Patterns in the Belousov-Zhabotinsky reaction in water-in-oil microemulsion induced by a temperature gradient.
We investigate the effect of changing temperature in the ferroin-catalysed Belousov-Zhabotinsky (BZ) reaction dispersed in the water nanodroplets of a water-in-oil aerosol OT (AOT) microemulsion, which undergoes a temperature-induced percolation transition at about 38 degrees C. We observe stationary Turing patterns at temperatures in the range 15-35 degrees C and bulk oscillations at T = 40-55 degrees C. When a temperature gradient DeltaT is applied normal to a thin layer of the BZ-AOT reaction mixture, the range of patterns observed is dramatically expanded. Anti-phase oscillatory Turing patterns, leaping waves, and chaotic waves emerge, depending on the temperature gradient and the average temperature. These new patterns originate from the coupling between a low temperature Turing mode and a high temperature Hopf mode. Simulations with a simple model of the BZ-AOT system give good agreement with our experimental results.


Safety of topotecan in the treatment of recurrent small-cell lung cancer and ovarian cancer.
The topoisomerase I inhibitor, topotecan, is approved for the treatment of recurrent small-cell lung cancer (SCLC) and ovarian cancer (OC). Patients with recurrent SCLC and OC typically experience multiple relapses and receive multiple rounds of chemotherapy. In these settings, disease stabilisation is considered a treatment benefit, and quality-of-life effects and cumulative toxicities of treatments should be considered. Many patients with recurrent cancer may be predisposed to treatment-related adverse events because of advanced age, renal impairment or extensive prior therapy. The standard regimen of topotecan, 1.5 mg/m(2) on days 1-5 of a 21-day cycle, has generally mild nonhaematological toxicity and a well-defined haematological toxicity profile characterised by reversible and noncumulative neutropenia. Alternative regimens may lower the incidence of haematological toxicities and maintain antitumour efficacy. Topotecan may provide physicians with a versatile therapeutic option for the treatment of patients with relapsed SCLC or OC.


Resonances and multistability in a Josephson junction connected to a resonator.
We study the dynamics of a Josephson junction connected to a dc current supply via a distributed parameter capacitor, which serves as a resonator. We reveal multistability in the current-voltage characteristic of the system; this multistability is related to resonances between the generated frequency and the resonator. The resonant pattern requires detailed consideration, in particular, because its basic features may resemble those of patterns reported in experiments with arrays of Josephson junctions demonstrating coherent stimulated emission. From the viewpoint of nonlinear dynamics, the resonances between a Josephson junction and a resonator are of interest because of the specificity of the former; its oscillation frequency is directly governed by control parameters of the system and can vary in a wide range. Our analytical results are in good agreement with the results of numerical simulations.


Immune responses in Mycoplasma pneumoniae infections.
All children with Mycoplasma pneumoniae infection showed a significant response in IgG immunofluorescent (IMF) antibody titers, which were similar to that of complement-fixing (CF) antibody titers. However, there was a certain degree of variation in IgM IMF antibody response and its persistence. This variation also occurred in cases with pre-existing specific antibodies and good CF and IgG IMF antibody titers. Thus, it was considered that a reinfection with M. pneumoniae might not have an important effect upon the individual variation in IgM immune response, and that after a secondary immune response with M. pneumoniae infection with specific IgM antibody could be detected in some patients.


Effects of social support and coping of family caregivers of older adults with dementia in Taiwan.
The purpose of this study was to explore the relationship of demographic characteristics, contextual factors, social support, and coping on health outcomes of family caregivers of older adults with dementia in Taiwan. This study also examined caregiving stress and whether support moderated the effects of caregiver stress on health. Lazarus and Folkman's (1984) Stress model guided this study. The descriptive cross-sectional study included subjects who were primary family caregivers of older adults with dementia from two settings in southern Taiwan. A convenience sample of 148 participants was interviewed. Data analysis consisted of Pearson's correlations, and simple and multiple regression analysis. Findings indicated that younger caregivers, those with paid assistants, and those with longer duration of caregiving had better health. Females with lower income and without assistants had more depressive symptoms. In addition, moderating effects of social support were supported. The results from this study provided a basis for developing interventions to minimize negative impacts on caregivers.


Implementation of a mobile 0.15-T intraoperative MR system in pediatric neuro-oncological surgery: feasibility and correlation with early postoperative high-field strength MRI.
We analyze our preliminary experience using the PoleStar N20 mobile intraoperative MR (iMR) system as an adjunct for pediatric brain tumor resection. We analyzed 11 resections in nine children between 1 month and 17 years old. After resection, we acquired iMR scans to detect residual tumor and update neuronavigation. We compared final iMR interpretation by the neurosurgeon with early postoperative MR interpretation by a neuroradiologist. Patient positioning was straightforward, and image quality (T1 7-min 4-mm sequences) sufficient in all cases. In five cases, contrast enhancement suspect for residual tumor was noted on initial postresection iMR images. In one case, a slight discrepancy with postoperative imaging after 3 months was no longer visible after 1 year. No serious perioperative adverse events related to the PoleStar N20 were encountered, except for transient shoulder pain in two. Using the PoleStar N20 iMR system is technically feasible and safe for both supra- and infratentorial tumor resections in children of all ages. Their small head and shoulders favor positioning in the magnet bore and allow the field of view to cover more than the area of primary interest, e.g., the ventricles in an infratentorial case. Standard surgical equipment may be used without significant limitations. In this series, the use of iMR leads to an increased extent of tumor resection in 45 % of cases. Correlation between iMR and early postoperative MR is excellent, provided image quality is optimal and interpretation is carefully done by someone sufficiently familiar with the system.


The clinical advances of fluorine-2-D-deoxyglucose--positron emission tomography/computed tomography in urological cancers.
Fluorine-18 labeled fluorine-2-D-deoxyglucose (FDG) is the most frequently used positron emission tomography (PET) probe but it has certain limitations when used in urological cancers. The introduction of co-registered PET and computed tomography (PET/CT) represents a major advance in technology and FDG-PET/CT has now become the new standard. The diagnostic performance of FDG-PET and PET/CT depends on the metabolic activity of tumor tissue, which is generally low in primary renal cell and prostate cancers and often in their metastatic deposits. In contrast, both seminomatous and nonseminomatous germ cell tumors are characterized by upregulated glucose metabolism with subsequently increased FDG uptake in tumor sites. Generally, the metabolic activity provides accurate information regarding the presence of a viable tumor, except in patients with residual mature teratoma. Although bladder cancer demonstrates sufficiently increased FDG uptake, primary tumors are difficult to identify due to the renal excretion of FDG. The accuracy of FDG-PET/CT in metabolically active metastases is generally higher compared to conventional CT except for identifying small lung deposits. With disease progression and subsequent de-differentiation of prostate cancer, castrate resistant disease is more likely to present with lesions that have increased glucose metabolism.


[TRENDS IN DEVELOPMENT OF GI-SAFE ANTI-INFLAMMATORY DRUGS].
Despite the introduction of anti-inflammatory drugs that selectively inhibit cyclo-oxygenase-2 (COX-2), and potent inhibitors of gastric acid secretion, the gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) remain a significant clinical problem. Combined use of antisecretory drugs and COX-2 inhibitors is helpful to limit the damage in the proximal gastrointestinal tract (stomach and duodenum), but it increases the risk of injury of small intestine and colon. It was proven that proton pump inhibitors and H2 receptor antagonists significantly worsen NSAID-induced small intestinal damage and microbiota balance. Nowadays, there is no proven effective preventative or curative treatment for NSAID-induced enteropathy. The new strategy of gastrointestinal protection is based on the discovery of endogenous cytoprotective molecules such as hydrogen sulfide (H₂S). H2S is a gaseous mediator that produces strong cytoprotective and antioxidant effect on the gastrointestinal tract. The role of H₂S in promoting mucosal integrity, healing of tissue injury and resolution of inflammation has been well documented. In addition, H₂S stimulates productions of other cytoprotective molecules including prostaglandins, carbon monoxide and nitric oxide. Nowadays, the new generation of H₂S-releasing non-steroidal anti-inflammatory drugs is developed and tested in clinical trials. H₂S-NSAIDs possess enhanced anti-inflammatory activity and high gastrointestinal safety.


The pathophysiology of stress urinary incontinence: a historical perspective.
This article provides a historical perspective on the evolution of theories regarding the pathophysiology of stress urinary incontinence (SUI). The progression of these theories has followed the development of the diagnostic technologies that have provided insight into different aspects of urethral dysfunction. The earliest theories tied SUI to anatomic failure of urethral support. Recognition that anatomic failure impacted the interplay of intra-abdominal pressure and the bladder and urethra led to theories focused on the dynamic interaction between the bladder and urethral pressures. Investigators then began to recognize the importance of urethral sphincteric dysfunction. More recently, investigators have attempted to combine the anatomic and functional etiologies into a consolidated theory. These efforts point to a multi-factorial etiology of SUI. Continuing research has provided new insight into the neurophysiology of urethral function, opening new avenues for tailoring therapy for SUI.


Effects of putative K+ channel blockers on beta-adrenoceptor-mediated vasorelaxation of rat mesenteric artery.
The aim of our study was to investigate the contribution of Ca(2+)-activated K+ channels (KCa channels) and ATP-sensitive K+ channels (KATP channels) to the vasodilator responses to beta-adrenoceptor agonists in the rat isolated mesenteric artery. Isoprenaline and fenoterol concentration-dependently relaxed the phenylephrine-precontracted endothelium-intact arterial rings with 50% inhibitory concentration (IC50) of 0.0314 +/- 0.027 microM (n = 20) and 0.40 +/- 0.04 microM (n = 11), respectively. Charybdotoxin (100 nM) displaced the isoprenaline or fenoterol logarithmic concentration-relaxation curve to the right in the absence and presence of endothelium. In contrast, glibenclamide (10 microM) did not affect the effects of isoprenaline and fenoterol, whereas glibenclamide (3 microM) significantly inhibited the cromakalim-induced vasorelaxation. Neither charybdotoxin (100 nM) nor glibenclamide (10 microM) influenced the vasorelaxation induced by forskolin. Ba2+, a nonselective blocker of K+ channels, inhibited the relaxant effects of isoprenaline and forskolin. These results suggest that KCa but not KATP channels contribute to beta-adrenoceptor-mediated vasodilator response in rat mesenteric artery, and cyclic adenosine monophosphate (cAMP) might not be involved in regulation of the activity of KCa channels.


