Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury.
Myocardial infarction is the major cause of cardiac injury in western countries and can result in a massive loss of heart cells, leading eventually to heart failure. A fibrotic collagen-rich scar may prevent ventricular wall rupture, but also may result in heart failure because of its stiffness. In zebrafish, cardiac cryoinjury triggers a fibrotic response and scarring. Unlike with mammals, zebrafish heart has the striking ability to regenerate and to resolve the scar. Thus, understanding the mechanisms of scar resolution in zebrafish heart might facilitate the design of new therapeutic approaches to improve the recovery of patients. To visualize the collagenolytic activity within the zebrafish heart following cryoinjury, we used an in situ collagen zymography assay. We detected expression of mmp2 and mmp14a and these matrix metalloproteinases might contribute to the collagenase activity. Collagenolytic activity was present in the wound area, but decreased as the myocardium regenerated. Comparison with neonatal mouse hearts that failed to regenerate after transmural cryoinjury revealed a similar collagenolytic activity in the scar. These findings suggest that collagenolytic activity may be key to how the zebrafish heart resolves its scar; however, it is not sufficient in mouse hearts that lack efficient myocardial regeneration.


Use of mutants to establish (+)-scytalone as an intermediate in melanin biosynthesis by Verticillium dahliae.
Melanin biosynthesis in Verticillium dahliae Kleb, was studied with mutants deficient for normal black melanin or for production of microsclerotia. Seven genetically different mutants had apparent blocks in melanin biosynthesis. Four mutants (brm-1 to -4) produced brown microsclerotia and extruded pigments into media; three (alm-1 to -3) produced albino microsclerotia. Other mutants produced no microsclerotia (nms) or had greatly reduced numbers of microsclerotia (rms). Mutation alm-1 was due to a single recessive gene; the other melanin-deficient characters were recessive but their genetic bases were not determined. Cultures of the brown mutants brm-1 and -3 extruded and accumulated a metabolite that blackened the albino microslerotia of alm-1 to -3. The metabolite was identified as (+)-scytalone (3,4-dihydro-3,6,8-trihydroxy-1(2H)naphthalenone). Pigment formed by alm-1 microsclerotia from (+)-scytalone had chemical and physical properties identical with those of melanin in the wild-type fungus. (+)-Scytalone was produced and converted to melanin by microsclerotia but not by conidia or hyphae. Conversion of (+)-scytalone to melanin appeared to involve two or more enzymes and probably involved conversions to 1,3,8,-trihydroxynaphthalene and 1,8-dihydroxynaphthalene. Albino mutants of Thielaviopsis basicola, Drechslera sorokiniana, Pleospora infectoria (Alternaria), Ulocladium sp., and Curvularia sp. also converted scytalone to pigments indistinguishable from the melanins found in their respective wild types. Scytalone melanin may be common in fungi with dark brown or black pigments.


Ralstonia mannitolilytica bacteremia in a neonatal intensive care unit.
Ralstonia mannitolilytica, a Gram-negative bacterium, is rarely isolated in clinical laboratories. It has been associated with outbreaks due to its ability to survive in liquid media and hospital devices. We describe three cases of bacteremia caused by R. mannitolilytica in a neonatal intensive care unit in Curitiba, Southern Brazil. All isolates presented the same PFGE profile. The common source of infection was undetected in surveillance cultures for the outbreak survey. All patients received antimicrobial treatment and were discharged from the maternity. Due to the characteristics of the microorganism, clinicians and microbiologists should pay attention to the emergence of Ralstonia spp. infections.


Neostigmine for postoperative surgical urine retention: A systematic review and meta-analysis.
Postoperative urinary retention (POUR) is a common surgical complication that can result in bladder overdistension, urinary tract infection and an extended hospital stay. Although neostigmine is an effective therapy for POUR, its usage remains controversial. The purpose of this study was to investigate the effectiveness of neostigmine in improving POUR after surgery. PubMed, Embase, Web of Science, and the Cochrane Library databases were reviewed. A methodical search approach was used for data extraction, while meta-analysis and bias analysis employed Review Manager 5.2 and MedCalc. Fourteen studies involving 4196 postoperative patients were included. With an odds ratio (OR) of 1.70, 95% confidence interval (95% CI) of 1.11-2.60 and an overall effect with p < 0.05, our analysis indicated that the patients receiving neostigmine had a greater effective urine retention rate than after other standard therapies. The subgroup analysis showed that neostigmine recipients had reduced residual urine volume (mean difference (MD) = -1.16, 95% CI: -2.05--0.27, overall p < 0.05, and I2 = 90%) and POUR (standardized MD (SMD) = 3.76, 95% CI: 2.19-5.34, overall p < 0.001, and I2 = 99% using a random effects model) as compared to controls. A random-effects model was utilized due to the substantial heterogeneity between trials. The studies were consistent and had no publication bias. Based on the findings of this meta-analysis, neostigmine can be considered an effective POUR treatment.


Stimuli Responsive Poly(Vinyl Caprolactam) Gels for Biomedical Applications.
Poly(vinyl caprolactam) (PNVCL) is one of the most important thermoresponsive polymers because it is similar to poly(N-isopropyl acrylamide). PNVCL precipitates from aqueous solutions in a physiological temperature range (32⁻34 °C). The use of PNVCL instead of PNIPAM is considered advantageous because of the assumed lower toxicity of PNVCL. PNVCL copolymer gels are sensitive to external stimuli, such as temperature and pH; which gives them a wide range of biomedical applications and consequently attracts considerable scientific interest. This review focuses on the recent studies on PNVCL-based stimuli responsive three dimensional hydrogels (macro, micro, and nano) for biomedical applications. This review also covers the future outlooks of PNVCL-based gels for biomedical applications, particularly in the drug delivery field.


Uptake of non-pathogenic E. coli by Arabidopsis induces down-regulation of heat shock proteins.
We recently demonstrated that non-pathogenic and non-symbiotic microbes E. coli and yeast are taken up by roots and used as a source of nutrients by the plant. Although this process appears to be beneficial for the plant, the nutritional gain of microbe incorporation has to exceed the energy expense of microbe uptake and digestion, and the question remains whether the presence of microbes triggers pathogen- and other stress-induced responses. Here, we present evidence that digesting microbes is accompanied by strong down-regulation of genes linked to stress response in Arabidopsis. Genome-wide transcription analysis shows that uptake of E. coli by Arabidopsis roots is accompanied by a pronounced down-regulation of heat shock proteins. Plants up-regulate heat shock proteins in response to environmental stresses including temperature, salt, light and disease agents including microbial pathogens. The pronounced down-regulation of heat shock proteins in the presence of E. coli indicates that uptake and subsequent digestion of microbes does not induce stress. Additionally it suggests that resources devoted to stress resistance in control plants may be re-allocated to the process of microbe uptake and digestion. This observation adds evidences to the notion that uptake of microbes is an active, purposeful and intentional behavior of the plant.


The impact of rest breaks on temporal trends in injury risk.
This study examined the impact of rest breaks on temporal trends in industrial accident risks in an attempt to replicate earlier findings of a linear increase in risk as a function of elapsed time on task. In two separate studies, the trend in work-related injuries were studied in relation to the timing of rest breaks. In study one, comparisons were made between on- and off-track workers on weekly rotating three-shift systems operating in a large engineering company. Records of on-duty injuries that occurred over 12 months were examined (N = 4645 incidents). Study two involved interviewing patients who had suffered work-related hand injuries in a variety of occupational settings (N = 407 patients). Hierarchical log linear analysis was used in both studies. In study one, risk increased from the first to the second half-hour of continuous work following a break, but then remained relatively constant in subsequent half-hour periods, although there was a fall in the third half-hour for on-track workers. In some of the data, there was also a decrease in risk in the period leading up to the end of a work period. There was a sharp decline in reported injuries toward the very end of a shift, but otherwise the observed trends did not differ between successive periods of continuous work or between morning, afternoon, and night shifts. In study two, risk increased from the first to the second half-hour of continuous work and then remained relatively constant in the third half-hour. The contrast between the current and previous findings may be due to the relatively unique work environment of the previous study. It is suggested that the current trends reflect the effects of working in a relatively unconstrained task environment, and that causes other than fatigue may underlie the trends observed in both the previous and current studies.


The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats.
To evaluate the effect of tadalafil in renal ischemia/reperfusion (I/R) injury in rats Methods: Group I/R saline rats (n=6) were subjected to 45 minutes of left renal ischemia and treated with saline; the I/R tadalafil rats (n=6) received oral 10mg/kg tadalafil microemulsion one hour before ischemia. In both groups, 8 hours after ischemia, laboratory analysis were performed Results: Better tissue perfusion was lower in ischemic left/kidney than in right/kidney in saline group, suggesting reduced kidney clearance. Fluorescence in left/kidneys of tadalafil treated rats was lower than in right/kidneys (difference not significant). The fluorescence signal intensity in kidneys of tadafil treated rats was higher than in saline rats. TNF-α levels were significantly lower in I/R tadalafil group rats compared to I/R saline group (154±10.3 vs 391.3±12.3), as well as IL-1β (163.4±13.2 vs 279±11.5pg/dL), and IL-6 (122.9±8.1 vs 173.7±6.3 respectively; p=0.0001). Urea, creatinine and C-reactive protein were significantly lower in tadafil treated rats then in saline group Conclusion: Tadalafil therapy decreased the expression of circulating pro-inflammatory cytokines in a renal I/R rodent model, while improving kidney function proofs.


Myocardial cholinergic receptor sites and enzyme activity in the Dahl model of essential hypertension.
The density of muscarinic receptor sites, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activity in the myocardium of the Dahl salt-sensitive (DS) and salt-resistant (DR) rat was investigated. Both normotensive and hypertensive (as a result of 8.0% NaCl added to the diet) DS rats displayed a lower concentration of muscarinic receptors and less ChAT and AChE activity in myocardial tissue than normotensive DR rats. Lower receptor site density and enzyme activity in the myocardial of the DS line may reflect decreased vagal tone. If true, this may produce dificits in the ability to appropriately adjust heart rate (HR) in response to elevations in blood pressure (BP). Therefore, the present results may be viewed as exacerbational factors in the pathogenesis of hypertension in the DS line.


