Metabolic responses of Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621 upon transition from glucose limitation to glucose excess.
When chemostat cultures of Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621, grown under glucose limitation, were pulsed with excess glucose, both organisms initially exhibited similar rates of glucose and oxygen consumption. However, striking differences were apparent between the two yeasts with respect to the production of cell mass in the culture and metabolite excretion. Upon transition from glucose limitation to glucose excess, S. cerevisiae produced much ethanol but the growth rate remained close to that under glucose limitation. C. utilis, on the other hand, produced little ethanol and immediately started to accumulate cell mass at a high rate. This high production rate of cell mass was probably due to synthesis of reserve material and not caused by a high rate of protein synthesis. Upon a glucose pulse both yeasts excreted pyruvate. In contrast to C. utilis, S. cerevisiae also excreted various tricarboxylic acid cycle intermediates, both under steady-state conditions and after exposure to glucose excess. These results and those of theoretical calculations on ATP flows support the hypothesis that the ethanol production as a consequence of pyruvate accumulation in S. cerevisiae, occurring upon transition from glucose limitation to glucose excess, is caused by a limited capacity of assimilatory pathways.


Revisiting the role of IL-1 signaling in the development of apical periodontitis.
Apical periodontitis (AP) develops as a result of an immune response to pulpal bacterial infection, and various cytokines are involved in the pathogenesis of AP, with Interleukin (IL)-1 being considered a key cytokine. The role of IL-1 in the pathogenesis of AP has been well studied. It is known that IL-1 expression in periapical lesions correlates closely with the development of AP. IL-1 is a potent bone-resorptive cytokine that induces osteoclast formation and activation. Hence, inhibiting its signaling with IL-1 receptor antagonist (IL-1RA) results in a reduction in periapical lesion size. On the other hand, IL-1 is also a central cytokine that combats bacterial infection by activating innate immune responses. Therefore, a complete loss of IL-1 signaling leads to a failure to limit bacterial dissemination and consequently exacerbates AP. In vivo, IL-1 expression is tightly regulated and its signaling is modulated to optimize the immune response. Obesity causes systemic low-grade chronic inflammation and increases the risk of cardiovascular, renal, and other disorders. In experimentally induced AP, obesity significantly increases periapical bone loss, albeit the underlying mechanism remains unclear. Recent technological innovations have enabled more comprehensive and detailed analyses than previously, leading to new insights into the role of IL-1RA in regulating IL-1 signaling, and modulating apical lesion progression in obesity. In this review, we provide a brief overview of the function of IL-1 in AP development, with special emphasis on the latest findings in normal weight and obese states.


Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.
Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.


Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.
Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.


New process for production of fermented black table olives using selected autochthonous microbial resources.
Table olives represent one important fermented product in Europe and, in the world, their demand is constantly increasing. At the present time, no systems are available to control black table olives spontaneous fermentation by the Greek method. During this study, a new protocol for the production of black table olives belonging to two Italian (Cellina di Nardò and Leccino) and two Greek (Kalamàta and Conservolea) cultivars has been developed: for each table olive cultivar, starter-driven fermentations were performed inoculating, firstly, one selected autochthonous yeast starter and, subsequently, one selected autochthonous LAB starter. All starters formulation were able to dominate fermentation process. The olive fermentation was monitored using specific chemical descriptors able to identify a first stage (30 days) mainly characterized by aldehydes; a second period (60 days) mainly characterized by higher alcohols, styrene and terpenes; a third fermentation stage represented by acetate esters, esters and acids. A significant decrease of fermentation time (from 8 to 12 months to a maximum of 3 months) and an significant improvement in organoleptic characteristics of the final product were obtained. This study, for the first time, describes the employment of selected autochthonous microbial resources optimized to mimic the microbial evolution already recorded during spontaneous fermentations.


Fast automatic frequency calibration assisted phase-locked highly stable optoelectronic oscillator.
Highly stable, low phase noise microwave oscillators are essential for various applications. An optoelectronic oscillator (OEO) can overcome the short-term phase noise limitation of pure electronic oscillators at high oscillation frequency. Nonetheless, the long-term frequency stability should be addressed. To stabilize the frequency of OEO, a phase-locked loop (PLL) is widely used to synchronize the OEO to a stable reference. However, due to the narrow free-spectral-range (FSR) of the oscillation cavity of the OEO, the pull-in range of the PLL is limited. It is challenging to acquire phase-locking at startup and phase-relocking when mode-hopping of OEO occurs. Here, by using an automatic frequency calibration (AFC) assisted PLL, we attain a highly stable 10 GHz phase-locked OEO with robust phase-locking at startup and phase-relocking when mode-hopping of OEO occurs, for the first time. With the use of a fast digitally-controlled frequency shifter and a real-time frequency error detection unit in the AFC loop, the phase-locking and phase-relocking time are below 120 ms. Furthermore, it shows the phase noise of -135 dBc/Hz at 10 kHz offset, side-mode suppression ratio (SMSR) of 128 dBc, and Allan deviation of 4.8×10-11 at 5000 s for the phase-locked OEO. We thoroughly investigate the dynamics of the automatic frequency calibration, the phase-locking process, the phase-relocking after OEO mode-hopping, the system under vibration, and the frequency switching. Our approach is promising to generate a highly stable, low phase noise, and determinate frequency microwave signal, which can be used as a low phase noise reference for a microwave frequency synthesizer and high performance sampling clock for a data conversion system.


