No Clinical Benefit to Treating Male Urinary Tract Infection Longer Than Seven Days: An Outpatient Database Study.
The optimal approach for treating outpatient male urinary tract infections (UTIs) is unclear. We studied the current management of male UTI in private outpatient clinics, and we evaluated antibiotic choice, treatment duration, and the outcome of recurrence of UTI. Visits for all male patients 18 years of age and older during 2011-2015 with International Classification of Diseases, Ninth Revision, Clinical Modification codes for UTI or associated symptoms were extracted from the EPIC Clarity Database of 2 family medicine, 2 urology, and 1 internal medicine clinics. For eligible visits in which an antibiotic was prescribed, we extracted data on the antibiotic used, treatment duration, recurrent UTI episodes, and patient medical and surgical history. A total of 637 visits were included for 573 unique patients (mean age 53.7 [±16.7 years]). Fluoroquinolones were the most commonly prescribed antibiotics (69.7%), followed by trimethoprim-sulfamethoxazole (21.2%), nitrofurantoin (5.3%), and beta-lactams (3.8%). Antibiotic choice was not associated with UTI recurrence. In the overall cohort, longer treatment duration was not significantly associated with UTI recurrence (odds ratio [OR] = 1.95; 95% confidence interval [CI], 0.91-4.21). Longer treatment was associated with increased recurrence after excluding men with urologic abnormalities, immunocompromising conditions, prostatitis, pyelonephritis, nephrolithiasis, and benign prostatic hyperplasia (OR = 2.62; 95% CI, 1.04-6.61). Our study adds evidence that men with UTI without evidence of complicating conditions do not need to be treated for longer than 7 days. Shorter duration of treatment was not associated with increased risk of recurrence. Shorter treatment durations for many infections, including UTI, are becoming more attractive to reduce the risk of resistance, adverse events, and costs.


[Mental health status and its influencing factors among college students during the epidemic of COVID-19].
To investigate the mental health status of college students during the epidemic of COVID-19 and identify the factors influencing the mental health of the students. Using a general questionnaire, a self-designed new coronavirus pneumonia knowledge and cognitive behavior questionnaire, the Generalized Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9), we conducted an internet-based questionnaire survey of 3881 college students in Guangdong Province. A multinomial-logistic regression model was used to analyze the collected data. The survey showed that 69.47% of the college students had a high level of awareness of COVID-19; the overall incidence of anxiety was 26.60%, and the incidences of mild, moderate and severe anxiety were 23.19%, 2.71%, and 0.70%, respectively. Depressive emotions were detected in 21.16% of the students, and the incidences of mild, moderate, and moderate-to-severe depression were 16.98%, 3.17%, and 1.01%, respectively. The results of multivariate analysis showed that an older age was associated with a higher level of awareness of COVID-19 and greater changes in future health behaviors were associated with less anxiety and depression among the students. The students currently in rural areas, of non-medical majors, and reporting half of their information concerning the epidemic being negative were more likely to have anxiety; female gender, residence in suburbs, a drinking history, and excessive negative information concerning the epidemic were all associated with the likeliness of depression. The college students have different levels of anxiety and depression during the epidemic. Depression and anxiety are closely related, but the factors contributing to different levels of such emotions can be different, and colleges and related departments are urged to provide precision mental health education for college students.


A naturally occurring Cu-thionein in Saccharomyces cerevisiae.
A naturally occurring monodisperse Cu-thionein was prepared using ammonium sulfate precipitation followed by ion exchange (DEAE 23) and gel chromatography (Sephadex G-75). The chromatographic steps were repeated at least twice, or until the Cu-thionein remained homogeneous when subjected to analytical polyacrylamide disc electrophoresis. The molecular weight of this copper protein was 9500+/-500. Up to 24.3% cysteine residues were determined, indicating the relationship to the metallothioneins. Aromatic amino acids were virtually absent, while there were about three times as many acidic amino acid residues, including aspartate and glutamate, as in metallothioneins. 10 g atoms of Cu were measured per mole of protein. The copper binding strength of thionein was extremely high. Displacement by protons (pH 1.5) and gel chromatography or dialysis employing EDTA were not effective. Dialysis against diethyldithiocarbamate produced a protein essentially free of copper. Both the ultraviolet properties and the circular dichroism measurements proved identical with those properties reported for artificially prepared Cu-thionein (see ref.[1]. The major absorption was in the far ultraviolet region with a weak shoulder at 270 nm attributable to copper charge-transfer transititions. 6 Cotton extrema were seen at 213, 283 and 302 nm (negative) and 245, 328 and 359 nm (positive). The possible role of Cu-thionein as an electron transport system was discussed.


General classification of rhinopaties: the need for standardization according to etiology and nasal cytology.
Rhinitis is as an inflammation of the nasal mucosa, characterized by high prevalence, widespread morbidity, and a significant financial burden on health care systems. Nevertheless, it is often considered as no more than a mere annoyance. This point of view has progressively led to underestimate and trivialize the disease. Therefore, there are numerous, mostly overlapping classifications of rhinopaties, but clear and standardized guidelines for diagnosis and treatment are still lacking. In the context of Precision Medicine, the development of a classification system focused on the endotypes of rhinitis to be widely adopted appears of utmost importance, also by virtue of study of the nasal immunophlogosis that, thanks to nasal cytology (NC), has recently allowed to better define the different forms of rhinitis, giving a new nosological dignity to several rhinopaties. We aimed to summarize the current knowledge regarding rhinitis and to propose a systematic classification of rhinitis, based on both etiology and cytological findings.


Laparoscopic repair of paraesophageal hiatal hernias.
Regardless of symptoms, paraesophageal hiatal hernias should be repaired in order to prevent complications. This study reports the University of California San Francisco experience with laparoscopic repair of paraesophageal hiatal hernias, emphasizing the technical steps essential for good results. From May 1993 to September 1997, 55 patients, 27 women and 28 men, with a mean age of 67 years (range, 35-102 years) underwent laparoscopic repair of paraesophageal hernias at the University of California San Francisco. Symptoms, which had been present an average of 85 months before surgery, consisted mainly of pain (55%), heartburn (52%), dysphagia (45%), and regurgitation (41%). Of the four patients who presented with acute illness, two had gastric obstruction, one had severe dyspnea, and one had gastric bleeding. Endoscopy demonstrated esophagitis in 25 (69%) of 36 patients, and 24-hour pH-monitoring demonstrated acid reflux in 22 (67%) of 33 patients. Manometry detected severely impaired distal esophageal peristalsis in 17 (52%) of 33 patients. The preferred operation consisted of reduction of the hernia, excision of the sack and the gastric fat pad, closure of the enlarged hiatus without mesh, and construction of a fundoplication anchored by sutures within the abdomen. Of the 55 patients, the operations of 49 were completed laparoscopically using the following reconstructions: Guarner (270-degree) fundoplication (30 patients); Nissen fundoplication (10 patients); and gastropexy (9 patients). Five (9%) operations were converted to laparotomies. The average operating time was 219 minutes; the average blood loss was less than 25 mL; resumption of an unrestricted diet, 27 hours; and mean hospital stay, 58 hours. Intraoperative technical complications occurred in five (9%) patients. One patient died during surgery from a sudden pulmonary embolus. Two (4%) patients required a second operation for recurrent paraesophageal hernias. Laparoscopic repair of paraesophageal hiatal hernias is safe and effective, but the operation is difficult and good results hinge on details of the operative technique and the surgeon's experience. In this series, the crus could always be closed securely without using mesh. We realized early that a fundoplication should be a routine step, because it corrects reflux and is the best method to secure the gastroesophageal junction in the abdomen.


Effect of pressure relaxation on the mechanisms of short-pulse laser melting.
The kinetics and microscopic mechanisms of laser melting of a thin metal film are investigated in a computational study that combines molecular dynamics simulations with a continuum description of the laser excitation and subsequent relaxation of the conduction band electrons. Two competing melting mechanisms, homogeneous nucleation of liquid regions inside the crystalline material and propagation of melting fronts from external surfaces, are found to be strongly affected by the dynamics of the relaxation of the laser-induced pressure.


Vancomycin-associated linear IgA disease mimicking toxic epidermal necrolysis.
Linear IgA dermatosis is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. In the last three decades, many different drugs have been associated with the drug-induced form of the disease, especially vancomycin. We report a case of vancomycin-induced linear IgA disease mimicking toxic epidermal necrolysis. The aim of this work is to emphasize the need to include this differential diagnosis in cases of epidermal detachment and to review the literature on the subject and this specific clinical presentation.


Early detection of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) remains an incurable disease associated with an unacceptably high early mortality, despite advances in therapeutic options. The disease is clinically silent until late in its natural history, when most of the distal pulmonary arteries have been obliterated. Early diagnosis of PAH is associated with improved long-term survival, and screening of at-risk populations is, therefore, a rational strategy to improve outcomes in this condition. Doppler echocardiography is the most widely used screening tool in current clinical practice. The role of evidence-based screening strategies has been clarified by research such as the DETECT study in patients with systemic sclerosis. A multimodal approach, using a range of noninvasive tests, improves the performance of screening algorithms. Right heart catheterization is mandatory to confirm a diagnosis of PAH. Uncertainties exist about the definition and prognostic relevance of pulmonary hypertension during exercise, but accumulating evidence suggests that stress testing of the pulmonary circulation can unmask clinically important early disease. Novel tools for the early detection of pulmonary vascular disease are urgently needed, given the substantial limitations of currently available techniques.