New combinations for Pacific endemic species: Marquesan Poaceae, and Micronesian Myrtaceae.
As part of the preparation for a comprehensive online flora of Pacific oceanic islands, numerous taxonomic changes have been necessary, primarily due to a new wealth of global molecular phylogenetic studies on genera that include Pacific islands species. In order to compile an accurate checklist of the Pacific island flora with up-to-date taxonomies, we are moving several species to their currently accepted genera. Two Marquesan Pennisetum Rich. are transferred to Cenchrus L. with the new combinations Cenchrus articularis (Trin.) M. Tornabene & W.L. Wagner, and Cenchrus henryanus (F. Br.) M. Tornabene & W.L. Wagner. A key to Marquesas Cenchrus is also provided to differentiate the two species. Additionally, one species of Eugenia L. is transferred to Syzygium Gaertn. with the new combination Syzygium stelechanthoides (Kaneh.) M. Tornabene & W.L. Wagner in accord with the aforementioned studies.


Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development.
Tissue-resident memory T cells (Trm) in the lung provide a frontline defence against respiratory pathogens. Vaccination models that lodge CD8+ Trm populations in the lung have been developed, all of which incorporate the local delivery of antigen plus adjuvant into the airways; a necessary approach as local cognate antigen recognition is required for optimal lung Trm development. Although pulmonary delivery of antigen is important for lung Trm development, the impact the co-administered adjuvant has on Trm differentiation is unclear. We show that while altering the adjuvant co-administered with the pulmonary delivered antigen does not impact the size of the lung Trm population, a particular adjuvant, zymosan, when administered into the airways without antigen can drive effector CD8+ T cells to differentiate into lung Trm. Zymosan signalling via dectin-1 receptor was sufficient to promote antigen-independent lung Trm development. When combined with an injectable influenza vaccination regime, intranasal zymosan delivery significantly boosted the size of the influenza virus-specific lung Trm population. Our results highlight that eliciting the appropriate local inflammatory milieu can by-pass the requirement for local antigen recognition in lung Trm development and emphasises that the appropriate selection of adjuvant can greatly improve vaccines that aim to elicit pulmonary Trm.


Frontal facial changes with the Fränkel appliance.
A study of 50 cases treated with the Fränkel appliance shows significantly greater increase in bigonial width and related decrease in frontofacial taper as seen in the P-A cephalometric view than in comparable cases treated with Edgewise therapy or in untreated norms from the Bolton and FOR studies.


Localization of speech parameters by brain scan.
Speech was studied in 18 patients who had a positive radioisotope brain scan within the left hemisphere and a history of a single stroke. Seventeen patients had definite language impariment. In most cases of either fluent or nonfluent aphasia, the center of the scan was behind the central sulcus. Patients with perisylvian involvement were much more likely to have severe comprehension deficit than those without such involvement. Those patients with the most severely decreased fluency were significantly more likely than those more fluent to have markedly decreased comprehension. In an occasional patient, involvement of fluency and comprehension was divergent, suggesting that these processes may be differentially affected.


A new species of Mexican parrot? Reasonable doubt on the status of Amazona gomezgarzai (Psittaciformes: Psittacidae).
We present arguments against the recognition of Amazona gomezgarzai Silva et al., 2017 as a valid species. This putative new species was stated to have been discovered in Becanchén town in the central Yucatan Peninsula by a veterinarian, who presented two live individuals to the authors for description. This description has numerous weaknesses, as follows: 1) the Yucatan Peninsula avifauna is well-known, having been extensively explored by collectors and other ornithologists; 2) the authors were never in the relevant field area, nor did they verify that the two individuals obtained for the description came from a natural population; 3) our field trip to the type locality and distribution area failed to verify the existence of the putative new species there; instead, inhabitants of these localities denied that such a person was there and denied having given anyone the birds, nor did they recognize that there were parrots matching the "new" species in the area; 4) the description was prepared without proper voucher specimens; 5) comparisons in existing museum collections were highly inadequate; 6) the characters on which the description is based fail to support that it represents a valid taxon, instead strongly supporting an hypothesis of hybrid origin, which was untested by nuclear DNA markers; and 7) no collecting permits were mentioned in the paper. Although earlier reviewers pointed out weaknesses of the original manuscript, the authors failed to rigorously address these questions and the paper was nevertheless published.


Tissue interactions in development of teeth and related ectodermal derivatives.
A number of traditional techniques have been used to examine epithelial-mesenchymal interactions; they remain to this day the only means to examine the problems of tissue interactions. Problems at the tissue level of organization require that the approaches to these problems ask questions and use techniques that address the issues of tissue organization and cellular morphology in the context of three-dimensional organization. Manipulating the embryo is exactly that--manipulating a three-dimensional organized organism that must express its differentiated functional organs and organ systems. When the parallel and correlative studies of cell biological function achieve new insights, they will have to be tested in terms of the cellular response at the tissue level of organization.


Modified Terminal Restriction Fragment Analysis for Quantifying Telomere Length Using In-gel Hybridization.
There are several different techniques for measuring telomere length, each with their own advantages and disadvantages. The traditional approach, Telomere Restriction Fragment (TRF) analysis, utilizes a DNA hybridization technique whereby genomic DNA samples are digested with restriction enzymes, leaving behind telomere DNA repeats and some sub-telomeric DNA. These are separated by agarose gel electrophoresis, transferred to a filter membrane and hybridized to oligonucleotide probes tagged with either chemiluminescence or radioactivity to visualize telomere restriction fragments. This approach, while requiring a larger quantity of DNA than other techniques such as PCR, can measure the telomere length distribution of a population of cells and allows measurement expressed in absolute kilobases. This manuscript demonstrates a modified DNA hybridization procedure for determining telomere length. Genomic DNA is first digested with restriction enzymes (that do not cut telomeres) and separated by agarose gel electrophoresis. The gel is then dried and the DNA is denatured and hybridized in situ to a radiolabeled oligonucleotide probe. This in situ hybridization avoids loss of telomere DNA and improves signal intensity. Following hybridization, the gels are imaged utilizing phosphor screens and the telomere length is quantified using a graphing program. This procedure was developed by the laboratories of Drs. Woodring Wright and Jerry Shay at the University of Texas Southwestern1,2. Here, we present a detailed description of this procedure, with some modifications.


Adenosine in renin-dependent renovascular hypertension.
Our previous studies support the hypothesis that activation of the renin-angiotensin system by renal ischemia elevates adenosine levels and that adenosine acts in a negative feedback loop to limit renin release and to mitigate some of the hypertension-producing effects of angiotensin II. To further test this hypothesis, we compared the time course of caffeine-induced increases in plasma renin activity with the time course of changes in plasma levels of adenosine in two models of renin-dependent renovascular hypertension. Also, we compared the effects of caffeine on plasma renin activity and arterial blood pressure in renin-dependent versus renin-independent renovascular hypertension. In comparison to sham-operated rats, plasma levels of adenosine in the left and right renal veins and aorta were elevated severalfold in two-kidney, one clip rats (2K1C) 1 week after left renal artery clipping. However, adenosine levels declined during the second and third weeks after clipping. In 2K1C rats treated chronically with caffeine, plasma renin activity was markedly elevated during the first week after operation as compared to non-caffeine-treated 2K1C rats. However, during the second and third weeks after clipping, caffeine had lesser effects on plasma renin activity. A temporal relationship between plasma adenosine levels and caffeine-induced hyperreninemia was also observed in rats with aortic ligation. Caffeine accelerated hypertension in 2K1C rats and rats with aortic ligation (renin-dependent renovascular hypertension), but it had no effect on plasma renin activity or blood pressure in one-kidney, one clip rats (renin-independent renovascular hypertension). These results lend further support to the hypothesis that adenosine functions to mitigate the renin-angiotensin system in renin-dependent renovascular hypertension.


Exploring different attributes of source information for speaker verification with limited test data.
This work explores mel power difference of spectrum in subband, residual mel frequency cepstral coefficient, and discrete cosine transform of the integrated linear prediction residual for speaker verification under limited test data conditions. These three source features are found to capture different attributes of source information, namely, periodicity, smoothed spectrum information, and shape of the glottal signal, respectively. On the NIST SRE 2003 database, the proposed combination of the three source features performs better [equal error rate (EER): 20.19%, decision cost function (DCF): 0.3759] than the mel frequency cepstral coefficient feature (EER: 22.31%, DCF: 0.4128) for 2 s duration of test segments.


Segmental and regional quantification of 3D cellular density of human meniscus from osteoarthritic knee.
The knee menisci have important roles in the knee joint. Complete healing of the meniscus remains a challenge in the clinics. Cellularity is one of the most important biological parameters that must be taken into account in regenerative strategies. However, knowledge on the 3D cellularity of the human meniscus is lacking in the literature. The aim of this study was to quantify the 3D cellular density of human meniscus from the osteoarthritic knee in a segmental and regional manner with respect to laterality. Human lateral menisci were histologically processed and stained with Giemsa for histomorphometric analysis. The cells were counted in an in-depth fashion. 3D cellular density in the vascular region (27 199 cells/mm3 ) was significantly higher than in the avascular region (12 820 cells/mm3 ). The cells were observed to possess two distinct morphologies, roundish or flattened. The 3D density of cells with fibrochondrocyte morphology (14 705 cells/mm3 ) was significantly greater than the 3D density of the cells with fibroblast-like cell morphology (5539 cells/mm3 ). The best-fit equation for prediction of the 3D density of cells with fibrochondrocyte morphology was found to be: Density of cells with fibrochondrocyte morphology = 1.22 × density of cells withfibroblast-like cell morphology + 7750. The present study revealed the segmental and regional 3D cellular density of human lateral meniscus from osteoarthritic knee with respect to laterality. This crucial but so far missing information will empower cellular strategies aiming at meniscus tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.


Reversible visual evoked potential abnormalities in vitamin E deficiency.
A patient with cystic fibrosis and cirrhosis developed a progressive neurological syndrome associated with ataxia, proximal weakness, and ophthalmoplegia. Profound deficiencies of vitamins A, D, and E were present. Visual acuity and results of retinal funduscopy were normal. The pattern reversal visual evoked potential was initially abnormal (P100 latency, 136 and 130 ms from left and right eyes, respectively) but became normal (less than 3 standard deviations from mean control P100 latency) over a two-month period when vitamin E was administered. This case documents a potentially reversible visual evoked potential abnormality in a visually asymptomatic patient with vitamin E deficiency.