Communication skills for telehealth interactions.
Telehealth technologies provide a challenging new home care approach. Through the use of cameras, video display services, and telephone lines, nurses can interact with patients located several miles away. In delivering services from a distance, the ease of equipment operation and installation, picture, and voice quality are important. Of equal importance are the nurse's communication skills in conducting telehome visits.


Am I My Brother's Keeper? African American Men's Health Within the Context of Equity and Policy.
African American men's health has at times been regarded as irrelevant to the health and well-being of the communities where they are born, grow, live, work, and age. The uniqueness of being male and of African descent calls for a critical examination and deeper understanding of the psycho-socio-historical context in which African American men have lived. There is a critical need for scholarship that better contextualizes African American Male Theory and cultural humility in terms of public health. Furthermore, the focus of much of the social determinants of health and health equity policy literature has been on advocacy, but few researchers have examined why health-related public policies have not been adopted and implemented from a political and theoretical policy analysis perspective. The purpose of this article will be to examine African American men's health within the context of social determinants of health status, health behavior, and health inequalities-elucidating policy implications for system change and providing recommendations from the vantage point of health equity.


Phenomenological and numerical analysis of power evolution and bunching in single-pass X-ray FELs.
The harmonic power and bunching evolution in X-ray single-pass free-electron lasers (FELs) is modelled and the harmonic generation in a phase-shifted two-frequency FEL is explored. The advanced phenomenological FEL model, which is validated numerically and experimentally, is employed. The model accounts for major losses for each harmonic individually; it is compared with reported experimental data and with PERSEO numerical simulations, which are performed here for a variety of experiments. The latter cover the radiation wavelength range 0.15-300 nm. The phenomenological description is based on a few key FEL parameters: electron beam section, current, energy and its spread and divergence. The model is employed for modelling harmonic bunching and power evolution in a phase-shifted X-ray FEL with a two-frequency undulator, where lower harmonics with numbers less than nth are suppressed by the electron-photon phase shift of kπ/n, k = 2, 4, …, between the undulator sections. The benefits of the two-frequency phase-shifted FEL are highlighted. FEL-induced energy spread is shown to be three times lower than in a FEL without the phase-shift. The high-power harmonic and sub-harmonic radiation in such a FEL is demonstrated. In particular, powerful ∼14 GW X-ray radiation at λ5 = 0.15 nm from electrons with energy of 5.47 GeV and beam current ∼3.66 kA is possible in a two-frequency phase-shifted FEL at 30 m; this constitutes half of a FEL length where a common planar undulator radiates the same wavelength and power at the fundamental harmonic. Moreover, about a three times lower energy spread is induced by the dominant fifth harmonic, and the harmonic power can be thousands of times higher than in a common planar undulator FEL.


807C/T polymorphism in the platelet glycoprotein Ia gene in young patients with ischemic stroke of undetermined etiology.
Platelet membrane glycoprotein receptors mediate key reactions in arterial thrombosis. The relationship between glycoprotein Ia polymorphisms and the risk of ischemic stroke, however, remains controversial. A matched case-control study was conducted to evaluate this question in young patients. Seventy patients with ischemic stroke of undetermined etiology, with ages ranging from 15 to 50 years, and 70 healthy control individuals, matched by age, gender and ethnicity, were tested for the 807C/T genotypes. Patients were excluded if they had systemic diseases known to predispose to thrombosis or any defined etiology of ischemic stroke. The frequencies of the 807T glycoprotein Ia variant and of conventional risk factors for arterial thrombosis (hypertension, smoking, diabetes mellitus, use of oral contraceptives, levels of serum cholesterol and body mass index) were compared in stroke patients and control individuals. The 807T allele was found in 61% of patients and 53% of control individuals (matched-pair odds ratio, 1.38; 95% confidence interval, 0.69-2.74; P = 0.42). Arterial hypertension and smoking were more frequent in patients than control individuals (matched-pair odds ratio, 2.83; 95% confidence interval, 1.05-8.02; P = 0.04; and odds ratio, 3.20; 95% confidence interval, 1.10-9.97, P = 0.03, respectively). In conclusion, our results do not support an independent association between the 807C/T polymorphism and stroke of undetermined etiology. The interplay of this polymorphism with arterial hypertension in the causation of ischemic stroke requires further evaluation.


Soft tissue tumors of the anorectum: rare, complex and misunderstood.
Anorectal soft tissue tumors are uncommon and often present both diagnostic and therapeutic challenges. Although many of these tumors are identified with imaging performed for unrelated reasons, most present with nonspecific symptoms that can lead to a delay in diagnosis. Historically, radical surgery (abdominoperineal resection) has been the mainstay of treatment for both benign and malignant anorectal soft tissue tumors. However, a lack of proven benefit in benign disease along with changes in technology has called this practice into question. In addition, the role of radiation and/or chemotherapy remains controversial. In this manuscript, we review the history and current status of anorectal soft tissue tumor management, with a particular focus on challenges in optimizing survival.


Test of firefighter's turnout gear in hot and humid air exposure.
Five students of a rescue training school cycled at 50 W for 20 min at 20 degrees C before walking at 5 km/hr up to 30 min in a climatic chamber at 55 degrees C and 30% relative humidity. 4 different types of clothing ensembles differing in terms of thickness and thermal insulation value were tested on separate days. All subjects completed 28-30 min in light clothing, but quit after 20-27 min in 3 firefighter ensembles due to a rectal temperature of 39.0 degrees C or subjective fatigue. No difference in the evolution of mean skin or rectal temperature was seen for the 3 turnout ensembles. Sweat production amounted to about 1000 g in the turnout gears of which less than 20% evaporated. It was concluded that the small differences between the turnout gears in terms of design, thickness and insulation value had no effect on the resulting heat physiological strain for the given experimental conditions.