The interaction and pathogenesis between cognitive impairment and common cardiovascular diseases in the elderly.
Both cognitive impairment and cardiovascular diseases have a high incidence in the elderly population, increasing the burden of care and reducing the quality of life. Studies have suggested that cognitive impairment interacts with cardiovascular diseases such as coronary heart disease, abnormal blood pressure, heart failure, and arrhythmia. On one hand, cognitive impairment in the elderly influences the progression and self-management of cardiovascular diseases and increases the risk of cardiovascular-related adverse events. On the other hand, coronary heart disease, heart failure, higher blood pressure variability, orthostatic hypotension, and atrial fibrillation may aggravate cognitive impairment. The role of blood pressure levels on cognition remains controversial. Several shared biological pathways have been proposed as the underlying mechanism for the association. Cardiovascular diseases may lead to cognitive decline even dementia through cerebral perfusion damage, brain structural changes, inflammation, β-amyloid deposition, and neuroendocrine disorders. It is of great significance to study the interaction and put forward effective interventions in an overall perspective to reduce care burden and improve the quality of life of the elderly patients.


The social costs of alcohol misuse in Estonia.
The aim of this study was to estimate the social costs of alcohol misuse in Estonia in 2006. Using a prevalence-based cost-of-illness approach, both direct and indirect costs were considered, including tangible costs associated with health care, criminal justice, rescue services, damage to property, premature mortality, incarceration, incapability of working due to illnesses, and lower labor productivity. The results show that alcohol misuse cost Estonia more than EUR 200 million in 2006. The costs involved are estimated to represent 1.6% of the gross domestic product (GDP), which is relatively high in comparison with many other countries. In addition, the state receives less receipts from the alcohol excise tax than the costs that it incurs as a consequence of alcohol misuse, which points to the existence of economic inefficiency with respect to the alcohol market. The results of this study suggest that there is definitely a need for further cost-benefit analysis to reach a conclusion regarding the possible utility of government intervention.


Rice XA21 binding protein 3 is a ubiquitin ligase required for full Xa21-mediated disease resistance.
XA21 is a receptor-like kinase protein in rice (Oryza sativa) that confers gene-for-gene resistance to specific races of the causal agent of bacterial blight disease, Xanthomonas oryzae pv oryzae. We identified XA21 binding protein 3 (XB3), an E3 ubiquitin ligase, as a substrate for the XA21 Ser and Thr kinase. The interaction between XB3 and the kinase domain of XA21 has been shown in yeast and in vitro, and the physical association between XB3 and XA21 in vivo has also been confirmed by coimmunoprecipitation assays. XB3 contains an ankyrin repeat domain and a RING finger motif that is sufficient for its interaction with the kinase domain of XA21 and for its E3 ubiquitin ligase activity, respectively. Transgenic plants with reduced expression of the Xb3 gene are compromised in resistance to the avirulent race of X. oryzae pv oryzae. Furthermore, reduced levels of Xb3 lead to decreased levels of the XA21 protein. These results indicate that Xb3 is necessary for full accumulation of the XA21 protein and for Xa21-mediated resistance.


RNase P of the Cyanophora paradoxa cyanelle: a plastid ribozyme.
Ribonuclease P (RNase P) is a ribonucleoprotein enzyme that generates the mature 5' ends of tRNAs. Ubiquitous across all three kingdoms of life, the composition and functional contributions of the RNA and protein components of RNase P differ between the kingdoms. RNA-alone catalytic activity has been reported throughout bacteria, but only for some archaea, and only as trace activity for eukarya. Available information for RNase P from photosynthetic organelles points to large differences to bacterial as well as to eukaryotic RNase P: for spinach chloroplasts, protein-alone activity has been discussed; for RNase P from the cyanelle of the glaucophyte Cyanophora paradoxa, a type of organelle sharing properties of both cyanobacteria and chloroplasts, the proportion of protein was found to be around 80% rather than the usual 10% in bacteria. Furthermore, the latter RNase P was previously found catalytically inactive in the absence of protein under a variety of conditions; however, the RNA could be activated by a cyanobacterial protein, but not by the bacterial RNase P protein from Escherichia coli. Here we demonstrate that, under very high enzyme concentrations, the RNase P RNA from the cyanelle of C. paradoxa displays RNA-alone activity well above the detection level. Moreover, the RNA can be complemented to a functional holoenzyme by the E. coli RNase P protein, further supporting its overall bacterial-like architecture. Mutational analysis and domain swaps revealed that this A,U-rich cyanelle RNase P RNA is globally optimized but conformationally unstable, since changes as little as a single point mutation or a base pair identity switch at positions that are not part of the universally conserved catalytic core led to a complete loss of RNA-alone activity. Likely related to this low robustness, extensive structural changes towards an E. coli-type P5-7/P15-17 subdomain as a canonical interaction site for tRNA 3'-CCA termini could not be coaxed into increased ribozyme activity.


Exceptional Entrainment of Circadian Activity Rhythms With Manipulations of Rhythm Waveform in Male Syrian Hamsters.
The activity/rest rhythm of mammals reflects the output of an endogenous circadian oscillator entrained to the solar day by light. Despite detailed understanding of the neural and molecular bases of mammalian rhythms, we still lack practical tools for achieving rapid and flexible adjustment of clocks to accommodate shift-work, trans-meridian jet travel, or space exploration. Efforts to adapt clocks have focused on resetting the phase of an otherwise unaltered circadian clock. Departing from this tradition, recent work has demonstrated that bifurcation of circadian waveform in mice facilitates entrainment to extremely long and short zeitgeber periods. Here we evaluate the formal nature of entrainment to extreme non-24 h days in male Syrian hamsters. Wheel-running rhythms were first bifurcated into a 24 h rest/activity/rest/activity cycle according to established methods. Thereafter the 24 h lighting cycle was incrementally adjusted over several weeks to 30 h or to 18 h. Almost without exception, wheel-running rhythms of hamsters in gradually lengthened or shortened zeitgebers remained synchronized with the lighting cycle, with greater temporal precision observed in the former condition. Data from animals transferred abruptly from 24 h days to long or short cycles suggested that gradual adaptation facilitates but is not necessary for successful behavioral entrainment. The unprecedented behavioral adaptation following waveform bifurcation reveals a latent plasticity in mammalian circadian systems that can be realized in the absence of pharmacological or genetic manipulations. Oscillator interactions underlying circadian waveform manipulation, thus, represent a tractable target for understanding and enhancing circadian rhythm resetting.


Effect of dietary fat on the fecal excretion of cholesterol and its degradation products in man.
Fecal bile acid and neutral sterol excretion rates were determined in five healthy young men when serum cholesterol changes were induced by isocaloric substitution of an unsaturated (safflower oil) for a saturated fat (butter). The isotope balance method was used after the intravenous injection of cholesterol-4-(14)C. A feces extraction method is presented which permits essentially complete separation of fecal neutral sterols and bile acids. There was a significant increase in the total excretion of the fecal end products of cholesterol metabolism from 966 +/- 42 mg/day on saturated fat to 1147 +/- 45 mg/day on unsaturated fat, and the increase was equally distributed between the neutral sterol and bile acid fractions. With the substitution of dietary fats, regardless of the sequence of their feeding, there was a 28% reduction in serum cholesterol concentration during ingestion of the unsaturated fat. There were reciprocal changes in serum cholesterol levels and fecal steroid excretion with the substitution of one type of fat for the other. The changes in plasma cholesterol content were more than adequately balanced by the reciprocal changes in fecal cholesterol end product excretion. The findings in this study agree with several previous reports in supporting the hypothesis that the hypocholesteremic action of dietary unsaturated fatty acids is associated with an increase in the fecal loss of bile acids and neutral sterols.


Labor and childbirth care in maternity facilities in Brazil's North and Northeast regions: perceptions of the evaluators of the Stork Network Program.
This article eevaluates delivery and birth care practices in maternity facilities in Brazil's North and Northeast regions. We conducted a qualitative evaluation of 91 facilities in the North and 181 facilities in the Northeast. The data was collected using systematic observation by a team of 44 previously trained evaluators and recorded in a field diary. A thematic analysis of the collected data was performed, resulting in three core themes: challenges of collegial management; challenges for coping with obstetric violence; and the potential of the evaluation process for driving change. Advances were made in the implementation of good labor and childbirth care practices; however, some maternity facilities still reproduce hierarchical models without spaces for collegial management and accounts of obstetric violence were common. Health professionals used the presence of risk to justify the low level of adoption of good practices. However, the findings reveal progress towards the humanization of care. The results also show the potential of the evaluation process for driving change. Although progress has been made towards the adoption of the good practices recommended by the Stork Network Program both in the area of management and care delivery, many challenges remain in view of the dominance of a hierarchical management model associated with an interventionist approach to health care.


Phase Behavior of Pure PSPC and PEGylated Multicomponent Lipid and Their Interaction with Paclitaxel: An All-Atom MD Study.
Exploring structural behavior of pure 1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine (PSPC) and multicomponent PSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[amino(poly(ethylene glycol))-2000] (DSPE-PEG2000) membranes and their interaction with pharmaceutically important drugs carry huge importance in drug delivery. Using all-atom molecular dynamics (MD) simulations, we investigated the phase behavior of pure and PEGylated membranes at the temperature range of 280-360 K. We observe a gel-to-liquid crystalline phase transition for pure PSPC between 320 and 330 K, and in the case of multicomponent membranes, at 320 K, a coexistence of order-disorder phases is observed, which gradually transform to a complete liquid crystalline to gel phase between 320 and 310 K. We further studied the interaction of Paclitaxel with pure PSPC and PEGylated bilayers and elucidated the interaction behavior of Paclitaxel at the bilayer interfaces. Understanding of structural and interaction behaviors of the PEGylated bilayers with Paclitaxel will help to explore Paclitaxel-based drug applications in the future.


