Does familiarity or conflict account for performance in the word-stem completion task? Evidence from behavioural and event-related-potential data.
The conflict monitoring theory (CMT) assumes that word-stems associated with several completions should lead to crosstalk and conflict due to underdetermined responding situation (Botvinick et al. in Psychol Rev 108(3):624-652, 2001). In contrast, the Multiple-Read-Out-Model (MROM) of Jacobs and Grainger (J Exp Psychol 20(6): 1311-1334, 1994) predicts a high level of general lexical activity (GLA) for word-stems with many completions, indicating a higher stimulus familiarity because these stems are more probable to be read. We compared word-stems with several completions against word-stems with one possible completion while measuring response times and electrophysiological recordings. Slowest response times and a distinct FN400 component, which has previously been related to the concept of familiarity (Curran in Memory Cogn 28(6):923-938, 2000), were apparent for word-stems that could only be associated with a single response. These findings support the claims of the MROM. Furthermore, the lack of the N2-component for word-stems with several completions continues to challenge the EEG-extension of the CMT (Yeung et al. in Psychol Rev 111(4):2004).


Effect of packaging during storage time on retail display microbial population of beef strip loins from two different production systems.
Two studies were conducted to evaluate the influence of packaging during storage of strip loins (to simulate export shipment) from steers fattened on intensive grazing systems (Uruguay; UR) or on a high-concentrate diet (United States; US) on retail display life microbial growth. Four or 3 different packaging treatments were applied to UR and US strip loin roasts or steaks during 35 d of storage; treatments were applied 7 d following slaughter. After 35 d of storage, the samples were evaluated during simulated retail display for up to 6 d. In Exp. 1, the treatments were vacuum packaging (VP), low-oxygen modified atmosphere packaging (MAP) with N and CO (MAP/CO), low-oxygen MAP with N plus CO and CO, and VP plus an application of peroxyacetic acid (VP/PAA). In Exp. 2, block 1, the treatments were VP, MAP/CO, and VP with ethyl--lauroyl--arginate HCl incorporated into the film as an antimicrobial agent (VP/AM). In Exp. 2, block 2, the treatments were VP, MAP/CO, MAP/CO, and VP/AM. For retail display, VP treatments were sliced and repackaged in PVC overwrap, and MAP treatments were actually PVC overwrap trays that were removed from a master bag with the prescribed gas treatment. Regardless of production system and packaging treatment, mesophilic and psychrotrophic counts of 6.9 to 7.8 and 6.7 to 7.7 log10 CFU/cm, respectively, were obtained at the end of retail display, except for US samples in Exp. 2 (5.5 to 6.3 log CFU/cm). No differences ( > 0.05) were detected for spp. counts among packaging treatments in US steaks at the end of the display time in Exp.1, whereas, for UR steaks, both MAP treatments had lower ( < 0.05) spp. counts than VP treatments. spp. counts were lower ( < 0.05) in the MAP/CO treatment than in the other 3 treatments in US samples on d 6 of retail display for Exp. 2. At the end of display time and for Exp. 1, US steaks under MAP/CO had greater ( < 0.05) lactic acid bacteria (LAB) counts than samples in both VP treatments; no differences ( > 0.05) among packaging were detected for UR steaks. Both MAP and VP/AM treatments in the US samples for Exp. 2 had lower ( < 0.05) LAB counts on d 6 of display than the VP treatment, but no differences ( > 0.05) were found among packaging treatments for the UR samples. To maximize shelf life (storage and display life) of exported fresh beef, it is critical to minimize bacterial populations during processing and storage.


Space allowance during commercial long distance transport of cattle in North America.
The objective of the present work was to study space allowance in cattle during commercial long haul transport (≥400 km; n = 6,152 journeys). Surveys, delivered to livestock transport carriers, gathered information on the number, BW, and distribution of cattle by trailer compartment as well as the characteristics of the transport vehicles used. Space allowance (SA; m(2)/animal), allometric coefficient (k = SA / BW(0.6667)), and the percentage of deviation from recommended SA (DRSA; %) in the Canadian Codes of Practice were calculated for each compartment of the trailers. All quad-axle (77%) and tri-axle (23%) cattle trailers were reported with 5 compartments (nose, deck, belly, back, and doghouse). Sixty percent of all animals were carried in the middle compartments (deck and belly), 30% in the rear (back and doghouse), and 10% in the front or nose. Approximately 30% of the journeys required that the cattle be redistributed at the Canada-USA border to comply with different axle weight regulations, and most journeys moved them between the deck and the doghouse. Total loaded weight increased and the number of animals decreased with increasing BW of the animals. space allowance, k-value, and DRSA were least for calves and feeders compared with fat and cull cattle (p < 0.01). Both total loaded weight and number of animals increased with the number of axles in the trailer, being greatest in quad-axle trailers pulled by push tractors, which were most frequently used. Space allowance (k-value) was least in vehicles with greater number of axles and transporting the lightest cattle (i.e., quad-axles trailers transporting calves and feeders). Space allowance, k-value, and variability among journeys were least in the middle compartments (belly and deck), followed by the back, then doghouse and nose compartments of the trailers showing the largest values (p < 0.05). Many factors contributed to the variability in SA such as body size (smaller animals are placed more densely), compartment of the trailer (greater density in belly and deck), and number of axles on the vehicle (greater density with more axles). The present study provides a framework to assess and understand factors affecting SA during commercial long distance transport of cattle. This information is vital in assessing the consequences of changing industry standards, guidelines, recommended values, laws and regulations on animal welfare, the industry, and economics.


A Treatable Genetic Disease Caused by CAD Mutation.
Type 50 early infantile epileptic encephalopathy, or EIEE-50 for short, is an autosomal recessive genetic disorder resulting from CAD mutations. So far, little has been reported on the disease. In this article, we will discuss the case of a male infant who is 8 years and 5 months old. A whole-exome sequencing of the boy revealed CAD compound heterozygous mutations. He suffered from global developmental delay and regression, refractory epilepsy, and anemia. After his diagnosis, we used uridine treatment and gained encouraging results. In this article, we will analyze our case studies in the context of the literature, so as to improve pediatricians' understanding of the disease.


[The compensatory light for car plate recognition].
In the intelligent traffic system, the automatic recognition system of the car plate is an important development field. This system must satisfy the requirement of all-day long inspection. In the course of inspection, the lack of natural light(such as at night, in rainy day...) could be a problem, that is to say there could be backlighting problem, and this problem can be solved by using compensatory light. By now, the high-power floodlight has been adopted. Because of its own characteristics of the floodlight, the satisfied result cannot be obtained. In the present thesis, how to select the right light is analyzed, including car lights' spectra and visual response, and so on. The results of the practices are very satisfied.


OsNRAMP3 is a vascular bundles-specific manganese transporter that is responsible for manganese distribution in rice.
Manganese (Mn) is an essential trace element for plants. Recently, the genes responsible for uptake of Mn in plants were identified in Arabidopsis and rice. However, the mechanism of Mn distribution in plants has not been clarified. In the present study we identified a natural resistance-associated macrophage protein (NRAMP) family gene in rice, OsNRAMP3, involved in Mn distribution. OsNRAMP3 encodes a plasma membrane-localized protein and was specifically expressed in vascular bundles, especially in phloem cells. Yeast complementation assay showed that OsNRAMP3 is a functional Mn-influx transporter. When OsNRAMP3 was absent, rice plants showed high sensitivity to Mn deficiency. Serious necrosis appeared on young leaves and root tips of the OsNRAMP3 knockout line cultivated under low Mn conditions, and high Mn supplies could rescue this phenotype. However, the necrotic young leaves of the knockout line possessed similar levels of Mn to the wild type, suggesting that the necrotic appearance was caused by disturbed distribution of Mn but not a general Mn shortage. Additionally, compared with wild type, leaf Mn content in osnramp3 plants was mostly in older leaves. We conclude that OsNRAMP3 is a vascular bundle-localized Mn-influx transporter involved in Mn distribution and contributes to remobilization of Mn from old to young leaves.


Rhamnolipid produced by Pseudomonas aeruginosa USM-AR2 facilitates crude oil distillation.
A biosurfactant-producing and hydrocarbon-utilizing bacterium, Pseudomonas aeruginosa USM-AR2, was used to assist conventional distillation. Batch cultivation in a bioreactor gave a biomass of 9.4 g L(-1) and rhamnolipid concentration of 2.4 g L(-1) achieved after 72 h. Biosurfactant activity (rhamnolipid) was detected by the orcinol assay, emulsification index and drop collapse test. Pretreatment of crude oil TK-1 and AG-2 with a culture of P. aeruginosa USM-AR2 that contains rhamnolipid was proven to facilitate the distillation process by reducing the duration without reducing the quality of petroleum distillate. It showed a potential in reducing the duration of the distillation process, with at least 2- to 3-fold decreases in distillation time. This is supported by GC-MS analysis of the distillate where there was no difference between compounds detected in distillate obtained from treated or untreated crude oil. Calorimetric tests showed the calorie value of the distillate remained the same with or without treatment. These two factors confirmed that the quality of the distillate was not compromised and the incubation process by the microbial culture did not over-degrade the oil. The rhamnolipid produced by this culture was the main factor that enhanced the distillation performance, which is related to the emulsification of hydrocarbon chains in the crude oil. This biotreatment may play an important role to improve the existing conventional refinery and distillation process. Reducing the distillation times by pretreating the crude oil with a natural biosynthetic product translates to energy and cost savings in producing petroleum products.


Toward a Graded Psycholexical Space Mapping Model: Sublexical and Lexical Representations in Chinese Character Reading Development.
Following a review of contemporary models of word-level processing for reading and their limitations, we propose a new hypothetical model of Chinese character reading, namely, the graded lexical space mapping model that characterizes how sublexical radicals and lexical information are involved in Chinese character reading development. The underlying assumption of this model is that Chinese character recognition is a process of competitive mappings of phonology, semantics, and orthography in both lexical and sublexical systems, operating as functions of statistical properties of print input based on the individual's specific level of reading. This model leads to several testable predictions concerning how the quasiregularity and continuity of Chinese-specific radicals are organized in memory for both child and adult readers at different developmental stages of reading.