[Children with mental retardation after special education].
44 children with mental retardation were tested 4 times with Hiskey-Nebraska test of learning aptitude (H-NTLA) and tested 2 times with personal and social self-sufficiency scales in a special education school in Taiyuan from 1989 to 1992. No significant difference of total IQ was found. The visual association, concept relationship, visual concentration and perceptual abilities were decreased consistently. The rising of IQ was positively associated with mother's higher education, child's higher IQ, mother's professional and technical occupation and child's younger age in beginning special education. The adaptive behavior was rising significantly.


Characterization of cucumber mosaic virus. III. Localization of sequences in the movement protein controlling systemic infection in cucurbits.
Cucumber mosaic virus (CMV), generated from biologically active cDNA clones of Fny-CMV RNA 1 plus 2 and Sny-CMV RNA 3, derived from the Fny- and Sny-strains of CMV, was able to infect tobacco but not squash plants systemically. In squash, viral RNA, movement protein, and coat protein all accumulated in the inoculated cotyledons. The lack of systemic infection was associated with a reduced rate of cell-to-cell movement within the cotyledons. The restricted movement mapped to two sequence changes in the codons of amino acids 51 and 240 of the Sny-CMV 3a gene. These same sequence changes previously were shown to be associated with high levels of 3a protein accumulation and chronic vs acute, cyclic infection typical of Sny-CMV vs Fny-CMV [Gal-on et al. (1996). Virology 226, 354-361]. Fny-CMV, mutated in the codons of 3a gene amino acids 51 and 240, was still able to infect several solanaceous hosts (tobacco, tomato, and pepper) systemically, but did not elicit a typical CMV systemic infection on any of several cucurbit hosts (cucumber, melon, or squash). The significance of the location of amino acid positions 51 and 240 in the 3a movement protein is discussed.


Design and Evaluation of a Potential Non-Invasive Neurostimulation Strategy for Treating Persistent Anosmia in Post-COVID-19 Patients.
A new pandemic was declared at the end of 2019 because of coronavirus disease 2019 (COVID-19). One of the effects of COVID-19 infection is anosmia (i.e., a loss of smell). Unfortunately, this olfactory dysfunction is persistent in around 5% of the world's population, and there is not an effective treatment for it yet. The aim of this paper is to describe a potential non-invasive neurostimulation strategy for treating persistent anosmia in post-COVID-19 patients. In order to design the neurostimulation strategy, 25 subjects who experienced anosmia due to COVID-19 infection underwent an olfactory assessment while their electroencephalographic (EEG) signals were recorded. These signals were used to investigate the activation of brain regions during the olfactory process and identify which regions would be suitable for neurostimulation. Afterwards, 15 subjects participated in the evaluation of the neurostimulation strategy, which was based on applying transcranial direct current stimulation (tDCS) in selected brain regions related to olfactory function. The results showed that subjects with lower scores in the olfactory assessment obtained greater improvement than the other subjects. Thus, tDCS could be a promising option for people who have not fully regained their sense of smell following COVID-19 infection.


Hearing loss in Muckle-Wells syndrome.
Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease characterized by fevers, rashes, arthralgia, conjunctivitis, and sensorineural hearing loss. In MWS, NLRP3 gene mutations are associated with excessive interleukin-1 release. The aims of this study were to determine the otologic characteristics of MWS, define trajectories of hearing loss, and explore the association with distinct NLRP3 genotypes. A prospective observational cohort study of children and adults diagnosed as having MWS was conducted at a single center. NLRP3 gene mutations were determined. Patients underwent standardized clinical, laboratory, and otologic assessments, including pure tone audiometry, vestibular organ testing, and tinnitus evaluation. Trajectories of hearing loss were defined for each genotype. The genotype-specific risk of progression of hearing loss was determined. A total of 33 patients ages 3-75 years who were members of 5 families with 4 different NLRP3 gene mutations were included. The majority of patients (67%) experienced bilateral sensorineural hearing loss. Even in cases of profound hearing loss vestibular reactivity remained normal. Fourteen adult patients reported nondebilitating tinnitus. Overall, hearing impairment progressed with age. Patients with the T348M mutation were at highest risk of rapid progression of sensorineural hearing loss. Patients with MWS are at risk of developing progressive sensorineural hearing loss without vestibular involvement. Hearing impairment starts at high frequencies and can subsequently progress to profound hearing loss. Progression is age dependent. Patients with different NLRP3 mutations had distinctly different trajectories of hearing loss, suggesting a mutation-specific risk that should be considered when making treatment decisions.


Obstetric cerebral venous thrombosis.
Pregnancy and puerperium are most prevalent prothrombotic states leading to cerebral venous thrombosis. Likelihood of stroke to be of venous origin is greater in stroke associated with pregnancy compared to stroke unrelated to pregnancy. Pregnancy induces several changes in coagulation system, which persists at least during early puerperium, rendering it a prothrombotic state. Hypercoaguability worsens further after delivery as a result of volume depletion and trauma. During puerperium additional risk factors include infection and instrumental delivery or Caesarean section. The management follows general rules as for the venous thrombosis unrelated to pregnancy, however the prognosis is different.