Tailored coating of gold nanostars: rational approach to prototype of theranostic device based on SERS and photothermal effects at ultralow irradiance.
The last decade has come across an increasing demand for theranostic biocompatible nanodevices possessing the double ability of diagnosis and therapy. In this work, we report the design, synthesis and step-by-step characterization of rationally coated gold nanostars (GNSs) for the SERS imaging and photothermal therapy of HeLa cancer cells. The nanodevices were realized by synthesizing GNSs with a seed growth approach, coating them with a controlled mixture of thiols composed of a Raman reporter and a polyethylene glycol with a terminal amino group, and then reacting these amino groups with folic acid (FA), in order to impart selectivity towards cancer cells which overexpress folate receptors on their membranes. After a complete characterization, we demonstrate that these FA-functionalized GNSs (FA-GNSs) are able to bind selectively to the membranes of HeLa cells, acting as SERS tags and allowing SERS imaging. Moreover, we demonstrate that once bound to HeLa cell membranes, FA-GNSs exhibit photothermal effect which can be exploited to kill the same cells in vitro using laser irradiation in the NIR at a very low and safe irradiance. We thus demonstrate that the FA-GNSs designed following the described approach are an efficient prototype of theranostic nanodevices.


Staging cutaneous squamous cell carcinoma metastases to the parotid gland.
The staging of cutaneous squamous cell cancers (cSCC) was revised by the American Joint Committee on Cancer in 2010 to incorporate known prognostic factors and expand the N (node) category. The purpose of this study was to validate this staging system using a North American cohort, and to compare it to the O'Brien P (Parotid) and N staging system. An exhaustive collaborative database search was performed for all patients with cSCC metastasis to the parotid gland treated at three major Canadian tertiary referral centers from December 1999 to March 2015. The data collected for each patient included overall survival; disease-free survival; tumor, node, and metastasis) staging; and postoperative radiation status. Post-hoc analysis was completed to discern the strongest prognostic factors of survival as they relate to the abovementioned staging systems. Of 136 patients identified, 80% had a documented history of previously treated head and neck cSCC an average of 27 months prior to presentation. Average size of the parotid lesion at recurrence was 4.5 cm. Ninety-six percent of patients underwent surgical resection of the parotid metastasis. Five-year overall and disease-free survival is 79% and 55%, respectively. Only cSCC staging and cSCC-N category had statistically significant differences between groups. cSCC staging had the largest percentage of variation in overall survival explained. Patients with cSCC metastasis to the parotid gland proved to have a moderate survival rate, despite presenting with advanced disease. cSCC staging in the setting of parotid metastasis, despite its limitations, currently offers the most predictive staging system available. 4. Laryngoscope, 127:2063-2069, 2017.


Singles' similarity preferences in an ideal partner: What, when, and why.
This study investigated singles' similarity preferences concerning their ideal partner's personality traits, physical attractiveness, and social resources, as well as potential moderators (fear of being single and mate value) and mediators (forecasted satisfaction). With 1,014 Chinese singles, we found that singles preferred their ideal partner to share similarities in the HEXACO traits, physical attractiveness, and social resources, and they preferred higher similarity in Honesty-Humility and Openness to Experience. Fear of being single, mate value, and forecasted satisfaction did not affect similarity preferences concerning Honesty-Humility and Openness to Experience but had some mixed influence over similarity preferences for other features.


Systematic identification and characterization of stress-inducible heat shock proteins (HSPs) in the salmon louse (Lepeophtheirus salmonis).
Salmon lice (Lepeophtheirus salmonis) are parasitic copepods, living mainly on Atlantic salmon and leading to large economical losses in aquaculture every year. Due to the emergence of resistances to several drugs, alternative treatments are developed, including treatment with hydrogen peroxide, freshwater or thermal treatment. The present study gives a first overview of the thermotolerance and stress response of salmon lice. Sea lice nauplii acclimated to 10 °C can survive heat shocks up to 30 °C and are capable of hardening by a sublethal heat shock. We searched in the genome for heat shock protein (HSP) encoding genes and tested their inducibility after heat shock, changes in salinity and treatment with hydrogen peroxide, employing microfluidic qPCRs. We assessed 38 candidate genes, belonging to the small HSP, HSP40, HSP70 and HSP90 families. Nine of these genes showed strong induction after a non-lethal heat shock. In contrast, only three and two of these genes were induced after changes in salinity and incubation in hydrogen peroxide, respectively. This work provides the basis for further work on the stress response on the economically important parasite L. salmonis.


A Superior Two-Dimensional Phosphorus Flame Retardant: Few-Layer Black Phosphorus.
The usage of flame retardants in flammable polymers has been an effective way to protect both lives and material goods from accidental fires. Phosphorus flame retardants have the potential to be follow-on flame retardants after halogenated variants, because of their low toxicity, high efficiency and compatibility. Recently, the emerging allotrope of phosphorus, two-dimensional black phosphorus, as a flame retardant has been developed. To further understand its performance in flame-retardant efficiency among phosphorus flame retardants, in this work, we built model materials to compare the flame-retardant performances of few-layer black phosphorus, red phosphorus nanoparticles, and triphenyl phosphate as flame-retardant additives in cellulose and polyacrylonitrile. Aside from the superior flame retardancy in polyacrylonitrile, few-layer black phosphorus in cellulose showed the superior flame-retardant efficiency in self-extinguishing, ~1.8 and ~4.4 times that of red phosphorus nanoparticles and triphenyl phosphate with similar lateral size and mass load (2.5~4.8 wt%), respectively. The char layer in cellulose coated with the few-layer black phosphorus after combustion was more continuous and smoother than that with red phosphorus nanoparticles, triphenyl phosphate and blank, and the amount of residues of cellulose coated with the few-layer black phosphorus in thermogravimetric analysis were 10 wt%, 14 wt% and 14 wt% more than that with red phosphorus nanoparticles, triphenyl phosphate and blank, respectively. In addition, although exothermic reactions, the combustion enthalpy changes in the few-layer black phosphorus (-127.1 kJ mol-1) are one third of that of red phosphorus nanoparticles (-381.3 kJ mol-1). Based on a joint thermodynamic, spectroscopic, and microscopic analysis, the superior flame retardancy of the few-layer black phosphorus was attributed to superior combustion reaction suppression from the two-dimensional structure and thermal nature of the few-layer black phosphorus.


Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution.
Resolution of inflammation is essential. Although supplementation of omega-3 fatty acids is widely used, their availability at sites of inflammation is not known. To this end, a multidisciplinary approach was taken to determine the relationship of circulating omega-3 to inflammatory exudates and the generation of resolution signals. In this study, we monitored resolvin precursors in evolving exudates, which initially paralleled increases in edema and infiltrating neutrophils. We also prepared novel microfluidic chambers to capture neutrophils from a drop of blood within minutes that permitted single-cell monitoring. In these, docosahexaenoic acid-derived resolvin D1 rapidly stopped neutrophil migration, whereas precursor docosahexaenoic acid did not. In second organ injury via ischemia-reperfusion, resolvin metabolically stable analogues were potent organ protectors reducing neutrophils. Together, these results indicate that circulating omega-3 fatty acids rapidly appear in inflammatory sites that require conversion to resolvins that control excessive neutrophil infiltration, protect organs, and foster resolution.


Gingival Augmentation in the Thin Phenotype Using Injectable Platelet-Rich Fibrin and Microneedling.
Objective This study set out to examine the results of microneedling (MN) with and without injectable platelet-rich fibrin (i-PRF) in treating individuals with thin periodontal phenotypes, specifically focusing on the effects on gingival thickness (GT) and keratinized tissue width (KTW). Materials and methods This was a split-mouth study involving 32 healthy patients with 64 sites having thin phenotypes classified into two groups. On the one side, i-PRF was injected (Group A), while on the other side (Group B), MN along with i-PRF was used at intervals of 10 days for a month. GT and KTW were measured at baseline, three months, and six months. The parameters were compared intra and intergroup-wise at baseline, three months, and six months using the IBM SPSS Statistics software version 24 (IBM Corp., Armonk, NY) and the chi-square test. Results The findings revealed that when comparing Group A, which received just i-PRF, to Group B, which had i-PRF in conjunction with MN, there was a statistically significant increase in GT in Group B. Conclusions This is a novel method in that it does not need surgical innervations to expand the gingiva in breadth or thickness. Although MN's neoangiogenesis impact contributed to thicker gingiva, i-PRF showed a greater capacity for the release of several growth factors.


Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice.
The chronic nature of prostate cancer growth and progression leading to metastasis provides a large window for intervention. Herein, for the first time, we investigated the effect and associated mechanisms of silibinin phosphatidylcholine (silybin-phytosome) on established prostate tumors in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Twenty-week-old TRAMP male mice having palpable prostate tumor were fed with control or 0.5% and 1%, w/w, silybin-phytosome diets for 11 weeks and then sacrificed. Dietary silibinin inhibited the growth of prostate tumors (up to 60%, P < 0.001) and suppressed tumor progression from prostatic intraepithelial neoplasia to differentiated adenocarcinoma and poorly differentiated adenocarcinoma, with a complete absence of poorly differentiated adenocarcinoma at higher doses. It also inhibited the incidence of tumor invasion of seminal vesicle (up to 81%, P < 0.001) with complete absence of distant metastasis. Silibinin moderately inhibited tumor cell proliferation and induced apoptosis, but strongly suppressed tumor microvessel density (up to 60%, P < 0.001), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2 expression. Antibody array analysis of plasma showed a decrease in the circulatory levels of vascular endothelial growth factor and basic fibroblast growth factor. Decreased levels of matrix metalloproteinases (MMP), snail-1, and vimentin, and an increased level of E-cadherin were also observed, indicating the anti-epithelial-mesenchymal transition effect of silibinin in tumors. Overall, silibinin treatment of TRAMP mice bearing prostate tumor inhibited tumor growth, progression, local invasion, and distant metastasis involving suppression of tumor angiogenesis and epithelial-mesenchymal transition. These findings would have greater relevance for the ongoing phase II clinical trial with silibinin-phytosome in prostate cancer patients.