New-Generation Thromboelastography: Comprehensive Evaluation of Citrated and Heparinized Blood Sample Storage Effect on Clot-Forming Variables.
- Thromboelastography (TEG) is a whole blood, real-time analyzer measuring the viscoelastic properties of the hemostasis process and allowing for individualized goal-directed therapy. However, routine use of TEG requires validation of sample storage effect on clot parameters. - To establish the minimum time required for equilibration time and the maximum time for sample storage for all commercially available TEG tests for the new-generation TEG 6s and to determine how those times compare with the older generation TEG 5000. - Citrated and heparinized whole blood samples obtained from 20 healthy donors were analyzed for clot parameters at multiple time points for both the TEG 6s and the TEG 5000. Samples were activated with the citrated multichannel cartridge or the platelet-mapping cartridge in the TEG 6s or with recalcified kaolin in the TEG 5000. - All blood samples yielded TEG parameter results within reference ranges and had a tendency toward hypercoagulable profiles with increased storage time. Sample storage resulted in increased platelet inhibition with significant differences at 4 hours in the platelet-mapping cartridge (arachidonic acid percentage of inhibition, P = .002; adenosine diphosphate percentage of inhibition, P = .02). - For nonemergent cases or in a central laboratory setting, all tests provided reliable results for up to 4 hours in the citrated multichannel cartridge and for 3 hours for platelet function information in the platelet-mapping cartridge. In emergent/urgent situations in which the sample needs to be run immediately, RapidTEG and functional fibrinogen tests may be preferred.


The complete mitochondrial genome of the longhorn beetle Xylotrechus grayii (Coleoptera: Cerambycidae).
We sequenced the complete mitochondrial genome of the longhorn beetle, Xylotrechus grayii. The total length of the X. grayii mitogenome was 15,540 bp with an A + T content of 75.29%, consisting of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes and an A + T-rich region. All the genes were arranged in the same order as that of the ancestral insect. All PCGs started with a typical ATN codon except for cox1 and nad1, which used TTG as start codon. Ten out of 13 PCGs terminated with incomplete codons (TA or T). The A + T-rich region was 893 bp in length with an A + T content of 85.89 %.


In-ovo green light photostimulation during different embryonic stages affect somatotropic axis.
Previous studies demonstrated that in-ovo photostimulation with monochromatic green light increased the somatotropic axis expression in broilers embryos. The objective of the current study was to detect the critical period for in-ovo GL photostimulation, in order to find the optimal targeted photostimulation period during the incubation process. Three hundred thirty-six fertile broiler eggs were divided into 4 groups. The first group was incubated under dark conditions as a negative control. The second incubated under intermittent monochromatic green light using light-emitting diode (LED) lamps with an intensity of 0.1 W\m2 at shell level from d 0 of the incubation as a positive control. The third group incubated under intermittent monochromatic green light from d 10 of the incubation. The last group incubated under intermittent monochromatic green light from d 15 of the incubation. In-ovo green light photostimulation from embryonic d 0 (ED0) increased plasma growth hormone (GH), as well as hypothalamic growth hormone releasing hormone (GHRH) and liver growth hormone receptor (GHR) and insulin-like growth factor-1 (IGF-1) mRNA levels. In-ovo green light photostimulation from ED10 increased the GH plasma levels compared to the negative control group, without affecting somatotropic axis mRNA genes expressions of GHRH, GHR, and IGF-1. In-ovo green light photostimulation from ED15 caused an increase in both the plasma GH levels and the somatotropic axis mRNA genes expressions of GHRH, GHR, and IGF-1, compared to the negative control group. These results suggest that the critical period of somatotropic axis acceleration by GL photostimulation start at 15 d of incubation.


The nodes focusing tool for clinical course data of hypergraph structure in the ontological framework CSX output from POMR-based EMR system.
Knowledge management is one of the significant issues in this century. In medical informatics, the concept of ontology is an important current topic. In addition, there is great interest in knowledge acquisition from clinical data. When doctors use clinical information systems (CIS), their operation implicitly represents, to some extent, their thinking processes with clear reasons and goals according to their intent. If we can capture such resources in an appropriate representation, considerable empirical knowledge could be utilized in various research fields. With this prospect, the authors built an experimental CIS and a nodes-focusing tool for abstracting a summary of the clinical course being examined. The information model is based on a thinking process model, and data are represented in the ontological framework CSX. Then we showed the knowledge-abstracting procedures with this tool. Some domain experts and intern students showed great interest. The authors thereby concluded that such an empirical knowledge acquisition environment is useful for research, education, and so on.


Systemic blastomycosis diagnosed by prostate needle biopsy.
A healthy 51-year-old man presented with a 1-month history of lower urinary tract irritative symptoms. Urinalysis was suggestive of infection, and the patient was treated with multiple antibiotics without relief of symptoms. A urological exam demonstrated abnormal induration of the prostate gland. Biopsy of the prostate gland revealed Blastomyces dermatitidis. In areas where Blastomyces dermatitidis is endemic, clinicians should be aware of the presence of this fungus and possible sites of infection.


Chlamydia trachomatis Genital Infections.
Etiology, transmission and protection: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infection (STI) globally. However, C. trachomatis also causes trachoma in endemic areas, mostly Africa and the Middle East, and is a leading cause of preventable blindness worldwide. Epidemiology, incidence and prevalence: The World Health Organization estimates 131 million new cases of C. trachomatis genital infection occur annually. Globally, infection is most prevalent in young women and men (14-25 years), likely driven by asymptomatic infection, inadequate partner treatment and delayed development of protective immunity. Pathology/Symptomatology: C. trachomatis infects susceptible squamocolumnar or transitional epithelial cells, leading to cervicitis in women and urethritis in men. Symptoms are often mild or absent but ascending infection in some women may lead to Pelvic Inflammatory Disease (PID), resulting in reproductive sequelae such as ectopic pregnancy, infertility and chronic pelvic pain. Complications of infection in men include epididymitis and reactive arthritis. Molecular mechanisms of infection: Chlamydiae manipulate an array of host processes to support their obligate intracellular developmental cycle. This leads to activation of signaling pathways resulting in disproportionate influx of innate cells and the release of tissue damaging proteins and pro-inflammatory cytokines. Treatment and curability: Uncomplicated urogenital infection is treated with azithromycin (1 g, single dose) or doxycycline (100 mg twice daily x 7 days). However, antimicrobial treatment does not ameliorate established disease. Drug resistance is rare but treatment failures have been described. Development of an effective vaccine that protects against upper tract disease or that limits transmission remains an important goal.


SOCS3 overexpression inhibits advanced glycation end product-induced EMT in proximal tubule epithelial cells.
Diabetic nephropathy (DN) is among the most severe complications of diabetes mellitus, and may lead to end-stage renal disease. Sustained exposure to advanced glycation end products (AGEs) typically causes renal tubular epithelial cells (TECs) to suffer from an epithelial-to-mesenchymal transition (EMT). However, there remains no consensus regarding the mechanism underlying the cause of EMT in TECs as induced by AGEs. In the present study, we investigated the promotion of EMT in TECs by AGEs, and the activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. In addition, we constructed a recombinant adenovirus (Ad) that overexpressed suppressor of cytokine signaling 3 (SOCS3), and examined the regulatory role of SOCS3 in the activation of JAK/STAT signaling and the promotion of EMT in TECs. The results demonstrated that AGE-bovine serum albumin (BSA) treatment significantly promoted the expression of EMT-associated proteins, while reducing the expression of the epithelial cell marker, E-cadherin. Furthermore, the Ad-mediated SOCS3 overexpression markedly inhibited the AGE-BSA-induced JAK2/STAT3 activation; phosphorylated JAK2 and phosphorylated STAT3 expression levels were reduced by the Ad-SOCS3 infection, compared with the control Ad (Ad-con) infection, in HK-2 cells subject to AGE-BSA. Moreover, the overexpression of SOCS3 markedly inhibited the AGE-BSA-promoted EMT in HK-2 cells. AGE-BSA-promoted EMT-associated proteins, such as α-smooth muscle actin and collagen I, were reduced by the Ad-SOCS3 virus infection, in contrast to the Ad-con virus infection. Furthermore, reduced E-cadherin expression was reversed by the Ad-SOCS3 virus infection, in contrast to the Ad-con virus infection, in epithelial HK-2 cells. In conclusion, the present study confirmed the inhibitory role of SOCS3 in the AGE-induced EMT in renal TECs, implying the protective role of SOCS3 in DN.


Journey to the heart of macrophages: the delicate relationship between HIV-1 and a multifaceted cell type.
Cells of the monocyte-macrophage lineage play multiple roles during the infection of primate lentiviruses serving as reservoirs for viral production or as vectors for viral spread to other cells and tissues. The human immunodeficiency type I virus is not only capable of establishing such complex and dynamic relations with this cell type, but is also able to modulate their physiology and behavior, thus shaping ensuing cellular immune responses. In this issue of Retrovirology, a series of reviews explores the multiple manners in which the virus and cells belonging to the monocyte-macrophage lineage interact and affect each other.


Effect of Host Genotype on Symbiont Titer in the Aphid-Buchnera Symbiosis.
Obligate nutritional symbioses require balance between the energetic needs of the host and the symbiont. The resident symbiont population size within a host may have major impacts on host fitness, as both host and symbiont consume and supply metabolites in a shared metabolite pool. Given the massive genome degradation that is a hallmark of bacterial endosymbionts of insects, it is unclear at what level these populations are regulated, and how regulation varies among hosts within natural populations. We measured the titer of the endosymbiont Buchnera aphidicola from different clones of the pea aphid, Acyrthosiphon pisum, and found significant variation in titer, measured as Buchnera genomes per aphid genome, among aphid clones. Additionally, we found that titer can change with the age of the host, and that the number of bacteriocytes within an aphid is one factor likely controlling Buchnera titer. Buchnera titer measurements in clones from a sexual cross indicate that the symbiont genotype is not responsible for variation in titer and that this phenotype is likely non-heritable across sexual reproduction. Symbiont titer is more variable among lab-produced F₁ aphid clones than among field-collected ones, suggesting that intermediate titer is favored in natural populations. Potentially, a low heritability of titer during the sexual phase may generate clones with extreme and maladaptive titers each season.


