic stroke [OR, 0.46 (95% CI, 0.26-0.80), P = 0.007]. These results were confirmed in an independent study. Our results provide evidence that the TT genotype (rs2507800) in the 3'-UTR of angiopoietin-1 might reduce the risk of stroke by interfering with miR-211 binding.


Alveolar bone biology in extrusion splint technique.
The moment after the tooth avulsion, blood supply to the pulp is interrupted and the periodontal ligament cells are exposed to injury from the external environment. Complete healing is possible if the tooth can be immediately replanted and favorable environment is created .A case of report of intruded and mobile upper left central incisor due to Road Traffic Accident of a twenty-two-year-old patient is presented here. In which, intentional extrusion traumatized tooth and then flexible acrylic wire splinting was done to stabilize it. Previously there was no periapical bone support but with nine months maintenance follow up bone has shown a significant improvement towards healing.


The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy.
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 4% and desperately needs novel effective therapeutics. Integrin αvβ6 has been linked with poor prognosis in cancer but its potential as a target in PDAC remains unclear. We report that transcriptional expression analysis revealed that high levels of β6 mRNA correlated strongly with significantly poorer survival (n = 491 cases, p = 3.17 × 10-8 ). In two separate cohorts, we showed that over 80% of PDACs expressed αvβ6 protein and that paired metastases retained αvβ6 expression. In vitro, integrin αvβ6 promoted PDAC cell growth, survival, migration, and invasion. Treatment of both αvβ6-positive human PDAC xenografts and transgenic mice bearing αvβ6-positive PDAC with the αvβ6 blocking antibody 264RAD, combined with gemcitabine, significantly reduced tumour growth (p < 0.0001) and increased survival (log-rank test, p < 0.05). Antibody therapy was associated with suppression of tumour cell activity (suppression of pErk growth signals, increased apoptosis seen as activated caspase-3) and suppression of the pro-tumourigenic microenvironment (suppression of TGFβ signalling, fewer αSMA-positive myofibroblasts, decreased blood vessel density). These data show that αvβ6 promotes PDAC growth through both tumour cell and tumour microenvironment mechanisms and represents a valuable target for PDAC therapy. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Verb aspect and the activation of event knowledge.
The authors show that verb aspect influences the activation of event knowledge with 4 novel results. First, common locations of events (e.g., arena) are primed following verbs with imperfective aspect (e.g., was skating) but not verbs with perfect aspect (e.g., had skated). Second, people generate more locative prepositional phrases as completions to sentence fragments with imperfective than those with perfect aspect. Third, the amplitude of the N400 component to location nouns varies as a function of aspect and typicality, being smallest for imperfective sentences with highly expected locations and largest for imperfective sentences with less expected locations. Fourth, the amplitude of a sustained frontal negativity spanning prepositional phrases is larger following perfect than following imperfective aspect. Taken together, these findings suggest a dynamic interplay between event knowledge and the linguistic stream.


Little hope for the polyploid endemic Pyrenean Larkspur (Delphinium montanum): Evidences from population genomics and Ecological Niche Modeling.
Species endemic to restricted geographical ranges represent a particular conservation issue, be it for their heritage interest. In a context of global change, this is particularly the case for plants which belong to high-mountain ecosystems and, because of their ecological requirements, are doomed to survive or disappear on their "sky islands". The Pyrenean Larkspur (Delphinium montanum, Ranunculaceae) is endemic to the Eastern part of the Pyrenees (France and Spain). It is now only observable at a dozen of localities and some populations show signs of decline, such as a recurrent lack of flowering. Implementing population genomics approach (e.g., RAD-seq like) is particularly useful to understand genomic patterns of diversity and differentiation in order to provide recommendations in term of conservation. However, it remains challenging for species such as D. montanum that are autotetraploid with a large genome size (1C-value >10 pg) as most methods currently available were developed for diploid species. A Bayesian framework able to call genotypes with uncertainty allowed us to assess genetic diversity and population structure in this system. Our results show evidence for inbreeding (mean G IS = 0.361) within all the populations and substantial population structure (mean G ST = 0.403) at the metapopulation level. In addition to a lack of connectivity between populations, spatial projections of Ecological Niche Modeling (ENM) analyses under different climatic scenarios predict a dramatic decrease of suitable habitat for D. montanum in the future. Based on these results, we discuss the relevance and feasibility of different conservation measures.