Vitamin C supplementation in pregnancy.
Vitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy. To evaluate the effects of vitamin C supplementation, alone or in combination with other separate supplements on pregnancy outcomes, adverse events, side effects and use of health resources. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies. All randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Twenty-nine trials involving 24,300 women are included in this review. Overall, 11 trials were judged to be of low risk of bias, eight were high risk of bias and for 10 trials it was unclear. No clear differences were seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I² = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08; 19,575 participants; 11 studies; I² = 0%), perinatal death (average RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I² = 35%), birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies; I² = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I² = 15%; high quality evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I² = 49%; high quality evidence), preterm PROM (prelabour rupture of membranes) (average RR 0.98, 95% CI 0.70 to 1.36; 16,825 participants; 10 studies; I² = 70%; low quality evidence), term PROM (average RR 1.26, 95% CI 0.62 to 2.56; 2674 participants; three studies; I² = 87%), and clinical pre-eclampsia (average RR 0.92, 95% CI 0.80 to 1.05; 21,956 participants; 16 studies; I² = 41%; high quality evidence).Women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.92; 15,755 participants; eight studies; I² = 0%; high quality evidence) and had a small increase in gestational age at birth (MD 0.31, 95% CI 0.01 to 0.61; 14,062 participants; nine studies; I² = 65%), however they were also more likely to self-report abdominal pain (RR 1.66, 95% CI 1.16 to 2.37; 1877 participants; one study). In the subgroup analyses based on the type of supplement, vitamin C supplementation alone was associated with a reduced risk of preterm PROM (average RR 0.66, 95% CI 0.48 to 0.91; 1282 participants; five studies; I² = 0%) and term PROM (average RR 0.55, 95% CI 0.32 to 0.94; 170 participants; one study). Conversely, the risk of term PROM was increased when supplementation included vitamin C and vitamin E (average RR 1.73, 95% CI 1.34 to 2.23; 3060 participants; two studies; I² = 0%). There were no differences in the effects of vitamin C on other outcomes in the subgroup analyses examining the type of supplement. There were no differing patterns in other subgroups of women based on underlying risk of pregnancy complications, timing of commencement of supplementation or dietary intake of vitamin C prior to trial entry. The GRADE quality of the evidence was high for intrauterine growth restriction, preterm birth, and placental abruption, moderate for stillbirth and clinical pre-eclampsia, low for preterm PROM. The data do not support routine vitamin C supplementation alone or in combination with other supplements for the prevention of fetal or neonatal death, poor fetal growth, preterm birth or pre-eclampsia. Further research is required to elucidate the possible role of vitamin C in the prevention of placental abruption and prelabour rupture of membranes. There was no convincing evidence that vitamin C supplementation alone or in combination with other supplements results in other important benefits or harms.


Calibration of the human immunoglobulin BRPs for ACA and molecular size (batch 1) and for Fc function and molecular size (batches 1 & 2).
The current European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation batch 3 (BRP3) for Human Immunoglobulin was established in 2005. Stocks of this BRP are dwindling and a replacement batch is needed to serve as working standard in the tests for distribution of molecular size by HPLC, anticomplementary activity (ACA) and Fc function, in accordance with the requirements of the Ph. Eur. monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The European Directorate for the Quality of Medicines & HealthCare (EDQM) carried out a project (BSP099) to establish replacement batches for this BRP. The project was run in 2 phases, a prequalification phase (Phase 1) and an international collaborative study (Phase 2) involving 19 laboratories. Three batches of candidate materials of various sizes, Samples A, B and C, were procured from 2 different manufacturers on the European market. Based on the results of the study, Sample A was shown to be suitable as a reference standard for the ACA test and for molecular size determination by HPLC, whereas Samples B and C were demonstrated to be suitable for the Fc function test and for the molecular size determination by HPLC. All 3 BRPs are to be used in conjunction with the monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The BRPs were adopted by the Ph. Eur. Commission at its 141st session in November 2011 as official Ph. Eur. Human Immunoglobulin BRPs for ACA and molecular size Batch 1 (Sample A) and Fc function and molecular size Batch 1 and Batch 2 (Samples B and C respectively).


Chemical Inactivation of Lipase in Organic Solvent: A Lipase from Pseudomonas aeruginosa TE3285 is More Like a Typical Serine Enzyme in an Organic Solvent than in Aqueous Media.
A microbial lipase from Pseudomonas aeruginosa TE3285 was treated in anhydrous diisopropyl ether with three kinds of serine-reactive reagents, ethyl p-nitrophenyl methylphosphonate (ENMP), diisopropyl fluorophosphate (DFP), and phenylmethylsulfonyl fluoride (PMSF) to lose its catalytic activity for both transesterification in an organic solvent and ester hydrolysis in aqueous system. In contrast with the facile inactivation in an organic solvent, no or very slow inactivation was observed in an aqueous solution. The lipase was shown to behave more like a typical serine enzyme in an organic solvent than in aqueous solution with regard to the chemical inactivation by serine-reactive reagents. The unique behavior of the lipase in an organic solvent may be associated with inferfacial activation of the lipase, which is one of the most distinct characteristics of the lipase family, and the activiation of lipase could be induced by a hydrophobic interaction with an organic solvent.


Characteristics and Outcomes of Female Infertility Treatment Programs Using Traditional Medicine in Korea: A Multisite Analysis.
Infertility has long been recognized as a treatable disease, and complementary and alternative medicine treatments, such as acupuncture and moxibustion, have been used in Korea and China. This study describes female infertility treatment programs that used traditional Korean medicine (TKM) and were conducted by local governments in Korea and evaluates its effectiveness and safety. The authors officially requested related information from the report of the infertility treatment programs and related sources from 2006 to 2016 from the Health & Welfare Ministry of Korea and the Association of Korean Medicine (AKOM). Additional information was obtained from six Korean databases. Data including basic information about the programs, participant information, interventions, and outcomes were abstracted. A total of 9 reports, including multiple years of data from 6 programs (total 13 programs), were identified. In these 13 programs, a total of 1023 female subjects participated, and 205 of the 887 subjects who completed the program reported a successful pregnancy, indicating a 23.1% pregnancy rate. The programs lasted 3-9 months, and interventional elements, such as herbal medicine, acupuncture, fumigation, and massage, were identified. Significant adverse effects were not reported. This study suggests that infertility treatment programs with TKM interventions exhibited a positive effect on pregnancy in females with infertility. Thus, the infertility treatment programs with TKM interventions are expected to be useful and might serve as the primary treatment before assisted reproduction techniques.


[Conventional and 3-D cephalometry: descriptive analysis].
Today, the three dimension (3D) teleradiographic different construction enable a three dimensional studies of different mandible structures. Then we can approach the result obtained with the news images processing techniques like scanner. In this paper we present the different between the measure provided by different pictures (lateralis, frontalis, axiales) and the three dimensional measure which is real. The best 3D values correlation is obtained with the frontalis.


Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria.
To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.


Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients.
Obinutuzumab (GA101; G) is a new treatment for follicular lymphoma (FL) that is anticipated to have greater efficacy than the current treatment, rituximab (R). The aim of this study was to evaluate the cost-effectiveness of G plus chemotherapy (G + Chemo) against that of R plus chemotherapy (R + Chemo) for patients in Japan with previously untreated FL. We localized a previously reported cost-effectiveness model using the Japanese cost data. For estimating costs adapted in the model, FL patients treated with R were identified from Japanese hospital-based claims database and classified into three treatment regimen groups according to chemotherapies used with R: CHOP, CVP, and bendamustine (B). Based on services per patient and cost items, parameters determining the cost amounts were derived using a multivariate generalized linear mixed model to estimate the direct medical costs for each treatment regimen group for G and R. For the utility, same values in the previous model were used. Lifetime cost and quality-adjusted life year (QALY) were estimated under the payer's perspective. The calculated incremental cost-effectiveness ratios (ICERs) in million JPY per QALY for G-CHOP vs. R-CHOP, G-CVP vs. R-CVP, and G-B vs. R-B were 5.4, 4.3, and 4.8, respectively. ICERs were lower than 7.5 million JPY per QALY, which is the cost-effectiveness threshold for cancer treatments, and showed that G + Chemo is a cost-effective treatment regimen for Japanese patients with previously untreated FL. Lifetime direct medical costs were lowest in the R-B group because hospitalization costs that accounted for most of the total cost were lowest in this group. Limitations and conclusions: The cost-effectiveness of G + Chemo is acceptable in Japan. Differences in the direct medical costs among treatment regimen groups were mostly due to hospitalization costs. This is probably because many Japanese hematologists choose inpatient treatments over outpatient treatments in CHOP-based induction therapy.


Parent-reported Mental Health Problems and Mental Health Services Use in South Australian School-aged Children.
Monitoring and reporting childhood mental health problems and mental health services utilization over time provide important information to identify mental health related issues and to guide early intervention. This paper aims to describe the recent prevalence of parent-reported mental health problems among South Australian (SA) children; to identify mental health problems associated characteristics; and to describe mental health services utilization and its related characteristics among this population. Parent-reported mental health problems were assessed against the first item of the Strength and Difficulties Questionnaire. School-aged children were randomly sampled monthly and data were collected using a surveillance system between 2005 and 2015. Associations between mental health problems and various factors were analysed using univariable analysis and multivariable logistic regression modelling. Prevalence of parent-reported mental health problems among children was 9.1% and 9.3% for children aged 5 to 11 years and children aged 12 to 15 years, respectively. No change in prevalence was observed during the past decade. Mental health problems were associated with male sex, long-term illness or pain, negative school experiences, not living with biological parents, and living in a rental dwelling. Less than half (48.7%) of the children with mental health problems received professional help. An increasing trend was found in mental health services utilisation among children aged 5 to 15 years. Utilization of mental health services was associated with male sex, older age, long-term illness or pain, and feeling unhappy at school. This study reports the prevalence of parent-reported mental and mental health services utilisation among SA school-aged children. Identified characteristics associated with mental health problems and mental health services utilisation provide useful information for the planning of catered population initiatives.