Accumulation, Persistence, and Effects of Indospicine Residues in Camels Fed Indigofera Plant.
Indospicine (l-2-amino-6-amidinohexanoic acid) is a natural hepatotoxin found in all parts of some Indigofera plants such as Indigofera linnaei and Indigofera spicata. Several studies have documented a susceptibility to this hepatotoxin in different species of animals, including cattle, sheep, dogs, and rats, which are associated with mild to severe liver disease after prolonged ingestion. However, there is little published data on the effects of this hepatotoxin in camels, even though Indigofera plants are known to be palatable to camels in central Australia. The secondary poisoning of dogs after prolonged dietary exposure to residual indospicine in camel muscle has raised additional food safety concerns. In this study, a feeding experiment was conducted to investigate the in vivo accumulation, excretion, distribution, and histopathological effects of dietary indospicine on camels. Six young camels (2-4 years old), weighing 270-390 kg, were fed daily a roughage diet consisting of Rhodes grass hay and lucerne chaff, supplemented with Indigofera and steam-flaked barley. Indigofera (I. spicata) was offered at 597 mg DM/kg body weight (bw)/day, designed to deliver 337 μg indospicine/kg bw/day, and fed for a period of 32 days. Blood and muscle biopsies were collected over the period of the study. Concentrations of indospicine in the plasma and muscle biopsy samples were quantitated by validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The highest concentrations in plasma (1.01 mg/L) and muscle (2.63 mg/kg fresh weight (fw)) were found at necropsy (day 33). Other tissues were also collected at necropsy, and analysis showed ubiquitous distribution of indospicine, with the highest indospicine accumulation detected in the pancreas (4.86 ± 0.56 mg/kg fw) and liver (3.60 ± 1.34 mg/kg fw), followed by the muscle, heart, and kidney. Histopathological examination of liver tissue showed multiple small foci of predominantly mononuclear inflammatory cells. After cessation of Indigofera intake, indospicine present in plasma in the remaining three camels had a longer terminal elimination half-life (18.6 days) than muscle (15.9 days), and both demonstrated monoexponential decreases.


Resting and Postexercise Heart Rate Detection From Fingertip and Facial Photoplethysmography Using a Smartphone Camera: A Validation Study.
Modern smartphones allow measurement of heart rate (HR) by detecting pulsatile photoplethysmographic (PPG) signals with built-in cameras from the fingertips or the face, without physical contact, by extracting subtle beat-to-beat variations of skin color. The objective of our study was to evaluate the accuracy of HR measurements at rest and after exercise using a smartphone-based PPG detection app. A total of 40 healthy participants (20 men; mean age 24.7, SD 5.2 years; von Luschan skin color range 14-27) underwent treadmill exercise using the Bruce protocol. We recorded simultaneous PPG signals for each participant by having them (1) facing the front camera and (2) placing their index fingertip over an iPhone's back camera. We analyzed the PPG signals from the Cardiio-Heart Rate Monitor + 7 Minute Workout (Cardiio) smartphone app for HR measurements compared with a continuous 12-lead electrocardiogram (ECG) as the reference. Recordings of 20 seconds' duration each were acquired at rest, and immediately after moderate- (50%-70% maximum HR) and vigorous- (70%-85% maximum HR) intensity exercise, and repeated successively until return to resting HR. We used Bland-Altman plots to examine agreement between ECG and PPG-estimated HR. The accuracy criterion was root mean square error (RMSE) ≤5 beats/min or ≤10%, whichever was greater, according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation EC-13 standard. We analyzed a total of 631 fingertip and 626 facial PPG measurements. Fingertip PPG-estimated HRs were strongly correlated with resting ECG HR (r=.997, RMSE=1.03 beats/min or 1.40%), postmoderate-intensity exercise (r=.994, RMSE=2.15 beats/min or 2.53%), and postvigorous-intensity exercise HR (r=.995, RMSE=2.01 beats/min or 1.93%). The correlation of facial PPG-estimated HR was stronger with resting ECG HR (r=.997, RMSE=1.02 beats/min or 1.44%) than with postmoderate-intensity exercise (r=.982, RMSE=3.68 beats/min or 4.11%) or with postvigorous-intensity exercise (r=.980, RMSE=3.84 beats/min or 3.73%). Bland-Altman plots showed better agreement between ECG and fingertip PPG-estimated HR than between ECG and facial PPG-estimated HR. We found that HR detection by the Cardiio smartphone app was accurate at rest and after moderate- and vigorous-intensity exercise in a healthy young adult sample. Contact-free facial PPG detection is more convenient but is less accurate than finger PPG due to body motion after exercise.


Truebeam Radiosurgery for the Treatment of Trigeminal Neuralgia: Preliminary Results at a Single Institution.
Radiosurgery is now an established method of satisfactory pain control in patients with trigeminal neuralgia (TN). The Varian Truebeam STx (Varian Medical Systems, Palo Alto, CA) linear accelerator (LINAC) system is an arc-based, frameless stereotactic radiosurgery system used for the treatment of TN. To our knowledge, there has been only one published series of patient histories that documents the use of a frameless LINAC system for the treatment of TN. We describe the treatment parameters, patient outcomes, and complications associated with the treatment of TN. All patients treated with the Truebeam system for TN between 2012 and 2015, with at least a six-month follow-up, were identified. A dose of 90 Gy was delivered to the isocenter using a 0.5 cm diameter cone. The cisternal segment of the trigeminal nerve was placed at the location of the LINAC isocenter using an ExacTrac™ (Brainlab, Munich, Germany) image guidance system. The radiosurgical dose, Barrow Neurologic Institute pain score (BNI PS), symptom recurrence, magnetic resonance imaging (MRI) radiographic changes, and other complications, including Barrow Neurologic Institute facial numbness score (BNI FN), were analyzed. A total of 18 patients-15 women and 3 men-with a mean age of 58 years (median: 59 years; range: 22-84 years) were treated at our institution. Fourteen patients (78%) had a BNI PS of IIIb or better, which was considered successful treatment. Twelve patients had excellent (BNI PS I) pain relief and two patients had good (BNI PS II-IIIB; recurrence after one year) pain relief. The pain of four patients recurred after a mean of 10 months. Truebeam radiosurgery can provide effective and safe treatment for patients suffering from TN. The efficacy appears similar to other frame- and frameless-based systems.


Isolated parenchymal splenic metastasis in epithelial ovarian cancer.
Metastatic parenchymal splenic disease in patients with ovarian cancer is unusual. It is most commonly seen in the presence of large-volume upper abdominal disease when parenchymal involvement occurs by surface extension. A patient with isolated parenchymal splenic metastasis and no peritoneal disease in the abdomen at primary surgery is described.


Liver impaction technique improves technical success rate of guidewire insertion during EUS-guided hepaticogastrostomy (with video).
If the guidewire becomes kinked by the needle, guidewire manipulation may be difficult, and can cause complications such as guidewire shearing or injury during endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). To overcome this matter, we have previously described a technical tip for preventing guidewire injury, termed 'liver impaction technique'. However, its technical feasibility has been not reported in the setting of a large patient cohort. The aim of study was to evaluate the clinical usefulness of the liver impaction technique during EUS-HGS. Retrospective, single-center study. This retrospective study included consecutive patients who underwent EUS-HGS between April 2018 and September 2022. The primary outcome of this study was the technical success rate of guidewire insertion using the liver impaction technique. A total of 166 patients were enrolled in this study. Initial successful guidewire insertion without using liver impaction technique was obtained in 108 patients (65.1%). Among 58 patients in whom guidewire insertion failed initially, guidewire advancement into the periphery of the bile duct was observed in 32 patients (55.2%) and into a non-interest bile duct branch was observed in 26 patients (44.8%). Liver impaction technique contributed to increasing the technical success rate of guidewire insertion from 65.1% to 95.8%. Overall, adverse events were observed in 12 patients (7.2%; bile peritonitis n = 9, cholangitis n = 3), and these adverse events were Grade I. Among patients who underwent liver impaction technique (n = 58), adverse events were observed in two patients (3.4%; bile peritonitis). Also, guidewire sharing was not observed in any patients during liver impaction technique. In conclusion, the liver impaction technique may be helpful during EUS-HGS to obtain successful guidewire insertion into the biliary tract of interest.


[The New European Questionnaire for Assessment of Quality of Life of Patients With Ischemic Heart Disease: HeartQoL].
Quality of life (QL) of patients with ischemic heart disease (IHD) is a combination symptoms of the disease, physical state, emotional status, and social-laboring functioning. Until recently there were no universal questionnaire allowing to perform comparative analysis of QL of patients with effort angina (EF), survivors of myocardial infarction (MI) and chronic heart failure (CHF). Therefore, European Association of Cardiovascular Prevention and Rehabilitation conducted a study with the aim of developing universal questionnaire for assessment of QL in patients with IHD - HeartQol. The study enrolled 6384 patients with angina, MI, or CHF across 22 countries (315 in Russia). Patients completed a battery of questionnaires and Mokken scaling analysis was used to identify most important guestions for assessment of QL questions to be included into the HeartQoL questionnaire.


Cardiac morbidity and mortality related to orthotopic liver transplantation.
This article briefly discusses the cardiac status of liver transplant recipients and their preoperative cardiac evaluation. It describes in detail perioperative and early and late postoperative complications as well as the cardiac problems associated with immunosuppression. The preoperative cardiovascular status of patients is important in determining how they cope with the stresses imposed by liver transplantation. Minor early cardiac events are common and may influence longer term cardiac morbidity. Immunosuppressive therapy may have short term effects but is likely to adversely affect long term cardiac risk.