A differential subcellular localization of two copper transporters from the COPT family suggests distinct roles in copper homeostasis in Physcomitrium patens.
The moss Physcomitrium (Physcomitrella) patens is a bryophyte that provides genetic information about the adaptation to the life on land by early Embryophytes and is a reference organism for comparative evolutionary studies in plants. Copper is an essential micronutrient for every living organism, its transport across the plasma membrane is achieved by the copper transport protein family COPT/CTR. Two genes related to the COPT family were identified in Physcomitrella patens, PpaCOPT1 and PpaCOPT2. Homology modelling of both proteins showed the presence of three putative transmembrane domains (TMD) and the Mx3M motif, constituting a potential Cu + selectivity filter present in other members of this family. Functional characterization of PpaCOPT1 and PpaCOPT2 in the yeast mutant ctr1Δctr3Δ restored its growth on medium with non-fermentable carbon sources at micromolar Cu concentrations, providing support that these two moss proteins function as high affinity Cu + transporters. Localization of PpaCOPT1 and PpaCOPT2 in yeast cells was observed at the tonoplast and plasma membrane, respectively. The heterologous expression of PpaCOPT2 in tobacco epidermal cells co-localized with the plasma membrane marker. Finally, only PpaCOPT1 was expressed in seven-day old protonema and was influenced by extracellular copper levels. This evidence suggests different roles of PpaCOPT1 and PpaCOPT2 in copper homeostasis in Physcomitrella patens.


Mild Hyperthermia-Enhanced Enzyme-Mediated Tumor Cell Chemodynamic Therapy.
The heterogeneity and diversity of tumors seriously attenuate the curative outcome of single treatment modes. Combined therapy has been demonstrated to be a promising candidate to enhance therapeutic efficacy compared with monotherapy. As an emerging therapeutic strategy, chemodynamic therapy (CDT) has drawn extensive attention in recent years. However, the therapeutic efficiency of CDT is still unsatisfying because the level of intracellular hydrogen peroxide (H2O2) restricts the production of hydroxyl radicals (•OH). In this study, a novel curative strategy which combines glucose oxidase (GOx)-mediated Fe3O4-based Fenton reaction and multiwalled carbon nanotube (MWNT)-produced mild hyperthermia enhancer is proposed, achieving a mild hyperthermia-enhanced enzyme-mediated tumor cell CDT. GOx can catalyze the conversion of glucose into gluconic acid and H2O2, which can elevate acidity in the tumor microenvironment and boost Fe3O4-based Fenton reaction, producing a myriad of •OH to induce tumor cell death. Furthermore, by using the theory that a temperature rise expedites the kinetics of a chemical reaction, producing a higher reaction rate and more resultants per unit time, we integrate MWNTs in this therapy system, which generate mild hyperthermia so as to accelerate the Fenton reaction for increasing the productivity of •OH. Therefore, an amplified CDT can be realized. The therapy platform, mild hyperthermia-enhanced GOx-mediated CDT, provides an effective treatment for cancer and takes CDT a step further.


Draft Genome Sequence of a Necrotoxigenic Escherichia coli Isolate.
Here, we present the draft genome sequence of a necrotoxigenic Escherichia coli strain isolated from a patient following a very rapidly evolving, lethal necrotizing fasciitis.