Preparation and magnetic properties of iron(3+) spin-crossover complexes bearing a thiophene substituent: toward multifunctional metallopolymers.
The synthesis of a new 3-ethynylthienyl-substituted QsalH ligand (QsalH is the short form for N-(8-quinolyl)salicylaldimine) (ThEQsalH 3), and the preparation, electronic, and magnetic properties of three homoleptic and cationic iron(3+) complexes containing this ligand with PF(6)(-) 4, SCN(-) 5, and ClO(4)(-) 6 counteranions are reported. In all three complexes a spin-crossover is observed in the solid state by variable temperature magnetic susceptibility measurements and Mossbauer spectroscopy, indicating that the synthetic modification of the QsalH ligand has not significantly altered the electronics at the metal center. This includes the observation of a very rare S = 5/2 to 3/2 spin-crossover in a non-porphyrin iron(3+) complex 5. The molecular structure and magnetic properties of an unusual iron(2+) complex 7 generated by reduction of complex 6 serendipitously during a recrystallization attempt in aerobic acetone solution is also reported. Complexes 4-6 feature iron(3+) reduction and oxidation of the thiophene ring at potentials of approximately -0.7 and +1.2 V (vs Fc), respectively.


Effect of Reduced Material Thickness on Fatigue Behavior and Failure Load of Monolithic CAD/CAM PICN Molar Crowns.
To analyze the effect of material thickness on the fatigue behavior and failure load of monolithic polymer-infiltrated-ceramic-network (PICN) computer-aided design/computer-assisted manufacture (CAD/CAM) crowns. PICN (VITA Enamic) molar crowns with standard (PICN-ST, 1.5 mm) and reduced (PICN-RED, 1.0 mm) thicknesses were investigated (n = 28). Monolithic zirconia (Z-ST, InCoris TZI) served as control. Failure loads before and after fatigue (1.2 million cycles, 198 N) were evaluated. Data were analyzed pairwise using Wilcoxon rank sum test, and resulting P values were adjusted using the Bonferroni-Holm method, with P < .05 considered significant and a prior power analysis. All crowns survived fatigue. Mean failure loads before and after fatigue (respectively) were as follows: PICN-ST: 1,889 ± 341 N and 2,547 ± 876 N; PICN-RED: 2,119 ± 338 N and 2,367 ± 719 N; and Z-ST 5,141 ± 1,194 N and 2,531 ± 682 N. PICN with a reduced thickness of 1 mm appeared to be a reliable CAD/CAM material for posterior crowns.


Effectiveness of a 2% chlorhexidine solution mixed with calcium hydroxide against Candida albicans.
The purpose of this investigation was to examine the in vitro susceptibility of Candida albicans to a mixture of chlorhexidine and calcium hydroxide using a tube dilution test. A suspension containing C. albicans was exposed to 2% chlorhexidine solution, calcium hydroxide paste and 2% chlorhexidine mixed with calcium hydroxide in plastic tissue culture wells. The tested agents were incubated with C. albicans for 1, 24, or 72 h. All agents were effective anti-fungals at all experimental time periods tested, with the exception of exposure to calcium hydroxide for 1 h. A mixture of 2% chlorhexidine and calcium hydroxide therefore is a very effective anti-fungal agent against C. albicans.


The Impact of the COVID-19 Pandemic on Mobility Trends and the Associated Rise in Population-Level Physical Inactivity: Insights From International Mobile Phone and National Survey Data.
The COVID-19 pandemic has reduced physical activity (PA) levels. This is important as physical inactivity is linked to poor COVID-19 outcomes. This study aimed to assess the impact of COVID-19 pandemic restrictions on greenspace and residence mobility, walking levels and in turn how these translated to trends in (UK) PA levels. Google Mobility Reports, the Oxford COVID-19 Government Response Tracker and Apple Mobility geospatial datasets were interrogated for international data. Residence mobility represents home mobility, greenspace mobility includes parks, walking direction requests is proportion of walking directions; stringency index measures lockdown intensity. The Sports England Active Lives Survey dataset was assessed for complementary changes in English PA levels. Using mobility data of 10 countries we observed that during lockdown there were reductions in greenspace mobility and walking directions alongside increased residence mobility; more pronounced changes were seen in countries with higher stringency indices. From a UK perspective, complementary English PA survey data demonstrated the impact of these mobility changes on the proportion and demographic characteristics of PA levels. The most vulnerable in society, the elderly (ages 75+) and Black and Asian minority ethnicity (BAME) individuals were more likely to become physically inactive. The COVID-19 pandemic reduced greenspace mobility and walking direction requests globally. Complementary assessment of English PA levels demonstrated a greater proportion of the population became inactive. Demographics (75+ and BAME) prone to worse COVID-19 outcomes became disproportionately inactive. UK Urban planning should prioritize greenspace development. This could improve city walkability and PA levels.


Using Morpholinos to Control Gene Expression.
Morpholino oligonucleotides are stable, uncharged, water-soluble molecules used to block complementary sequences of RNA, preventing processing, read-through, or protein binding at those sites. Morpholinos are typically used to block translation of mRNA and to block splicing of pre-mRNA, though they can block other interactions between biological macromolecules and RNA. Morpholinos are effective, specific, and lack non-antisense effects. They work in any cell that transcribes and translates RNA, but must be delivered into the nuclear/cytosolic compartment to be effective. Morpholinos form stable base pairs with complementary nucleic acid sequences but apparently do not bind to proteins to a significant extent. They are not recognized by any proteins and do not undergo protein-mediated catalysis-nor do they mediate RNA cleavage by RNase H or the RISC complex. This work focuses on techniques and background for using Morpholinos. © 2017 by John Wiley & Sons, Inc.