[The "new carcinogens' directive" from the European Union: new tasks waiting for us, new opportunities in front of us (and that we need not to waste) in Italy].
The new EU directive on the protection of workers from the risks related to exposure to carcinogens and mutagens at work, issued on December 2017, will be integrated inside the Member States' national laws not later than 17th January 2020. The new directive brings in force new binding occupational exposure limit values (BOELVs) for several agents, some of great importance such as hard wood dusts, a set of hexavalent chromium compounds and crystalline silica dust; for some cases, the entry into force of the new limits is delayed in time. The new directive clarifies that the limit values are established considering factors distinct from health necessities too. The Member States are bound to adopt national limit values not avexceeding the corresponding EU ones, but are empowered to lower them. It is essential that the control of the actual respect of the limit values results not only from the application of theoretic previsional models, but is entrusted mainly to high quality exposure measurements and to estimates directly derived from measurements, on the base of publicly available JEMs. The specific health surveillance to be provided to any person both exposed and previously exposed to carcinogens at work should not be limited to proper oncological screening actions, but should include programs for biological monitoring of both exposures and related pre-neoplastic effects, every time any of these is possible and useful. A fair mapping of the exposures to carcinogens and mutagens at work and a systematical registration of cases of cancers attributable to occupational exposures will be placed side to side.


Association of IL1R1 Coding Variant With Plasma-Level Soluble ST2 and Risk of Aortic Dissection.
Objective: Aortic dissection (AD) is characterized by an acute onset, rapid progress, and high mortality. Levels of soluble ST2 (sST2) on presentation are elevated in patients with acute AD, which can be used to discriminate AD patients from patients with chest pain. sST2 concentrations were found to be highly heritable in the general population. The aim of this study was to investigate the associations of variations in ST2-related gene expression with sST2 concentrations and AD risk. Methods: This case-control study involving a total of 2,277 participants were conducted, including 435 AD patients and age- and sex-matched 435 controls in the discovery stage, and 464 patients and 943 controls in the validation stage. Eight ST2-related genes were selected by systematic review. Tag single-nucleotide polymorphisms (SNPs) were screened out from the Chinese population of the 1,000 Genomes Database. Twenty-one ST2-related SNPs were genotyped, and plasma sST2 concentrations were measured. Results: In the discovery stage, rs13019803 located in IL1R1 was significantly associated with AD after Bonferroni correction (p = 0.0009) and was correlated with circulating sST2 levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) CI: 0.002 - 0.357] but not in type B. Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 (95% CI: 0.055-0.227) for per C allele]. Odds ratio of rs13019803 on the risk of AAD is 1.67 (95% CI: 1.33-2.09). Conclusions: The IL1R1 SNP rs13019803C is associated with higher sST2 levels and increased risk of AAD.


High density lipoprotein influences the response of rat adrenocortical cells to gamma 3-melanotropin.
Gamma 3-melanotropin (gamma 3-MSH) exhibits a marked dose-dependent synergism with ACTH1-24 on corticosterone production by cells isolated from the inner zones of the rat adrenal cortex. This phenomenon is demonstrated to best advantage when donor animals are killed after stress or pretreatment with ACTH. If adrenal cells are prepared from quiescent or hypophysectomized animals, the inclusion of high density lipoprotein (HDL) in the incubation medium is required for a significant gamma 3-MSH response. Dibutyryl cAMP can successfully substitute for ACTH1-24 in these incubations but rat low density lipoprotein does not reproduce the HDL effect. These data are consistent with our in vivo studies demonstrating that gamma 3-MSH potentiation is a product of increased cholesterol mobilization within the adrenal cortex and suggest that in the rat, a significant source of the cholesteryl ester pool which is responsive to gamma 3-MSH may derive from circulating HDL.


Heat-induced electrical signals affect cytoplasmic and apoplastic pH as well as photosynthesis during propagation through the maize leaf.
Combining measurements of electric potential and pH with such of chlorophyll fluorescence and leaf gas exchange showed heat stimulation to evoke an electrical signal (propagation speed: 3-5 mm s(-1)) that travelled through the leaf while reducing the net CO(2) uptake rate and the photochemical quantum yield of both photosystems (PS). Two-dimensional imaging analysis of the chlorophyll fluorescence signal of PS II revealed that the yield reduction spread basipetally via the veins through the leaf at a speed of 1.6 +/- 0.3 mm s(-1) while the propagation speed in the intervein region was c. 50 times slower. Propagation of the signal through the veins was confirmed because PS I, which is present in the bundle sheath cells around the leaf vessels, was affected first. Hence, spreading of the signal along the veins represents a path with higher travelling speed than within the intervein region of the leaf lamina. Upon the electrical signal, cytoplasmic pH decreased transiently from 7.0 to 6.4, while apoplastic pH increased transiently from 4.5 to 5.2. Moreover, photochemical quantum yield of isolated chloroplasts was strongly affected by pH changes in the surrounding medium, indicating a putative direct influence of electrical signalling via changes of cytosolic pH on leaf photosynthesis.


[Prevention -- a topic in social-psychiatric research?].
Currently, substantial effort is made to establish prevention as one of the main parts of the German health care system. In this context we investigated the current role of prevention in social-psychiatric research. We analysed original papers published in the journal Psychiatrische Praxis in the years 2003-2004 by computer-aided full text analysis. 16.5 % of the studies mentioned prevention, in one fourth of these, prevention was the main topic. Subject of these papers were suicide prevention in psychiatric patients, relapse prevention in mentally ill offenders, and prevention of acute confusional state after hip surgery. Most of the work was dedicated to tertiary prevention, followed by secondary prevention. Two papers mentioned primary preventive aspects and only one report was dedicated to primary prevention as a main topic. Although early diagnosis and intervention as well as rehabilitation of mental disorders are main topics of social psychiatry, only few reports relate explicitly to prevention. The role of social psychiatry in primary prevention has to be defined.


Prediction of ProteinProtein Interaction Pocket Using L-Shaped PLS Approach and Its Visualizations by Generative Topographic Mapping.
Proteinprotein interaction (PPI) pockets in a hostguest protein system were predicted using an L-shaped partial least squares (LPLS) method. LPLS is an extension of standard PLS regression, where, in addition to response vector y and regressor matrix X, an extra data matrix Z is constructed which summarizes the background information on X. The regressor matrix X is a similarity matrix of Tanimoto coefficients of the paired fingerprints of pockets, while the background information Z constitutes eleven physico-chemical and geometrical parameters for describing a pocket. The Boolean response vector y specifies whether each pocket is PPI or non-PPI (indicated by 1 and 0, respectively). Constructing two LPLS models, we successfully predicted the PPI pockets of two protein clusters. Clusters 1 and 2 comprised the X-ray crystal structures of protein-peptide complexes and protein-protein complexes, respectively. From the loading plots derived from each model, we could speculate the geometrical constraints of the PPI pockets. These two models are exclusively unique and it was validated by the cross-prediction simulations. The PPI pockets of cluster 1 were projected onto 2D maps by generative topographic mapping (GTM) and the molecular lipophilic potentials (MLP). Among three examples, the MLP distributions were highly similar because the specimens shared the same p53 guest peptides. Contribution to the Autumn School of Chemoinformatics in Nara, Japan, November 27-28, 2013.


A concise synthesis of pyrazole analogues of combretastatin A1 as potent anti-tubulin agents.
Combretastatin A1 (CA1) binds to the β-subunit at the colchicine binding site of tubulin and inhibits polymerization. As such, it is both an antitumor agent and a vascular disrupting agent. It has been shown to be at least tenfold more potent than combretastatin A4 (CA4) in terms of vascular shutdown, which correlates with its metabolism to reactive ortho-quinone species that are assumed to be directly cytotoxic in tumor cells. A series of 3,4-diarylpyrazoles were concisely synthesized, one of which, 3-methoxy-6-[4-(3,4,5-trimethoxyphenyl)-1H-pyrazol-3-yl]benzene-1,2-diol (27), proved to be a cytotoxic anti-tubulin agent with low nanomolar potency. We also report that combretastatins, including CA1, CA4, and 27, are effective against mesothelioma cell lines and therefore have significant clinical promise. Metabolism experiments demonstrate that 27 retains the ability to form ortho-quinone species, while the pyrazole ring shows high metabolic stability, suggesting that this compound might result in better pharmacokinetic profiles than CA1, with similar pharmacodynamic properties and clinical potential.


Refractory pneumothorax secondary to lung cancer in a patient with idiopathic pulmonary fibrosis.
An unusual case of refractory pneumothorax secondary to lung cancer in a 69-year-old man patient with idiopathic pulmonary fibrosis (IPF) is described. High-pressure suction applied through chest tube did not resolve the large right pneumothorax. Acute exacerbation of IPF has also appeared. Respiratory state worsened acutely, and the patient died on the fifth hospital day. In the present case, the large right pneumothorax was initially thought to be associated with IPF because pneumothorax is common in patients with IPF. However, postmortem microscopic examination revealed that the refractory pneumothorax was secondary to perforation of the pleura due to a necrotic peripheral lung cancer.


NHC-Au(i) complexes bearing trispyrazolyl borate (Tp) ligands: efficient platforms for bimetallic species.
Treatment of NHC-AuCl (NHC = IPr and IMes) complexes with equimolar amounts of KTpR2 (R = Me, H) salts in tetrahydrofuran produces in high yields the heteroleptic complexes 3-6 with the general formula NHC-Au-TpR2. As the TpR ligand in complexes 3-6 features a k1-N type coordination toward the gold(i) center, the subsequent addition of group 10 and 11 metal precursors (NiII, PtII, CuII) results in the isolation of heterobimetallic Au/M complexes supported by TpR platforms. All new metal complexes have been fully characterized by elemental analysis and NMR spectroscopy, and in the case of 3, 4 and 6 by X-ray crystallography.


Theoretical study of graded-index fiber for beam quality improvement and SRS suppression.
A confined-doped graded-index fiber model was established with reference to Nufern's 42C ytterbium-doped fiber. The core NA of the fiber is ∼0.06; the doping/core/cladding diameter is 30/42/250 µm; and the gain ion doping distribution is double parabolic. Based on a forward tandem-pumped amplifier structure, the numerical simulation was carried out on the physics characters of the fiber model. The fourth-order Runge-Kutta method was used to solve the boundary value problem during the numerical simulation. The differences between the graded-index fiber (GIF) and the step-index fiber (SIF) were studied theoretically, and the results illuminated that the beam quality of the GIF was better than the SIF. The stimulated Raman scattering (SRS) power in the GIF was lower than that in the SIF. These results show that the GIF has great potential for increasing the laser output power while maintaining good beam quality and can provide theoretical guidance and reference to experimental research of the high-power fiber laser.


IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells.
Regulatory T (T(reg)) cells play a key role in the maintenance of the immune system homeostasis. T(reg) cells can be generated in the periphery under control of TGF-beta, a cytokine involved in the negative control of the immune system. However, TGF-beta cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF-beta emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF-beta-dependent expression of FoxP3, the master regulator of T(reg) cell commitment, and the induction of suppressive capacity in naive CD4(+) T cells, while promoting the differentiation of Th17 cells. In vivo, CD4(+) naive T cells activated in the presence of TGF-beta and IL-21 failed to suppress colitis while inducing an inflammatory response characterized by high levels of IL-17 and RORgammat, the transcription factor expressed by Th17 cells. Therefore, IL-21 emerges as a key modulator of TGF-beta signaling, leading to the reciprocal differentiation of T(reg) and Th17 cells.


Reactivation of and primary infection with human herpesvirus 8 among solid-organ transplant recipients.
Human herpesvirus 8 (HHV-8) is the causal agent of all forms of Kaposi's sarcoma, including the iatrogenic form that presents in solid-organ transplant recipients. A longitudinal study of HHV-8 seropositivity was conducted among a cohort consisting of children and adult solid-organ transplant recipients. Antibodies to HHV-8 lytic proteins were detected by an indirect immunofluorescence assay in serum samples of 100 transplant recipients. HHV-8 seropositivity increased significantly, from 5.3% before transplantation to 15.8% after transplantation (P<.01). Seropositivity was not related to the age of the patient or the type of organ transplanted. HHV-8 seroconversion occurred in both children and adult recipients. None of the seroconversion events was related to the source of the donor organ. These findings suggest that HHV-8 infection is not uncommon among both adult and children transplant recipients and that viral infection may be acquired from an outside source other than the transplanted organ.


Hepatitis B virus DNA in unusual serological profiles of hepatitis B surface antigen-positive sera.
On the basis of a seroepidemiological survey of hepatitis B virus (HBV) infection conducted on 6208 random serum samples from four provinces of Thailand, we found 19 of 246 (7.7%) hepatitis B surface antigen (HBsAg)-positive samples with unusual serological constellations of HBV infection. Ten samples tested positive for HBsAg, anti-HBc (anti-hepatitis B core antibody), and anti-HBs (anti-hepatitis B surface antibody) markers (group I), 3 specimens were HBsAg and anti-HBs positive without detectable anti-HBc (group II), and the remaining 6 specimens showed only HBsAg (group III). In group I, 7 of 10 HBsAg-positive sera could be confirmed by HBsAg neutralization, yielding positive results for all samples. None of the group II sera were available in sufficient amounts for confirmation. In group III, five of six sera were confirmed by HBsAg neutralization, with four showing a positive reaction. HBV DNA was detected in 7 of 10 (70%) specimens in group I, in 1 of 3 (33.3%) specimens in group II, and in 3 of 6 (50%) specimens in group III. On the basis of HBsAg neutralization, HBV DNA was found in five of seven (71.4%) HBsAg-positive samples in group I and in three of four (75%) HBsAg-positive samples in group III, whereas the one confirmed HBsAg-negative sample in group III also remained negative for HBV DNA. Amino acid sequences were compared with those specifying the "a" determinant of the wild-type virus, particularly focusing on HBV-S protein variations between positions 110 and 160. Among 11 HBV DNA-positive sera, G145A was detected in 2 samples in group I, with the remaining samples identical to the wild-type virus. These unusual serological profiles may be due to the altered immune response of the host or to HBV variants.


[A computerized manual for assessing the dosage absorbed by breast tissue in mammography].
The computerized translation of "Handbook of glandular tissue doses in mammography" (HHS publication FDA 85-8239) is presented. It is registered on floppy disk and suitable for use in MS-DOS on IBM personal computer, Olivetti or compatible. The manual collects data published by many authors and suggests a method to estimate the dose released to the glandular tissue (considered at risk for breast cancer) in the most commonly used conditions for mammography. Besides translation manual, the program holds an algorithm developed by the authors, which allows the dose to the glandular tissue to be evaluated, given the following data: projection: craniocaudal or mediolateral; compression level: firm or moderate; breast size: small, medium or large; breast composition: percentage of glandular tissue content (by weight); X-ray beam quality: HVL mm Al. The algorithm is obtained from a bidimensional fit of the original data and is based on the terms contained in the manual. The program flow is guided by menus that make the procedure suitable for inexperienced operators too, both for consulting and printing and for computing program.


Has the Internet changed everything or nothing? Thoughts on examining and using emerging technologies in adolescent health research.
There are 2 ways to think about emerging technology and adolescent health research. First, one can try to understand the relationship between technology and adolescent health. This line examines whether time spent using emerging technologies or being exposed to messages and applications are associated with poorer or better health. The second way looks at how technology is and can be used through delivering interventions, data collection, or analyses. This article examines both ways of thinking. Given the limited (albeit growing) number of published studies, we use a case-study approach to illustrate relationships and methods. After discussing the purpose and findings, we highlight a study's strengths and weaknesses, not to praise or disparage a researcher's work but to critique the research. We conclude by describing common concerns in adolescent research suggesting ways to advance the field of emerging technologies and adolescent health research.


Ionic Liquid-Mediated Approach for the Synthesis of Site-Specific Thioether Conjugates.
Site-specific conjugation approaches are of great importance in drug discovery, notably for the synthesis of biochemical probes or molecular conjugates for targeted delivery. Herein, we report a mild ionic liquid (IL)-mediated thiolation technique that relies on the use of 1,3-ethyl-methyl imidazolium acetate, [C2 mim][OAc] as a solvent and precursor to generate activated IL, as well as a solvent for the conjugation reaction. First, a focused library of active ILs was prepared for functionalizing/conjugating cysteine-containing small molecules and unprotected peptides. Interestingly, a bifunctional active IL could also be successfully employed as a linker for the conjugation of peptides lacking Cys. This study sets the ground for further investigation of the use of active ILs for modifying, labeling or conjugating larger and more complex therapeutic modalities such as proteins and antibodies.


Epidemiology of otitis media and the role of the general practitioner in management.
Acute otitis media and otitis media with effusion are common diseases of children. Though related to each other, they are clinically separate entities. In order to assess the effectiveness of medical interventions it is important to know the epidemiology of the condition. This paper reviews the incidence, natural history and risk factors for otitis media. In most cases acute otitis media and otitis media with effusion are self-limiting disorders. Complications and an abnormal course are rare. There are, however, subgroups of otitis-prone children, identifiable on the basis of risk factors. These children need special attention from the general practitioner, for example a more frequent use of medical interventions and surveillance. It is important to realize that individual and family factors have more influence on the outcome of otitis media than do the various available medical interventions.


Emerging Semitransparent Solar Cells: Materials and Device Design.
Semitransparent solar cells can provide not only efficient power-generation but also appealing images and show promising applications in building integrated photovoltaics, wearable electronics, photovoltaic vehicles and so forth in the future. Such devices have been successfully realized by incorporating transparent electrodes in new generation low-cost solar cells, including organic solar cells (OSCs), dye-sensitized solar cells (DSCs) and organometal halide perovskite solar cells (PSCs). In this review, the advances in the preparation of semitransparent OSCs, DSCs, and PSCs are summarized, focusing on the top transparent electrode materials and device designs, which are all crucial to the performance of these devices. Techniques for optimizing the efficiency, color and transparency of the devices are addressed in detail. Finally, a summary of the research field and an outlook into the future development in this area are provided.


Implementing Microstream End-Tidal CO2 in the PACU.
Managing patients with undiagnosed Obstructive Sleep Apnea (OSA) can be a challenge in the postoperative phase. OSA is a chronic disease defined by pauses in breathing that are repetitive during sleep that can last for one minute or longer. This can occur more than five times in an hour. As many as 80-90% of patients undergoing elective surgery have undiagnosed sleep apnea and an increased risk of respiratory complications postoperatively. Capnography is a monitoring tool that can detect increases in end-tidal carbon dioxide levels, which is a sign of respiratory decline.


Mechanisms of action of triptolide against colorectal cancer: insights from proteomic and phosphoproteomic analyses.
Triptolide is a potent anti-inflammatory agent that also possesses anticancer activity, including against colorectal cancer (CRC), one of the most frequent cancers around the world. In order to clarify how triptolide may be effective against CRC, we analyzed the proteome and phosphoproteome of CRC cell line HCT116 after incubation for 48 h with the drug (40 nM) or vehicle. Tandem mass tagging led to the identification of 403 proteins whose levels increased and 559 whose levels decreased in the presence of triptolide. We also identified 3,110 sites in proteins that were phosphorylated at higher levels and 3,161 sites phosphorylated at lower levels in the presence of the drug. Analysis of these differentially expressed and/or phosphorylated proteins showed that they were enriched in pathways involving ribosome biogenesis, PI3K-Akt signaling, MAPK signaling, nucleic acid binding as well as other pathways. Protein-protein interactions were explored using the STRING database, and we identified nine protein modules and 15 hub proteins. Finally, we identified 57 motifs using motif analysis of phosphosites and found 16 motifs were experimentally verified for known protein kinases, while 41 appear to be novel. These findings may help clarify how triptolide works against CRC and may guide the development of novel treatments.


Interstitial lung disease of infancy caused by a new NKX2-1 mutation.
Patients with personal or family history of congenital hypothyroidism, and/or neurological findings that also have chronic respiratory symptoms may have a mutation in the NKX2.1 gene as the unifying cause of their disease. Brain-lung-thyroid disease is the ensuing condition, which although rare, needs to be part of the differential diagnosis.