Patient-Centered Medical Home Undergraduate Internship, Benefits to a Practice Manager: Case Study.
Health services management interns become practice facilitators for primary care clinics interested in pursuing patient-centered recognition for their practice. This experience establishes a collaborative relationship between the university and clinic practices where students apply their academic training to a system of documentation to improve the quality of patient care delivery. The case study presents the process undertaken, benefits, challenges, lessons learned, and recommendations for intern, practice mangers, and educators. The practice manager benefits as interns become Patient-Centered Medical Home facilitators and assist practice managers in the recognition process.


Histone H4 histidine kinase displays the expression pattern of a liver oncodevelopmental marker.
Protein phosphorylation is a vital process in the regulation of mammalian cell division and the protein kinases that catalyze the phosphorylation of proteins on serine, threonine and tyrosine residues have been well characterized. In contrast, little is known about the kinases involved in protein histidine phosphorylation, which have been described in various mammalian cells that are highly proliferative. Histone H4 histidine kinase (HHK) activity is highly active in regenerating rat liver. Using a novel and specific assay, we demonstrate that it is active in human fetal liver, essentially absent in adult liver and highly expressed in liver tumours. 'Normal' liver surrounding the HCC contains low to undetectable levels of HHK. In a rodent model of chronic liver injury that leads to HCC, its activity is induced. Two lines of evidence suggest that liver progenitor (oval) cells, which populate the liver at early stages following induction of liver damage are responsible for the increased activity. Purified oval cells, as well as cell lines established from primary cultures of oval cells express high levels of HHK. We propose that the pattern of expression of histone H4 histidine kinase activity justifies its classification as an oncodevelopmental marker and suggest it may be useful as a diagnostic marker for hepatocellular carcinoma as well for identifying preneoplastic lesions.


Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29.
Because of their deleterious effects on developing organisms, ribosomal protein (RP) mutations have been poorly described in mammals, and only a few heterozygous mutations have been shown to be viable. This observation is believed to be due to the fact that each RP is an essential component in the assembly of a functional stable ribosome. Here, we created gene targeted mutant mice lacking HIP/RPL29, an RP associated with translationally active ribosomes in eukaryotes. In contrast to other RP mutants, HIP/RPL29 null mice are viable but are up to 50% smaller than their control littermates at weaning age. In null embryos, delayed global growth is first observed around mid-gestation, and postnatal lethality due to low birth weight results in distortion of the Mendelian ratio. Prenatal growth defects are not fully compensated for during adulthood, and null animals display proportionately smaller organs and stature, and reach sexual maturity considerably later when compared with their control siblings. Additionally, HIP/RPL29 null embryonic fibroblasts have decreased rates of proliferation and protein synthesis and exhibit reduced steady state levels of core RPs. Altogether, our findings provide conclusive genetic evidence that HIP/RPL29 functions as an important regulator of global growth by modulating the rate of protein synthesis.


[Child sexual abuse].
The present paper gives an overview on the development of professional discourse on sexual abuse over the last 20 years in the field of child protection. After the introduction, definitions from different professional perspectives (civil law, criminal law, psychotherapy, counseling, etc.) are given. Based on these definitions an epidemiological range of prevalence figures is described. In the literature, rates ranging from 6 to 25 % in girls and 2 to 8 % in boy as victims of sexual abuse can be observed. Psychiatric consequences of sexual abuse are described based on an overview of the literature. Diagnostic approaches to posttraumatic problems are discussed and distinguished from obsolete measures. Some neurobiological findings are presented. Finally the foundations of counseling, psychotherapy and pharmacotherapy of behavioral of symptoms and PTSD are discussed on the bases of a literature review of controlled clinical trials. In conclusion, further developments in psychotherapy and research are discussed for the German practical child protection field.


Assessing Clinical Embryology Research: A Global Bibliometric Analysis.
Background and Objectives: The evaluative strength of available bibliometric tools in the field of clinical embryology has never been examined in the literature. The aim is to bring insight regarding the identity of clinical embryology research, introducing concerns when solely relying on the methodology of bibliometric analysis. Methods: An all-inclusive analysis of the most bibliometrically highlighted scientific contributions regarding the cornerstones of clinical embryology was performed employing the Scopus, Web of Science (WoS) and PubMed databases, between 1978-2018. An analysis of the number of publications, respective citations and h-index, g-index, along with m-quotient is presented. The top 30 contributing authors for each distinctive area of research are listed. An attempt at visualizing the yearly published articles, clusters, and collaborations of authors, along with the geographic origin of publications, is also presented. Results: Combining all searches and keywords yielded 54,522 results. In the Scopus database, employing the keyword "In Vitro Fertilization" yielded 41,292 results. The publications of the top five authors in each research field were analytically presented and compared to the total number of publications for each respective field. The research field of Preimplantation Genetic Diagnosis/Screening/Testing was allocated the highest percentage of publications produced by the top five authors. Regarding journal bibliometrics, based on the year 2017 metrics, there are only 29 journals according to WoS that refer to "Reproductive Biology", ranking it 187th among 235 disciplines. The USA produced the highest number of publications (12,537). Conclusion: Results indicate an explosion of interest published in the literature regarding the field of clinical embryology. Further analysis on collaborations and the trends involved should be of added value as productivity between countries varies significantly. This may guide researchers, in vitro fertilization professionals, and prospective authors during literature search, while proving useful regarding manuscript design and concurring on keywords and abstract content.


Photonic topological subspace-induced bound states in the continuum.
Bound states in the continuum (BICs) are intriguing localized states that possess eigenvalues embedded within the continuum of extended states. Recently, a combination of topological band theory and BIC physics has given rise to a novel form of topological matter known as topological BICs. In this work, we experimentally demonstrate the photonic topological subspace-induced BICs. By using femtosecond-laser writing, we experimentally establish a photonic nontrivial three-leg ladder lattice, thereby directly observe the localized propagation of two kinds of topological edge states which exist at different boundaries. Interestingly, such edge states appear in the continuum of the bulk modes, and the topological properties are inherited from its independent subspace Hamiltonian which contains a celebrated Su-Schrieffer-Heeger lattice. This work not only presents a novel, to the best of our knowledge, platform for investigating topological physics in optics, but also unveils exciting prospects for future exploration of other remarkable BICs.


Evolution of specificity in protein-protein interactions.
Hub proteins are proteins that maintain promiscuous molecular recognition. Because they are reported to play essential roles in cellular control, there has been a special interest in the study of their structural and functional properties, yet the mechanisms by which they evolve to maintain functional interactions are poorly understood. By combining biophysical simulations of coarse-grained proteins and analysis of proteins-complex crystallographic structures, we seek to elucidate those mechanisms. We focus on two types of hub proteins: Multi hubs, which interact with their partners through different interfaces, and Singlish hubs, which do so through a single interface. We show that loss of structural stability is required for the evolution of protein-protein-interaction (PPI) networks, and it is more profound in Singlish hub systems. In addition, different ratios of hydrophobic to electrostatic interfacial amino acids are shown to support distinct network topologies (i.e., Singlish and Multi systems), and therefore underlie a fundamental design principle of PPI in a crowded environment. We argue that the physical nature of hydrophobic and electrostatic interactions, in particular, their favoring of either same-type interactions (hydrophobic-hydrophobic), or opposite-type interactions (negatively-positively charged) plays a key role in maintaining the network topology while allowing the protein amino acid sequence to evolve.


Validation and Normalization of Grasha-Riechmann Teaching Style Inventory in Faculty Members of Zahedan University of Medical Sciences.
Considering the importance of teaching styles and their impact on promoting higher education, and the lack of a valid and reliable tool in universities of medical sciences for measuring this concept, as well as no instruments normalized for Faculty of Medical Sciences, the aims of this study were to 1) evaluate and normalize Grasha-Riechmann Teaching Style Inventory and 2) determine the teaching style of the faculty members of Zahedan University of Medical Sciences during 2018-2019. This was a methodological study. In order to carry out this study, Grasha-Riechmann Teaching Style Inventory was translated and culturally adopted. To measure validity, reliability, and normalize the questionnaire, it was distributed among the study population composed of 361 faculty members (instructor, assistant professor, associate professor, and professor) who were taught theoretical and practical courses in Zahedan University of Medical Sciences, Zahedan, Iran, during the academic year 2018-2019. Confirmatory factor analysis (CFA) and Cronbach's alpha using SPSS version 16 were used to analyze the data. The results of data analysis showed that of the 361 participants, 212 were men and 149 were women. The mean age of the participants was 42.52 ± 7.72 years and their average work experience was 10.12 ± 7.61 years. Content validity was calculated using content validity index (CVI) and content validity ratio (CVR) for each item, and it was reported 97.4 and 68.5, respectively. Cronbach's alpha was used to determine the internal consistency, and its value was 95%. The construct validity of the Grasha-Riechmann Teaching Style Inventory was assessed using CFA by EQS version 6.1. The value of root mean square error of approximation (RMSEA) was 0.075 with the 90% confidence interval, and the GFI value was 0.74. The mean scores and standard deviations (SD) of teaching styles were 5.61 ± 0.61 for Expert teaching style, 5.23 ± 0.72 for formal authority teaching style, 5.39 ± 0.66 for personal model teaching style, 5.43±0.71 for facilitator teaching style, and 4.99 ± 0.82 for delegator teaching style. Our results suggested dominance of the expert (88.6%) and delegator (79.8%) teaching styles as well as the modest use of personal model (65.9%), formal authority (59.3%), and facilitator (55.7%) teaching styles among the faculty members of Zahedan University of Medical Sciences. The results of the current study will be effective in promoting education level and increasing students' satisfaction with the academic courses. Researchers and those interested in university medical education and development centers can benefit from the results of this study. For the first time, the psychometric test (normalizing and validating) of Grasha-Riechmann Teaching Style Inventory has been carried out at Zahedan University of Medical Sciences. Also, this questionnaire has been applicable to determine teaching styles of faculty members. Overall, the results of the present study showed that the Grasha-Riechmann teaching Style Inventory had a good internal consistency and can be used as a valid tool for evaluating teachers' teaching style.