Apparent encoding of sequential context in rat medial prefrontal cortex is accounted for by behavioral variability.
Simple sequences can be represented via asymmetrically linked neural assemblies, provided that the elements of the sequence are unique. When elements repeat, however (e.g., A-B-C-B-A), the same element belongs to two separate "sequential contexts," and a more complex encoding mechanism is required. To enable correct sequence performance, some neural structure must provide a disambiguating signal that differentiates the two sequential contexts (i.e., B as an element of "A-B" as opposed to "C-B"). The disambiguating signal may derive from a form of working memory, or, in some cases, a simple timing mechanism may suffice. To investigate the possible role of medial prefrontal cortex in complex sequence encoding, rats were trained on a spatial sequence containing two adjacent repeated segments (e.g., A-B-C-D-B-C-E). The double-repeat procedure minimized behavioral differences in the second leg (C) of the repeat subsequence that arise in the first leg (B) because of differences in the entry point (e.g., A-B vs D-B). Far more cells were context sensitive along the first leg than along the second (36 vs 9%), and most of the differences were accounted for by systematic variations in the rat's trajectory, which were much larger along the first leg. There is thus little evidence for sequential context-discriminative activity in the medial prefrontal cortex that cannot plausibly be accounted for by context-dependent behavior. The finding that the rodent medial prefrontal cortex is highly sensitive to sensory-behavioral variables raises doubts about previous experiments that purport to show working memory-related activity in this region.


Reduction of vesicular acetylcholine transporter mRNA in the rat septum following lead exposure.
We have previously observed that maternal exposure to lead (Pb) results in a reduction of levels of mRNA coding for cholineacetyltransferase (ChAT) in the septum of developing rat without affecting the dams. Here we report that Pb similarly affects the expression of vesicular acetylcholine transporter (VAChT) mRNA in the rat septum. In close agreement with the time course of ChAT mRNA expression, septal VAChT mRNA levels increased from 30% at postnatal day 7 to 78% and 100% of adult levels at days 14 and 21, respectively. Maternal exposure to 0.2% lead acetate in drinking water from gestational day 16 resulted in an approximately 30% reduction of VAChT in 7 and 21-day-old rat pups without affecting VAChT mRNA levels in the dams. These results indicate a developmental stage-dependent interference by Pb with ChAT/VAChT gene expression in the rat septum.


[Care-research interface in nursing].
In this study, the authors have as a goal to discuss the care-investigation interface in the caring practice of Nursing in the hospital ambit, starting from their professional experiences. The bases of the discussion is the career/cared being. We surpass care as the object of research and the importance of investigation for the improvement of care quality. Interdisciplinarity is pointed out as one of the possible resources for the construction of integral care and of a therapeutical action that exceeds the biological, in a perspective of co-participation, as well as the need of promoting and stimulating the accomplishment of investigations in the units of hospital care. The meaning of the investigation about care goes beyond its internality, requiring technical competence, ethical compromise and coherence among the different areas of knowledge which involves it. We enlighten the need of overcoming the dichotomies of caring/investigating, researching while caring, and caring while researching. We stress out the importance of creating research groups in Universities; the stimulus to the accomplishment of graduation courses with leave-out time from work; the availability of financial resources; and the incentive to subscribe periodicals and to acquire books.


A study of streptokinase therapy in acute pulmonary embolism.
A study of Streptokinase therapy in major pulmonary emboli is reported and attention is drawn to some of the factors which can influence the results of this as yet controversial therapy.


Electroretinographic changes induced by organophosphorus pesticides in rats.
Electroretinographic changes induced by organophosphorus pesticides (OPs) were studied in rats. Male Wistar rats were intraperitoneally injected with fenthion, chlorpyrifos, fenitrothion, dichlorvos or chlorfenvinphos at doses of 0.01 mmol/kg and/or 0.05 mmol/kg. The electroretinogram (ERG) was recorded at 5 hours and 2 days after the administration, and brain and retinochoroid cholinesterase (ChE) activities was assayed at 3 days after the injections. The brain and retinochoroid ChE activities were reduced in rats treated with the OPs. Notably, the reduction of ChE activities by fenthion, chlorpyrifos and dichlorvos were similar. The administration of OPs induced a change in the ERG, characterized by alteration of the amplitudes of a- and b-waves. Nevertheless the ChE activities in the brain and retinochoroid were inhibited by all of the OPs, the OPs affected the amplitude of ERG differently. Fenthion and chlorpyrifos decreased the amplitudes; dichlorvos and chlorfenvinphos increased; and fenitrothion transiently decreased at 5 hours but increased 2 days after the injection. These results indicate that a factor or factors other than inhibition of ChE activities contributes to the alteration of ERG induced by OPs.