Functional gaps in attaining a national health information network.
We describe the health information technology (HIT) required for a model of a national health information network (NHIN). Specifically, we define the functional HIT capabilities of an attainable NHIN and determine the gap between the current state of HIT and its likely state in five years, given current trends of adoption. Administrative functionalities will be more prevalent than clinical functionalities in five years. Smaller stakeholders, such as home health care agencies, will lag in adoption. Policy changes, such as financial incentives to HIT end users or regulatory measures, may help accelerate the adoption of HIT for a model NHIN.


Adverse drug reactions in Ghanaian children: review of reports from 2000 to 2012 in VigiBase.
The aim of this article is to describe adverse drug reactions (ADRs) reported for children aged 0 - 17 years in Ghana. Paediatric reports submitted by the Ghana National Centre for Pharmacovigilance to the World Health Organisation (WHO) Global ADR database, VigiBase up to December 2012 were extracted. The data were analysed for number of reports per year, types of reporters and suspected ADRs and drugs. A total of 343 reports for children were received during the period. The drug classes most frequently reported were vaccines (115, 31%), antimalarials (106, 28%) and antibiotics (57, 15%). Of the top 20 individual drugs, 19 were anti-infectives. The most frequently reported ADRs were injection site infection, fever and rash. There were 23 deaths reported, and antimalarials were implicated in 12 cases. Vaccines, antimalarials and antibiotics are the leading medicines reported to cause ADRs in Ghanaian children. There was a high mortality rate, with many of the deaths due to causes explained in the individual case safety reports.


Release of Type II phospholipase A2 immunoreactivity and phospholipase A2 enzymatic activity from human placenta.
The aim of this study was to determine whether Type II phospholipase A2 (PLA2) is released from late pregnant human placental tissue. Placental explants were incubated in vitro and the release of immunoreactive (ir) Type II PLA2 and PLA2 enzymatic activity into the medium was determined. Both irType II PLA2 and PL2 enzymatic activity accumulated in the incubation medium in a time-dependent manner (P < 0.0001). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation medium. The concentration of irType II PLA2 and PLA2 enzyme activity present in incubation medium were significantly correlated (P < 0.01). Consistent with the hypothesis that Type II PLA2 may be store in secretory granules within human placental tissue, incubation in the presence of a membrane depolarising concentration of KCI (60 mM) caused the release of irType II PLA2 2.0-fold (P < 0.001). PLA2 enzyme activity released into the incubation medium displays biochemical characteristics consistent with those previously reported for secretory PLA2 isozymes, that is, a requirement for millimolar concentrations of calcium for optimal enzyme activity, inhibited by reducing agents, such as dithiothreitol and insensitive to heat inactivation. The data obtained in this study establish that irType PLA2 is released from term placenta, when incubated in vitro. The release of this extracellularly-active PLA2 isozyme may contribute to gestational and labour-associated increases in glycerophospholipid metabolism and prostaglandin formation.


Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles.
Progesterone has been implicated to play a critical role in mediating LH induction of ovulation and possibly luteinization. The present study was undertaken to determine the effects of various agonists (LH, FSH, forskolin, and GnRH) known to stimulate ovulation on their abilities to induce progesterone receptor (PR) mRNA and protein in rat preovulatory follicles and in cultured rat granulosa cells exhibiting a preovulatory phenotype. In cultured granulosa cells, PR mRNA was induced by LH in a dose- and time-dependent manner. Transcripts of approximately 11.0, 7.2, 6.8, 6.2, 3.4, and 3.1 kilobases in size were induced by ovulatory (500 ng/ml), but not low (50 ng/ml), concentrations of LH and FSH as well as by forskolin (10 microM), GnRH (1 microM), and phorbol 12-myristate 13-acetate (200 nM). Two forms (A and B) of PR protein were also induced in an agonist- and time-dependent manner, with the shorter form A (mol wt, 83,000-85,000) appearing in greater abundance than the longer form B (mol wt, 115,000). Indirect immunofluorescent analyses verified nuclear localization of the induced receptor. Forskolin and progesterone, but not progesterone alone, were able to activate a glucocorticoid (progesterone) response element-E1b-chloramphenicol acetyltransferase reporter construct (12-fold) after transfection into cultured granulosa cells. The antiprogestins RU486 and ZK98299 did not inhibit induction of PR mRNA and protein, but effectively blocked agonist activation of glucocorticoid response element2-E1b-chloramphenicol acetyltransferase, as well as LH stimulation of luteinization in vitro. These results provide direct evidence that agonists stimulating diverse intracellular pathways can induce PR in granulosa cells, that progesterone plays a functional role in the luteinization process triggered by the LH surge, and that the effects are mediated at least in part by induction of PR.