The acute haemodynamic effects of intravenous enalaprilic acid (MK422) in patients with left ventricular dysfunction.
Intravenous enalaprilic acid (2.5 mg) was given to 11 patients with stable cardiac failure (NYHA functional class II-IV). Reductions in mean right atrial, pulmonary artery and pulmonary capillary wedge pressure of 25%, 18% and 30% respectively (P less than 0.01), were observed. Cardiac output rose by 13% (NS) and mean blood pressure fell by 20% (P less than 0.01) with a decrease in systemic vascular resistance of 24% (P less than 0.01). Heart rate was unaltered. The haemodynamic effects correlated with control plasma renin activity (r = 0.78, P less than 0.01). Marked hypotension occurred in several subjects but no other side-effects were noted. The rapid onset of action and mixed venous and arteriolar dilating activity of intravenous enalaprilic acid may be an advantage in some clinical situations where parenteral vasodilating therapy is required.


Radiopharmaceutical chemistry of targeted radiotherapeutics, part 1: effects of solvent on the degradation of radiohalogenation precursors by 211At alpha-particles.
The high energy and short range of alpha-particles make them attractive for targeted radiotherapy. However, these properties can be problematic when the production of high activity levels of alpha-particle-emitting radiotherapeutics is required. For example, difficulties were encountered in the production of N-succinimidyl 3-[211At]-astatobenzoate (SAB), when 370-MBq doses of 211At-labeled antibody were required. The purpose of this study was to investigate a potential cause of this behavior--radiolytic degradation of the radiohalogenation precursor. Both N-succinimidyl 3-(tri-n-butylstannyl)benzoate (BuSTB) and N-succinimidyl 3-trimethylstannylbenzoate (MeSTB) were incubated with various 211At time-activity combinations such that the radiation dose received by the reaction medium ranged from about 0 to 20,000 Gy. Studies were performed using chloroform, methanol, and benzene as the solvent, and both at neutral pH and at a pH of approximately 5.5, as used in SAB synthesis. The fraction of tin precursor remaining and the generation of unlabeled byproducts were determined from high-performance liquid chromatograms and then plotted against radiation dose. Extensive radiolytic decomposition of BuSTB and MeSTB was observed in chloroform, with 50% degradation taking place even at doses below 500 Gy. Formation of a byproduct, most likely N-succinimidyl 3-chlorobenzoate, increased with radiation dose. A greater degree of stability was seen in both methanol and benzene, with more than 85% of the precursor remaining at 3,500 Gy. No cold byproducts were observed with either solvent. The nature of the solvent profoundly influences the ability to synthesize high activity levels of SAB and possibly other 211At-labeled radiopharmaceuticals.


Expression of pattern recognition receptors in cholesteatoma.
Although many immunologic mechanisms have been investigated in studies of the pathogenesis of cholesteatoma, the role of pattern recognition receptors (PRRs) has not been fully determined. Therefore, we assessed innate immune responses in patients with cholesteatoma. We prospectively evaluated 21 patients with acquired cholesteatoma between August 2010 and July 2012. Cholesteatoma specimens were obtained during surgery, and skin from the external meatus of each patient was used as a control. RNA was extracted from these tissue samples, followed by real-time PCR to quantitatively assess the relative expression of toll-like receptors (TLRs), NOD-like receptors (NLRs), retinoic acid-inducible gene (RIG)-I, NO synthase (NOS) and cytokines. The levels of TLR-2, -3, -4, -6, -7, and -10, NOD-2, and IL-1 and -8 mRNAs were significantly higher in the cholesteatoma than in the skin specimens (p < .05). The expression levels of TLR-2 and -3, RIG-I, IL-6, and TNF-α mRNAs were significantly higher in cholesteatomas from women than from men. The levels of TLR-8, NOD-2, IL-12, and TNF-α mRNAs were significantly higher in recurrent than in initial cholesteatoma specimens (p < .05). Hearing level did not correlate with the levels of expression of mRNAs encoding TLRs, NLRs, NOS, RIG-I and related cytokines (p > .05). In conclusion, alterations in innate immunity triggered by PRRs are important in the pathophysiology of cholesteatoma. Gender differences and frequency of surgery may affect the expression of PRRs in cholesteatomas.


[On the mode of action of heterologous antileukemic sera. Growth of syngeneically transplanted leukemias in serum-treated sublethally irradiated mice (author's transl)].
Heterologous antisera against mouse leukemias prevented the outgrowth of syngeneically transplanted leukemia cells only in non irradiated but not in sublethally irradiated animals. Mice irradiated with 500 R and controls were subcutaneously injected with 50000 leukemia cells at the day following irradiation. They were given 5 injections each of 0,1 ml of heterologous antiserum. Whilst 22 out of 27 irradiated mice developed tumors non-irradiated controls were protected, only 2 out of 30 animals developed a tumor. Cytotoxicity tests with leukemia cells as targets and mouse serum as complement source showed that the complement activity of mouse serum had not been suppressed by the whole body irradiation. We suppose a cooperation between heterologous antiserum and a radiosensitive host cell as responsible for the antileukemic effect.


[The biological time].
Fabio Colonna's De glossopetris dissertatio is part of the biological time. Announces the dawn of a paleontology that understood nature as a closed and orderly system ruled by a perfect, natural codex. The Neapolitan intellectual climate, characteristic of the transit from XVIIth to XVIIIth century, converge in a process of institutionalization of science.


Sesquiterpenes from the roots of Illicium jiadifengpi.
Two new sesquiterpenes (1, 2) and two new sesquiterpene glycosides (3, 4) with a seco-prezizaane skeleton, three new allo-cedrane sesquiterpene glycosides (5-7), and a new acorane sesquiterpene (8) as well as 15 known analogues were isolated from the roots of Illicium jiadifengpi used for the treatment of rheumatoid arthritis. The structures of these compounds were elucidated by extensive spectroscopic analysis and chemical methods. The absolute configurations of compounds 5-7 were confirmed by CD experiments. The configuration of compound 8 was assigned by single-crystal X-ray crystallographic analysis and CD experiments. Compounds 4, 6, 7, 14, and 23 showed moderate antiviral activities against Coxsackie virus B3, and all compounds were inactive when evaluated for their cytotoxic activities against five human tumor cell lines and neuroprotection.


Biochemical characterization and epididymal localization of the maturation-dependent ram sperm surface antigen ESA152.
We examine here the biochemical properties and epididymal localization of a maturation dependent ram sperm surface antigen. A monoclonal antibody, ESA152, identifies an antigen that is present on the surface of ejaculated sperm, but is absent from testicular sperm. Crosslinking of the ESA152 antigen with bivalent antibodies induces the acrosome reaction, redistributing the antigen into the anterior region of the sperm head where it associates with the fusion product of the plasma membrane and the outer acrosomal membrane. The ESA152 antigen appears as a polypeptide of 18 kDa on immunoblots of SDS-polyacrylamide gels. The ESA152 epitope includes the sialic acid termini of N-linked oligosaccharides, as shown by its sensitivity to neuraminidase and endoglycosidase F. The ESA152 antigen is a highly hydrophobic integral membrane protein that resists aqueous extraction, partitions into the detergent phase of Triton-X-114, and solubilizes in chloroform-methanol mixtures. The anchoring of ESA152 is unaffected by phosphtidylinositol specific phospholipase C. The antigen is absent from extracts of caput and corpus epididymidis but appears abruptly in the first segment of the cauda. Immunofluorescence reveals that the ESA152 epitope first appears in clusters of cells in the luminal epithelium of the proximal cauda, prior to or concurrent with its appearance on sperm.


Phase I, dose-escalation study of the targeted cytotoxic LHRH analog AEZS-108 in patients with castration- and taxane-resistant prostate cancer.
AEZS-108, formerly AN-152, is a cytotoxic hybrid molecule consisting of a luteinizing hormone-releasing hormone (LHRH) agonist moiety covalently coupled to doxorubicin, allowing it to deliver doxorubicin selectively to cells expressing LHRH receptors. LHRH receptors are expressed on the cell membrane of many tumors, including prostate cancer. This phase I study determined the maximum tolerated dose (MTD) of AEZS-108 in men with taxane- and castration-resistant prostate cancer (CRPC) while providing additional information on the safety profile and efficacy of this agent. AEZS-108 was administered as an intravenous infusion every 21 days until progression or unacceptable toxicity in cohorts of 3 or 6 patients until the MTD was reached. Blood was collected for capture of circulating tumor cells (CTC) to visualize internalization of AEZS-108, an autofluorescent molecule. The MTD of AEZS-108 in this cohort was 210 mg/m(2), which was lower than that seen in a phase I study conducted in women with endometrial or ovarian cancers. The dose-limiting toxicity was persistent neutropenia. Three patients had a PSA response with an additional 10 patients maintaining PSA stable disease. Of the 10 patients evaluable by RECIST criteria, 9 achieved stable disease. AEZS-108 internalization in CTCs was routinely visualized using its autofluorescence. These findings show that AEZS-108 has an acceptable safety profile and a signal of efficacy, lowering PSA in heavily pretreated patients with prostate cancer, and that internalization of AEZS-108 in prostate cancer CTCs may be a viable pharmacodynamic marker. A phase II study in men with prostate cancer is ongoing.


Stimulation of calcium mobilization but not proliferation by bombesin and tachykinin neuropeptides in human small cell lung cancer cells.
The tachykinin family of neuropeptides, including substance P and neurokinins A and B, induce a transient increase in intracellular free calcium concentration in human small cell lung carcinoma (SCLC) cells, as measured with a calcium indicator fura-2. The effects are dose dependent and even greater than that of bombesin at equimolar concentrations in these cells. The tachykinins, like bombesin, induce calcium mobilization mainly from intracellular store(s). None of the peptides, however, shows a stimulatory effect on DNA synthesis. In addition, exogenously applied bombesin does not stimulate DNA synthesis at any concentration tested. We also examined the effects of a recently reported bombesin antagonist [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P in SCLC cells, and compared them to those in Swiss 3T3 fibroblasts in which the mitogenic effect of bombesin is well characterized. The antagonist at 10(-5) M completely abolishes the Ca2+-mobilizing effect of 10(-7) M bombesin in SCLC cells, and that of 10(-9) M but not 10(-7) M bombesin in Swiss 3T3 cells. The antagonist at this concentration effectively inhibits the mitogenic action of bombesin (10(-9) M) in Swiss 3T3 cells; however, much higher doses (approximately 10(-4) M) are needed to inhibit DNA synthesis in SCLC cells. Moreover, the antagonist inhibits DNA synthesis in bombesin/gastrin-releasing peptide-nonproducing cells with a similar dose dependency as in producing cells. These results indicate that bombesin/gastrin-releasing peptide and other calcium mobilizing peptides do not always act as a growth factor in SCLC cells, and that the bombesin antagonist could inhibit growth of SCLC cells through a mechanism other than bombesin antagonism.