Modulating Electronic Structure by Etching Strategy to Construct NiSe2 /Ni0.85 Se Heterostructure for Urea-Assisted Hydrogen Evolution Reaction.
Exploring and developing novel strategies for constructing heterostructure electrocatalysts is still challenging for water electrolysis. Herein, a creative etching treatment strategy is adopted to construct NiSe2 /Ni0.85 Se heterostructure. The rich heterointerfaces between NiSe2 and Ni0.85 Se emerge strong electronic interaction, which easily induces the electron transfer from NiSe2 to Ni0.85 Se, and tunes the charge-state of NiSe2 and Ni0.85 Se. In the NiSe2 /Ni0.85 Se heterojunction nanomaterial, the higher charge-state Ni0.85 Se is capable of affording partial electrons to combine with hydrogen protons, inducing the rapid formation of H2 molecule. Accordingly, the lower charge-state NiSe2 in the NiSe2 /Ni0.85 Se heterojunction nanomaterial is more easily oxidized into high valence state Ni3+ during the oxygen evolution reaction (OER) process, which is beneficial to accelerate the mass/charge transfer and enhance the electrocatalytic activities towards OER. Theoretical calculations indicate that the heterointerfaces are conducive to modulating the electronic structure and optimizing the adsorption energy toward intermediate H* during the hydrogen evolution reaction (HER) process, leading to superior electrocatalytic activities. To expand the application of the NiSe2 /Ni0.85 Se-2h electrocatalyst, urea is served as the adjuvant to proceed with the energy-saving hydrogen production and pollutant degradation, and it is proven to be a brilliant strategy.


Probing Spatial Proximity of Supported Lipid Bilayers to Silica Surfaces by Localized Surface Plasmon Resonance Sensing.
On account of high surface sensitivity, localized surface plasmon resonance (LSPR) sensors have proven widely useful for studying lipid membrane configurations at solid-liquid interfaces. Key measurement capabilities include distinguishing adsorbed vesicles from supported lipid bilayers (SLBs) as well as profiling the extent of deformation among adsorbed vesicles. Such capabilities rely on detecting geometrical changes in lipid membrane configuration on a length scale that is comparable to the decay length of the LSPR-induced electromagnetic field enhancement (∼5-20 nm). Herein, we report that LSPR sensors are also capable of probing nanoscale (∼1 nm) variations in the distance between SLBs and underlying silica-coated surfaces. By tuning the electrostatic properties of lipid membranes, we could modulate the bilayer-substrate interaction and corresponding separation distance, as verified by simultaneous LSPR and quartz crystal microbalance-dissipation (QCM-D) measurements. Theoretical calculations of the expected variation in the LSPR measurement response agree well with experimental results and support that the LSPR measurement response is sensitive to subtle variations in the bilayer-substrate separation distance.


Diffusion kinetics of tritiated uridine into HeLa cells previously exposed to hyperthermia.
Hyperthermic treatment of HeLa cells at 42 degrees C for 60 min depressed the specific activity of these cells when incubated with 3H-uridine both during and post heating compared to cells maintained at 37 degrees C. These changes were unlikely to arise from increased leakage from the cells and may partially be attributed to membrane damage influencing facilitated diffusion. Diffusion kinetic data for incorporation of the radiolabel into the T.C.A. soluble and T.C.A. insoluble fractions of HeLa cells indicated that a significant depression of Vmax and a significant elevation of Km for incorporation of 3H UdR into RNA may possibly result from an isotope dilution effect attributed to degrading pre-ribosomal RNA under the effect of hyperthermia.


Nanoparticles for tumor targeted therapies and their pharmacokinetics.
Various types of nanoparticles, such as liposomes, polymeric micelles, dendrimers, superparamagnetic iron oxide crystals, and colloidal gold, have been employed in targeted therapies for cancer. Both passive and active targeting strategies can be utilized for nano-drug delivery. Passive targeting is based on the enhanced permeability and retention (EPR) effect of the vasculature surrounding tumors. Active targeting relies on ligand-directed binding of nanoparticles to receptors expressed by tumor cells. Release of loaded drugs from nanoparticles may be controlled in response to changes in environmental condition such as temperature and pH. Biodistribution profiles and anticancer efficacy of nano-drugs in vivo would be different depending upon their size, surface charge, PEGylation and other biophysical properties. This review focuses on the recent development of nanoparticles for tumor targeted therapies, including physicochemical properties, tumor targeting, control of drug release, pharmacokinetics, anticancer efficacy and safety. Future perspectives are discussed as well.


Is cytology reliable for epidermal growth factor receptor gene evaluation in non-small cell lung cancer?
Epidermal growth factor receptor (EGFR) gene copy number has been proposed as predictor of response to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer (NSCLC). Cytologic and matched histologic samples from 33 primary non-small cell lung cancers were analyzed by fluorescence in situ hybridization (FISH) for epidermal growth factor receptor gene. FISH was positive in 52% and negative in 35% of the 31 matched evaluable samples. Four of 31 (13%) cases were discordant (K = 0.736; p < 0.001). Our data support the feasibility and reliability of epidermal growth factor receptor gene assessment by FISH on cytology.


When the embryonic genome flexes its muscles.
During the development of multicellular organisms, both transient and stable gene expression patterns have to be established in a precisely orchestrated sequence. Evidence from diverse model organisms indicates that this epigenetic program involves not only transcription factors, but also the local structure, composition, and modification of chromatin, which define and maintain the accessibility and transcriptional competence of the nucleosomal DNA template. A paradigm for the interdependence of development and chromatin is constituted by the mechanisms controlling the specification and differentiation of the skeletal muscle cell lineage in vertebrates, which is the topic of this review.


Immediate fundus complications after retinal scatter photocoagulation. I. Clinical picture and pathogenesis.
Fifty diabetics with severe background retinopathy or early proliferative retinopathy underwent retinal scatter photocoagulation with either the argon laser or the xenon arc photocoagulators. Choroidal detachment, exudative retinal detachment, shallowing of the anterior chamber, and secondary angle-closure glaucoma were observed. Exudative retinal detachment and choroidal detachment subsided in two days to 2-1/2 weeks. Glaucoma secondary to choroidal detachment with angle closure was observed in 11 eyes, three of which required medical treatment, although surgical therapy was not needed. This secondary glaucoma was detected in the first two days and subsided in subsequent days, with intraocular pressure reaching pretreatment values at the fifth day. No long-term sequelae were observed in these complications, except in one eye that developed macular edema that lasted for four months with decreased visual acuity; nevertheless, vision returned to the pretreatment level one year after photocoagulation.


The Clinical Features and Outcomes of Renal Amyloidosis in Tunisia.
Systemic amyloidosis is a rare disease characterized by clinical polymorphism. Indeed, the kidney is the most common organ involved and represents a real turning point in the disease. We aimed to determine the clinicopathological prognostic factors of renal amyloidosis (RA). We conducted a retrospective study including 40 cases with biopsy-proven RA collected in our department over a period of 10 years. Biochemical, demographic, and clinicopathological findings at diagnosis, as well as the follow-up data, were evaluated for each patient. The prevalence of amyloidosis was 2.7 per 100 nontransplant renal biopsies. The mean age at presentation was 55.5 ± 15.6 years with a male-to-female ratio of 1.85. The diagnosis of RA was confirmed by a renal biopsy in 85% of cases. Amyloid A (AA) amyloidosis was the most common type of amyloidosis (65%), and chronic infections ranked first in the panel of etiologies (41%). Amyloid light chain amyloidosis was mainly associated with multiple myeloma (57%). The median patient survival was 59 months versus 12 months for kidney survival. Age and extrarenal localization were independent predictors of mortality, whereas renal failure at presentation significantly influenced renal survival. The results of our study emphasize the rarity but also the severity of RA. AA amyloidosis was the most common type identified, which was mainly caused by chronic infections. Prevention remains the best solution until we can achieve therapeutic advances in inflammatory diseases.


Nematode eel parasite found inside acanthocephalan cysts--a "Trojan horse" strategy?
The invasive eel parasite Anguillicoloides crassus (syn. Anguillicola crassus) is considered one of the major causes for the decline of the European eel (Anguilla anguilla) panmictic population. It impairs the swim bladder function and reduces swimming performance of its host. The life cycle of this parasite involves different intermediate and paratenic hosts. Despite an efficient immune system of the paratenic fish hosts acting against infections with A. crassus, levels of parasitized eels remain high in European river systems. Recently, the round goby Neogobius melanostomus (Gobiidae) has become dominant in many rivers in Europe and is still spreading at a rapid pace. This highly invasive species might potentially act as an important, so far neglected paratenic fish host for A. crassus. Based on own observations and earlier single sightings of A. crassus in N. melanostomus, 60 fresh individuals of N. melanostomus were caught in the Rhine River and examined to assess the infection levels with metazoan parasites, especially A. crassus. Glycerin preparations were used for parasite identification. The parasite most frequently found in N. melanostomus was the acanthocephalan Pomphorhynchus sp. (subadult stage) which occurred mainly encysted in the mesenteries and liver. Every third gobiid (P = 31.7%) was infected by A. crassus larvae (L3) which exclusively occurred inside the acanthocephalan cysts. No intact or degenerated larvae of A. crassus were detected elsewhere in the goby, neither in the body cavity and mesenteries nor in other organs. Affected cysts contained the acanthocephalan larvae and 1-12 (mI =3) living A. crassus larvae. Additionally, encysted larvae of the nematode Raphidascaris acus were detected in the gobies, but only in the body cavity and not inside the acanthocephalan cysts. Based on our observations, we suggest that A. crassus might actively bypass the immune response of N. melanostomus by invading the cysts of acanthocephalan parasites of the genus Pomphorhynchus using them as "Trojan horses". Providing that eels prey on the highly abundant round goby and that the latter transfers viable infective larvae of A. crassus, the new paratenic host might have a strong impact on the epidemiology of A. crassus.


Effect of neonatal 6-hydroxydopamine treatment on alpha 1- and alpha 2-adrenoceptors in rat cerebral cortex.
Neonatal 6-hydroxydopamine (6-OHDA) treatment was used to destroy the noradrenergic nerve endings in rat cerebral cortex and thus give some insight into the development and regulation of alpha-adrenoceptor subtypes, which in turn provides information concerning the anatomical localization of alpha 1- and alpha 2-adrenoceptors. In cerebral cortex of rats treated in the neonatal period with 6-OHDA, we have observed an irreversible decrease in noradrenaline levels. Differences in 3H-clonidine and 3H-prazosin binding occurred which varied depending upon the time between denervation and the binding assay. In 7-14 day-old rats we observed a 20% decrease in the number of alpha 2-adrenoceptors and a marked increase in alpha 1-adrenoceptors. In older rats (45-50 day-old) both types of alpha-adrenoceptors were increased. Results of this study indicate that alpha 2-adrenoceptors located on presynaptic noradrenergic terminals represent only a minor fraction of the total alpha 2- adrenoceptors in rat cerebral cortex that are lost after denervation. Conversely, noradrenergic denervation resulted in supersensitivity of the alpha 1-adrenoceptors and nonnoradrenergic terminals located on alpha 2-adrenoceptors.