Feasibility of the Glissonian approach during right hepatectomy.
The Glissonian approach during hepatectomy is a selective vascular clamping procedure associated with low rates of technical failure and complications. The aim of the present study was to assess the feasibility of a right Glissonian approach in relation to portal vein anatomy. This was a prospective study conducted over a 12-month period, which included 32 patients for whom preoperative three-dimensional reconstruction using contrast-enhanced computed tomography in the portal venous phase and portography for right portal vein embolization were available, and in whom a right Glissonian approach was applied during right hepatectomy. Preoperative imaging data were correlated with intraoperative Doppler ultrasound findings (considered as the reference dataset). Causes of failures and complications specifically related to the Glissonian approach were identified. Right hepatectomy was performed for colorectal liver metastases (n = 25), hepatocellular carcinoma on cirrhosis (n = 6) and intrahepatic cholangiocarcinoma (n = 1). The Glissonian approach was effective in 24 (75%) patients. In the remaining eight (25%) patients, failure was caused by incomplete clamping (n = 2) or clamping of the left portal pedicle (n = 6). The portal anatomy was aberrant in six patients with failure, showing portal trifurcation (n = 1), right portal trifurcation (n = 1) and a common trunk between the right anterior and left portal branch (n = 4). An angle of less than 50° between the portal vein and left portal branch was reported in association with extended clamping to the left portal branch (selectivity = 72%, specificity = 71%). Intraoperative bleeding and biliary fistula occurred in two patients with non-normal portal anatomy. The right Glissonian approach was effective in 75% of patients. Failure of the procedure (including the extension of clamping to the left pedicle) mostly occurred in patients with portal vein variations, which can be accurately assessed using a combination of preoperative imaging and intraoperative Doppler ultrasound.


Comparison of Monoamine Oxidase-A, Aβ Plaques, Tau, and Translocator Protein Levels in Postmortem Human Alzheimer's Disease Brain.
Increased monoamine oxidase-A (MAO-A) activity in Alzheimer's disease (AD) may be detrimental to the point of neurodegeneration. To assess MAO-A activity in AD, we compared four biomarkers, Aβ plaques, tau, translocator protein (TSPO), and MAO-A in postmortem AD. Radiotracers were [18F]FAZIN3 for MAO-A, [18F]flotaza and [125I]IBETA for Aβ plaques, [124/125I]IPPI for tau, and [18F]FEPPA for TSPO imaging. Brain sections of the anterior cingulate (AC; gray matter GM) and corpus callosum (CC; white matter WM) from cognitively normal control (CN, n = 6) and AD (n = 6) subjects were imaged using autoradiography and immunostaining. Using competition with clorgyline and (R)-deprenyl, the binding of [18F]FAZIN3 was confirmed to be selective to MAO-A levels in the AD brain sections. Increases in MAO-A, Aβ plaque, tau, and TSPO activity were found in the AD brains compared to the control brains. The [18F]FAZIN3 ratio in AD GM versus CN GM was 2.80, suggesting a 180% increase in MAO-A activity. Using GM-to-WM ratios of AD versus CN, a >50% increase in MAO-A activity was observed (AD/CN = 1.58). Linear positive correlations of [18F]FAZIN3 with [18F]flotaza, [125I]IBETA, and [125I]IPPI were measured and suggested an increase in MAO-A activity with increases in Aβ plaques and tau activity. Our results support the finding that MAO-A activity is elevated in the anterior cingulate cortex in AD and thus may provide a new biomarker for AD in this brain region.


Vine Nitrogen Status Does Not Have a Direct Impact on 2-Methoxy-3-isobutylpyrazine in Grape Berries and Wines.
Methoxypyrazines (MP) constitute a large family of compounds that contribute to the vegetative varietal aroma of many grapevine varieties and wines. The berry content in 2-methoxy-3-isobutylpyrazine (IBMP), a major MP reminiscent of green-pepper aroma, can be influenced by environmental factors or cultural practices such as water status or mineral nutrition. To date, no study has investigated a possible direct effect of nitrogen (N) on IBMP synthesis without possible interference from water status and vigor variations. In this study, only vine nitrogen status was significantly different among treatments. Water status was controlled during the season, and vine vigor was similar among treatments. IBMP level was maximal at bunch closure and decreased during the season. There was no significant effect of nitrogen nutrition on this metabolite. Moreover, the expression profiles of VvOMT3 and VvOMT4, key genes in the IBMP biosynthetic pathway, were similar between treatments. This result indicates that when an effect of N on IBMP was found in previous studies, it was likely mediated through the modification of bunch-zone microclimate, induced by the higher vigor of high N-status vines.


Hole transport in Poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] and high-efficiency polymer solar cells from its blends with PCBM.
We report herein a detailed study of the thermal and hole-transport properties of poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] (F6T2) and its photovoltaic performance in a bulk-heterojunction (BHJ) solar cell. This crystalline polymer has a high weight-average molecular weight (M(w) = 52 400) with a polydispersity index of 1.99. With a band gap of 2.36 eV, F6T2 exhibits strong absorption in the 300-500 nm region. BHJ solar cells blending F6T2 with [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) (1:3 weight ratio) as the active layer present a high open-circuit voltage (V(oc) approximately 0.9 V) and a promising power conversion efficiency of 2.4% under simulated solar light AM1.5G (100 mW/cm(2)). Furthermore, F6T2 shows sufficient hole mobility [ca. 8.4 x 10(-5) cm(2)/(V s) at 310 K and 2.5 x 10(5) V/cm applied electric field] by a time-of-flight transient photocurrent technique, allowing efficient charge extraction and a good fill factor for solar cell application. Nanoscale phase separation was observed in F6T2/PCBM films with a surface roughness lower than 60 nm.