Stable expression and function of EBV/C3d receptor following genomic transfection into murine fibroblast L cells.
The Epstein-Barr virus (EBV) and the C3d component of complement bind to the same cell surface receptor (EBVR/CR2) which is part of the B lymphocyte differentiation antigen recognized by the monoclonal antibodies (mAb) of the cluster of differentiation 21 (CD21). To analyze EBV and C3d binding to this receptor, mouse fibroblasts were transfected with human genomic DNA and rare CD21-positive cells were selected and cloned by cell sorting. The presence of the human gene in host cell DNA as well as its transcription product were assayed with a cloned EBVR/CR2 cDNA by Southern and Northern blotting analysis, respectively. A glycoprotein of apparent molecular mass of 140 kDa, similar to that found in human B lymphocytes, was immunoprecipitated with anti-CD21 mAb and proved to be functional since both C3d and EBV bound efficiently and specifically to mouse cells expressing EBVR/CR2. However, no expression of EBV nuclear antigens, early antigens and viral capsid antigens was detected in cells exposed to EBV. This indicates that the presence of EBVR/CR2 is not sufficient to allow full infection of mouse fibroblasts.


The latex sap of the 'Old World Plant' Lagenaria siceraria with potent lectin activity mitigates neoplastic malignancy targeting neovasculature and cell death.
Lifestyle and dietary modifications have contributed much to somatic genetic alteration which has concomitantly led to increase in malignant diseases. Henceforth, plant based and dietary interventions to mitigate and impede oncogenic transformation are in great demand. We investigated the latex sap (LSL) of the dietary Lagenaria siceraria vegetable, the first domesticated plant species with the potent lectin activity for its functional role against the tumor progression and its mechanism. LSL has markedly stimulated proliferation of lymphocytes and displayed strong cytotoxic activity against cancer both in-vitro and in-vivo. The tumor regression was paralleled with drastic reduction in tumoral neovasculature as evidenced from angiogenic parameters and abrogated related gene expressions. LSL has also triggered apoptotic signaling cascade in cancer cells through activation of caspase-3 mediated activation of endonuclease and inducing apoptotic cellular events. Collectively our study provides tangible evidences that latex sap from L. siceraria with immunopotentiating ability significantly regresses the tumor progression by targeting angiogenesis and inducing cell death.


APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians.
The cytosine deaminase APOBEC3G has been identified as a host factor that inhibits HIV-1 replication. We investigated whether genetic variants of APOBEC3G that could potentially affect the protein's expression or function were associated with the risk of infection in 122 Caucasians highly exposed to HIV-1. A novel C40693T variant was significantly associated with an increased risk of infection, suggesting that there might be a role for APOBEC3G in susceptibility to HIV-1 infection that warrants further investigation.


Beneficial effect of cerium excess on in situ grown Sr0.86Ce0.14FeO3-CeO2 thermocatalysts for the degradation of bisphenol A.
Ce-doped SrFeO3 perovskite-type compounds are known as good thermocatalysts for the abatement of wastewater contaminants of emerging concern. In this work, Sr0.86Ce0.14FeO3-CeO2 perovskite-oxide systems with increasing amounts of cerium excess (0, 5, 10 and 15 mol% Ce), with respect to its maximum solubility in the perovskite, were prepared in one-pot by solution combustion synthesis and the effects of cerium excess on the chemical physical properties and thermocatalytic activity in the bisphenol A degradation were evaluated. The powders were characterized by powder X-ray diffraction combined with Rietveld refinement, X-ray photoelectron spectroscopy, thermal gravimetry, temperature programmed reduction, nitrogen adsorption, scanning electron microscopy and energy dispersive X-ray spectroscopy techniques. Results highlight that the perovskite structural, redox, surface, and morphological properties are affected by the in situ co-growth of the main perovskite phase and ceria and that a larger cerium excess has a beneficial effect on the thermocatalytic performance of the perovskite oxide-ceria biphasic system, although ceria is not active as a thermocatalyst itself. Perovskite properties and performance are enhanced by the tetragonal distortion induced by the introduction of cerium excess in the synthesis. It is supposed that a larger oxygen mobility and an easier reducibility are among the most relevant features that contribute to superior thermocatalytic properties of these perovskite oxide-based systems. These results also suggest new perspectives in the nanocomposite preparation and their catalytic applications.


Chronic Exposure to Bisphenol A Exacerbates Dental Fluorosis in Growing Rats.
Enamel defects resulting from environmental conditions and way of life are public health concerns because of their high prevalence. Because their etiology is unclear, the aim of this study was to analyze the various forms of enamel hypomineralization, and to characterize the genes involved in this process to determine the mechanisms involved in disruptions of amelogenesis. We used bisphenol A (BPA) and fluoride as models; both are commonly encountered in human populations and utilized in dentistry. Wistar rats were chronically exposed to 5 μg/kg/day BPA from day 1 of gestation to day 65 after birth (P65) and 5 mM fluoride from P21 to P65. Resulting enamel defects were comparable to the human enamel pathologies molar incisor hypomineralization (MIH) and dental fluorosis (DF) respectively, and were more severe in rats exposed to both agents than to each agent alone. Large-scale transcriptomic analysis of dental epithelium showed a small group of genes the expression of which was affected by exposure to BPA or NaF. Among the most modulated, many are directly involved in amelogenesis (Amelx, Enam, Klk4, Mmp12, Slc26a4, and Slc5a8), and can be regrouped as forming the "hypomineralization enameloma." Each of these gene expression perturbations may contribute to enamel defects. Exposure to BPA weakens enamel, making it more prone to generate frequent mineralization defects MIH and DF. Our study identifies hypomineralization genes that may enable the use of dental enamel as an early marker of exposure to environmental toxicants because of its unique ability to retrospectively record ameloblast pathophysiology. © 2016 American Society for Bone and Mineral Research.


Molecular determinants of acrylamide neurotoxicity through covalent docking.
Acrylamide (ACR) is formed during food processing by Maillard reaction between sugars and proteins at high temperatures. It is also used in many industries, from water waste treatment to manufacture of paper, fabrics, dyes and cosmetics. Unfortunately, cumulative exposure to acrylamide, either from diet or at the workplace, may result in neurotoxicity. Such adverse effects arise from covalent adducts formed between acrylamide and cysteine residues of several neuronal proteins via a Michael addition reaction. The molecular determinants of acrylamide reactivity and its impact on protein function are not completely understood. Here we have compiled a list of acrylamide protein targets reported so far in the literature in connection with neurotoxicity and performed a systematic covalent docking study. Our results indicate that acrylamide binding to cysteine is favored in the presence of nearby positively charged amino acids, such as lysines and arginines. For proteins with more than one reactive Cys, docking scores were able to discriminate between the primary ACR modification site and secondary sites modified only at high ACR concentrations. Therefore, docking scores emerge as a potential filter to predict Cys reactivity against acrylamide. Inspection of the ACR-protein complex structures provides insights into the putative functional consequences of ACR modification, especially for non-enzyme proteins. Based on our study, covalent docking is a promising computational tool to predict other potential protein targets mediating acrylamide neurotoxicity.


Spectroscopic analyses of the binding kinetics of 15d-PGJ2 to the PPARgamma ligand-binding domain by multi-wavelength global fitting.
PPARgamma (peroxisome proliferator-activated receptor gamma) is a nuclear receptor that is activated by natural lipid metabolites, including 15d-PGJ2 (15-deoxy-Delta(12,14)-prostaglandin J2). We previously reported that several oxidized lipid metabolites covalently bind to PPARgamma through a Michael-addition to activate transcription. To separate the ligand-entering (dock) and covalent-binding (lock) steps in PPARgamma activation, we investigated the binding kinetics of 15d-PGJ2 to the PPARgamma LBD (ligand-binding domain) by stopped-flow spectroscopy. We analysed the spectral changes of 15d-PGJ2 by multi-wavelength global fitting based on a two-step chemical reaction model, in which an intermediate state represents the 15d-PGJ2-PPARgamma complex without covalent binding. The extracted spectrum of the intermediate state in wild-type PPARgamma was quite similar to the observed spectrum of 15d-PGJ2 in the C285S mutant, which cannot be activated by 15d-PGJ2, indicating that the complex remains in the inactive, intermediate state in the mutant. Thus 'lock' rather than 'dock' is one of the critical steps in PPARgamma activation by 15d-PGJ2.


Surfactant-dependent exciton mobility in single-walled carbon nanotubes studied by single-molecule reactions.
Measurements of stepwise photoluminescence quenching in individual, (n,m)-selected single-walled carbon nanotubes (SWCNTs) undergoing chemical reaction have been analyzed to deduce mobilities of optically generated excitons. For (7,5) nanotubes, the mean exciton range varies between approximately 140 and 240 nm for different surfactant coatings and correlates weakly with nanotube PL intensity. The results are consistent with a model of localized SWCNT excitons having substantial diffusional mobility along the nanotube axis.


Breast reduction for asymmetrical hypertrophy.
Design details of reduction of asymmetrical hypertrophy of the breasts are discussed. The concepts apply to nearly any breast reduction technique, although here they are presented in the context of the inferior segment method, which we favor. Although most of these points may seem self-evident to the experienced plastic surgeon, there has been little written about the details.