Eosinophilic Gastrointestinal Disorders Pathology.
Eosinophilic gastrointestinal disorders (EGID) are characterized pathologically by excess eosinophils in mucosal biopsies of one or multiple sites in the gastrointestinal (GI) tract, simultaneously or sequentially. Eosinophilic esophagitis (EoE) is the best characterized EGID, and in most patients it is an abnormal immune-mediated response to food antigens. Current recommendations for diagnosis include signs and symptoms of esophageal dysfunction that do not respond to proton-pump inhibitor therapy, and esophageal biopsies that exhibit at least 15 intraepithelial eosinophils in at least one high power field (HPF). Therapy consists of swallowed glucocorticoids or dietary elimination. Eosinophilic gastritis (EG) is the second most common form of EGID, but like all forms of EGID except EoE consensus recommendations for either clinical or pathological diagnosis do not exist. EG may be associated clinically with peripheral blood eosinophilia, hypoalbuminemia, and anemia, and pathologically with marked expansion of lamina propria by dense eosinophilic infiltrates. Eosinophilic enteritis (EE) may be subdivided into eosinophilic duodenitis, eosinophilic jejunitis, and eosinophilic ileitis. Most investigators believe that EE rarely, if ever, exists as a solitary form of EGID and is encountered only in patients who have at least one other affected portion of the GI tract. Eosinophilic colitis (EC) is perhaps the most enigmatic EGID. Distinction of EC from inflammatory bowel disease may be problematic especially in children. Multiple possible etiologies for EGID include hypereosinophilic syndrome, drug reactions, etc. Currently, the only etiology that can be identified histologically is parasitic infestation, if a portion of an invasive parasite is found in mucosal biopsies. This review will provide guidelines for the pathologic diagnosis of the various forms of EGID.


Vagal control of gastrin release in the dog: pathways for stimulation and inhibition.
The vagus has a dual effect on gastrin: it both stimulates and inhibits its release. To determine the gastric vagal pathways for these opposing effects, plasma gastrin and acid responses to meal (intragastric titration of 15% liver extract, pH 5.5) and to insulin (0.5 U regular insulin intravenously) were studied in seven dogs in three consecutive stages: a control stage, after antral vagotomy (AV), and after subsequent proximal gastric vagotomy (PGV). AV abolished the plasma gastrin response to insulin but had no effect on either basal or meal-stimulated gastrin release. Subsequent PGV caused significant elevation in basal plasma gastrin concentration, no further change in the gastrin response to insulin, but a significant increase in meal-stimulated gastrin release. AV decreased acid response to insulin nonsignificantly and had no effect on meal-stimulated acid secretion. Subsequent PGV reduced by 90% the acid response to insulin, had negligible effect on the gastric fistula acid response to meal, but increased Heidenhain pouch response sixfold. These studies show that vagal stimulation of gastrin release is mediated along direct antral vagal pathways, while vagal inhibition requires intact vagal fibers to the proximal stomach. The mechanism by which the fundic vagal pathways exert an inhibitory influence on the G cell in the antrum is yet to be elucidated.


Influence of rumen-protected choline on liver composition and blood variables indicating energy balance in periparturient dairy cows.
Rumen-protected choline (RPC) was evaluated for effects on the lipid and glycogen content of the liver and metabolic variables in the blood plasma of dairy cows. Thirty-two Holstein cows were allocated into two groups (RPC group with RPC supplementation and control group without RPC supplementation) 28 days before the expected calving. Cows were fed the experimental diet from 21 days before calving until day 60 of lactation. The diet of the RPC group was supplemented with 100 g/day of RPC from 21 days prepartum until calving and 200 g/day of RPC for 60 days postpartum, providing 25 and 50 g of choline, respectively. Liver samples were taken by percutaneous needle biopsy, then analysed for total lipid (TLl), triglyceride (TGl) and glycogen (GLYl) contents on days -21, +7, +35 and +60 relative to calving. Blood was collected on the same sampling days and 21 days after calving. Glucose, non-esterified fatty acid (NEFA), β-hydroxybutyrate (BHBA), triglyceride (TGp), total cholesterol (TCh), urea, ammonia and aspartate aminotransferase (AST) were determined from blood samples. The TLl and TGl contents were 25.0 ± 4.3 g and 25.3 ± 3.8 g per kg wet weight (mean ± SEM), respectively, lower in the RPC group than in the control animals. No significant differences were observed in the GLYl concentrations between the two groups. However, a lower TGl: GLYl ratio was shown in the liver of cows fed the RPC diet as compared to the controls. RPC supplementation decreased BHBA while increasing TGp concentrations were shown in the blood of cows fed the RPC diet, possibly as a consequence of improved lipoprotein synthesis in, and triglyceride excretion from, the liver, together with a reduced rate of ketogenesis.


Adaptation and validation of the HIV Knowledge Questionnaire-18 for the general population of Indonesia.
Despite a global decline in new HIV/AIDS cases in low-middle countries, cases are increasing in Indonesia. Low knowledge about the disease among the general population is one of the major factors responsible for this trend. Indonesia does not have a validated instrument to assess HIV/AIDS knowledge. The HIV Knowledge Questionnaire-18 (HIV-KQ-18) has been translated into several languages and is one of the most extensively used instruments for assessing HIV/AIDS knowledge. This paper describes the process of adapting and validating the HIV-KQ-18, an instrument to assess the level of HIV/AIDS knowledge in the general population of Indonesia. In the adaptation phase, feedback for the initial Bahasa Indonesia version was gathered from two HIV activists, an obstetrician, two general practitioners, and 60 pilot participants. At the validation stage, we distributed the instrument link via Google Form to 6 major regions in Indonesia. Validity was measured using known-group validity and construct validity. The construct validity was assessed using an exploratory factor analysis (EFA) with a polychoric correlation matrix. Cronbach's alpha was used to analyze the internal consistency. Based on the findings in the adaptation phase, additional descriptions (namely synonyms or examples) were added to 6 items to make them more understandable. In the validation phase, 1,249 participants were recruited. The a priori hypothesis in known-group validity was supported. We also found three items that did not meet the construct validity. Based on the acceleration factor approach to interpret the scree tree in the factor analysis, using only two factors was preferable. Cronbach's alpha values were 0.75 and 0.71 representing good internal reliability. The HIV-KQ-18 Bahasa Indonesia is considered a valid and reliable instrument to assess the level of HIV/AIDS knowledge in Indonesia.


Two strains of Epstein-Barr virus (B95-8 and a P3HR-1 subclone) that lack defective genomes induce early antigen and cause abortive infection of Raji cells.
The heterogeneity of Epstein-Barr virus (EBV) obtained from P3HR-1 cells has permitted derivation of a distinct subclone of P3HR-1 (L. Heston, M. Rabson, N. Brown, and G. Miller, Nature (London) 295:160-163, 1982). We have analyzed the biologic properties and genomic structure of this subclonal virus (clone 13) compared with those of parental P3HR-1 and B95-8 viruses. Synthesis of EBV compared with those of parental P3HR-1 and B95-8 viruses. Synthesis of EBV proteins in Raji cells superinfected with virus derived from P3HR-1, clone 13, and B95-8 was analyzed both by fluorography of radiolabeled proteins and by immunoblotting. Highly concentrated preparations of clone 13 and B95-8 virus induced most of the spectrum of EBV proteins in Raji cells with the exception of the 145,000-, 140,000-, and 110,000-molecular-weight proteins, which were either undetectable or reduced. Moreover, both clone 13 and B95-8 viruses also induced the same patterns of early antigen diffuse components as the parental P3HR-1 virus did. However, only P3HR-1 virus could induce EBV DNA synthesis in superinfected Raji cells, as determined both by buoyant density centrifugation and by in situ cytohybridization with biotinylated recombinant EBV DNA probes. Defective heterogeneous molecules present in P3HR-1 virus have been implicated in early antigen induction after superinfection of Raji cells. Therefore, Southern blots of clone 13, P3HR-1, and B95-8 viruses were hybridized to recombinant EBV fragments representing the sequences contained within the defective molecules in P3HR-1. The parental P3HR-1 contained the previously described defective molecules. No evidence for defective molecules was found in clone 13 or B95-8 viruses. These data indicate that concentrated preparations of both clone 13 and B95-8 viruses can induce abortive infection in Raji cells, but while the defective molecules are not needed for induction of early antigen diffuse components, they may be required for the induction of viral DNA synthesis.


Boosting Material Utilization via Direct Growth of Zn2 (V3 O8 )2 on the Carbon Cloth as a Cathode to Achieve a High-Capacity Aqueous Zinc-Ion Battery.
Aqueous zinc-ion batteries (AZIBs) have attracted the attention of researchers because of their high theoretical capacity and safety. Among the many vanadium-based AZIB cathode materials, zinc vanadate is of great interest as a typical phase in the dis-/charge process. Here, a remarkable method to improve the utilization rate of zinc vanadate cathode materials is reported. In situ growth of Zn2 (V3 O8 )2 on carbon cloth (CC) as the cathode material (ZVO@CC) of AZIBs. Compared with the Zn2 (V3 O8 )2 cathode material bonded on titanium foil (ZVO@Ti), the specific capacity increases from 300 to 420 mAh g-1 , and the utilization rate of the material increases from 69.60% to 99.2%. After the flexible device is prepared, it shows the appropriate specific capacity (268.4 mAh g-1 at 0.1 A g-1 ) and high safety. The method proposed in this work improves the material utilization rate and enhances the energy density of AZIB and also has a certain reference for the other electrochemical energy storage devices.


Purification of an endogenous protein inhibitor of the high affinity binding of gamma-aminobutyric acid to synaptic membranes of rat brain.
In a medium without Na+, gamma-aminobutyric acid (GABA) binds at 0 degrees to freshly prepared crude synaptic membranes from rat cerebral cortex with an apparent dissociation constant of 218 nM. An endogenous inhibitor of the Na+-independent GABA binding was removed from these membranes by freezing and thawing and by repeated washing with Tris citrate buffer (50 mM, pH 7.1) containing 0.01% Triton X-100. As a result, the crude synaptic membranes bind GABA at 0 degrees with two dissociation constants, 20 nM and 111 nM. The endogenous inhibitor is a thermostable (95 degrees for 15 min) acidic protein of approximately 1.5 X 10(4) daltons. It was purified (about 500-fold) with a series of procedures including gel chromatography on Sephadex G-100 and ion exchange chromatography on Dowex 50W-X8 (H+). Recombination of the purified endogenous inhibitor with crude synaptic membrane preparations deprived of the endogenous inhibitor showed that the purified inhibitor blocked noncompetitively the sites for high-affinity GABA binding. A role of this endogenous regulator in the functional of GABA-ergic synapses is discussed.