Biological Predictors of Clozapine Response: A Systematic Review.
Background: Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia (TRS) but there is significant variability between patients in the degree to which clozapine will improve symptoms. The biological basis of this variability is unknown. Although clozapine has efficacy in TRS, it can elicit adverse effects and initiation is often delayed. Identification of predictive biomarkers of clozapine response may aid initiation of clozapine treatment, as well as understanding of its mechanism of action. In this article we systematically review prospective or genetic studies of biological predictors of response to clozapine. Methods: We searched the PubMed database until 20th January 2018 for studies investigating "clozapine" AND ("response" OR "outcome") AND "schizophrenia." Inclusion required that studies examined a biological variable in relation to symptomatic response to clozapine. For all studies except genetic-studies, inclusion required that biological variables were measured before clozapine initiation. Results: Ninety-eight studies met the eligibility criteria and were included in the review, including neuroimaging, blood-based, cerebrospinal fluid (CSF)-based, and genetic predictors. The majority (70) are genetic studies, collectively investigating 379 different gene variants, however only three genetic variants (DRD3 Ser9Gly, HTR2A His452Tyr, and C825T GNB3) have independently replicated significant findings. Of the non-genetic variables, the most consistent predictors of a good response to clozapine are higher prefrontal cortical structural integrity and activity, and a lower ratio of the dopamine and serotonin metabolites, homovanillic acid (HVA): 5-hydroxyindoleacetic acid (5-HIAA) in CSF. Conclusions: Recommendations include that future studies should ensure adequate clozapine trial length and clozapine plasma concentrations, and may include multivariate models to increase predictive accuracy.


Effects of radiolabelled murine antibody infusion on TNF-alpha, IL-1 beta, and soluble IL-2 receptor in cancer patients.
This study evaluates the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclonal antibodies (MAbs) for the purpose of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact 111In-MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-alpha when preinfusion concentrations were compared to 4 day (P < 0.01) or to 7 day (P < 0.05) postinfusion values. A 50% or greater decrease in IL-1 beta was also observed in most individuals with time after infusion. In contrast, sIL-2R concentrations remained relatively stable during the 1 week follow-up period. However, strikingly different patterns in the IL-1 beta and sIL-2R levels were noted in the subject who had received two previous murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-alpha and IL-1 beta. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth.


Tripal and Galaxy: supporting reproducible scientific workflows for community biological databases.
Online biological databases housing genomics, genetic and breeding data can be constructed using the Tripal toolkit. Tripal is an open-source, internationally developed framework that implements FAIR data principles and is meant to ease the burden of constructing such websites for research communities. Use of a common, open framework improves the sustainability and manageability of such as site. Site developers can create extensions for their site and in turn share those extensions with others. One challenge that community databases often face is the need to provide tools for their users that analyze increasingly larger datasets using multiple software tools strung together in a scientific workflow on complicated computational resources. The Tripal Galaxy module, a 'plug-in' for Tripal, meets this need through integration of Tripal with the Galaxy Project workflow management system. Site developers can create workflows appropriate to the needs of their community using Galaxy and then share those for execution on their Tripal sites via automatically constructed, but configurable, web forms or using an application programming interface to power web-based analytical applications. The Tripal Galaxy module helps reduce duplication of effort by allowing site developers to spend time constructing workflows and building their applications rather than rebuilding infrastructure for job management of multi-step applications.


Abdominal lymphangioleiomyomatosis in a man with Klinefelter syndrome: the first reported case.
Lymphangioleiomyomatosis (LAM) is an uncommon progressive disease characterized by a hamartomatous tumor-like proliferation of smooth muscle cells that occurs most often in women. This disease commonly involves the lymph nodes, lungs, and mediastinum, and rarely the abdominal sites. We report a case of mesenteric LAM occurring in a 37-year-old man affected by Klinefelter syndrome with a 17-year history of androgen replacement therapy. Histology revealed a hamartomatous proliferation of spindle cells surrounding multiple ectatic lymphatic spaces intermixed with lymphatic follicles. When subjected to immunohistochemical studies, the tumor cells stained positive for muscular markers and negative for estrogen, progesterone, and androgen receptors. The occurrence of LAM in association with Klinefelter syndrome has never been reported in the literature and could represent a further clue in the still unclear pathogenesis of this disease.


Pyrazinamide and Pyrazinoic Acid Derivatives Directed to Mycobacterial Enzymes Against Tuberculosis.
Tuberculosis (TB) is an infectious diseases responsible for thousands of deaths worldwide. Due to the use of antimycobacterial drugs, TB prevalence seemed to be controlled, but with the appearance of resistant tuberculosis cases, the concern about the disease had become significant again, as well as the need for new alternatives to TB treatment. Since pyrazinamide (PZA) is part of the firstline agents in TB treatment, several derivatives of this drug were described, besides pyrazinoic acid (POA) derivatives, the active form of PZA. POA has been used mainly to design prodrugs to be activated by mycobacterial esterases, while PZA derivatives should be activated specifically by the nicotinamidase/ pyrazinamidase (PZAse), or other PZAse-independent pathways. The intention of this paper is to discuss the state of art of PZA and POA derivatives and their activity against Mycobacterium tuberculosis and other mycobacteria, besides the therapeutic potential. Focus was given in prodrugs and derivatives directed to mycobacterial enzymes involved in its activation or mechanism of action.


Gadolinium nephrotoxicity: case report of a rare entity and review of the literature.
Radiocontrast exposure has now become an important cause of iatrogenic acute kidney injury (AKI) in hospitalized patients due to an increase in the number of diagnostic and interventional procedures done. Gadolinium, a well-known paramagnetic contrast agent used primarily for magnetic resonance imaging (MRI), has attracted a lot of attention for its safety in patients at risk for AKI, namely those with chronic kidney disease (CKD) and diabetes. Since its widespread use, a few cases of gadolinium nephrotoxicity have been reported in the literature. However, this remains a largely unrecognized complication in the field of nephrology. Here we describe such a case of AKI due to gadolinium toxicity in a 65-year-old African-American man with a history of hypertension, diabetes and chronic kidney disease, who was admitted for a toe infection and consequently developed AKI from multiple imaging studies involving the use of gadolinium.


Nucleon Energy Correlators.
We introduce the concept of the nucleon energy correlators, a set of novel objects that encode the microscopic details of a nucleon, such as the parton angular distribution in a nucleon, the collinear splitting to all orders, as well as the internal transverse dynamics of the nucleon. The nucleon energy correlators complement the conventional nucleon or nucleus tomography, but without introducing the nonperturbative fragmentation functions or the jet clustering algorithms. We demonstrate how the nucleon energy correlators can be measured in the lepton-nucleon deep inelastic scattering. The predicted distributions display a fascinating phase transition between the perturbative and nonperturbative regime. In the perturbative phase, a polar angle version of the Bjorken scaling behavior is predicted. We discuss its possible applications and expect it to aggrandize the physics content at the electron ion colliders with a far-forward detector.


A spatially adaptive nonparametric regression image deblurring.
We propose a novel nonparametric regression metthod for deblurring noisy images. The method is based on the local polynomial approximation (LPA) of the image and the paradigm of intersecting confidence intervals (ICI) that is applied to define the adaptive varying scales (window sizes) of the LPA estimators. The LPA-ICI algorithm is nonlinear and spatially adaptive with respect to smoothness and irregularities of the image corrupted by additive noise. Multiresolution wavelet algorithms produce estimates which are combined from different scale projections. In contrast to them, the proposed ICI algorithm gives a varying scale adaptive estimate defining a single best scale for each pixel. In the new algorithm, the actual filtering is performed in signal domain while frequency domain Fourier transform operations are applied only for calculation of convolutions. The regularized inverse and Wiener inverse filters serve as deblurring operators used jointly with the LPA-design directional kernel filters. Experiments demonstrate the state-of-art performance of the new estimators which visually and quantitatively outperform some of the best existing methods.


[Theoretical evaluation of the risk of decompression illness during simulated extravehicular activity].
Theoretical analysis of the risk of decompression illness (DI) during extravehicular activity following the Russian and NASA decompression protocols (D-R and D-US, respectively) was performed. In contrast to the tradition approach to decompression stress evaluation by the factor of tissue supersaturation with nitrogen, our probabilistic theory of decompression safety provides a completely reasoned evaluation and comparison of the levels of hazard of these decompression protocols. According to this theory, the function of cumulative DI risk is equal to the sum of functions of cumulative risk of lesion of all body tissues by gas bubbles and their supersaturation by solute gases. Based on modeling of dynamics of these functions, growth of the DI cumulative risk in the course of D-R and D-US follows essentially similar trajectories within the time-frame of up to 330 minutes. However, further extension of D-US but not D-R raises the risk of DI drastically.


Puerarin attenuates inflammation and oxidation in mice with collagen antibody-induced arthritis via TLR4/NF-κB signaling.
Puerarin is an important active ingredient in the root of kudzu vine due to its pharmacological properties. The aim of the present study is to contribute to the existing knowledge of the effect of puerarin in the attenuation of inflammation and oxidation in mice with collagen antibody-induced arthritis via toll‑like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling. Arthritis was induced using injection of anti‑type II collagen antibodies. Treatment with puerarin was observed to significantly decrease clinical scoring of the collagen antibody‑induced arthritis and suppress oxidative stress and the inflammatory response in mice. Furthermore, puerarin was demonstrated to inhibit mRNA expression of matrix metalloproteinase‑9 and protein expression of TLR4 following collagen antibody-induced arthritis in mice. The effect of puerarin may be associated with the suppression of NF‑κB activity in collagen antibody‑induced arthritis mice. Furthermore, upregulation of phosphorylated (p)‑Janus kinase 2 and p‑signal transducer and activator of transcription 3 protein expression was suppressed by puerarin. The results of the present study indicate, for the first time, the effect of puerarin to attenuate inflammation and oxidation in mice with collagen antibody‑induced arthritis via TLR4/NF-κB signaling.