CD44/Folate Dual Targeting Receptor Reductive Response PLGA-Based Micelles for Cancer Therapy.
In this study, a novel poly (lactic-co-glycolic acid) (PLGA)-based micelle was synthesized, which could improve the therapeutic effect of the antitumor drug doxorubicin hydrochloride (DOX) and reduce its toxic and side effects. The efficient delivery of DOX was achieved by active targeting mediated by double receptors and stimulating the reduction potential in tumor cells. FA-HA-SS-PLGA polymer was synthesized by amidation reaction, and then DOX-loaded micelles were prepared by dialysis method. The corresponding surface method was used to optimize the experimental design. DOX/FA-HA-SS-PLGA micelles with high drug loading rate and encapsulation efficiency were prepared. The results of hydrophilic experiment, critical micelle concentration determination, and hemolysis test all showed that DOX/FA-HA-SS-PLGA micelles had good physicochemical properties and biocompatibility. In addition, both in vitro reduction stimulus response experiment and in vitro release experiment showed that DOX/FA-HA-SS-PLGA micelles had reduction sensitivity. Molecular docking experiments showed that it can bind to the target protein. More importantly, in vitro cytology studies, human breast cancer cells (MCF-7), human non-small cell lung cancer cells (A549), and mouse colon cancer cells (CT26) were used to demonstrate that the dual receptor-mediated endocytosis pathway resulted in stronger cytotoxicity to tumor cells and more significant apoptosis. In and in vivo antitumor experiment, tumor-bearing nude mice were used to further confirm that the micelles with double targeting ligands had better antitumor effect and lower toxicity. These experimental results showed that DOX/FA-HA-SS-PLGA micelles have the potential to be used as chemotherapeutic drugs for precise tumor treatment.


[Successful multidisciplinary treatment of a case of lymph node recurrence with invasion to adjacent organs after curative resection of esophageal cancer].
In the present report, we describe a case of a woman who underwent esophagectomy for esophageal carcinosarcoma in October 2008. Computed tomography (CT) and endoscopy indicated lymph node recurrence with invasion into adjacent organs and oropharyngeal carcinoma in September 2009. She subsequently received 2 courses of chemotherapy (5-fluorouracil+ cisplatin+adriamycin) plus radiotherapy with a total dose of 60 Gy. Although a partial response was achieved after this treatment, CT still indicated the presence of residual lesions. Therefore, surgical excision was performed at the site of the lymph node recurrence and for oropharyngeal carcinoma. Thus, we performed a radical operation by resecting the skin, sternum, clavicle, ribs, innominate vein, bronchus, oropharyngeal, larynx, and lymph node; transplanted a free thigh flap; and performed a mediastinal tracheostomy. She has been alive without recurrence for 3 years and 4 months after the operation.


Value, obligation and the asymmetry question.
Is there a prima facie obligation to produce additional individuals whose lives would be worth living? In his paper 'Is it good to make happy people?', Stuart Rachels argues not only that there is, but, also, that precisely as much weight should be assigned to the quality of life that would be enjoyed by such potential persons, if they were to be actualized, as to the quality of life enjoyed by actually existing persons. In response, I shall argue, first, that Rachels' view is exposed to very serious objections, and secondly, that his arguments in support of his position involve a crucial assumption, which cannot be sustained, concerning the relation between, on the one hand, propositions about good-making and bad-making properties, and, on the other, propositions about right-making and wrong-making ones. I shall then argue that there is a very plausible position concerning the conditions under which an action can be morally wrong which entails the following asymmetry: there is a prima facie obligation not to bring into existence individuals whose lives are not worth living, but there is no corresponding obligation to create additional individuals whose lives would be worth living.


Participation in research and access to experimental treatments by HIV-infected patients.
Although there is concern that minority groups and women are underrepresented in research involving patients with human immunodeficiency virus (HIV) infection, the available data are inconclusive. We used nationally representative data from the HIV Cost and Services Utilization Study to determine the characteristics of the participants and nonparticipants in trials of medications for HIV infection and whether or not patients had access to experimental treatments. A probability sample of 2864 persons, representing all 231,400 adults with known HIV infection who are cared for in the contiguous United States, were interviewed on three occasions between 1996 and 1998. They were asked about participation in clinical research studies of medications and past receipt of experimental medications for HIV. We estimate that 14 percent of adults receiving care for HIV infection participated in a medication trial or study; 24 percent had received experimental medications; and 8 percent had tried and failed to obtain experimental treatments. According to multivariate models, non-Hispanic blacks and Hispanics were less likely to be participating in trials than non-Hispanic whites (odds ratio for participation among non-Hispanic blacks, 0.50 [95 percent confidence interval, 0.28 to 0.91]; odds ratio among Hispanics, 0.58 [95 percent confidence interval, 0.37 to 0.93]) and to have received experimental medications (odds ratios, 0.41 [95 percent confidence interval, 0.32 to 0.54] and 0.56 [95 percent confidence interval, 0.41 to 0.78], respectively). Patients who were cared for in private health maintenance organizations were less likely to participate in trials than those with fee-for-service insurance (odds ratio, 0.43 [95 percent confidence interval, 0.21 to 0.88]). Women were not underrepresented in research trials and had a similar likelihood of receiving experimental treatments. Among patients with HIV infection, participation in research trials and access to experimental treatment is influenced by race or ethnic group and type of health insurance.


Increasing aging and advocacy competency: the intergenerational advocacy pilot project.
The Council on Social Work Education's (CSWE) Strengthening Aging and Gerontology Education for Social Work (SAGE-SW) project, funded by the John A. Hartford Foundation partnered with the National Committee to Preserve Social Security and Medicare (NCPSSM) to develop an Intergenerational Policy and Advocacy Project (IAP). This curriculum pilot project, based on a community organization model, was conducted with 13 baccalaureate social work (BSW) and master's social work (MSW) programs across the country and 122 students. The project was one method to pursue CSWE SAGE-SW's efforts to infuse aging content into social work foundation curricula, to support intergenerational teaching, to strengthen social work advocacy skills, and to provide social work students with positive experiences working with older adults. Pilot sites were asked to carry out the project as part of an existing course foundation or field practicum course. Project activities included collaboration with a variety of community agencies, holding issues or "town hall" forums in order to educate community members about critical policy issues affecting older adults; making contacts and establishing relationships with local, state and/or federal legislators; and conducting assessments of the service needs of older adults in the students' communities. Questionnaires, feedback, pre-post evaluations as well as brief accounts of each project are presented. Participants considered the IAP to be a successful project in terms of the objectives of increasing awareness and competency among social work students of aging issues and of promoting intergenerational linkages between older people and social work students.


Prevention and treatment of the post-thrombotic syndrome.
Post-thrombotic syndrome (PTS) is a complication that develops in up to 50% of patients with deep vein thrombosis (DVT) and manifests as symptoms and signs of chronic venous insufficiency of varying severity. PTS negatively affects patient's quality of life and causes significant burden to the healthcare system. The risk for PTS development can be markedly reduced by preventing DVT and providing appropriate anticoagulation once it develops. Patients with extensive proximal (iliofemoral) DVT may benefit from invasive interventions, such as catheter-directed thrombolysis. The effectiveness of elastic compression stockings (ECS) for PTS prevention has not been conclusively demonstrated in randomized trials. Treatment of PTS is primarily based on ECS, exercise and lifestyle modifications. The effectiveness of various pharmacologic agents for PTS treatment remains controversial. Surgical or radiological interventions for vein reconstruction or revascularization may be considered in refractory cases. This review summarizes current evidence regarding prevention and treatment of PTS of the lower limbs in adults.


The Incorporation of Host Proteins into the External HIV-1 Envelope.
The incorporation of biologically active host proteins into HIV-1 is a well-established phenomenon, particularly due to the budding mechanism of viral egress in which viruses acquire their external lipid membrane directly from the host cell. While this mechanism might seemingly imply that host protein incorporation is a passive uptake of all cellular antigens associated with the plasma membrane at the site of budding, this is not the case. Herein, we review the evidence indicating that host protein incorporation can be a selective and conserved process. We discuss how HIV-1 virions displaying host proteins on their surface can exhibit a myriad of altered phenotypes, with notable impacts on infectivity, homing, neutralization, and pathogenesis. This review describes the canonical and emerging methods to detect host protein incorporation, highlights the well-established host proteins that have been identified on HIV-1 virions, and reflects on the role of these incorporated proteins in viral pathogenesis and therapeutic targeting. Despite many advances in HIV treatment and prevention, there remains a global effort to develop increasingly effective anti-HIV therapies. Given the broad range of biologically active host proteins acquired on the surface of HIV-1, additional studies on the mechanisms and impacts of these incorporated host proteins may inform the development of novel treatments and vaccine designs.


microRNAs are dysregulated in the cerebral microvasculature of CKD mice.
Vascular calcification arises during chronic kidney disease (CKD), and increases the risk of cardiovascular mortality. In CKD, alterations of cerebral circulation were linked with an increase in ischemic strokes and behavioral troubles. Studying pathophysiological mechanisms of calcifications and detecting new biomarkers in the cerebral circulation is thus an important issue. microRNAs are small non-coding, single-stranded RNAs that regulate messenger RNAs at the post-transcriptional level. They are involved in numerous pathologies and represent new opportunities to develop disease predictors. We used RT-qPCR to quantify endothelial-specific microRNAs in cerebral arterioles from WT mice and from pathological models of CKD. We used four mice groups: WT SHAM, WT CKD, Apolipoprotein E Knock-Out (ApoE-KO) SHAM, ApoE-KO CKD. Brains were removed after two and ten weeks of uremia and RNA from cerebral arterioles was extracted. miR-17 and miR-126 were the most dysregulated in the pathological conditions, at both the second week and tenth week of uremia. Our results suggest that miR-17 and miR-126 are potential new biomarkers of cerebral troubles of CKD patients and new therapeutic targets for innovative treatments.


Posttranslational acetylation of the human immunodeficiency virus type 1 integrase carboxyl-terminal domain is dispensable for viral replication.
A recent report sought to demonstrate that acetylation of specific lysines within integrase (IN) by the histone acetyltransferase (HAT) p300 regulates human immunodeficiency virus type 1 (HIV-1) integration and is essential for viral replication (A. Cereseto, L. Manganaro, M. I. Gutierrez, M. Terreni, A. Fittipaldi, M. Lusic, A. Marcello, and M. Giacca, EMBO J. 24:3070-3081, 2005). We can corroborate the efficient and specific acetylation of the IN carboxyl-terminal domain (CTD) (amino acids 212 to 288) by p300 using purified recombinant components. Although arginine substitution mutagenesis of the isolated CTD confirms that the majority of p300 acetylation occurs at lysine residues 264, 266, and 273, the pattern of acetylation is not uniform and a hierarchy of reactivity can be established. Several combinatorial mutations of the CTD lysines modified by p300 in vitro were reconstructed into an otherwise infectious proviral plasmid clone and examined for viral growth and frequency of productive chromosomal integration. In contrast to the findings of Cereseto and coworkers, who used epitope-tagged viruses for their experiments, we find that an untagged mutant virus, IN K(264/266/273)R, is fully replication competent. This discrepancy may be explained by the use of an acidic epitope tag placed at the extreme carboxyl terminus of integrase, near the target site for acetylation. Although the tagged, wild-type virus is viable, the combination of this epitope tag with the RRR substitution mutation results in a replication-defective phenotype. Although IN belongs to the very small set of nonhistone proteins modified by HAT-mediated activity, an obligate role for acetylation at the reactive CTD lysines in HIV-1 IN cannot be confirmed.