The role of surgery in recurrent ependymomas.
The role of surgery in recurrent ependymomas and its contribution to the outcome are not well defined. While gross-total resection (GTR) has shown benefit in newly diagnosed patients with improvement in progression-free survival (PFS), its impact after recurrence is not known. Its role in distant relapses or multiple local recurrences is similarly less well understood. The objective of this study was to investigate whether GTR could prolong survival after recurrence. In this paper, the authors identified patients with ependymomas who underwent surgery at Texas Children's Hospital for recurrent ependymomas between December 2000 and December 2021. Surgical treatment was stratified as GTR, subtotal resection (STR), or a biopsy. Kaplan-Meier analysis was performed for PFS and overall survival (OS), and the log-rank test was used to assess statistical significance. The Cox regression model was used for multivariable analysis. Forty children were identified with a first ependymoma recurrence and follow-up data were collected. The median age was 5.46 years (95% CI 4.52-6.39 years) with a mean follow-up of 3.92 years (95% CI 2.42-5.42 years). In 26 patients (65%), the original tumor was located in the infratentorial space. Twenty-nine patients (72.5%) presented with local recurrence. Within this group, the 5-year PFS rates for the GTR and STR groups were 40.1% and 26.8%, respectively. The 5- and 10-year OS rates were 58.3% and 50% in the GTR group and 51% and 16.7% in the STR group, respectively. Fifteen patients presented with a second recurrence. The 5-year PFS and OS rates in patients who had GTR after a second recurrence were 33% and 50%, respectively. GTR of local recurrent ependymomas can result in long-term survival in first and second recurrences. Further and larger studies are necessary to elucidate the role of surgery in distal recurrences.


Development of RNR3- and RAD54-GUS reporters for testing genotoxicity in Saccharomyces cerevisiae.
S. cerevisiae RNR3 and RAD54 gene transcription becomes strongly activated upon DNA damage. This property was used to construct yeast strains in which DNA damage can be monitored by a very sensitive fluorogenic assay in a convenient 96-well microtiter plate format. These strains carried stably integrated fusions of RNR3 or RAD54 promoters to the E. coli beta-glucuronidase GUS gene. GUS activity was measured by fluorogenic detection, a method that greatly increases the precision and sensitivity of the assay. Detection levels were similar to those of real-time quantitative PCR methods and close to the limits of biological response. The two reporters differed in terms of fold-induction, activation kinetics, sensitivity and specificity upon exposure to a variety of genotoxic compounds. While RNR3-GUS showed the fastest response, RAD54-GUS showed the highest sensitivity: similar to previous reported sensitivities for bacterial and eukaryotic genotoxic detection systems. These reporter strains may complement current genotoxicity tests, but they also have the advantages of higher flexibility, requirement for shorter incubation times, and the capability of being fully automated. In addition, the intrinsic features of the system facilitate its easy improvement by genetic manipulating the yeast strain or by introducing mammalian metabolizing enzymes.


[Consequences of clinical genetic analysis of RET proto-oncogene].
Preliminary results of treatment of inherited medullary thyroid carcinoma, diagnosed primarily with genetic analysis of mutation of protooncogene RET are presented. Among 16 carriers of mutation identical with mutation diagnosed earlier in proband, there were 4 patients with clinically obvious medullary thyroid carcinoma and 12 asymptomatic carriers. In all patients, in whom calcitonin level was increased preoperatively, its normalization was obtained. The paper summarizes these aspects of cooperation between geneticians and physicians in which diagnostic results influence clinical decisions (indication and time of thyroid and lymph nodes surgery and it's spectrum, range of diagnostic procedures towards pheochromocytoma and parathyroid hyperplasia in relation to the found mutation).


Manganese-induced turnover of TMEM165.
TMEM165 deficiencies lead to one of the congenital disorders of glycosylation (CDG), a group of inherited diseases where the glycosylation process is altered. We recently demonstrated that the Golgi glycosylation defect due to TMEM165 deficiency resulted from a Golgi manganese homeostasis defect and that Mn2+ supplementation was sufficient to rescue normal glycosylation. In the present paper, we highlight TMEM165 as a novel Golgi protein sensitive to manganese. When cells were exposed to high Mn2+ concentrations, TMEM165 was degraded in lysosomes. Remarkably, while the variant R126H was sensitive upon manganese exposure, the variant E108G, recently identified in a novel TMEM165-CDG patient, was found to be insensitive. We also showed that the E108G mutation did not abolish the function of TMEM165 in Golgi glycosylation. Altogether, the present study identified the Golgi protein TMEM165 as a novel Mn2+-sensitive protein in mammalian cells and pointed to the crucial importance of the glutamic acid (E108) in the cytosolic ELGDK motif in Mn2+-induced degradation of TMEM165.


ThermusQ: Toward the cell simulation platform for Thermus thermophilus.
ThermusQ is a website (https://www.thermusq.net/) that aims to gather all the molecular information on Thermus thermophilus and to provide a platform to easily access the whole view of the bacterium. ThermusQ comprises the genome sequences of 22 strains from T. thermophilus and T. oshimai strains, plus the sequences of known Thermus phages. ThermusQ also contains information and map diagrams of pathways unique to Thermus strains. The website provides tools to retrieve sequence data in different ways. By gathering the whole data of T. thermophilus strains, the strainspecific characteristics was found. This bird's-eye view of the whole data will lead the research community to identify missing important data and the integration will provide a platform to conduct future biochemical simulations of the bacterium.


Atherosclerotic plaque evolution in the descending thoracic aorta in familial hypercholesterolemic patients. A transesophageal echo study.
We explored the concept that transesophageal echocardiography can be used as a tool to detect, characterize, and study plaque morphology in the descending thoracic aorta. The pattern of atherosclerotic plaques in the descending thoracic aorta in familial hypercholesterolemic (FH) patients was evaluated. Additionally, evolution of plaque characteristics as a result of therapy was analyzed. In a randomized prospective protocol, eight FH patients (five men and three women, aged 23 to 65 years [mean +/- SD, 42 +/- 14 years]) receiving standard therapy (n = 3; baseline low-density lipoprotein [LDL] cholesterol, 222 +/- 71 mg/dL, mean +/- SD) or LDL apheresis (n = 5; baseline LDL cholesterol, 262 +/- 51 mg/dL) were studied. Baseline and follow-up (mean, 12 months) transesophageal echocardiographic studies were performed. Measurements obtained were atherosclerotic plaque area (PA), aortic wall area (WA), total arterial area (TAA), and plaque-to-wall area ratio (PWR). LDL cholesterol decreased in both groups. The greatest severity of plaque was detected at 30 to 35 cm from the incisors (approximately 15 to 20 cm from the aortic arch). The smallest plaques were present at the arch and more distal descending aorta. In the control group, TAA, PA, and PWR did not change significantly (P = NS versus baseline). In the LDL-apheresis group, TAA increased (P < .05 versus baseline), PA decreased in three of five patients (P = NS versus baseline), and PWR fell (P < .05 versus baseline).(ABSTRACT TRUNCATED AT 250 WORDS)


Maturity and change in personality: developmental trends of temperament and character in adulthood.
We studied the developmental trends of temperament and character in a longitudinal population-based sample of Finnish men and women aged 20-45 years using the Temperament and Character Inventory model of personality. Personality was assessed in 1997, 2001, and 2007 (n = 2,104, 2,095, and 2,056, respectively). Mean-level changes demonstrated qualitatively distinct developmental patterns for character (self-directedness, cooperativeness, and self-transcendence) and temperament (novelty seeking, harm avoidance, reward dependence, and persistence). Character developed toward greater maturity, although self-transcendence decreased with age. However, self-transcendence was the strongest predictor of overall personality change. Cohort effects indicated lower level of self-transcendence and higher level of self-directedness and cooperativeness in younger birth cohorts. Regarding temperament, novelty seeking decreased and persistence increased slightly with age. Both high novelty seeking and high persistence predicted overall personality change. These findings suggest that temperament and character traits follow different kinds of developmental trajectories.


Gaps in primary healthcare electronic medical record research and knowledge: findings of a pan-Canadian study.
While the barriers to electronic medical record (EMR) adoption by physicians are well-known, we have much less knowledge about the broader challenges regarding EMR use faced by primary healthcare (PHC) EMR stakeholders in Canada. Therefore, we conducted interviews (from June 2009 to September 2010) and consultation sessions (in October and November 2009) with these stakeholders, as well as carrying out a research capacity assessment, to identify, describe and prioritize gaps in PHC EMR knowledge and research. Twelve thematic gaps emerged; four were identified as the most important: the need to ascertain the value of EMRs, the need to better understand elements of EMR implementation and adoption, the need to develop innovative data entry and extraction procedures, and a lack of agreement and understanding of data sharing. To advance EMR use, Canada needs to address these gaps; yet, we currently have a lack of research capacity with which to accomplish this.


Alternatives to Acellular Dermal Matrix: Utilization of a Gore DualMesh Sling as a Cost-Conscious Adjunct for Breast Reconstruction.
Objective: This study seeks an alternative to acellular dermal matrix in 2-staged breast reconstruction while minimizing cost. It was hypothesized that use of a Gore DualMesh would allow for similar intraoperative tissue expander fill volumes, time to second-stage reconstruction, and number of postoperative fills compared with acellular dermal matrix at only a fraction of the expense. Methods: Retrospective analysis comparing Gore DualMesh (59 breasts, 34 patients), acellular dermal matrix (13 breasts, 8 patients), and total muscle coverage (25 breasts, 14 patients) for postmastectomy breast reconstruction was performed. Time to second-stage reconstruction, number of expansions, and relative initial fill volumes were compared between the 3 groups. Secondarily, complication rates were also considered, including seroma, infection, expander/implant explantation, removal of mesh, and capsular contracture. Statistical analysis was performed utilizing the Fisher exact test and the χ2 test for categorical variables and the Mann-Whitney U test for continuous variables. Results: Relative initial fill volumes, number of expansions, and time to second-stage reconstruction showed no statistical difference between the acellular dermal matrix and Gore DualMesh groups (P = .494, P = .146, and P = .539, respectively). Furthermore, the Gore DualMesh group underwent significantly fewer fills (P < .001) and had a higher relative initial fill volume (P < .001) than the total muscle coverage group. The additional cost per breast as a result of including DualMesh was on average $385 versus $4287 for acellular dermal matrix. Complication rates were similar between all 3 groups without statistically significant differences. Conclusions: Gore DualMesh represents a safe alternative to acellular dermal matrix for breast reconstruction with similar aesthetic results in certain patients at a fraction of the cost.