Effects of mammalian target of rapamycin on proliferation, apoptosis and differentiation of myoblasts undergoing mechanical stress.
Myoblasts characterize by the potential to transform into skeletal muscle, and involve in processes of proliferation, differentiation and apoptosis. Mammalian target of rapamycin (mTOR) is an important protein of PI3K signaling pathway in muscle metabolism and physiology. This study aimed to investigate effects of mTOR on proliferation, apoptosis and differentiation of myoblasts undergoing mechanical stress. We paid much attention on mTOR function undergoing mechanical stress in myoblasts. C2C12 myoblasts were cultured and mTOR gene was knocked down by using Crisper/Cas9 method. Western blot assay and quantitative polymerase chain reaction (Q-PCR) were used to test 4E-binding protein 1 (4EBP1) and p70 ribosomal protein S6 kinase (p70S6k) expression. Cell counting kit 8 (CCK-8) was used to measure cell proliferation, and flow cytometry to used to detect cell apoptosis. Differentiation was counted by using immunofluorescence staining. Rresults showed that the knockdown of mTOR reduced the phosphorylation of 4EBP1 and p70S6k levels undergoing mechanical stress and decreased PI3K signaling pathway proteins synthesis. In addition, proliferation of myoblasts was decelerated by the mTOR knockdown. However, when mTOR knocked down cells treated with mechanical stress, apoptosis rate increased significantly and the differentiation speed was slow down. In conclusion, our study revealed the mTOR function on regulating myoblast proliferation, apoptosis and differentiation undergoing mechanical stress.


Clinical and molecular analyses of Beckwith-Wiedemann syndrome: Comparison between spontaneous conception and assisted reproduction techniques.
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by an excessive prenatal and postnatal growth, macrosomia, macroglossia, and hemihyperplasia. The molecular basis of this syndrome is complex and heterogeneous, involving genes located at 11p15.5. BWS is correlated with assisted reproductive techniques. BWS in individuals born following assisted reproductive techniques has been found to occur four to nine times higher compared to children with to BWS born after spontaneous conception. Here, we report a series of 187 patients with to BWS born either after assisted reproductive techniques or conceived naturally. Eighty-eight percent of BWS patients born via assisted reproductive techniques had hypomethylation of KCNQ1OT1:TSS-DMR in comparison with 49% for patients with BWS conceived naturally. None of the patients with BWS born via assisted reproductive techniques had hypermethylation of H19/IGF2:IG-DMR, neither CDKN1 C mutations nor patUPD11. We did not find differences in the frequency of multi-locus imprinting disturbances between groups. Patients with BWS born via assisted reproductive techniques had an increased frequency of advanced bone age, congenital heart disease, and decreased frequency of earlobe anomalies but these differences may be explained by the different molecular background compared to those with BWS and spontaneous fertilization. We conclude there is a correlation of the molecular etiology of BWS with the type of conception. © 2016 Wiley Periodicals, Inc.


lncRNA PANTR1 Upregulates BCL2A1 Expression to Promote Tumorigenesis and Warburg Effect of Hepatocellular Carcinoma through Restraining miR-587.
Hepatocellular carcinoma (HCC) is one of the most common subtypes of malignant liver tumors, characterized by high morbidity and mortality. Due to its poor diagnosis strategy and inefficient clinical intervention, HCC has brought terrible life experiences for patients worldwide. Finding novel curative agents for HCC is urgently needed. In the current study, we hypothesized that lncRNA PANTR1 participates in HCC initiation or progression. Our study found that lncRNA PANTR1 was upregulated in HCC tumor tissues and abundantly expressed in HCC cell lines. PANTR1 knockdown inhibited cell growth and migration, promoted cell apoptosis in vitro, and suppressed tumor cell growth in vivo. Moreover, our results suggest that downregulated PANTR1 inhibited the Warburg effect in HCC cells. Underlying mechanisms of PANTR1 in HCC progression were investigated. PANTR1 acted as a competent sponge for miR-587 and downregulated miR-587 expression in HCC cells. Further, MiR-587 directly targets BCL2A1. lncRNA PANTR1 promotes HCC progression via mediating the miR-587-BCL2A1 axis. Our study identified a novel lncRNA PANTR1/miR-587/BCL2A1 axis in HCC progression. We might provide a new target for HCC basic research and clinical management.


Community pharmacists' attitudes towards patient leaflets: Exploring perceptions underlying an electronic local production of tailored written information.
Low health literacy in Portugal, revealed by limited patients' knowledge of their medication, may be improved by written information that is individually tailored for each patient. Tailored content can be produced through computer software and delivered by community pharmacies to patients. To assess community pharmacists' real-life management, usage and perceived utility of software developed to produce individually tailored patient leaflets at community pharmacies. The software contained five different pharmacist-selected clinical information fields which allows for the adjustment of information to each patient's information needs. Using an exploratory study design, community pharmacists' perceptions were purposively selected and qualitatively assessed. Interviews were recorded, transcribed verbatim and iteratively coded using a thematic approach outlined by attitudinal theory. Eight participants took part in the study. Emerging codes led to the construction of two main themes: Current PLs usage in Portuguese community pharmacy; and Tailored PLs usage in Portuguese community pharmacy. Pharmacists exhibited a generally positive attitude concerning the relevance and use of patient leaflets to address individual patient's information needs, including an improvement in health literacy. The model was considered effective, functional, satisfying and user-friendly. Although additional studies are needed, the introduction of a leaflet-tailoring software in Portuguese community pharmacies seems to be feasible as an additional resource to improve the quality of patient information and counselling. The next research steps should address the impact on patients' medicines-related information, including the level to which patients are able to correctly interpret the information and to adjust accordingly their health behaviours. The software fits present community pharmacy practice and routines, bringing advantages to pharmacists' willingness to deliver meaningful written information to patients, thus contributing to improved patient health literacy.


Exposure to traumatic events at work, posttraumatic symptoms and professional quality of life among midwives.
in their line of duty, midwives are often exposed to traumatic births that may lead to symptoms of compassion fatigue (CF), which includes burnout (BO) and secondary traumatic stress (STS).Conversely, midwives derive pleasure and great satisfaction in seeing the positive effect they have on their clients. This experience is known as compassion satisfaction (CS). Together, CS and CF comprise the professional quality of life (ProQOL). The aim of this paper was to study midwives' professional quality of life and traumatic experiences. The highly stressful environment of midwives may also include primary exposure to traumatic experiences and therefore PTSD levels were also assessed. the participants (N=93) were professional midwives from four medical centers in Israel. The participants answered selfreport questionnaires that assessed their ProQOL and PTSD symptoms. results indicated relatively high levels of CS which may mitigate, at least to some degree, the negative aspects of CF. PTSD levels significantly and positively correlated with STS and BO. Sixteen per cent presented with PTSD symptoms of clinical significance. Also, seniority was significantly and positively correlated with BO and PTSD symptoms. high ProQOL was found amongst the participants, with more than 74% scoring on the high range of CS. Nevertheless, we recommend further research and implementing strategies to maintain or further enhance CS and decrease CF levels. Finally, a more comprehensive understanding of the development of PTSD amongst midwives is vital in order to minimize its occurrence in the future.


[Apolipoprotein A5 gene: association with triglyceride metabolism and cardiovascular disease].
Hypertriglyceridemia constitutes an independent risk factor for coronary disease. The gene apolipoprotein A5 (ApoA5) is a newly discovered member in the ApoA1/C3/A4/A5 cluster, and its product, apolipoprotein A5, influences on triglycerides through an unknown mechanism. Recently, there have been described the clinical consequences and the functional effects over more than 10 variants of the ApoA5 gene, associated with atherosclerosis. In different studies carried out in different ethnic groups, it has been observed a great variation in the distribution of the ApoA5 genotypes for the respective polymorphisms. Different authors have described associations among the ApoA5 gene, high triglyceride concentrations and an increase in the cardiovascular risk. In this context, the ApoA5 gene is considered as a probable biochemical and genetic marker of increased triglyceride concentrations and also a risk factor of coronary disease in some populations.


[Experiences with perioperative short-term prevention in thoracic wall and colorectal surgery in children].
This is a report on prophylaxis with antibiotics in chest wall deformities and colorectal surgery in childhood. The analysis shows a significant reduction of wound infections and general infections after administration of Cefamandol (150 mg/kg in 4 doses) or Cefotaxim (100 mg/kg in 3 doses) and Metronidazol (25 mg/kg in 3 doses) for one day only, starting one hour before operation. The positive effect of prophylaxis with antibiotics in these operations is compared with results in the literature.


A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan.
The association of chronic hepatitis B virus (HBV) infection with end-stage renal disease (ESRD) is unclear. To help clarify this we conducted a nationwide cohort study to measure the association by analyzing the claims data from the Taiwan National Health Insurance Research Database with ICD-9 codes used to identify diseases. We identified 17,758 adults who had chronic HBV infection and had not taken nucleos(t)ide analogs from 1999 to 2010 and randomly selected 71,032 matched controls without HBV in the same data set. The risk of ESRD was compared between these two cohorts. Cumulative incidences and hazard ratios were calculated after adjusting for competing mortality. The risk of ESRD was significantly higher in the HBV cohort (12-year cumulative incidence, 1.9%) than in the non-HBV cohort (0.49%) with a significant adjusted hazard ratio of 3.85. Multivariable stratified analysis further verified significant associations of ESRD with HBV in men of any age and women under the age of 60 years, but no significant association in women aged ⩾60 years. Thus, a large national cohort study indicates that untreated chronic HBV infection is associated with increased risk of ESRD. Hence, high-risk HBV-infected patients should have targeted monitoring for the development of ESRD.