CD4+ T cells from IL-10-deficient mice transfer susceptibility to NSAID-induced Rag colitis.
Products of arachidonic acid metabolism are important for mucosal homeostasis, because blockade of this pathway with an NSAID triggers rapid onset of severe colitis in the IL-10 knockout (IL-10(-/-)) model of IBD. Rag mice do not make T or B cells. This study determined whether reconstitution of Rag mice with T cells from IL-10(-/-) mice transferred NSAID colitis susceptibility. Rag mice were reconstituted by intraperitoneal injection with splenocytes from wild-type (WT) or IL-10(-/-) animals. Colitis was induced by using piroxicam and was graded histologically. Isolated lamina propria mononuclear cells (LPMC), lamina propria T cells, and LPMC depleted of T cells from reconstituted Rag mice were studied for cytokine production. Only animals reconstituted with IL-10(-/-) CD4(+) T cells and administered piroxicam developed severe colitis. LPMC from these colitic animals made IFN-gamma, whose production was dependent on T cells. Some IL-10 was produced but only from non-T cells. LPMC from the healthy Rag mice that were reconstituted with WT T cells and were piroxicam resistant made much more IL-10. This was mostly T cell dependent. In conclusion, only CD4(+) T cells from IL-10(-/-) animals leave Rag mice susceptible to NSAID-induced, Th1 colitis. Lamina propria T cells normally make large quantities of IL-10, suggesting that IL-10 from T cells may be protective.


Developing skills for thoracic aortic surgery with hypothermic circulatory arrest.
To examine the performance curves of 8 early-career aortic surgeons with the use of hypothermic circulatory arrest (HCA) and to analyze the impact of the learning curve on perioperative outcomes. A total of 1025 consecutive patients who underwent aortic reconstruction with HCA between 2002 and 2017 were analyzed for mortality and 5 other complications (stroke, reoperation for bleeding, dialysis, prolonged ventilation, and sternal wound complications), subdivided into 3 consecutive time periods. This cohort represents the complete inaugural experience of 8 Canadian academic aortic surgeons. A risk-adjusted cumulative sum analysis was used to evaluate the performance curve with respect to predetermined 80% alert and 95% alarm boundary lines. Mean age was 62 ± 13 years, 71% of patients were male, and 24% presented nonelectively. Hemiarch repair was performed in 80% and total arch replacement in 20%. There was a reduction in the incidence of the primary composite outcome over time (P1: 26%, P2: 23%, and P3: 16%; P = .010). Overall in-hospital mortality was 5% and remained stable throughout the 3 periods. Rates of stroke were lower in the late period (P1: 4%, P2: 6%, and P3: 2%; P = .035). Risk-adjusted cumulative sum analysis demonstrated that all surgeons remained within the 95% reassurance boundary throughout their experience, with 6 surgeons performing as expected and 2 performing better than expected. Early-career surgeons can safely perform operations with HCA from the initiation of their practice. The cumulative sum analysis method is valuable for monitoring competence in aortic surgery and could prove useful in structuring training programs.


Basement membrane: structure function relationships.
Basement membranes perform several functions including filtration and elastic support. In the glomerular capillary two regions of extracellular matrix are recognized: the laminae rarae and the lamina densa. Procollagen and noncollagen glycoproteins occupy the laminae rarae and lamina densa. Proteoglycans are present in the laminae rarae. The nature and spatial organization of the macromolecules within the basement membrane determine their filtration and elastic properties. The persistence of the procollagen molecules assures the low order of fibril organization and permits selective filtration, whereas the persistence of the noncollagen extension peptides in the procollagen and the presence of the glycoprotein confers elasticity. The anionic nature of basement membranes is determined primarily by the acidic amino acid content and to much lesser extent by sialic acid and proteoglycans.


Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes.
Hamsters infected with Treponema pallidum Nichols (venereal syphilis), T. pallidum Bosnia A (endemic syphilis), or T. pertenue (frambesia, or yaws) developed substantial resistance to homologous reinfection. Hamsters infected for 10 weeks developed no lesions, and their lymph nodes contained fewer treponemes after reinfection with the same strain. The degree of cross-resistance among the treponemes correlated well with pathological changes occurring in infected hamsters and with the persistence of treponemal antigen during primary infection. Only hamsters infected with T. pallidum Bosnia A developed substantial resistance to heterologous reinfection. These animals also had extensive chronic skin lesions and lymph nodes containing measurable numbers of treponemes. Frambesial hamsters had less extensive lesions and were resistant to T. pallidum Nichols and, to a lesser extent, to T. pallidum Bosnia A. Hamsters infected with T. pallidum Nichols developed no cutaneous lesions and were resistant only to reinfection with T. pertenue. Confirmation of these results was obtained in normal hamsters infused with syphilitic (Nichols or Bosnia A) or frambesial immune cells and challenged with homologous or heterologous treponemes.


[New aspects of calcium metabolism in kidney calculus disease].
Recurrent calcium stone disease appears to be related to a high dietary intake of animal protein. The following mechanisms have been discussed to explain the relationship between dietary protein and calciuria: increased glomerular filtration rate (GFR), increased rate of sulphate excretion, acidosis-induced increase in ionised serum calcium ("filtered load") and decrease in tubular reabsorption, and mobilisation of bone mineral. Protein also diminishes urinary citrate. However, it has not been established in controlled trials whether a reduced dietary intake of protein diminishes the recurrence rate of renal stones. Determination of the normal range of urinary calcium is dependent on numerous variables: size; GFR; age; excretion of Na, Mg and Pi; dietary intake of Ca and protein; season. Ideally, all these variables should be evaluated. In many patients with recurrent stone formation hypercalciuria will be found. There is a consensus of opinion that intestinal Ca absorption is increased, but elevated frequency of a renal Ca leak has not been established. For patient management discrimination between absorptive and resorptive hypercalciuria is important; a simple test that can be performed as an outpatient procedure is proposed in order to make this distinction.


Biochemical analysis of three putative KaiC clock proteins from Synechocystis sp. PCC 6803 suggests their functional divergence.
Cyanobacteria have been shown to have a circadian clock system that consists mainly of three protein components: KaiA, KaiB and KaiC. This system is well understood in the cyanobacterium Synechococcus elongatus PCC 7942, for which robust circadian oscillations have been shown. Like many other cyanobacteria, the chromosome of the model cyanobacterium Synechocystis sp. PCC 6803 contains additional kaiC and kaiB gene copies besides the standard kaiABC gene cluster. The respective gene products differ significantly in their amino acid sequences, especially in their C-terminal regions, suggesting different functional characteristics. Here, phosphorylation assays of the three Synechocystis sp. PCC 6803 KaiC proteins revealed that KaiC1 phosphorylation depends on KaiA, as is well documented for the Synechococcus elongatus PCC 7942 KaiC protein, whereas KaiC2 and KaiC3 autophosphorylate independently of KaiA. This was confirmed by in vivo protein-protein interaction studies, which demonstrate that only KaiC1 interacts with KaiA. Furthermore, we demonstrate that the three different Kai proteins form only homomeric complexes in vivo. As only KaiC1 phosphorylation depends on KaiA, a prerequisite for robust oscillations, we suggest that the kaiAB1C1 gene cluster in Synechocystis sp. PCC 6803 controls circadian timing in a manner similar to the clock described in Synechococcus elongatus PCC 7942.


Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.
The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.


[Application of amplitude of low-frequency fluctuation to the temporal lobe epilepsy with bilateral hippocampal sclerosis: an fMRI study].
To study the changes of amplitude of low-frequency fluctuation (ALFF) of the resting-fMRI in the mesial temporal lobe epilepsy (mTLE) with bilateral hippocampal sclerosis (HS), and discussed its underlying neuro-pathophysiological mechanism. The resting-fMRI data of 20 TLE patients with HS and 20 normal volunteers were performed ALFF analysis. The amplitude of the blood oxygenation level-dependent activation of the resting-state brain was investigated. The brain structures showing increased and decreased ALFF in TLE patients were demonstrated by comparing to normal subjects with 2-sample t-test with threshold of P < 0.01. By comparison with that of normal subjects, the regions showing increased and decreased ALFF in TLE patients were distributed in the brain symmetrically and bilaterally. The regions showing increased ALFF were distributed with center of limbic system, such as parahippocampal gyri, amygdala, hypothalamus, dorsal anterior cingulate gyrus and part of posterior insular lobe, as well as the neocortices such as primary sensorimotor cortices, occipital cortices, inferior temporal gyri, orbital gyri, and the subcortical structures of verbal brainstem and mesial cerebellum. The point with maximal increased ALFF (T = 6.02) located in the right precentral gyru (15, - 12.51). While the regions showing decreased ALFF covered the areas of default mode, such as posterior cingulate cortex/ precuneus and medial prefrontal cortex /ventral anterior cingulate cortex, as well as other structures such as dorsal lateral prefrontal cortices, superior temporal gyri, caudate heads, dorsal brain stem and the posterior cerebellum (3, -78, -21) with the maximal decreased ALFF (T = -4.42). The method of ALFF allows the direct observation to the epileptic activation in TLE. The increased ALFF is considered the facilitation such as the epileptic activity generation and propagation; while the ALFF decrease is considered the function inhibition in these regions, especially implies the suspension in the default mode activity.