Glutathione dimerization-based plasmonic nanoswitch for biodetection of reactive oxygen and nitrogen species.
Reactive oxygen and nitrogen species (ROS and RNS) are continuously produced in the cellular systems and are controlled by several antioxidant mechanisms. Here, we developed a straightforward, sensitive, and quantitative assay for the colorimetric and spectroscopic detection of various ROS and RNS such as H2O2, ·OH, (-)OCl, NO·, and O2(-) using glutathione-modified gold nanoparticles (GSH-AuNPs). A basic principle here is that the GSHs on the AuNP surface can be readily detached via the formation of glutathione disulfides upon the addition of ROS and RNS, and destabilized particles can aggregate to generate the plasmonic couplings between plasmonic AuNPs that trigger the red shift in UV-vis spectrum and solution color change. For nonradical species such as H2O2, this process can be more efficiently achieved by converting them into radical species via the Fenton reaction. Using this strategy, we were able to rapidly and quantitatively distinguish among cancerous and normal cells based on ROS and RNS production.


Clinical and Radiographic Predictors for Worsened Clinical Outcomes After Hip Arthroscopic Labral Preservation and Capsular Closure in Developmental Dysplasia of the Hip.
Patients with developmental dysplasia of the hip (DDH) have a greater risk of acetabular labral tearing and joint instability, which predispose them to developing osteoarthritis. The arthroscopic management of DDH, however, remains controversial. Specific clinical characteristics and radiographic parameters correlate with and predict a worsened clinical outcome after hip arthroscopic surgery for DDH. Case control study; Level of evidence, 3. Of patients with DDH who underwent an arthroscopic procedure between March 2009 and June 2011, there were 28 hips in 28 patients (6 male and 22 female) that met the inclusion criteria. The mean patient age was 28.4 years. Clinical and radiographic follow-up evaluations up to a minimum of 2 years after surgery were performed for all patients. Failure of the procedure was defined as conversion to subsequent surgery or having a Tönnis osteoarthritis grade of 2 and modified Harris Hip Score (mHHS) that remained <85, and success was defined as patients who did not need subsequent surgery and had an mHHS >85. Univariate analysis and Cox hazard proportional analysis were performed on the 2 subpopulations. There were 9 patients in the failure group (including 3 hips with T nnis grade 2) and 19 patients in the success group. In 22 of 28 patients, the mean mHHS significantly improved from 61.6 ± 18.8 (range, 12.0-85.0) preoperatively to 94.3 ± 7.0 (range, 73.7-100.0) at final follow-up, and the mean Non-Arthritic Hip Score (NAHS) improved from 56.2 ± 13.9 (range, 35.0-81.3) preoperatively to 92.7 ± 9.5 (range, 65.0-100.0) at final follow-up (P < .001, Wilcoxon signed-rank test). Univariate analysis showed that a broken Shenton line was significantly more prevalent in the failure group compared with the success group (8/9 [89%] vs 3/19 [16%] patients, respectively; P < .001). High-grade cartilage delamination (Multicenter Arthroscopy of the Hip Outcomes Research Network [MAHORN] grades 3-5) was significantly higher in the failure group than in the success group (8/9 [89%] vs 3/19 [16%] patients, respectively; P < .001). The median femoral neck-shaft (FNS) angle in the failure group was significantly higher than that in the success group (139° vs 134°, respectively; P = .01). Further, Cox hazard proportional analysis of the failure group showed that the predictors for a poor clinical outcome were the presence of a broken Shenton line, FNS angle >140°, center-edge (CE) angle <19°, body mass index (BMI) >23 kg/m(2), acetabular cartilage damage (MAHORN grades 3-5), and cartilage damage of the femoral head (International Cartilage Repair Society grades 2-4). The most important predictors for a poor clinical outcome at the time of surgery were a broken Shenton line and an FNS angle >140°. Patients with a broken Shenton line, FNS angle >140°, CE angle <19°, or BMI >23 kg/m(2) at the time of surgery are not good candidates for the arthroscopic management of DDH.