The Potential Benefit by Application of Kinetic Analysis of PET in the Clinical Oncology.
PET is an appropriate method to display the functional activities in target tissue using many types of traces. The visual assessment of PET images plus the semiquantitative parameter (SUV) are the main diagnostic standards considered in identifying the malignant lesion. However, these standards lack occasionally the proper specificity and/or sensitivity. That emphasizes the importance of considering supplemental diagnostic criteria such as the kinetic parameter. The latter gives the way to image the ongoing metabolic processes within the target tissue as well as to identify the alterations occurring at the microscale level before they become observable in the conventional PET-imaging. The importance of kinetic analysis of PET imaging has increased with newly developed PET devices that offer images of good quality and high spatial resolution. In this paper, we highlighted the potential contribution of kinetic analysis in improving the diagnostic accuracy in intracranial tumour, lung tumour, liver tumour, colorectal tumour, bone and soft tissue tumours, and prostate cancer. Moreover, we showed that the appropriate therapy monitoring can be best achieved after considering the kinetic parameters. These promising results indicate that the kinetic analysis of PET imaging may become an essential part in preclinical and clinical molecular imaging as well.


An observational study of child safety seat use in an international safe community: Tehran, Iran.
Despite strong evidence of the effectiveness of child safety seats in reducing injuries, the use of these devices in some communities is still rare. The purpose of this study was to determine the prevalence of child safety seat use and the factors influencing its use in the safe community of Tehran. This roadside observational study was conducted in 2015 and 2,178 personal cars with a child under 12 years aboard were observed on Tehran's streets in regard to use of child safety seats. Other variables such as the gender of the driver, driver's age group, type of street, region of municipality, time of day, and day of the week were also collected. Prevalence of child safety seat use was 4.3% and was significantly higher among women drivers, on freeways, and in municipal regions 1, 4, and 7. The prevalence of child safety seat use in Tehran as a most populous member of the international safe community was very low and most children commuted in insecure situations in the vehicle. Therefore, it is proposed that plans should be made to increase the use of child safety seats in international safe communities.


Ilizarov principles of deformity correction.
Ilizarov frames provide a versatile fixation system for the management of bony deformities, fractures and their complications. The frames give stability, soft tissue preservation, adjustability and functionality allowing bone to realise its full osteogenic potential. It is important that we have a clear and concise understanding of the Ilizarov principles of deformity correction to best make use of this fixation system. In this review article, the history of Ilizarov frame, the basic sciences behind it, the mechanical principles governing its use and the clinical use of the fixation system are discussed.


Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents.
We prepared 1-(4'-azido-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4'-substituted nucleosides. Compounds 10 and 11 were synthesized from 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-D-arabinofuranoside in multiple steps, and their structures were unequivocally established by IR, (1)H NMR, (13)C NMR, and (19)F NMR spectroscopy, HRMS, and X-ray crystallography. Compounds 10 and 11 exhibited potent anti-HIV-1 activity (EC(50): 0.3 and 0.13 nM, respectively) without significant cytotoxicity in concentrations up to 100 μM. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC(50) values of 0.086, 0.15, and 0.11 nM, respectively. Due to the high potency of 11, it was also screened against an NIH Reagent Program NRTI-resistant virus panel containing eleven mutated viral strains and for cytotoxicity against six different human cell lines. The results of this screening indicated that 11 is a novel NRTI that could be developed as an anti-AIDS clinical trial candidate to overcome drug-resistance issues.


[Multiple ruptures of atherosclerotic plaques in acute coronary syndrome. Endocoronary ultrasonography study of three arteries].
The aim of this study was to assess the three coronary arteries systematically by endocoronary ultrasonography in patients with unstable angina to check the hypothesis of global destabilisation of atherosclerotic plaques in acute coronary syndromes (ACS). Sixty two coronary arteries were examined (2.6 per patient). Fifty plaque ruptures were diagnosed (2.08 per patient). Rupture of a plaque of the culprit lesion of the ACS was clearly detected in 9 patients (37.5%). At least one ruptured plaque on a site other than the culprit lesion was observed in 19 patients (79%), on another artery in 70.8% of cases and on two other arteries in 12.5% of cases. A complete endocoronary ultrasonic examination of the three coronary arteries in patients with a first ACS demonstrated that: multiple atherosclerotic plaque rupture may be detected by endocoronary ultrasonography; these multiple plaque ruptures occur simultaneously with the culprit lesion; they are frequent and can be situated on the three main coronary vessels and multiple plaque rupture other than the culprit lesion are less severe, non stenotic and less calcified. Thus, although a single lesion is clinically symptomatic, ACS seems to be associated with global coronary instability.


Collection and 28-day storage of human placental blood.
Placental blood was harvested using a novel collection system into packs containing citrate-phosphate-dextrose-adenine and then stored for 28 d. Before and during storage, sterility, adequacy of anticoagulation, blood chemistry, and red cell viability were assessed weekly. The average volume of blood collected was 65 mL (range 30-110 mL) with a 0.42 hematocrit once diluted in anticoagulant. All blood culture specimens were sterile at collection and during storage. Adequate anticoagulation (activated partial thromboplastin time > 90 s) on the day of collection was achieved in 15 specimens, all less than 65 mL of blood volume. Ten specimens, in blood volumes ranging from 65 to 110 mL, had mean activated partial thromboplastin time values of 65.3 +/- 10.2 s. Activated partial thromboplastin time values for all 25 specimens at 1, 2, 3, and 4 wk storage were > 90 s, presumably because of the decline in labile clotting factors after 24 h of storage. Hematocrit, red cell ATP, and red cell shape were maintained during storage. As expected, red cell 2,3-diphosphoglycerate declined and potassium levels rose significantly but were not different than levels reported for adult cells similarly preserved. Based on our results, it appears that placental blood represents a potential source of autologous transfusion for the sick neonate over the first month of life.