Cholangiocarcinoma Prognosis Varies over Time Depending on Tumor Site and Pathology.
Cholangiocarcinoma is a relatively rare cancer that is difficult to diagnose and has a poor prognosis. Currently, knowledge concerning its etiology, tumor localization, and pathological features remains limited. The present study aimed to clarify the clinico-epidemiologic nature of cholangiocarcinoma with its clinical subtypes using the largest regional cancer registry in Japan. Using a regional cancer registry in Kanagawa prefecture, Japan, we estimated three-year and five-year survival rates of cholangiocarcinoma patients, who were classified into two groups: intrahepatic (i-CCA) and extrahepatic cholangiocarcinoma (e-CCA) cases. The hazard ratio for each subtype, including pathological tissue type and tumor site, was calculated. During the period from 1976 to 2013, 14,287 cases of cholangiocarcinoma were identified. The prognosis markedly improved after 2006, when a new type of chemotherapy for cholangiocarcinoma was introduced in Japan. Patients with i-CCA were more likely to be younger, and less likely to undergo surgery than those with e-CCA. The prognosis of cases with i-CCA was poor compared to that of patients with e-CCA. In Japan, i-CCA was more likely to develop in younger people and to have a poor prognosis. The prognosis of both i-CCA and e-CCA cases markedly improved after 2006. The present study describes clinico-epidemiological features of cholangiocarcinoma that may be useful for determining therapeutic strategies for this disease.


[EVALUATION OF BODY MASS INDICES AND ARTERIAL PRESSURE AS CARDIOVASCULAR RISK FACTORS IN THE ADULT POPULATION OF THE CITY OF VORONEZH].
To determine body mass index (BMI) and blood pressure (BP) of the Voronezh city adult population. 1108 residents of Voronezh city at the age from 20 to 75 years were examined in 2015 including measurement of their height, body mass, arterial pressure, and BMI calculation. Medical histories were analyzed to reveal arterial hypertension in the preceding period in the following age groups: 20-29, 30-39, 40-49, 50-59, 60-75 yr and the entire study group (20-75 yr). The mean BMI of the residents of Voronezh was 28.5 (23.8; 33.1) kg/m. The highest values were found between 40 and 59 years. BMI in women under 40 was lower than in men of the same age. The education level affected the prevalence of obesity in that people with secondary vocational education were more likely to be obese than those given higher education. At the age of 40, the incidence of hypertension among women was lower than among men of the same age, it more frequently occurred at the age of 60-75 years. Both age and BMI were related to the level of blood pressure: higher BMI and blood pressure were recorded at an older age. The prevalence of hypertension also increased with age. Obesity was detected in 29.7% of the Voronezh population recruited to the study. The prevalence of obesity among young adults (20-29 years) iproved lower than in the middle and old age groups. 30.9% of the residents suffered from AH.


The CREST-2 experience with the evolving challenges of COVID-19: A clinical trial in a pandemic.
The coronavirus disease 2019 pandemic has disrupted the lives of whole communities and nations. The multinational multicenter National Institute of Neurological Disorders and Stroke Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial stroke prevention trial rapidly experienced the effects of the pandemic and had to temporarily suspend new enrollments and shift patient follow-up activities from in-person clinic visits to telephone contacts. There is an ethical obligation to the patients to protect their health while taking every feasible step to ensure that the goals of the trial are successfully met. Here, we describe the effects of the pandemic on the trial and steps that are being taken to mitigate the effects of the pandemic so that trial objectives can be met.


Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine.
We hypothesized that the hyperexcitability of occipital cortex neurons may predispose migraine subjects to develop spreading depression, the putative basis of migraine with aura (MwA). To date there is no direct physiologic correlate confirming this in patients. Accordingly, we evaluated the differences in the threshold of occipital cortex excitation between MwA patients and normal controls (C) using transcranial magnetic stimulation (TMS). TMS was performed using the Cadwell MES 10 stimulator. A circular coil 9.5 cm in diameter was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulation intensity was then fine-tuned to determine the threshold at which phosphenes were just visualized. Eleven MwA patients, mean age 37 +/- 7 years, were compared with 11 C, mean age 37.7 +/- 7 years. The difference in the proportion of subjects with phosphene generation between MwA patients and C was significant (MwA patients 100% versus C 27.3%, p = 0.001). The mean threshold level for MwA patients was 44.2 +/- 8.6 versus 68.7 +/- 3.1 for C (p = 0.0001). All threshold levels for MwA patients were lower than the lowest threshold for C; the MwA patient with the lowest threshold had an aura after stimulation. The threshold for excitability of occipital cortex is lower in MwA patients compared with C. This is a direct neurophysiologic correlate for clinical observations that have indicated hyperexcitability of the occipital cortex in migraineurs.


Isovolumic pressure-to-early rapid filling decay rate relation: model-based derivation and validation via simultaneous catheterization echocardiography.
Transmitral Doppler echocardiography is the preferred method of noninvasive diastolic function assessment. Correlations between catheterization-based measures of isovolumic relaxation (IVR) and transmitral, early rapid filling (Doppler E-wave)-derived parameters have been observed, but no model-based, causal explanation has been offered. IVR has also been characterized in terms of its duration as IVR time (IVRT) and by tau, the time-constant of IVR, by approximating the terminal left ventricular IVR pressure contour as Pt= Pinfinity + P(o)e(-t/tau), where Pt is the continuity of pressure, Pinfinity and Po are constants, t is time, and tau is the time constant of IVR. To characterize the relation between IVR and early rapid filling more fully, simultaneous (micromanometric) left ventricular pressure and transmitral Doppler E-wave data from 25 subjects undergoing elective cardiac catheterization and having normal physiology were analyzed. The time constant tau was determined from the dP/dt vs. P (phase) plane and, simultaneous Doppler E-waves provided global indexes of chamber viscosity/relaxation (c), chamber stiffness (k), and load (xo). We hypothesize that temporal continuity of pressure decay at mitral valve opening and physiological constraints permit the algebraic derivation of linear relations relating 1/tau to both peak atrioventricular pressure gradient (kxo) and E-wave-derived viscosity/relaxation (c) but does not support a similar, causal (linear) relation between deceleration time and tau or IVRT. Both predicted linear relations were observed: kxo to 1/tau (r = 0.71) and viscosity/relaxation to 1/tau (r = 0.71). Similarly, as anticipated, only a weak linear correlation between deceleration time and IVRT or tau was observed (r = 0.41). The observed in vivo relationship provides insight into the isovolumic mechanism of relaxation and the changing-volume mechanism of early rapid filling via a link of the respective relaxation properties.


Sleep/Wake Disorders After Sports Concussion: Risks, Revelations, and Interventions.
Sleep-wake disturbances (SWDs) are among the most prevalent, persistent, and often disregarded sequelae of traumatic brain injury. Identification and treatment of SWDs in patients with traumatic brain injury is important and can complement other efforts to promote maximum functional recovery. SWDs can accentuate other consequences of traumatic brain injury, negatively affect mood, exacerbate pain, heighten irritability, and diminish cognitive abilities and the potential for recovery. The risk for sports injuries increases when athletes are sleep deprived. Sleep deprivation increases risk-taking behaviors, predisposing to injuries. SWDs are an independent risk factor for prolonged recovery after sports-related concussion. SWDs following sports-related concussion have been shown to impede recovery, rehabilitation, and return to preinjury activities.


Long-term effects of testicular cancer on sexual functioning in married couples.
Long-term sequelae of testicular cancer have not been reported from the perspective of patient and spouse. As part of a larger study, both members of 34 married couples were interviewed individually, almost 4 years after treatment ended. Spouse and patient responses were compared for concordance (agreement) regarding psychosexual functioning and fertility issues. Wives perceived fewer long-term problems than husbands and were extremely supportive throughout their husbands' illnesses. At interview, whereas 23.5% of patients still felt less attractive as a result of treatment, no spouses shared this perception. Patients were more likely to report decreased, and wives increased sexual satisfaction compared to before cancer. However, both patients and spouses were more likely to report decreased frequency of intercourse than increased. In other areas as well, concordance was generally high. Few couples reported that infertility would pose a problem, but 53% were parents; men who banked sperm were less likely to already have children.


Immunoglobulin A proteases in gram-negative bacteria isolated from human urinary tract infections.
Several strains of gram-negative bacteria (seven genera, eight species) isolated from patients with urinary tract infections were found to hydrolyze myeloma immunoglobulin A (IgA) protein. Human IgG and IgM and colostrum IgA were not degraded by these organisms. Examination of cleavage digests showed two fragments of different electrophoretic mobilities, with antigenic reactivity and sodium dodecyl sulfate polyacrylamide gel electrophoresis profiles consistent with their identification as Fc and Fab components. The immunoelectrophoresis patterns of cleavage digests suggested that the proteases responsible for this hydrolysis may be dissimilar in the specificity of their IgA cleavage sites.


Clinical and Biological Predictors of Cancer Incidence and Mortality in Patients with Stable Coronary Artery Disease.
Clinical and epidemiological evidence has recently revealed a link between coronary artery disease (CAD) and cancer. Shared risk factors and common biological pathways are probably involved in both pathological conditions. The aim of this paper was to evaluate whether and which conventional risk factors and novel circulating biomarkers could predict cancer incidence and death in patients with CAD. The study included 750 CAD patients, who underwent blood sampling for the evaluation of systemic inflammatory indexes (NLR and SII) and specific biomarkers of oxidative damage (leukocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)). Study participants were followed up for a mean of 5.4 ± 1.2 years. Sixty-seven patients (8.9%) developed cancer during the follow-up time, and nineteen (2.5%) died of cancer. Cox multivariable analysis revealed that age (HR = 1.071; 95% CI: 1.034-1.109; p < 0.001), smoking habit (HR = 1.994; 95% CI: 1.140-3.488; p = 0.016), obesity (HR = 1.708; 95% CI: 1.022-2.854; p = 0.041) and SII (HR = 1.002; 95% CI: 1.001-1.003; p = 0.045) were associated with cancer incidence, while only age (HR = 1.132; 95% CI: 1.052-1.219; p = 0.001) was a predictor of cancer death. Patients with lung and gastrointestinal cancers had significantly higher median mtDNAcn levels than those without cancer. Our study suggests that aggressive risk factor modification and suppression of chronic inflammation may be essential to preventing cancer in CAD patients.