Collision induced absorption in the a1Δ(v = 2) ← X3Σg(-)(v = 0) band of molecular oxygen.
Using cavity ring-down spectroscopy we measured the collision induced absorption spectrum associated with the a(1)Δ(v = 2) ←X(3)Σ(g)(-)(v = 0) band of oxygen near 922 nm both in pure oxygen and in mixtures of oxygen and nitrogen. For pure oxygen, we report for this band an integrated absorption of (1.56 - 0.04/+0.40) × 10(-5) cm(-2) amg(-2). We find that collisions between oxygen and nitrogen do not result in any measurable CIA signal. At 1 bar of oxygen, this collision induced transition is much stronger than the allowed magnetic dipole and electric quadrupole transitions.


Development of a SYBR Green II Real-Time Polymerase Chain Reaction for the Clinical Detection of the Duck-Origin Goose Parvovirus in China.
To establish an efficient, convenient and quantitative method for the clinical detection of the duck-origin goose parvovirus. In the present study, a real-time polymerase chain reaction (PCR) method was established for detecting the duck-origin goose parvovirus using the fluorescent chimeric dye SYBR Green II. Specific primers were designed to target a highly conserved region of the VP3 gene of the duck-origin goose parvovirus. This method was able to detect a minimum of 19.6 copies/μL of viral genomic DNA. Results showed that this method was faster and had a higher sensitivity than the traditional PCR in the clinical specimen test. In this paper, we developed a rapid, sensitive detection and quantitative analysis technology for the duck-origin goose parvovirus by real-time PCR assay. This test provides improved technical support for studies regarding the clinical diagnosis and epidemiological investigations of the duck-origin goose parvovirus.


Balance Rehabilitation Unit (BRU™) posturography in relapsing-remitting multiple sclerosis.
To evaluate balance control with Balance Rehabilitation Unit (BRU™) posturography in patients with multiple sclerosis (MS). A cross controlled study was performed including 39 relapsing-remitting multiple sclerosis patients with scores less than or equal to 4 in the Expanded Disability Status Scale (EDSS), and a homogeneous control group consisting of 65 healthy individuals, matched by the age and gender. The experimental group was distributed according to the EDSS scale scores in 0-2.5 and 3-4. To assess the vestibular system function, the patients underwent a neurotological evaluation, including posturography of the Balance Rehabilitation Unit (BRU™). Statistically significant differences were observed when comparing the values of the sway velocity and the ellipse area of the MS 0-2.5 group with the control and the MS 3-4 group with the control. A statistically significant difference was verified between the MS 0-2.5 and the MS 3-4 groups in the condition 3 ellipse area values. The evaluation of the balance control with posturography of Balance Rehabilitation Unit (BRU™) enables the identification of abnormalities of the sway velocity and confidential ellipse in patients with relapsing-remitting multiple sclerosis.


Contorted polycyclic aromatics.
CONSPECTUS: This Account describes a body of research in the design, synthesis, and assembly of molecular materials made from strained polycyclic aromatic molecules. The strain in the molecular subunits severely distorts the aromatic molecules away from planarity. We coined the term "contorted aromatics" to describe this class of molecules. Using these molecules, we demonstrate that the curved pi-surfaces are useful as subunits to make self-assembled electronic materials. We have created and continue to study two broad classes of these "contorted aromatics": discs and ribbons. The figure that accompanies this conspectus displays the three-dimensional surfaces of a selection of these "contorted aromatics". The disc-shaped contorted molecules have well-defined conformations that create concave pi-surfaces. When these disc-shaped molecules are substituted with hydrocarbon side chains, they self-assemble into columnar superstructures. Depending on the hydrocarbon substitution, they form either liquid crystalline films or macroscopic cables. In both cases, the columnar structures are photoconductive and form p-type, hole- transporting materials in field effect transistor devices. This columnar motif is robust, allowing us to form monolayers of these columns attached to the surface of dielectrics such as silicon oxide. We use ultrathin point contacts made from individual single-walled carbon nanotubes that are separated by a few nanometers to probe the electronic properties of short stacks of a few contorted discs. We find that these materials have high mobility and can sense electron-deficient aromatic molecules. The concave surfaces of these disc-shaped contorted molecules form ideal receptors for the molecular recognition and assembly with spherical molecules such as fullerenes. These interfaces resemble ball-and-socket joints, where the fullerene nests itself in the concave surface of the contorted disc. The tightness of the binding between the two partners can be increased by creating more hemispherically shaped contorted molecules. Given the electronic structure of these contorted discs and the fullerenes, this junction is a molecular version of a p-n junction. These ball-and-socket interfaces are ideal for photoinduced charge separation. Photovoltaic devices containing these molecular recognition elements demonstrate approximately two orders of magnitude increase in charge separation. The ribbon-shaped, contorted molecules can be conceptualized as ultranarrow pieces of graphene. The contortion causes them to wind into helical ribbons. These ribbons can be formed into the active layer of field effect transistors. We substitute the ribbons with di-imides and therefore are able to transport electrons. Furthermore, these materials absorb light strongly and have ideal energetic alignment of their orbitals with conventional p-type electronic polymers. In solar cells, these contorted ribbons with commercial donor polymers have record efficiencies for non-fullerene-based solar cells. An area of interest for future exploration is the merger of these highly efficient contorted ribbons with the well-defined interfaces of the ball-and-socket materials.


Sodium molybdate - an additive of choice for enhancing the performance of AC/AC electrochemical capacitors in a salt aqueous electrolyte.
Sodium molybdate (Na2MoO4) has been used as an additive to 1 mol L(-1) lithium sulfate electrolyte for electrochemical capacitors based on activated carbon (AC) electrodes, in order to reduce the corrosion of stainless steel current collectors. We demonstrate that the MoO4(2-) anions improve the overall capacitance owing to pseudofaradaic processes. In a two-electrode cell, capacitance values of 121 F g(-1) have been achieved up to 1.6 V using 1 mol L(-1) Li2SO4 + 0.1 mol L(-1) Na2MoO4, as compared to 103 F g(-1) when 1 mol L(-1) Li2SO4 is used. Further, by using a two-electrode setup equipped with a reference electrode, we could demonstrate that, at 1.6 V, the positive electrode potential reaches a value of 0.96 V vs. NHE in 1 mol L(-1) Li2SO4, crossing the thermodynamic potential limit of oxygen evolution (Eox = 0.846 V vs. NHE), and the pitting potential, Epit = 0.95 V vs. NHE. By contrast, in 1 mol L(-1) Li2SO4 + 0.1 mol L(-1) Na2MoO4, the pseudofaradaic contribution occurring at -0.05 V vs. NHE due to MoO4(2-) anions drives the positive electrode to reach only 0.798 V vs. NHE. Hence, the oxidation of the AC and corrosion of the stainless steel current collector at the positive electrode are unlikely in Li2SO4 + Na2MoO4 when the capacitor operates at 1.6 V. During potentiostatic floating of the capacitor at 1.6 V for 120 hours in Li2SO4 + Na2MoO4, the capacitance and resistance remain constant at 125 F g(-1) and ~1.0 Ω, respectively, while the resistance increases from 1.4 Ω to 3.1 Ω in Li2SO4. Overall, the addition of MoO4(2-) anions to Li2SO4 aqueous electrolyte allows the capacitance to be enhanced, corrosion of the positive stainless steel current collector to be inhibited and the AC/AC electrochemical capacitor to demonstrate stable performance up to 1.6 V.


A Reliable Method for the Separation and Detection of Synthetic Cannabinoids by Supercritical Fluid Chromatography with Mass Spectrometry, and Its Application to Plant Products.
A reliable method using supercritical fluid chromatography with mass spectrometry (SFC-MS) was developed for cannabinoids using compressed carbon dioxide (CO2) and methanol as the mobile-phase. The cannabinoids, i.e., cannabicyclohexanol (CCH: cis-isomer), trans-CCH, 5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (CP-47497), 5-(1,1-dimethylheptyl)-2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP-55940), 3-(1,1'-dimethylheptyl)-6aR,7,10,10aR-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol (HU-210), 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol (CBD), (1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-018), (1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073) and 1-(1-pentyl-1H-indol-3-yl)-2-(2-methoxyphenyl)-ethanone (JWH-250), were determined within 12 min using a conventional column (2-EP) for SFC. Furthermore, two optical isomers of CCH and trans-CCH were completely and rapidly separated by a chiral stationary phase column (AMY1). A highly sensitive detection (0.002-3.75 ppb) was also obtained by these methods using 2-EP and AMY1 columns. These methods were applied to the qualitative and quantitative determination of cannabinoids in dried plant products. Although the concentration and species were different in the products, JWH-018, JWH-073 and CCH, including the cis-isomer, trans-isomer and the optical isomers, were detected in the products. Therefore, the proposed SFC-MS method seems to be useful as an alternative method to GC-MS and LC-MS for illegal drugs, such as cannabinoids.


Persistence of chlorfluazuron in cabbage under different agro-climatic conditions of India and its risk assessment.
A multilocational field trial was conducted at 4 locations in India-Rajasthan, Gujarat, Madhya Pradesh, and West Bengal-to determine the persistence in cabbage of chlorfluazuron applied twice at 75 and 150 g active ingredient ha-1 . Cabbage head samples were collected from each replicated plot on 0 (2 h after spraying), 1, 3, 5, 7, 10, and 15 d after final insecticide application, including an untreated control. Chlorfluazuron residue in cabbage and field soil was estimated by high-performance liquid chromatography using a photo diode array detector. The limit of determination and limit of quantification of the method were recorded as 0.05 and 0.10 μg g-1 , respectively. Results revealed that chlorfluazuron dissipated linearly with progress of time, following first-order kinetics. The mean (± standard deviation) half-life value of chlorfluazuron in cabbage was found to be 7.18 ± 0.71 d, considering different locations and treatments. The residue was below the level of quantification in the harvested cabbage and soil samples. Harvesting cabbage in the experimental location, at least on day 7, after 2 applications of chlorfluazuron at the recommended dose, may not pose any ill effect for Indian adults. Environ Toxicol Chem 2017;36:3028-3033. © 2017 SETAC.