Antimicrobial effects of sanitizers against planktonic and sessile Listeria monocytogenes cells according to the growth phase.
This study was designed to investigate the individual or combined effects of sanitizers on survival of planktonic or sessile Listeria monocytogenes cells at different phase of growth. The sanitizers tested included: (i) acetic acid (pH 5.0), (ii) NaOH (pH 12.0), (iii) 10% Na2SO4, (iv) 10% Na2SO4 and acetic acid (pH 5.0), (v) 10% Na2SO4 and NaOH (pH 12.0), (vi) a quaternary ammonium (20 ppm) and (vii) glyceryl monolaurate (75 ppm). Results revealed a great efficacy of alkaline treatments on both sessile and planktonic cells with a slightly higher resistance of 6 h biofilms. Quaternary ammonium appeared very effective in killing more than 98% of cells, but a resistance of 7 days biofilm was observed. Other sanitizers did not succeed in inhibiting totally the pathogen but acted in a similar way on both sessile and planktonic cells. Renewing the medium or not do not seem to be the major cause of a resistance emergence.


Comparison of clinical outcomes using stents versus no stents after percutaneous coronary intervention for proximal left anterior descending versus proximal right and left circumflex coronary arteries.
Previous studies have demonstrated that proximal left anterior descending (LAD) stenoses have higher rates of restenosis after angioplasty than stenoses in other coronary segments. Stenting strategies may reduce this high rate of LAD restenosis. The study population included 1,289 patients with proximal coronary artery stenoses treated with percutaneous coronary interventions (PCI) with or without stents for single-vessel coronary disease between 1994 and 1999. Patients were divided into 4 groups: non-stent PCI in the proximal LAD artery (n = 168), non-stent PCI in proximal right/circumflex artery (n = 217), stent in the proximal LAD artery (n = 364), and stent to proximal right/circumflex artery (n = 540). Procedural success was higher in the stenting groups, but there were no significant differences in the major in-hospital events between the different lesion locations among the groups. At 1-year follow-up, there was no difference in mortality or myocardial infarction between the groups. There was no significant difference in the rate of target lesion revascularization (TLR) in the patients with proximal LAD stents compared with the patients with proximal right/circumflex coronary artery stents (10.1% vs 13.8%, p = 0.11). In the patients who did not receive stents with proximal narrowings, there was a significant increase in TLR in the LAD group compared with the right/circumflex group (21.1% vs 12.5%, p = 0.04). Thus, patients with proximal stenoses treated with non-stenting strategies have lower procedural success than those treated with stenting strategies; the patients with proximal LAD non-stent PCI have significantly higher rates of clinical restenosis than patients with proximal right and circumflex stenoses. A stenting strategy for proximal LAD stenoses appears to attenuate the differences of clinical restenosis noted after non-stent PCI.


Orientation-Independent Human Activity Recognition Using Complementary Radio Frequency Sensing.
RF sensing offers an unobtrusive, user-friendly, and privacy-preserving method for detecting accidental falls and recognizing human activities. Contemporary RF-based HAR systems generally employ a single monostatic radar to recognize human activities. However, a single monostatic radar cannot detect the motion of a target, e.g., a moving person, orthogonal to the boresight axis of the radar. Owing to this inherent physical limitation, a single monostatic radar fails to efficiently recognize orientation-independent human activities. In this work, we present a complementary RF sensing approach that overcomes the limitation of existing single monostatic radar-based HAR systems to robustly recognize orientation-independent human activities and falls. Our approach used a distributed mmWave MIMO radar system that was set up as two separate monostatic radars placed orthogonal to each other in an indoor environment. These two radars illuminated the moving person from two different aspect angles and consequently produced two time-variant micro-Doppler signatures. We first computed the mean Doppler shifts (MDSs) from the micro-Doppler signatures and then extracted statistical and time- and frequency-domain features. We adopted feature-level fusion techniques to fuse the extracted features and a support vector machine to classify orientation-independent human activities. To evaluate our approach, we used an orientation-independent human activity dataset, which was collected from six volunteers. The dataset consisted of more than 1350 activity trials of five different activities that were performed in different orientations. The proposed complementary RF sensing approach achieved an overall classification accuracy ranging from 98.31 to 98.54%. It overcame the inherent limitations of a conventional single monostatic radar-based HAR and outperformed it by 6%.


Formation of vinylidenes from internal alkynes at a cyclotriphosphato ruthenium complex.
A ruthenium cyclotriphosphato (P(3)O(9)(3-)) complex with a labile MeOH ligand can affect the vinylidene rearrangement of general internal alkynes via the 1,2-migration of alkyl, aryl, and acyl groups. This provides the first internal alkyne-to-vinylidene isomerization with high generality. Several intermediary eta(2)-alkyne complexes could be isolated and were successfully transformed into the corresponding vinylidene complexes. The reaction mechanism is also discussed on the basis of a kinetic study and migratory aptitude of alkyl, aryl, and acyl groups; the present reaction proceeds via an intramolecular process and is viewed as an uncommon electrophilic rearrangement.


Excited-State Proton Transfer in Luminescent Dyes: From Theoretical Insight to Experimental Evidence.
The effective utilization of luminescent dyes often relies on a comprehensive understanding of their excitation and relaxation pathways. One such pathway, Excited-State Proton Transfer (ESPT), involves the tautomerization of the dye in its excited state, resulting in a new structure that exhibits distinct emission properties, such as a very large Stokes' shift or dual-emission. Although the ESPT phenomenon is well-explained theoretically, its experimental demonstration can be challenging due to the presence of numerous other phenomena that can yield similar experimental observations. In this review, we propose that an all-encompassing methodology, integrating experimental findings, computational analyses, and a thorough evaluation of diverse mechanisms, is essential for verifying the occurrence of ESPT in luminescent dyes. Investigations have offered significant understanding of the elements impacting the ESPT process and the array of approaches that can be used to validate the existence of ESPT. These discoveries hold crucial ramifications for the advancement of molecular probes, sensors, and other applications that depend on ESPT as a detection mechanism.


Heterologous expression of a gene encoding cholesterol oxidase in probiotic strains of Lactobacillus plantarum and Propionibacterium freudenreichii under the control of native promoters.
To develop systems for the expression of heterologous genes in probiotic strains of Lactobacillus and Propionibacterium, we used Lactobacillus plantarum and Propionibacterium freudenreichii and a modified gene encoding cholesterol oxidase (choA) from Streptomyces sp. to generate working models. The acetyl coenzyme A carboxylase (acc) promoter derived from the acc operon of L. plantarum L137 and a previously constructed shuttle vector, pRN14, were used to construct vectors for the expression of heterologous genes in lactic acid bacteria. The concentration of cholesterol oxidase in recombinant L. plantarum carrying choA fused to the NH2-terminal region of the first open reading frame of the acc operon was 3.6 mU/mg of protein. Using the promoters from Propionibacterium, namely, P4, P8, and P138, which enabled high-level expression of choA in Escherichia coli, and a previously constructed shuttle vector pPK705, we constructed expression vectors for Propionibacterium. In recombinant P. freudenreichii subsp. shermanii IFO12426, the activities of cholesterol oxidase generated under the control of promoters P4, P8, and P138 were 1.6, 4.3, and 7.2 U/mg of protein, respectively. The expression of heterologous genes may facilitate the production of useful proteins in these economically important bacteria.


Modeling the assembly of the multiple domains of α-actinin-4 and its role in actin cross-linking.
The assembly of proteins into multidomain complexes is critical for their function. In eukaryotic nonmuscle cells, regulation of the homodimeric actin cross-linking protein α-actinin-4 (ACTN4) during cell migration involves signaling receptors with intrinsic tyrosine kinase activity, yet the underlying molecular mechanisms are poorly understood. As a first step to address the latter, we validate here an atomic model for the ACTN4 end region, which corresponds to a ternary complex between the N-terminal actin-binding domain (ABD) and an adjacent helical neck region of one monomer, and the C-terminal calmodulin-like domain of the opposite antiparallel monomer. Mutagenesis experiments designed to disrupt this ternary complex confirm that its formation reduces binding to F-actin. Molecular dynamics simulations show that the phosphomimic mutation Y265E increases actin binding by breaking several interactions that tether the two calponin homology domains into a closed ABD conformation. Simulations also show a disorder-to-order transition in the double phosphomimic mutant Y4E/Y31E of the 45-residue ACTN4 N-terminal region, which can inhibit actin binding by latching both calponin homology domains more tightly. Collectively, these studies provide a starting point for understanding the role of external cues in regulating ACTN4, with different phenotypes resulting from changes in the multidomain assembly of the protein.


A Survey of Lost-in-Space Star Identification Algorithms since 2009.
The lost-in-space star identification algorithm is able to identify stars without a priori attitude information and is arguably the most critical component of a star sensor system. In this paper, the 2009 survey by Spratling and Mortari is extended and recent lost-in-space star identification algorithms are surveyed. The covered literature is a qualitative representation of the current research in the field. A taxonomy of these algorithms based on their feature extraction method is defined. Furthermore, we show that in current literature the comparison of these algorithms can produce inconsistent conclusions. In order to mitigate these inconsistencies, this paper lists the considerations related to the relative performance evaluation of these algorithms using simulation.