Results of the first 1000 radioreceptorassays for the determination of human chorionic gonadotropin: a new, rapid, reliable, and sensitive pregnancy test.
One thousand radioreceptorassays for human chorionic gonadotropin (hCG) for the diagnosis of pregnancy were analyzed under eight categories. The high sensitivity (50 pg/ml) and specificity, coupled with performance time of the assay (1 hour), provided a new modality for the early diagnosis and management of normal and abnormal pregnancy in the first trimester. The radioreceptorassay becomes positive 1 week after conception. In the normal pregnancy this assay has been 100% correct at the time of the first missed menses. All ectopic pregnancies demonstrated positive tests, and no false negatives occurred. On the other hand, a negative assay excluded ectopic pregnancy.


The effects of an educational intervention on antipsychotic-induced weight gain.
To assess the effect of an educational intervention on antipsychotic-induced weight gain among patients with schizophrenia. Quasi-experimental. Seventy patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder entered this 6-month study condicted in the United States. All participants began receiving olanzapine treatment when they entered the study. The patients were then randomly assigned to an intervention group or a standard care group. Over the next 4-months, the intervention group participated in weekly psychoeducation classes focused on nutrition, exercise, and living a healthy lifestyle. Patients were followed for an additional 2 months to assess weight change. A statistically significant difference in weight change between the two groups was observed post-treatment and at endpoint. At endpoint, the mean weight change of the intervention group was -.06 pounds, while the mean weight change in the standard care group was 9.57 pounds. In both groups, men gained significantly more weight than did women. The results indicate that a structured educational intervention might have a positive effect on antipsychotic-induced weight gain among patients with schizophrenia.


Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer.
Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLC patients. CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform; Rarecells) from 106 NSCLC patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor cells and WBCs. CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥1 PD-L1-positive CTCs and 11 patients (15%) showed ≥1% PD-L1-positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity = 100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥1% PD-L1-positive immune infiltrates in tumor tissue and 39 patients (53%) showed ≥1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells (progression-free and overall survival), similar to the effects of PD-L1 expression in matched-patient tumors. These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.


Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma.
Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found in lung cancer, leading to the alternation of the immunomodulatory function in tumorigenesis. However, the mechanism of transcriptional regulation of IRF-3 in lung cancer has not been extensively studied. Here, we investigated the characterization of IRF-3 promoter and found that GATA-1 bound to a specific domain of IRF-3 promoter in vitro and in vivo. We found elevated IRF-3 and decreased GATA-1 gene expression in lung adenocarcinoma in Oncomine database. Additionally, higher IRF-3 gene expression was observed in human lung adenocarcinoma, accompanied by aberrant GATA-1 protein expression. We further analyzed the relationship of GATA-1 and IRF-3 expression in lung adenocarcinoma cell lines and found that inhibition of GATA-1 by siRNA increased the promoter activity, mRNA and protein levels of IRF-3, while over-expression of GATA-1 down-regulated IRF-3 gene expression. Taken together, we conclude that reduced GATA-1 could be responsible for the upregulation of IRF-3 in lung adenocarcinoma cells through binding with a specific domain of IRF-3 promoter.


A new and improved method for 3'-end labelling DNA using [alpha-32P]ddATP.
We have synthesised dideoxyadenosine-5'-[alpha-32P]triphosphate [( alpha-32P] ddATP ) at a specific activity of 3000 Ci/mmol and directly compared it with cordycepin-5'-[alpha-32P]triphosphate [( alpha-32P] KTP ) as a means to 3'-end label DNA. The [alpha-32P] ddATP was found to be three to five times more efficient than [alpha-32P] KTP . Blunt and 3'-protruding ends were labelled more efficiently with [alpha-32P] ddATP using terminal transferase than were the 5'-ends with [gamma-32P]ATP using polynucleotide kinase by standard methods. This improvement in efficiency of labelling DNA and the simplicity of the method allows 3'-end labelling of DNA to become a realistic alternative to 5'-end labelling. We have also compared [alpha-32P] ddATP - and [alpha-32P] KTP -labelled DNA in Maxam and Gilbert sequencing procedures and find that both give equally good results.