The thoracic stomach: a study of gastric emptying, bile reflux and mucosal change.
The clinical progress, histological state of the gastric mucosa, gastric emptying of a liquid meal and duodenogastric reflux were studied postoperatively in 15 patients with a vagotomized intrathoracic stomach without a drainage procedure. The intact though denervated pylorus did not impede the emptying of liquids. Bile reflux into the thoracic stomach in both the erect and supine positions was significantly greater than that measured in control subjects. While posture did not affect duodenogastric reflux in the normal adult, bile reflux across the denervated pylorus was significantly increased in the supine position. Chronic active gastritis was noted in 12 patients but could not be correlated with the degree of bile reflux. Nine patients had evidence of pulmonary aspiration and gastric food residue was a common finding at endoscopy. The vagotomized intrathoracic stomach may need a drainage procedure to facilitate solid emptying.


Time to wave good-bye to phase scrambling: creating controlled scrambled images using diffeomorphic transformations.
To isolate the neural mechanisms associated with recognizing objects from those processing basic visual properties, control stimuli are required that contain the same perceptual properties as the objects but are unrecognizable. We demonstrate that conventional methods for generating control stimuli (phase scrambling, box scrambling, texture scrambling) yield poor controls because they dramatically distort the basic visual properties (e.g., spatial frequency, perceptual organization) to which even the earliest stages of visual processing are sensitive. We developed a new scrambling method, using a diffeomorphic transformation that preserves the basic perceptual properties of the image while removing meaning. We acquired perceptual ratings to determine the least amount of scrambling necessary to remove recognition. We hypothesized that our "diffeomorphic" images would produce neural activity at the earliest stages of the visual system that more closely matched activity in response to intact images relative to the other scrambling methods. To test this hypothesis, we used the HMAX computational model of object recognition and compared the simulated neural activity at the earliest stages of the visual system (layers S1, C1, and S2) between a set of 149 images scrambled using each distortion method to their intact version. We found that scrambled "diffeomorphed" images were indistinguishable to intact images in each layer of the model, but all of the other distortion methods yielded quite different patterns. Our results indicate that "diffeomorphed" images serve as more appropriate control stimuli in neuroimaging studies that aim to disentangle the representations of perceptual and semantic object properties.


Racial/ethnic concordance between patients and researchers as a predictor of study attrition.
The differential attrition of racial/ethnic minority participants in clinical research is a major threat to advancing medical and behavioral science. Our aim was to examine the influence of racial/ethnic concordance between participants and research staff on study attrition. Data were pooled from participants and clinical research coordinators (CRCs) in six longitudinal studies of respiratory illness. Dyads were classified as concordant if the patient and CRC were of the same racial/ethnic group. Multilevel modeling examined the effect of racial/ethnic concordance on attrition at the first and one-year follow-ups. Spanish language, lower education, and greater depressive symptoms predicted greater attrition, but these effects disappeared in adjusted models. Race/ethnicity, age, gender and health literacy did not predict attrition. Contrary to hypotheses, attrition was greater among concordant than discordant dyads: Attrition was almost five times greater at first follow-up for Black and Hispanic participants in concordant dyads, and almost four times greater at one year. Racial/ethnic concordance between participant and CRCs was related to greater attrition in a highly diverse sample of adults with respiratory illness. Differential attrition of racial/ethnic minorities is a major threat to advancing public health. Interactions with research staff may be critical to bridging the disparities gap.


Increased intensities of fas expression on peripheral T-cell subsets in severe autoimmune thyroid disease.
Fas (CD95)-Fas ligand (FasL; CD178)-induced apoptosis is necessary for the maintenance of self-tolerance. To clarify whether or not any abnormalities in the Fas-FasL system exist in patients with autoimmune thyroid disease (AITD), we examined the expression of Fas and FasL on peripheral T lymphocytes by three-color flow cytometry in 113 patients with AITD and 49 healthy controls. The intensities of Fas expression in both CD4(+) and CD8(+) T cells decreased in thyrotoxic patients with Graves' disease (GD), but increased in both patients with severe Hashimoto's disease (HD) undergoing treatment and seriously intractable patients with GD continuously positive for thyrotropin (TSH) receptor antibody despite treatment with antithyroid drugs for more than 5 years. The proportion of Fas expression was increased in CD4(+) T cells from patients with untreated GD, and in CD8(+) T cells from patients with severe HD. The proportion of CD8(+) T cells decreased in patients with severe HD. FasL were not expressed on T cells in controls and patients with AITD. These results indicate that (1). the intensities of Fas expression on peripheral T cells increase in severe autoimmune thyroid diseases and (2). both the intensity and the proportion of Fas expression may be important for the induction of apoptosis.


Microscopic evaluation of the tooth-bond-composite interface. Images from SEM. Preliminary report.
Systems that bond composite material to enamel are constantly modernized (application is simplified and the number of system components is reduced). The latest products are one-coat systems combining etchant, primer, and bond. Use of such systems is easier for the dentist and adds to patient's comfort. The aim of this work was to evaluate microscopically the composite material--bond-enamel interface in a tooth processed with an abrasive technique. The material comprised premolar human teeth extracted for orthodontic reasons. Cavities reaching the enamel-dentin border were created on the buccal surface of the teeth with the dental-prosthetic micropreparator (MSP). A self-etching Adper Prompt L-Pop system was applied (separate use of etchant was unnecessary). Bond application was according to manufacturer's recommendations. The cavities were filled with Point composite material from Kerr. Tooth samples were placed in the chamber of JEOL JSM 5500 LV scanning electron microscope and images were obtained at 15 kV. Strong bonding at the composite material-bond interface was observed as evidenced by the melting of composite particles into the self-etching bonding system.


Assay of acyl-CoA dehydrogenase activity in frozen muscle biopsies: application to medium-chain acyl-CoA dehydrogenase deficiency.
The acyl-CoA dehydrogenases (ACDs) are mitochondrial enzymes that dehydrogenate acyl-coenzyme A esters of different chain lengths. Inherited deficiencies of these dehydrogenases are commonly associated with muscle weakness and lipid storage. Numerous assays including spectrophotometric, fluorometric, chemical, and radiochemical procedures have been used, but there is need for a rapid, reproducible assay for the different acyl-CoA dehydrogenases in small frozen samples of human muscle biopsies. We describe a comparative study of dye-linked spectrophotometric assays of the long, medium, and short chain acyl-CoA dehydrogenases in frozen rat and human muscle samples. An optimal procedure is described confirming the value of glass-glass homogenization and assay of a 600g supernatant. Higher activities for all acyl-CoA dehydrogenases, citrate synthase, and cytochrome c oxidase were obtained in rat in contrast to human. The substrate-linked dye reduction method was found superior to the ferricenium or electron transfer flavoprotein acceptor systems. Application of the phenazine ethosulfate-DCPIP-linked method to medium-chain acyl-CoA dehydrogenase (MCAD) was studied in detail and the effect of immunoprecipitation of MCAD allowed for the determination of substrate specificity and the degree of crossover between long-, medium-, and short-chain ACD activity following immunoprecipitation. Finally, a comparison of the specificity and validity of the assay in a patient with MCAD deficiency was performed.


Prognostic Value of ER and PgR Expression and the Impact of Multi-clonal Expression for Recurrence in Ductal Carcinoma in situ: Results from the UK/ANZ DCIS Trial.
The prognostic value of estrogen receptor (ER)/progesterone receptor (PgR) expression in ductal carcinoma in situ (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS. Formalin-fixed paraffin embedded tissues were collected from UK/ANZ DCIS trial participants (n = 755), and ER/PgR expression was evaluated by IHC in 181 cases (with recurrence) matched to 362 controls by treatment arm and age. Assays were scored by the Allred method and by a newly devised clonal method-analyses categorizing multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed. ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared with DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of in situ IBE [OR 4.99; 95% confidence interval (CI), 2.66-9.36; P < 0.0001], but the risk of invasive IBE was not significantly higher (OR 1.72; 95% CI, 0.84-3.53; P = 0.14), P heterogeneity = 0.03. ER was an independent predictor in multivariate analyses (OR 2.66; 95% CI, 1.53-4.61). PgR status did not add to the prognostic information provided by ER. ER expression is a strong predictor of ipsilateral recurrence risk in DCIS. ER-positive DCIS with distinct ER-negative clones has a recurrence risk similar to ER-negative DCIS. ER should be routinely assessed in DCIS, and ER scoring should take clonality of expression into account.


Predictive Models and Algorithms for the Need of Transfusion Including Massive Transfusion in Severely Injured Patients.
BACKGROUND: Despite improvements on how to resuscitate exsanguinating patients, one remaining key to improve outcome is to expeditiously and reproducibly identify patients most likely to require transfusion including massive transfusion (MT). This work summarizes yet developed algorithms/scoring systems for transfusion including MT in civilian and military trauma populations. METHODS: A systematic search of evidence was conducted utilizing OVID/MEDLINE (1966 to present) and the 'Medical Algorithms Project'. RESULTS AND CONCLUSIONS: The models developed suggest combinations of physiologic, hemodynamic, laboratory, injury severity and demographic triggers identified on the initial evaluation of the bleeding trauma patient. Many approaches use a combination of dichotomous variables readily accessible after arrival but others rely on time-consuming calculations or complex algorithms and may have limited real-time application. Weighted and more sophisticated systems including higher numbers of variables perform superior. A common limitation to all models is their retrospective nature, and prospective validations are urgently needed. Point-of-care viscoelastic testing may be an alternative to these systems.


A method for the calibration of wideband ultrasonic sensors for optoacoustics.
A method for calibration of ultrasonic sensors for optoacoustics that provides both frequency response and sensitivity is presented. In order to obtain the bandwidth and the frequency response of an uncalibrated sensor, a point source with broadband spectra generated by a laser-induced bubble on a copper wire submerged in water is employed. On the other hand, the sensitivity measurement relies on the spatial symmetry of the pressure pulse and on a calibrated transducer. Therefore, two sensors are employed to detect the pressure pulse at the same distance from the source. The symmetry of the acoustic field that arrives at both transducers is adjusted and verified by means of an optical interferometer that provides a null signal when the copper wire is placed at the right position. The method is tested on the characterization of a thin-film polymeric piezoelectric transducer with a cylindrical focused shape.