Immunoglobulin A in Graves' orbital tissue: deoxyribonucleic acid amplification by polymerase chain reaction.
A role for IgA autoantibodies in Graves' ophthalmopathy is suggested by the presence of immunoglobulins of this class in Graves' orbital tissue, as detected by immunohistochemistry. We, therefore, investigated the possibility of using the polymerase chain reaction (PCR) to amplify IgA immunoglobulin genes from plasma cells infiltrating Graves' eye tissue. Template cDNA was reverse-transcribed from orbital muscle (M) mRNA of one patient (#7) and from orbital connective tissue/fat (F) mRNA of two patients (#1 and #7), both undergoing surgery for exophthalmos because of severe infiltrative ophthalmopathy. Preliminary studies to establish the PCR procedure were performed for kappa light chain DNA amplification. With the very small amount of orbital tissue template available, the sensitive "hot start" modification of the PCR was necessary to amplify significant amounts of kappa light chain DNA. Using this procedure, IgA heavy chain DNA was amplified from both connective tissue/fat (F7) and muscle (M7) cDNA of patient #7. The DNA yield was less for IgA than for IgG using the same template. There was no significant IgA (or IgG) DNA product using the connective tissue/fat cDNA of patient #1. While not implying that IgA-infiltrating plasma cells are specific for Graves' orbital tissue, our studies nevertheless demonstrate the feasibility of amplifying the genes coding for IgA antibodies from Graves' orbital tissue plasma cells. Expression of these immunoglobulin genes in future studies will make it possible to determine the antigen specificity of the antibodies expressed by Graves' orbital tissue plasma cells.


Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus.
Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett's esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett's lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett's esophagus.


Does experimental pain affect auditory processing of speech-relevant signals? A study in healthy young adults.
To assess the effect of tonic pain stimulation on auditory processing of speech-relevant acoustic signals in healthy pain-free volunteers. Sixty university students, randomly assigned to either a thermal pain stimulation (46 degrees C/6 min) group (PS) or no pain stimulation group (NPS), performed a rate change detection task (RCDT) involving sinusoidally frequency-modulated vowel-like signals. Task difficulty was manipulated by changing the rate of the modulated signals (henceforth rate). Perceived pain intensity was evaluated using a visual analog scale (VAS) (0-100). Mean pain rating was approximately 33 in the PS group and approximately 3 in the NPS group. Pain stimulation was associated with poorer performance on the RCDT, but this trend was not statistically significant. Performance worsened with increasing rate of signal modulation in both groups (p < 0.0001), with no pain by rate interaction. The present findings indicate a trend whereby mild or moderate pain appears to affect auditory processing of speech-relevant acoustic signals. This trend, however, was not statistically significant. It is possible that more intense pain would yield more pronounced (deleterious) effects on auditory processing, but this needs to be verified empirically.


Coupling of peroxidase to poliovirus antibody: characteristics of the conjugates and their use in virus detection.
Antibody to poliovirus type 1 (Po-1) was coupled to peroxidase by use of glutaraldehyde or 4, 4' -difluoro,3, 3' -dinitro diphenyl sulfone. Glutaraldehyde was found to be the superior coupling agent, yielding conjugates that had up to 2.8 x 10(4) enzyme units/ml (75% of total enzyme input). Conjugates migrated as a single band when centrifuged in sucrose density gradients, demonstrating that the purification procedure used was effective in removing both noncoupled enzyme and heterogeneous antibody components. Conjugates were specific for Po-1 and did not adsorb to cells infected with unrelated enterovirus types. Adsorption of conjugates to Po-1-infected cells was demonstrable within 6 h postinfection.


A Unified Machine Reading Comprehension Framework for Cohort Selection.
Cohort selection is an essential prerequisite for clinical research, determining whether an individual satisfies given selection criteria. Previous works for cohort selection usually treated each selection criterion independently and ignored not only the meaning of each selection criterion but the relations among cohort selection criteria. To solve the problems above, we propose a novel unified machine reading comprehension (MRC) framework. In this MRC framework, we design simple rules to generate questions for each criterion from cohort selection guidelines and treat clues extracted by trigger words from patients' medical records as passages. A series of state-of-the-art MRC models based on BiDAF, BIMPM, BERT, BioBERT, NCBI-BERT, and RoBERTa are deployed to determine which question and passage pairs match. We also introduce a cross-criterion attention mechanism on representations of question and passage pairs to model relations among cohort selection criteria. Results on two datasets, that is, the dataset of the 2018 National NLP Clinical Challenge (N2C2) for cohort selection and a dataset from the MIMIC-III dataset, show that our NCBI-BERT MRC model with cross-criterion attention mechanism achieves the highest micro-averaged F1-score of 0.9070 on the N2C2 dataset and 0.8353 on the MIMIC-III dataset. It is competitive to the best system that relies on a large number of rules defined by medical experts on the N2C2 dataset. Comparing these two models, we find that the NCBI-BERT MRC model mainly performs worse on mathematical logic criteria. When using rules instead of the NCBI-BERT MRC model on some criteria regarding mathematical logic on the N2C2 dataset, we obtain a new benchmark with an F1-score of 0.9163, indicating that it is easy to integrate rules into MRC models for improvement.


Seroprevalence study of anti diphtheria antibodies in two age-groups of Romanian adults.
Diphtheria represents a serious infectious disease with high epidemic potential. It is a vaccine preventable disease (a minimum vaccine coverage of 95% for children of 1 year and 90% in adults could prevent the disease). Diphtheria vaccination is included in the National Immunization Program (NIP). Complete vaccination for children consists in DTaP (diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine) vaccine administration from the age of 2 months until 4 years and dT vaccine (tetanus toxoid and a reduced dose of diphtheria toxoid) at 14 years old. The aim of this paper was to highlight the protection against diphtheria of an age segment of the Romanian adult population (20 to 39 years old) using a seroprevalence study. The Romanian subjects were selected from two age groups: 20-29 years (n = 219) and 30-39 years (n = 229), representative for all counties of Romania. The commercial kit Anti-Diphtheria Toxoid ELISA (IgG) (EUROIMMUN) was used to detect the antibodies of IgG class against diphtheria toxoid in the sera obtained from our subjects. We detected a 56.6% rate of positive sera (> 0.1 IU/ml--protection level) for the 20-29 age group and 31.7% positivity for the 30-39 age group. These data show a low protection level against diphtheria of the Romanian adult population, which decreases with age. The serologic data on preventable vaccine diseases are useful in order to evaluate the success of the immunization programs.


A critical perspective on cross-cultural contexts for addiction and multiculturalism: their meanings and implications in the substance use field.
Despite evidence of the antiquity and ubiquity of psychoactive substance use, much of the literature is devoted to addiction in minority ethnocultural subgroups. When researchers study drug use in isolated "primitive" communities, they consider drug use to serve as a mechanism of social integration; when they study drug use in ethnocultural subgroups in contact with mainstream society, they consider drug use as a marker, or sometimes as a cause of social disorganization. The implicit assumption appears to be that addiction and race, ethnicity, or other minority ethnocultural subgroup membership are linked, and more prevalent and/or more problematic in minorities, further problematizing the status of minorities. Empirical studies identified through ETOH, the U.S. National Institute of Alcohol and Alcoholism (NIAAA)'s Internet-accessible computerized database, were subjected to content analysis of their abstracts (n(abs) = 44) as well as actual reports (n(rep) = 40). It was found that the content of neither abstracts nor actual reports supported the contention that there was a greater prevalence of drug use, drug-use-associated problems, or drug-use-enhancing attitudes in minority ethnocultural subgroups when compared to mainstream society (chi2(abs) = 2.16, d.f. = 3, n.s., and chi2(rep) = 3.52, d.f. = 2, n.s. respectively). Researchers need to be aware of possible implicit assumptions about the relation between ethnicity and addiction.


A rare case of chordoma cutis.
Chordoma is a rare locally aggressive bone malignancy that originates from the notochord. It typically involves the sacrococcygeal area, spheno-occipital region of the skull, and spine. Cutaneous involvement of chordoma, termed as chordoma cutis, is uncommon and usually occurs via direct invasion or local recurrence. Distant metastasis to the skin is very rare. We report a case of chordoma cutis on the scalp, which lacked characteristic physaliferous cells but tested positive for brachyury, thus supporting the diagnosis of chordoma cutis. The patient, who presented with a solitary translucent nodule on the scalp, was previously diagnosed with chordoma on the vertebral column and skull 8 months prior. Microscopic examination showed a cord-like arrangement of plasmacytoid cells within a myxoid stroma. Physaliferous cells were not observed, and cytokeratin AE1/AE3 staining was negative; however, brachyury and epithelial membrane antigen staining was positive, leading to the diagnosis of chordoma cutis. Therefore, clinicians must include chordoma cutis in the differential diagnosis of translucent nodular lesions on the skin of patients formerly diagnosed with chordoma.


Characterization of BRCAA1 and its novel antigen epitope identification.
Looking for novel breast cancer antigen epitopes is helpful for its treatment, diagnosis, and prevention. brcaa1 gene is mapped at 1q42.1-q43, its whole genome is 93.857 kb, including 18 exons and 17 introns. BRCAA1 protein is composed of 1,214 amino acids with 10 glycosylate sites, and shares 37% amino acid identity and an identical antigen epitope with Rb binding protein 1. The novel antigen epitope, SSKKQKRSHK, was predicted to locate in the region 610 to 619 sites, was synthesized, and its antibody was fabricated. Competent inhibition analysis showed that SSKKQKRSHK is the shortest effective peptide. The antigen epitope was mapped in the cytoplasm of MCF-7 cells. Immunohistochemistry analysis showed that the antigen epitope exhibited positive expression in 65% (39 of 60) breast cancer specimens and negative expression in 60 non-cancerous tissues. Statistical analysis shows that its expression is closely associated with status of ER and PR, with sensitivity of 100% and specificity of 81%, and confidence interval of 85.9% to 96.9%. ELISA analysis showed that the mean absorbance of sera antibody titers from breast cancer patients and healthy donors were 0401 +/- 0.163 SD and 0.137 +/- 0.121 SD, respectively. Sixty-four percent breast cancer patient sera and 13% healthy donor sera had higher titer than mean titer of healthy donors, and there exists significant difference between breast cancer patients and healthy donors (P < 0.001). In this study, a novel breast cancer antigen epitope, SSKKQKRSHK, is identified. Its expression is associated with characteristics that are themselves associated with prognosis of breast cancer, and its sera antibody level may be helpful for breast cancer diagnosis.