Dose measurements near a non-radioactive gold seed using radiographic film.
The dose distribution near a non-radioactive gold seed under a 6 MV photon beam was measured using radiographic film, water equivalent bolus and solid water slabs. This type of small seed is typically used as a marker in target positional verification using a portal imager for conformal prostate treatment such as intensity modulated radiation therapy. A stack of three films was placed on top of the seed located on a soft bolus. Solid water slabs were then placed on top of the film. The films were exposed using a small 1x1 cm2 field. Then, using a similar experimental set-up and exposure, another stack of three films was placed under the seed, which was then covered by the soft bolus and solid water slabs. The cross-plane axial beam profiles at different depths, depending on the thickness of the film package, were measured. From the group of beam profiles above and below the seed, the dose distribution along a selected vertical line within the profiles was easily plotted. Compared to the dose with no seed at the isocentre and 5 cm of solid water, there was about a 21% increase in dose at 0.35 mm above the seed. On the other hand, there was about a 22% decrease in dose at the same distance below the seed. The dosimetry of the calibrated film was verified with a MOSFET detector. The change in dose due to the seed by varying the incident beam angles was also measured for this note.


Hydralazine-induced liver injury: a review and discussion.
Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.


Mental health of mothers and fathers of twins conceived via assisted reproduction treatment: a 1-year prospective study.
Although twin deliveries after assisted reproduction treatment (ART) are common, the mental health of the parents has scarcely been addressed. Therefore, we evaluated the psychological well-being of ART and spontaneously conceiving parents of twins and singletons. Furthermore, the impact of parity and children's health-related factors on mental health was evaluated. We conducted a prospective longitudinal questionnaire study among ART parents of 91 pairs of twins and of 367 singletons and on control parents of 20 pairs of twins and of 379 singletons in the 2nd trimester of pregnancy (T1), and when the children were 2 months (T2) and 1-year old (T3). Symptoms of depression and anxiety, sleeping difficulties and social dysfunction were addressed via a questionnaire. The effects of parity and child-related factors were assessed at T2. At T1, ART mothers of twins showed fewer symptoms of depression than control mothers of twins (P < 0.05). At T2, both ART and control mothers of twins had more symptoms of depression and anxiety than all mothers of singletons (F = 5.20, P < 0.05 and F = 3.93, P < 0.05, respectively). At T3, both ART and control mothers of twins continued to report more symptoms of depression than the mothers of singletons (F = 10.01, P < 0.01), but a difference in anxiety symptoms was seen only in the control group. All fathers had similar mental health at T1. At T2, ART and control fathers of twins reported more symptoms of depression (F = 4.15, P < 0.05) and social dysfunction than fathers of singletons. At T3, both ART and control fathers of twins had more symptoms of depression (F = 4.29, P < 0.05) and anxiety (F = 5.40, P < 0.05) than fathers of singletons. Control fathers of twins had more sleeping difficulties than fathers of singletons (F = 6.66, P < 0.01). Parity did not differently affect parental mental health at T2 in the study groups. Prematurity did not affect maternal mental health, but it had a negative impact on control fathers' social dysfunction (F = 3.34, P < 0.05). Twin parenthood, but not ART, has a negative impact on the mental health of mothers and fathers during the transition to parenthood. ART parents' mental health was not affected by parity or children's health-related factors.


Hypercalcemia in breast cancer. Reassessment of the mechanism.
Hypercalcemia in patients with breast cancer is usually attributed to osteolytic bone metastases. Seventeen patients with biopsy-proved breast cancer and hypercalcemia were identified in a prospective, unselected manner. Biochemical and clinical evaluation included measurements of parathyroid hormone, nephrogenous cAMP, vitamin D metabolites, fasting calcium excretion, and maximal tubular phosphate reabsorption, and bone radionuclide scanning. Tumor histologic findings were also reviewed. Four of the 17 patients (23.5 percent) had no evidence of bone involvement by bone scanning or radiography. Two additional patients (a total of 35 percent) appeared to have a humoral component to their hypercalcemia as determined by the presence of elevated nephrogenous cAMP excretion. These observations suggest that humoral, tumor-derived products may play a more important role in the hypercalcemia of breast cancer than has been previously recognized.


The behavioral genetics of nonhuman primates: Status and prospects.
The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed.


[Autoimmune thyroid disorders and reproductive failures].
At recent ten years have concluded influence of thyroid autoantibodies in normal beginning, development and growing up of pregnancy. Changing in thyroid autoimmunity, even in the absence of evident thyroid dysfunction, is associated with an increased risk of subfertility. The disturbances in thyroid autoimmunity have associated with a significantly increased risk of recurrent pregnancy loss. Although of pathophysiologic mechanism is still not unclear has suggested that thyroid autoantibodies started abnormal immune response and following disturbances in maternal-fetal thyroid function. This can easily be prevented by systematic screening, for thyroid dysfunction and antibody presence during early gestation, followed by the administration of levothyroxine treatment.


Effectiveness of an image analyzing AI-based Digital Health Technology to identify Non-Melanoma Skin Cancer and other skin lesions: results of the DERM-003 study.
Identification of skin cancer by an Artificial Intelligence (AI)-based Digital Health Technology could help improve the triage and management of suspicious skin lesions. The DERM-003 study (NCT04116983) was a prospective, multi-center, single-arm, masked study that aimed to demonstrate the effectiveness of an AI as a Medical Device (AIaMD) to identify Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC), pre-malignant and benign lesions from dermoscopic images of suspicious skin lesions. Suspicious skin lesions that were suitable for photography were photographed with 3 smartphone cameras (iPhone 6S, iPhone 11, Samsung 10) with a DL1 dermoscopic lens attachment. Dermatologists provided clinical diagnoses and histopathology results were obtained for biopsied lesions. Each image was assessed by the AIaMD and the output compared to the ground truth diagnosis. 572 patients (49.5% female, mean age 68.5 years, 96.9% Fitzpatrick skin types I-III) were recruited from 4 UK NHS Trusts, providing images of 611 suspicious lesions. 395 (64.6%) lesions were biopsied; 47 (11%) were diagnosed as SCC and 184 (44%) as BCC. The AIaMD AUROC on images taken by iPhone 6S was 0.88 (95% CI: 0.83-0.93) for SCC and 0.87 (95% CI: 0.84-0.91) for BCC. For Samsung 10 the AUROCs were 0.85 (95% CI: 0.79-0.90) and 0.87 (95% CI, 0.83-0.90), and for the iPhone 11 they were 0.88 (95% CI, 0.84-0.93) and 0.89 (95% CI, 0.86-0.92) for SCC and BCC, respectively. Using pre-determined diagnostic thresholds on images taken on the iPhone 6S the AIaMD achieved a sensitivity and specificity of 98% (95% CI, 88-100%) and 38% (95% CI, 33-44%) for SCC; and 94% (95% CI, 90-97%) and 28% (95 CI, 21-35%) for BCC. All 16 lesions diagnosed as melanoma in the study were correctly classified by the AIaMD. The AIaMD has the potential to support the timely diagnosis of malignant and premalignant skin lesions.


Drosophila mushroom bodies integrate hunger and satiety signals to control innate food-seeking behavior.
The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses. These controls are mediated by six types of dopaminergic neurons (DANs). By manipulating these DANs, we could inhibit food-seeking behavior in hungry flies or promote food seeking in fed flies. Finally, we show that the DANs potentially receive multiple inputs of hunger and satiety signals. This work demonstrates an information-rich central circuit in the fly brain that controls hunger-driven food-seeking behavior.


Effect of 6% hydroxyethyl starch pre-administration for reduction of pain on propofol injection: A placebo-controlled randomised study.
Colloids modify the vascular endothelium and prevent contact activation of various substances. Pre-administration of colloids may prevent contact activation of vascular endothelium by propofol. The objective of this study was to evaluate the effect of 6% hydroxyethyl starch (HES) 130/0.4 pre-administration on propofol injection pain. Adult patients of the American Society of Anesthesiologists physical status I and II patients, 18-65 years old, of either gender and undergoing elective surgery were randomised into two groups. 100 mL bolus of HES or 0.9% normal saline (NS) was administered over three to five minutes through an 18 G cannula placed in the hand or forearm vein, followed by induction with 1% propofol premixed with 2% lidocaine. Pain during propofol injection was assessed every 10 seconds before the loss of verbal contact as 0- no pain; 1- mild pain evident only on questioning after 10 seconds without any obvious discomfort; 2-moderate pain self-reported by patients within 10 seconds with some discomfort; and 3- severe pain accompanied by withdrawing of hand, and behavioural signs. 126 patients completed the study. Overall incidence of pain was significantly higher in the NS group vs HES group (53% vs 28%; P = 0.004; relative risk 1.54, 95% confidence interval 1.13-2.09). Incidence of severe (8% vs 0%) and moderate pain (16% vs 5%) was higher in the NS group, while the incidence of mild pain was comparable (29% vs 23%; NS vs HES). A significant difference was seen in the severity of pain between the groups (P = 0.002). Pre-administration of 100 mL bolus of 6% HES 130/0.4 significantly reduced propofol injection pain.