Cytotoxicity of flavonoids and isoflavonoids from Crotalaria bracteata.
A new flavonoid, crotakanda (1), and seven known compounds including a flavonoid, four isoflavonoids, a pterocarpan and a cinnamaldehyde were isolated from the stems and roots of Crotalaria bracteata. Their structures were elucidated by a combination of spectroscopic methods. Compound 2 showed cytotoxicity against MCF-7 with an IC50 value of 79.90 μM whereas 2 and 4 exhibited cytotoxicity against the NCI-H187 cell line with IC50 values of 71.57 and 95.47 μM, respectively.


Intra-aortic balloon counterpulsation in a patient with the failing Fontan circulation.
We report a 23-year-old patient undergoing functionally univentricular repair who developed cardiac failure due primarily to systemic ventricular dysfunction. The failing Fontan circulation was successfully re-established using intra-aortic balloon counterpulsation. Aortic counterpulsation facilitates recovery of systemic ventricular function, and appears to be a reasonable alternative in select instances of cardiac failure in patients with the Fontan circulation.


Intracellular behavior of Nocardia seriolae and its apoptotic effect on RAW264.7 macrophages.
Nocardia seriolae, an intracellular gram-positive pathogen, is prone to infecting immunocompromised and surface-damaged fish, causing serious losses to the aquaculture industry. Although a previous study has demonstrated that N. seriolae infects macrophages, the persistence of this bacterium in macrophages has not been well characterized. To address this gap, we used the macrophage cell line RAW264.7, to investigate the interactions between N. seriolae and macrophages and deciphered the intracellular survival mechanism of N. seriolae. Confocal and light microscopy revealed that N. seriolae entered macrophages 2 hours post-inoculation (hpi), were phagocytosed by macrophages at 4-8 hpi, and induced the formation of multinucleated macrophages by severe fusion at 12 hpi. Flow cytometry, evaluation of mitochondrial membrane potential, release of lactate dehydrogenase, and observation of the ultrastructure of macrophages revealed that apoptosis was induced in the early infection stage and inhibited in the middle and later periods of infection. Additionally, the expression of Bcl-2, Bax, Cyto-C, Caspase-3, Capase-8, and Caspase-9 was induced at 4 hpi, and then decreased at 6-8 hpi, illustrating that N. seriolae infection induces the activation of extrinsic and intrinsic apoptotic pathways in macrophages, followed by the inhibition of apoptosis to survive inside the cells. Furthermore, N. seriolae inhibits the production of reactive oxygen species and releases large amounts of nitric oxide, which persists in macrophages during infection. The present study provides the first comprehensive insight into the intracellular behavior of N. seriolae and its apoptotic effect on macrophages and may be important for understanding the pathogenicity of fish nocardiosis.


Psychometric Properties of a Machine Learning-Based Patient-Reported Outcome Measure on Medication Adherence: Single-Center, Cross-Sectional, Observational Study.
Medication adherence plays a critical role in controlling the evolution of chronic disease, as low medication adherence may lead to worse health outcomes, higher mortality, and morbidity. Assessment of their patients' medication adherence by clinicians is essential for avoiding inappropriate therapeutic intensification, associated health care expenditures, and the inappropriate inclusion of patients in time- and resource-consuming educational interventions. In both research and clinical practices the most extensively used measures of medication adherence are patient-reported outcome measures (PROMs), because of their ability to capture subjective dimensions of nonadherence. Machine learning (ML), a subfield of artificial intelligence, uses computer algorithms that automatically improve through experience. In this context, ML tools could efficiently model the complexity of and interactions between multiple patient behaviors that lead to medication adherence. This study aimed to create and validate a PROM on medication adherence interpreted using an ML approach. This cross-sectional, single-center, observational study was carried out a French teaching hospital between 2021 and 2022. Eligible patients must have had at least 1 long-term treatment, medication adherence evaluation other than a questionnaire, the ability to read or understand French, an age older than 18 years, and provided their nonopposition. Included adults responded to an initial version of the PROM composed of 11 items, each item being presented using a 4-point Likert scale. The initial set of items was obtained using a Delphi consensus process. Patients were classified as poorly, moderately, or highly adherent based on the results of a medication adherence assessment standard used in the daily practice of each outpatient unit. An ML-derived decision tree was built by combining the medication adherence status and PROM responses. Sensitivity, specificity, positive and negative predictive values (NPVs), and global accuracy of the final 5-item PROM were evaluated. We created an initial 11-item PROM with a 4-point Likert scale using the Delphi process. After item reduction, a decision tree derived from 218 patients including data obtained from the final 5-item PROM allowed patient classification into poorly, moderately, or highly adherent based on item responses. The psychometric properties were 78% (95% CI 40%-96%) sensitivity, 71% (95% CI 53%-85%) specificity, 41% (95% CI 19%-67%) positive predictive values, 93% (95% CI 74%-99%) NPV, and 70% (95% CI 55%-83%) accuracy. We developed a medication adherence tool based on ML with an excellent NPV. This could allow prioritization processes to avoid referring highly adherent patients to time- and resource-consuming interventions. The decision tree can be easily implemented in computerized prescriber order-entry systems and digital tools in smartphones. External validation of this tool in a study including a larger number of patients with diseases associated with low medication adherence is required to confirm its use in analyzing and assessing the complexity of medication adherence.


Prevention of diabetes in non-obese diabetic mice by a single immunization with Mycobacterium leprae.
The incidence of overt diabetes was completely prevented by a single intradermal inoculation of Mycobacterium leprae (M. leprae) into Non-obese diabetic (NOD) mice as young as 6-7 weeks. Partial prevention was also observed in cases when 65 kD heat-shock protein (hsp65) with Freund's incomplete adjuvant (FIA) was injected, and no prevention was observed by 38 kD with FIA immunization. Histological examination of pancreata demonstrated that control and M. leprae-immunized mice at 24 weeks of age developed the insulitis even though the number of lymphocytes infiltrated in the treated ones were less than the controls. However, later, at 47 weeks of age, even the immunized mice become to develop very severe insulitis. Thus, M. leprae-immunization did not prevent the incidences of insulitis. The spontaneous development of serum antibody against hsp65 and 38 kD protein preceded the onset of diabetes in NOD mice. Lymphocytes response, IFN-gamma and IL-10 production of splenocytes cultures stimulated with hsp65 were examined to clue the reasons for the prevention of IDDM incidence by M. leprae immunization. The spontaneous development of anti-hsp65 T lymphocytes preceded the outbreak of overt IDDM in control NOD mice, but also appeared in M. leprae immunized cases in which the IDDM incidence was prevented, and both control and M. leprae immunized groups produced IFN-gamma and IL-10 by stimulation with hsp65.


[Genital self-injury behavior--phenomenologic and differential diagnosis considerations from the psychiatric viewpoint].
There is only a small number of publications concerning psychiatric aspects of genital-self-mutilation, all of these are case reports. This presentation adds results of self-inflicted genital injuries in another seven males which are discussed in relation to relevant scientific literature focussing on psychopathology and dynamic considerations. It is argued that genital self-mutilations should primarily be considered as symptomatic behavioural patterns and that-beside quasi-normal psychological procedures as part of certain religious or cultural rituals-such acts can be interpreted as a common final pathway of a variety of psychopathological problems. The inclusion of sexually (co-)motivated genital-automutilations in a complete work up and analysis of this topic seems to be reasonable and is advocated by the authors. The assumption that genital self-injuries are more often seen in non-psychotic conditions than in productive psychotic states is substantiated. Finally, the relation between genital automutilations and self-harm in general is discussed and some recommendations on the management are listed.


[Prolactin adenoma. Study of gonadotrophic function by the sassoles G LHRH test].
An intravenous injection of synthetic LHRH (50mug) was given in 10 patients with prolactin secreting pituitary adenomas. Variations in circulating levels of gonadotrophic hormones were measured by radioimmunological estimation. The increase in blood level of luteinizing hormone was constant, low in three cases, normal in 3 and high in 4. An increase in follicle stimulating hormone (FSH) was absent in only two cases. The data obtained indicates the absence of any characteristic value of the LHRH test in the aetiological diagnosis of amenorrhoea/galactorrhoea syndromes. They represent an argument in favour of the relative character and of the functional nature of the gonadotrophic insufficiency of prolactin adenomas.


[Hypercalcemia in breast cancer].
In a total of 277 patients with advanced breast cancer treated between July 1977 and November 1983 at Cancer Institute Hospital, there were 26 cases (9.4%) showing hypercalcemia (Ca greater than or equal to 11.0 mg/dl). All these patients had bone metastasis examined by either X-ray films or bone scintigram during clinical course of the disease and confirmed at the time of autopsy, thus an overall incidence of hypercalcemia in 149 patients with bone metastasis was 17.4%. Major clinical signs due to hypercalcemia were gastrointestinal symptoms such as anorexia, nausea and vomiting, renal dysfunction and neurological symptoms but there was no definitive correlation in between clinical signs and values of serum calcium. Among various treatments performed, a combination of hydration, steroids and calcitonin was the most effective. Mean survival time from the diagnosis of hypercalcemia was 288 + days for responders, and 28.8 days for non-responders (p less than 0.001). Seven patients expired due to hypercalcemia and were died suddenly, while others died of renal failures.


Three-dimensional image registration as a tool for forensic odontology: a preliminary investigation.
Frequently, human dentition is utilized for victim identification. This report introduces a new human identification technique based on the principle of 3-dimensional (3D) image registration of the dentition. With the aid of a dry human skull, postmortem (PM) and antemortem (AM) scenarios were assumed. The skull in its initial state composed the PM scenario. Virtual 3D PM images were reconstructed from medical CT images. The AM scenario was achieved by reconstructing the missing hard and soft tissues of the skull by dental waxes. Virtual 3D AM images were obtained by laser surface scanning. The virtual PM and AM images were registered at 2 levels: arch level and tooth level. At arch level, the deviation between the 2 images was 0.147 mm for the maxilla and 0.166 mm for the mandible. At tooth level, the deviation average ranged from 0.077 to 0.237 mm. Qualitatively, even image fit was observed for the arches, intact teeth, and teeth with minimal deficiencies. As the tooth defect increased, the alignment discrepancy increased. It is concluded that 3D image registration ensured an accurate superimposition of the 3D images and can be used as a robust tool for forensic identification.