Physical modelling of tsunamis generated by three-dimensional deformable granular landslides on planar and conical island slopes.
Tsunamis generated by landslides and volcanic island collapses account for some of the most catastrophic events recorded, yet critically important field data related to the landslide motion and tsunami evolution remain lacking. Landslide-generated tsunami source and propagation scenarios are physically modelled in a three-dimensional tsunami wave basin. A unique pneumatic landslide tsunami generator was deployed to simulate landslides with varying geometry and kinematics. The landslides were generated on a planar hill slope and divergent convex conical hill slope to study lateral hill slope effects on the wave characteristics. The leading wave crest amplitude generated on a planar hill slope is larger on average than the leading wave crest generated on a convex conical hill slope, whereas the leading wave trough and second wave crest amplitudes are smaller. Between 1% and 24% of the landslide kinetic energy is transferred into the wave train. Cobble landslides transfer on average 43% more kinetic energy into the wave train than corresponding gravel landslides. Predictive equations for the offshore propagating wave amplitudes, periods, celerities and lengths generated by landslides on planar and divergent convex conical hill slopes are derived, which allow an initial rapid tsunami hazard assessment.


[Sensory after-discharges of the rat visual cortex during elaboration and extinction of a temporary connection].
Sensory after-discharges (SAD) in the rat's visual cortex became more intense at the background of an unconditioned drinking reaction. During the elaboration of a conditioned reflex to light (ten successive flashes of which the last five were reinforced) the SAD enhancement proceeded in two stages; the first coincided with the reinforcement, the second was developing in the phase of a stable conditioned reflex to the second or third flash of the rhythmic series. When reinforcement was omitted in a test with acute extinction. SAD was depressed, and was replaced by an increased number of after-effect waves, related to the appearance of "substituting" movements of the hygienic routine. It is assumed that the enhanced synchronized activity on the EEG at this moment plays an adaptive part, eliminating desynchronization and reducing the destructive action of the emotional stress.


Novel LaCl3(Ce)-based spectrometer for deuterium plasma neutron diagnostics.
This work studies in detail the application possibility of a chlorine-based cerium-doped scintillator crystal [LaCl3(Ce)] to the task of D-D neutron spectrometry. We conducted an experimental campaign aimed at deriving the optimal setup parameters and energy calibration using a variety of available neutrons and γ-sources. The GEANT4 code was used for modeling the detector response to γ-ray irradiation. By observing the intrinsic background α-activity of the crystal, we were able to fine-tune the pulse-shape discrimination parameters, achieving a satisfactory α/n/γ pulse selection. We also investigated the LaCl3(Ce)-based spectrometer response under D-D-neutron irradiation by means of the ING-07D neutron generator with the yield of 1 × 107 n/s. The GEANT4 simulation provided us with the comprehensive overview of detector performance. The acquired results demonstrate the possibility of using the LaCl3(Ce) scintillation spectrometer for the purposes of deuterium plasma neutron diagnostics.


Synanthropy and temporal variability of Calliphoridae living in Cosenza (Calabria, southern Italy).
The aim of this study was to investigate the synanthropy of Diptera: Calliphoridae, insects of forensic importance, in Calabria (southern Italy). The study lasted 2 years, from February 2010 to January 2012, and was carried out in three areas of Cosenza province representing "urban", "rural", and "wild" environments. Bottle traps baited with pork were used to catch Calliphoridae. Six species were identified, Calliphora vicina Robineau-Desvoidy 1830, Calliphora vomitoria (L.), Chrysomya albiceps (Wiedemann 1819), Lucilia ampullacea Villeneuve 1922, Lucilia caesar (L.), and Lucilia sericata (Meigen 1826). Data on phenologies in the study areas are reported for these species and the Synanthropy Index was calculated to evaluate their relationship with the human environment.


Pancreatic tuberculosis: case reports and review of the literature.
Tuberculosis affecting the pancreas is rare. Its occurrence may pose a diagnostic problem in differentiating it from carcinoma of the pancreas. Two cases of tuberculosis affecting the pancreas are reported, illustrating the value of fine needle aspiration in such a situation. The response of the disease to antituberculous drugs was slow, but sure.


Evidence for an altered T-cell receptor repertoire in Crohn's disease.
We have compared the frequencies of T cells expressing each of four different T cell receptor (TCR) V beta segments in lamina propria and peripheral blood lymphocytes of 12 Crohn's disease (CD), six ulcerative colitis (UC), and 10 control patients in an attempt to identify disease-specific changes. The frequencies of CD4+ and CD8+ cells reacting with each of four fluoresceinated TCR-specific monoclonal antibodies directed against V beta 5, V beta 6.7a, V beta 8, and V beta 12 were determined by flow cytometry. There was no difference among the groups in the average frequency of any single V beta segment in either the CD4+ or CD8+ subpopulations. However, when the sum of the differences in V beta frequencies (delta score) between peripheral blood lymphocytes (PBL) and lamina propria lymphocytes (LPL) were determined for each individual, significant differences were observed between the CD4+ and CD8+ populations and among the patient groups. In all three patient groups, there were significant individual differences between LPL and PBL in the frequencies of CD8+ and CD4+ cells reacting with the four V beta-specific mAb. In Controls and UC, this difference was, on average, two-fold greater in CD8+ cells than in CD4+. In CD, however, this difference was, on average, the same for CD8+ and CD4+ cells. These observations suggest that (1) the human colonic LPL TCR repertoire is normally different from that of PBL, especially in the CD8+ population and (2) there is an alteration in the LPL TCR repertoire in CD which is not observed in Controls or UC.


From the Brazilian Income Transfer Program to Brazil Assistance: challenges and achievements according to a theory-driven evaluation research on the program.
The recent COVID-19 pandemic has led many countries to adopt emergency cash transfer policies as a way to contain the economic and humanitarian crisis. Such initiatives were developed in a context of exacerbated gender, race, ethnicity and class inequalities resulting from physical and social distancing measures. The article analyzes, by means of an exploratory study and the so-called theory-driven evaluation of the program, the theoretical premises of the Brazilian Income Transfer Program (2003), Brazilian Emergency Assistance (2020) and Brazil Assistance (2021) programs, and their corresponding implementation dynamics. As cash transfer programs are given centrality in the contemporary public agenda, the conclusion is that evaluating their limits and advances - as to theoretical conception and mechanisms triggered in each context - contributes to trace evidence about their effectiveness in addressing long-term inequalities and those inequalities that arise in health emergency contexts.


Influence of a Counteranion on the Zero-Field Splitting of Tetrahedral Cobalt(II) Thiourea Complexes.
Four mononuclear cobalt(II) complexes with pseudo tetrahedral geometry were isolated with different counteranions; their structure solution reveals the molecular formula as [Co(L1)4]X2 [where L1 = thiourea (NH2CSNH2) and X = NO3 (1), Br (2), and I (3)] and [Co(L1)4](SiF6) (4). The detailed analysis of direct-current (dc) magnetic data reveals a zero-field splitting (ZFS; D) with mS = ±3/2 as the ground levels (D < 0) for the four complexes. The magnitude of the ZFS parameter is larger, in absolute value, for 1 (D = -61.7 cm-1) than the other three complexes (-5.4, -5.1, and -12.2 cm-1 for 2-4, respectively). The sign of D for 1, 2, and 4 was unambiguously determined by X-band electron paramagnetic resonance (EPR) spectroscopy of the diluted samples (10%) at 5 K. For 3, the sign of D was naturally endorsed from the frequency-dependent out-of-phase signal (χM″) observed in the absence of an external dc magnetic field and confirmed by high-frequency EPR (70-600 GHz) experiments performed on a representative pure polycrystalline 3, which gave a quantitative D value of -5.10(7) cm-1. Further, the drastic changes in the spin Hamiltonian parameters and their related relaxation dynamics phenomena (of 2-4 compared to 1) were rationalized using ab initio complete-active-space self-consistent field/n-electron valence perturbation theory calculations. Calculations disclose that the anion-induced structural distortion observed in 2-4 leads to a nonfavorable overlap between the π orbital of cobalt(II) and the π* orbital of the sulfur atom that reduces the overall |D| value in these complexes compared to 1. The present study demonstrates that not only the first but also the second coordination sphere significantly influences the magnitude of the ZFS parameters. Particularly, a reduction of D of up to ∼90% occurs (in 2-4 compared to 1) upon a simple variation of the counteranions and offers a viable approach to modulate ZFS in transition-metal-containing single-molecule magnets.


Modification of carbon nanotubes using poly(vinylidene fluoride) with assistance of supercritical carbon dioxide: the impact of solvent.
We report herein a typical piezoelectric polymer, poly(vinylidene fluoride) (PVDF) to be successfully wrapped on single-walled carbon nanotubes (SWCNTs) using a simple supercritical carbon dioxide (SC CO(2)) antisolvent-induced polymer epitaxy method. Our study focused on the effect of different solvents on the morphology of PVDF wrapping on SWCNTs. Three organic solvents, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMAc) were chosen for PVDF. When DMSO was used as solvent, the decorating degree of PVDF on the surface of SWCNTs increases significantly with the increase of SC CO(2) pressure, and nanocrystals wrapping on SWCNTs can be observed at high pressure. FTIR and Raman spectra indicated that there exist interactions between SWCNTs and PVDF chains. What's more, FTIR results also show that there exists a transformation from the beta-phase to the alpha-phase of PVDF in DMSO with the assistance of SC CO(2), which is similar to the action of elongation/shear flow field. It indicated that the alpha-phase is the predominant form occurring on the surface of SWCNTs after treatment with SC CO(2). And the helical structure on SWCNTs observed from the TEM image reflected the alternate trans- and gauche-bond conformation of the alpha-form. When DMF or DMAc was used as the solvent, although nanocrystal wrapping and helical structure was not visible, the samples had more excellent dispersion than that in DMSO. Particularly, for DMF, a typical network structure was observed, which is similar to a spider web. Therefore, this work supplies a clue that the various morphologies of nanohybrid structure can be obtained just by changing the solvent during the treatment process of SC CO(2), and accordingly, the tailored nanohybrid structure are promising and important for functional design as a basic component in microfabrication and other fields.