Impact of Lung-Related Polygenic Risk Scores on Chronic Obstructive Pulmonary Disease Risk and Their Interaction with w-3 Fatty Acid Intake in Middle-Aged and Elderly Individuals.
Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory disorder with persistent airflow limitation and tissue destruction. We aimed to explore the genetic impact of COPD and its interaction with nutrient intake in 8840 middle-aged and elderly individuals from the Ansan/Ansung cohorts. Participants were diagnosed with COPD if the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was less than 0.7 using spirometry, and if they were previously diagnosed with COPD by a physician. Genome-wide association studies (GWAS) were performed to screen for genetic variants associated with COPD risk. Among them, we selected the genetic variants that exhibited interactions using the generalized multifactor dimensionality reduction (GMDR) method. The polygenic risk score (PRS) was computed by summing the number of risk alleles in the SNP-SNP interaction models that adhered to specific rules. Subsequently, participants were categorized into low-PRS, medium-PRS, and high-PRS groups. The participants with COPD exhibited significantly lower FEV1/FVC ratios (0.64) than those without COPD (0.82). It was positively associated with inflammation markers (serum C-reactive protein and white blood cell levels). A higher proportion of COPD participants were smokers and engaged in regular exercise. The 5-SNP model consisted of FAM13A_rs1585258, CAV1_rs1997571, CPD_rs719601, PEPD_rs10405598, and ITGA1_rs889294, and showed a significant association with COPD risk (p < 0.001). Participants in the high-PRS group of this model had a 2.2-fold higher risk of COPD than those in the low-PRS group after adjusting for covariates. The PRS interacted with w-3 fatty acid intake and exercise, thus influencing the risk of COPD. There was an increase in COPD incidence among individuals with a higher PRS, particularly those with low consumption of w-3 fatty acid and engaged in high levels of exercise. In conclusion, adults with a high-PRS are susceptible to COPD risk, and w-3 fatty acid intake and exercise may impact the risk of developing COPD, potentially applying to formulate precision medicines to prevent COPD.


The effect of low frequency and low intensity ultrasound combined with microbubbles on the sonoporation efficiency of MDA-MB-231 cells.
Ultrasound can produce certain biophysical effects including thermal and non-thermal effects on cells. Sonoporation, the most widely studied non-thermal biological effect of ultrasound, is considered to be the basis for new therapeutic applications. Ultrasound irradiation can increase the permeability of cell membranes through sonoporous effect, which makes molecules like those of drugs, protein, and DNA that normally cannot pass through the cell membranes be able to enter cells. Considering the poor therapeutic effect and poor prognosis of triple negative breast cancer, we aimed to explore the experimental conditions and find the optimal parameters to improve the therapeutic efficacy of chemotherapeutic drugs for MDA-MB-231 cells. By establishing an experimental and control group, our study investigated the effect of low frequency and low intensity ultrasound combined with microbubbles on MDA-MB-231 cell membrane permeability at different times. We conducted factorial cross-design and set 3 levels of ultrasound intensity: 230, 300, and 370 mW/cm2; 3 levels of irradiation time: 1, 2, and 3 minutes; and 6 levels of microbubble doses: 0, 0.2, 0.4, 0.6, 0.8, and 1 mL. Results show that ultrasound intensity, time of irradiation, and microbubbles concentration are not only related to but also have interactive effects on the sonoporation efficiency of MDA-MB-231 cells, with the rank order being sound intensity, irradiation time, and microbubble concentration. The average positive rates (%) of FD4 staining in sound intensities of 230, 300, and 370 mW/cm2 levels were 1.20±0.71, 13.80±5.86, and 10.71±4.36, respectively; and in irradiated times of 1, 2, and 3 min they were 7.54±5.95, 9.74±8.42, and 8.59±5.80, respectively. When the microbubbles increased according to the gradient of 0, 0.2, 0.4, 0.6, 0.8, and 1 mL, the positive rates (%) of FD4 staining were 7.32±5.89, 9.26±7.39, 8.31±5.67, 10.12±8.42, 8.67±7.23, and 7.72±6.24. In our study, the optimal parameters of the sonoporous effect for MDA-MB-231 cells were 300 mW/cm2 of ultrasound intensity, 2 minutes of irradiation time, and 20% microbubbles concentration.


[Epidural lipomatosis as a complication of a long-term glucocorticoid therapy].
In a 47-year-old patient with asymmetrical proximal paraparesis a long cervical and thoracic spinal epidural lipomatosis was found, by computed tomography and (the first such case) magnetic resonance imaging, to be the cause of the signs of a transverse cord lesion. Such a space-occupying mass is a rare complication of long-term corticosteroid medication--in this case administered for over seven years for bronchial asthma. Contrary to the majority of similar reported cases, no decompression operation was performed, because the neurological signs had not progressed and the clinical findings in fact quickly regressed once the steroid dosage had been reduced and they showed a clear dependence on the amount of steroid administered.


Impact of perceived consensus on stereotypes about obese people: a new approach for reducing bias.
In 3 experiments, the authors tested the effect of perceived social consensus on attitudes toward obese people. Participants completed self-report measures of attitudes toward obese people prior to and after manipulated consensus feedback depicting attitudes of others. In Study 1 (N=60), participants decreased negative and increased positive stereotypes after learning that others held more favorable attitudes toward obese people. In Study 2 (N=55), participants improved attitudes when they learned about favorable attitudes of obese people from an in-group versus an out-group source. In Study 3 (N=200), a consensus approach was compared with other stigma reduction methods. Social consensus feedback influenced participants' attitudes and beliefs about causes of obesity. Providing information about the uncontrollable causes of obesity and supposed scientific prevalence of traits also improved attitudes.


Evolving role of oral chemotherapy for the treatment of patients with neoplasms.
The past 20 years has seen an increasing trend toward the use of oral chemotherapy for the treatment of patients with a variety of malignancies. The advantages of oral chemotherapy include lower treatment cost, compared with that of intravenous (i.v.) administration, and more convenient treatment for patients. Several oral drugs are now used routinely for cancer treatment, and others are under investigation. Hormonal agents, such as tamoxifen, flutamide, and megestrol acetate, and antimetabolites, such as hydroxyurea, which are available only in oral formulation, have proven both safe and efficacious. Several other oral drugs, including etoposide and cyclophosphamide, have been shown to be useful and often as effective as their i.v. formulations, and more data on the bioavailability of these agents have become available. In addition, several new and promising oral agents (platinum compounds, fluorinated pyrimidines, topoisomerase I inhibitors, and others) are likely to be introduced into clinical practice in the near future. It is possible that eventually, oral combination chemotherapy will be an accepted and standard approach for the treatment of patients with many types of cancer.


Perceptions of causes of performance-related injuries by music health experts and injured violinists.
Skilled violin and viola players, all of whom had a current performance-related musculoskeletal injury, were asked to report their perceptions of contributing risk factors, consistent with a participatory ergonomics approach. The 26 players, age 18 to 60 years, had been playing for a minimum of 10 years and averaged three hours of practice per day. In addition, 7 music health experts, all with more than 10 years of clinical experience in treating musicians, were asked to report on the risk factors for musicians' performance-related injuries. A high correlation between the perceptions of these two groups was found, with the same top five factors in terms of severity indicated by both groups. Factors rated as high risk were primarily intrinsic and related to the manner in which respondents practiced, to playing posture, and to flaws in skill technique.


Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance.
Cisplatin chemoresistance is a clinical problem that leads to treatment failure in various human epithelial cancers. Members of tumor protein (TP) p53 family play various critical roles in the multiple molecular mechanisms underlying the chemoresistance of tumor cells. However, the in-depth mechanisms of the cellular response to cisplatin-induced cell death are still under thorough investigation. We previously showed that squamous cell carcinoma (SCC) cells exposed to cisplatin display an ATM-dependent phosphorylation of ΔNp63α, leading to a specific function of the phosphorylated (p)-ΔNp63α transcription factor in cisplatin-sensitive tumor cells. We further found that SCC cells expressing non-p-ΔNp63α-S385G became cisplatin-resistant. Using quantitative mass-spectrometry of protein complexes labeled with isobaric tags, we showed that TP53 and ΔNp63α are involved in numerous protein-protein interactions, which are likely to be implicated in the response of tumor cells to cisplatin exposure. We found that p-ΔNp63α binds to the splicing complex, leading to repression of mRNA splicing and activation of ACIN1-mediated cell death pathway. In contrast to p-ΔNp63α, non-p-ΔNp63α fails to bind the critical members of the splicing complex, thereby leading to activation of RNA splicing and reduction of cell death pathway. Overall, our studies provide an integrated proteomic platform in making a case for the role of the p53/p63 interactome in cisplatin chemoresistance.


Grey-Theory-Based Optimization Model of Emergency Logistics Considering Time Uncertainty.
Natural disasters occur frequently in recent years, causing huge casualties and property losses. Nowadays, people pay more and more attention to the emergency logistics problems. This paper studies the emergency logistics problem with multi-center, multi-commodity, and single-affected-point. Considering that the path near the disaster point may be damaged, the information of the state of the paths is not complete, and the travel time is uncertainty, we establish the nonlinear programming model that objective function is the maximization of time-satisfaction degree. To overcome these drawbacks: the incomplete information and uncertain time, this paper firstly evaluates the multiple roads of transportation network based on grey theory and selects the reliable and optimal path. Then simplify the original model under the scenario that the vehicle only follows the optimal path from the emergency logistics center to the affected point, and use Lingo software to solve it. The numerical experiments are presented to show the feasibility and effectiveness of the proposed method.


Construction of Highly Porous Pillared Metal-Organic Frameworks: Rational Synthesis, Structure, and Gas Sorption Properties.
Different from the conventional method to construct pillared-layer metal-organic frameworks (MOFs) by using mixed bipyridyl and dicarboxylate ligands, herein, we present a new approach to build pillared-layer frameworks based on the pyridyldicarboxylate ligands which were predesigned with a certain shape. As exemplified, the ligands of 3-(2',5'-dicarboxyphenyl)benzoic acid (H3dbba) and 3-(2',5'-dicarboxylphenyl)pyridine acid (H2dcpy) were selected and employed to construct three pillared-layer MOFs, [Zn3(dbba)2(bipy)(DMF)]·3DMF·4H2O (1) (bipy = 4,4'-bipyridine), and a pair of crystal polymorphs of [Zn(dcpy)]·1.5DMF·1.5H2O (2 and 3), under solvothermal reactions, respectively. In the structures of 1-3, the [Zn2(COO)4] clusters are bridged by the terephthalate units of dbba3-/dcpy2- to form 2D layers; these layers are further pillared by bipy and the benzoate units of dbba3- or the pyridine units of dcpy2- to furnish the 3D frameworks. All of them possess high porosity characterized by N2 adsorption and exhibit high selective adsorption of C2H4 and CO2 over CH4.