Development and assessment of relative validity and reliability of the Workplace Beverage Intake Questionnaire in UK office workers.
There are no beverage measurement tools evaluated for use in UK working-age adults. This study aimed to develop and evaluate a novel beverage intake questionnaire. A 57-item online tool (Workplace Beverage Intake Questionnaire [WBIQ]) was developed through stakeholder consensus. Relative validity was measured against 7-day food records, and reliability was tested across three time points. Evaluation outcomes of interest were total beverage intake and beverage intake during working hours, intake from seven beverage categories (plain water, sugar sweetened, low/zero calorie, tea, coffee, milk based and 100% fruit based) and energy, caffeine and free sugar intake from beverages. Reliability was determined by intraclass correlation coefficients (ICC) and validity via correlation analyses and visual assessment of Bland-Altman plots. The evaluation study population comprised office workers (n = 71, 74.6% women, mean age: 32, standard deviation: 8.5 years). The WBIQ had moderate reliability (ICC: 0.50-0.75) across total fluid intake and all beverage categories except milk-based drinks and 100% fruit-based drinks where it was rated poor. Caffeine, free sugar and energy from beverages had poor-to-moderate reliability. Correlation coefficients were large (r > 0.50, p < 0.001) comparing diet records and WBIQ across all categories of beverage except low-/zero-calorie soft drinks (r = 0.34, p < 0.01). Bland-Altman plots showed a similar trend across all variables, with better agreements at lower intake and the absolute difference increasing proportionally at higher intakes. Over 90% of respondents agreed/strongly agreed that the tool was easy to navigate and understand. The WBIQ is the first stage in the development of a tool for UK-specific beverage intake measurement in working-age adults. Further refinement and testing are required to improve reliability.


[Colonic necrosis following a pancreatic pseudocyst embolization].
A 43-year-old man with chronic alcohol pancreatitis was admitted in our intensive care unit for an haemorrhagic shock. An abdominal CT-scan performed on admission showed bleeding from a vessel in a pancreatic pseudocyst. Initial treatment included intravenous fluids, transfusion, mechanical ventilation and vasopressive support. Percutaneous arterial embolization (PAE) of a bleeding right superior colon artery was performed with an initial good result. Nevertheless after initial clinical improvement, hypotension refractory to fluid management occurred. An abdominal CT-scan disclosed pneumatosis in right colon. A right hemicolectomy was performed. Histologic analysis confirmed ischemic colitis. The patient recovered and was discharged from the intensive care unit. Colitis necrosis after PAE for pancreatic pseudoaneurysm had never been described before. It should be suspected when haemodynamic instability occurs following PAE.


Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling.
Transmembrane signaling by plant receptor kinases (RKs) has long been thought to involve reciprocal trans-phosphorylation of their intracellular kinase domains. The fact that many of these are pseudokinase domains, however, suggests that additional mechanisms must govern RK signaling activation. Non-catalytic (pseudo)kinase signaling mechanisms have been described in metazoans, but information is scarce for plants. Recently, a non-catalytic function was reported for the leucine-rich repeat (LRR)-RK subfamily XIIa member EFR (ELONGATION FACTOR TU RECEPTOR) and phosphorylation-dependent conformational changes were proposed to regulate signaling of RKs with non-RD kinase domains. Here, using EFR as a model, we describe a non-catalytic activation mechanism for LRR-RKs with non-RD kinase domains. EFR is an active kinase, but a kinase-dead variant retains the ability to enhance catalytic activity of its co-receptor kinase BAK1/SERK3 (BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1/SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3). Applying hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis and designing homology-based intragenic suppressor mutations, we provide evidence that the EFR kinase domain must adopt its active conformation in order to activate BAK1 allosterically, likely by supporting αC-helix positioning in BAK1. Our results suggest a conformational toggle model for signaling, in which BAK1 first phosphorylates EFR in the activation loop to stabilize its active conformation, allowing EFR in turn to allosterically activate BAK1.


Dynamical response of an excitatory-inhibitory neural network to external stimulation: an application to image segmentation.
Neural network models comprising elements that have exclusively excitatory or inhibitory synapses are capable of a wide range of dynamical behavior, including chaos. In this paper, a simple excitatory-inhibitory neural pair, which forms the building block of larger networks, is subjected to external stimulation. The response shows transition between various types of dynamics, depending upon the magnitude of the stimulus. The corresponding network model, obtained by coupling such pairs over a local neighborhood in a two-dimensional plane, can achieve a satisfactory segmentation of an image into "object" and "background." Results for synthetic and "real-life" images are given.


Interactive effects of cholecystokinin-8S and various serotonin receptor agonists on the firing activity of neostriatal neuronesin rats.
In rats anaesthetized with urethane single unit activity was extracellularly recorded in the neostriatum, and several drugs were microiontophoretically ejected. Separate administration of the sulfated octapeptide cholecystokinin (CCK-8S), serotonin (5-HT) or 8-OH-DPAT (a 5-HT(1A/7) receptor agonist) predominantly induced increases in the neuronal discharge rates (Wilcoxon test significant P<0.05), whereas the 5-HT(2A/2C) receptor agonist DOI affected only a few neurones and mainly reduced firing. After coadministration of CCK-8S and serotonin, activating effects also predominated (Wt P<0.05), but the neuronal responsiveness was significantly reduced (Chi2P<0.01). Similarly, concomitant application of CCK-8S and 8-OH-DPAT led to significant activation accompanied with a reduction of inhibitory effects. The block of serotonin- or 8-OH-DPAT-effects through specific 5-HT(1A) receptor antagonists implies the involvement of this receptor subtype within the striatum. In conclusion, concomitant action of CCK-8S and serotonin induces a mean level of neuronal activation that might promote normal function.


[Stationary and migratory avifauna as reservoirs of Salmonella, Yersinia and Campylobacter].
Domestic and wild animals have been always considered very important as reservoir of agents of human infections. Particularly birds, because of their great mobility from a continent to another or within the limits of the same ecosystem may transfer pathogenic micro-organisms. The present survey was undertaken in order to evaluate the presence of Campylobacter, Yersinia and Salmonella in migratory and permanent birds. During the period October 1986 to March 1988 intestinal loops were collected from a total of 217 birds representing 17 different species shot, during hunting seasons, in the inland of Versilia in the district of Lucca. Each sample was divided into three parts and examined for the presence of Campylobacter, Yersinia and Salmonella. Campylobacter was isolated from 74 of the 217 birds examined (34.10%). Yersinia was recovered from 26 birds (11.98%), while only 8 birds (3.68%) harboured Salmonella. Most of the samples carried only one of the three bacterial genera investigated while 9 harboured at the same time Yersinia and Campylobacter, 1 Salmonella and Campylobacter, and 1 Salmonella, Yersinia and Campylobacter. Campylobacter spp.: On the ground of Lior's biotyping scheme, the 74 strains, isolated from 16 of the 17 species of birds examined, have assigned to three biochemically different species. C. coli was the most commonly isolated followed by C. jejuni and C. laridis. Of the 54 isolates of C. coli 30 belonged to biotype I and 24 to biotype II. 19 C. jejuni organisms were differentiated into 5 belonging to biotype I and 14 to biotype II. The only C. laridis isolated belonged to biotype I. Yersinia spp.: 37 strains belonging to the genus Yersinia were isolated from 26 birds. In 10 samples different types of Yersinia were identified. Most of the strains could be ascribed to Yersinia enterocolitica (28 strains), 3 to Yersinia frederiksenii, 3 to Yersinia intermedia and 1 to Yersinia pseudotuberculosis. 2 strains were identified as atypical Yersinia. Salmonella spp.: 8 strains belonging to the genus Salmonella were isolated from 3 different species of birds. The isolates were identified as Salmonella typhi-murium (7 strains) and Salmonella blockley (1 strain). Salmonella has been isolated from 8 birds, six of which were pheasants shot during the same day in the same area and probably coming from the same breeding. In fact, in Tuscany, pheasants are bred and then set free in many hunting areas.(ABSTRACT TRUNCATED AT 400 WORDS)


Leucocyte migration inhibition test in human Plasmodium vivax malaria.
Specific antigen-induced T-lymphocyte response in human P. vivax malaria has been studied by a leucocyte migration inhibition test. The test was performed in four groups: (1) American/European controls; (2) Indians with acute P. vivax malaria; (3) immune Indians with no clinical attacks of malaria for 5 years; and (4) Indians with chronic infection. Group 3 showed significantly high inhibition as compared to group 1 (P less than 0.001) and group 2 (P less than 0.01). There was however no significant difference between the 'immune' and 'chronic' groups. Indirect haemagglutinating antibodies were also monitored in the test sera and there was an inverse correlation (r = -0.613; P less than 0.01) between IHA antibodies in serum and percentage leucocyte migration inhibition.


Relationship between children's physical activity, sedentary behavior, and childcare environments: A cross sectional study.
The purpose of this study was to investigate the relationship between the childcare environment and physical activity and sedentary behavior of toddlers and preschoolers. A total of 68 toddlers (1.0-2.9 years) and 233 preschoolers (3.0-5.9 years) were recruited from 11 childcare services in 2013 within the Illawarra and Shoalhaven region of NSW, Australia. For this study analysis was conducted in 2016. The childcare environment was assessed using the Environment and Policy Assessment Observation (EPAO) instrument, and childcare services categorized as low, medium, or high based on their scores. Time spent in physical activity and sitting was assessed over one week using activPAL accelerometers. Relationship between EPAO and children's physical activity and sedentary behavior was assessed using multilevel mixed-effects linear regression. Toddlers who attended high EPAO services sat more (8.73 min [- 10.26, 27.73]) and stood less (- 13.64 min [- 29.27, 2.00]) than those who attended low EPAO services. Preschoolers who attended high EPAO services sat less than those in low and medium services (mean [95%CI] = - 7.81 min [- 26.64, 11.02]). Sub-categories of the EPAO that were associated with less time sitting were: sedentary environments for toddlers and portable play equipment for preschoolers. This study extends previous research by identifying differences between toddlers and preschooler's physical activity and sedentary behaviors in relation to childcare environments. A greater understanding of how the childcare environment relates to sitting time for both toddlers and preschool aged children is needed.