On the potential of drug repurposing in dysphagia treatment: New insights from a real-world pharmacovigilance study and a systematic review.
Background: Polypharmacy is common in patients with dysphagia. Routinely used drugs may influence swallowing function either improving or worsening it. We aimed to explore the potential effects of three commonly used drug classes on dysphagia and aspiration pneumonia through a systematic review and a real-world data analysis to probe the possibility of drug repurposing for dysphagia treatment. Material and Methods: Five electronic databases were searched. Studies on adults at risk for dysphagia, treated with Dipeptidyl-Peptidase IV Inhibitors (DPP-4i), Adrenergic Beta-Antagonists (beta-blockers), or Angiotensin-Converting Enzyme Inhibitors (ACEi), and reporting outcomes on dysphagia or aspiration pneumonia were included. A nested case/non-case study was performed on adverse events recorded in the FDA Adverse Event Reporting System (FAERS) on patients >64 years. Cases (dysphagia or aspiration pneumonia) were compared between patients only treated with Levodopa and patients who were concomitantly treated with the drugs of interest. Results: Twenty studies were included in the review (17 on ACEi, 2 on beta-blockers, and 1 on DPP-4i). Contrasting findings on the effects of ACEi were found, with a protective effect mainly reported in Asian studies on neurological patients. Beta-blockers were associated with a reduced dysphagia rate. The study on DPP-4i suggested no effect on dysphagia and an increased risk of aspiration pneumonia. The FAERS analysis showed a reduction of the risk for dysphagia/aspiration pneumonia with ACEi, beta-blockers, and DPP-4i. Conclusion: Our study explores the potential drug repurposing of ACEi, beta-blockers and DPP-4i in neurological patients with dysphagia to improve swallowing function and reduce aspiration pneumonia risk. Future randomized controlled studies should confirm these results and clarify the underlying mechanisms of action.


Novel mitogen-activated protein kinase MpkC of Aspergillus fumigatus is required for utilization of polyalcohol sugars.
The genome of Aspergillus fumigatus has four genes that encode mitogen-activated protein kinases (MAPKs), sakA/hogA, mpkA, mpkB, and mpkC. The functions of the MpkB and MpkC MAPKs are unknown for A. fumigatus and the closely related and genetically amenable species Aspergillus nidulans. mpkC deletion mutants of A. fumigatus were made and their phenotypes characterized. The mpkC deletion mutants were viable and had normal conidial germination and hyphal growth on minimal or complete media. This is in contrast to deletion mutants with deletions in the closely related MAPK gene sakA/hogA that we previously reported had a nitrogen source-dependent germination phenotype. Similarly, the growth of the mpkC deletion mutants was wild type on high-osmolarity medium. Consistent with these two MAP kinase genes regulating different cellular responses, we determined that the mpkC deletion mutants were unable to grow on minimal medium with sorbitol or mannitol as the sole carbon source. This result implicates MpkC signaling in carbon source utilization. Changes in mRNA levels for sakA and mpkC were measured in response to hypertonic stress, oxidative stress, and a shift from glucose to sorbitol to determine if there was overlap in the SakA and MpkC signaling pathways. These studies demonstrated that SakA- and MpkC-dependent patterns of change in mRNA levels are distinct and have minimal overlap in response to these environmental stresses.


Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study.
We conducted a retrospective analysis on the identification and antibiogram of all bacteria isolated from urine samples with microbiological confirmation of urinary tract infection (UTI) in a Spanish reference hospital over a 7-year period. A retrospective analysis was performed of the identification and antibiogram data. A total of 31,758 uropathogens were isolated. Escherichia coli accounted for the majority (55.2%) of these, followed by Enterococcus faecalis (18.0%) and Klebsiella spp (10.3%). The highest E coli susceptibility rates were to imipenem (93.0%-99.8%), amikacin (97.3%-99.5%), nitrofurantoin (96.7%-98.9%), and fosfomycin (95.3%-100%), and the lowest were to cefuroxime (67.8%-86.4%), ciprofloxacin (61.2%-69.8%), and co-trimoxazole (55.0%-65.5%). We highlight the overall high activity of imipenem, piperacillin-tazobactam, nitrofurantoin, and fosfomycin on isolates versus the low activity of fluoroquinolones, co-trimoxazole, or cephalosporins. The activity of amoxicillin-clavulanic acid and fosfomycin decreased significantly over the 7-year study period. Imipenem and piperacillin-tazobactam appear to be good options for the empiric treatment of UTI acquired in hospital or requiring hospitalization, whereas nitrofurantoin and fosfomycin can be first-choice antibiotics for the treatment of uncomplicated community-acquired cystitis. However, surveillance studies are required to detect resistance to these antibiotics, given that an increase in uropathogen resistance rates may contraindicate its future use in empiric UTI therapy.


Extracellular ATP and UTP control the generation of reactive oxygen intermediates in human macrophages through the opening of a charybdotoxin-sensitive Ca2+-dependent K+ channel.
Human monocyte-derived macrophages possess a NADPH oxidase that catalyzes superoxide formation upon phagocytosis. Extracellular ATP per se does not activate NADPH oxidase but potentiates superoxide generation triggered by opsonized zymosan. UTP can substitute for ATP with the same efficiency, suggesting that ATP mediates its effects specifically through P2U receptors. Extracellular UTP stimulates a rapid increase in cytoplasmic Ca2+ concentration in monocytic cells, which results from a release of intracellular Ca2+ stores. Moreover, UTP-induced calcium increase is sufficient to activate a charybdotoxin-sensitive Ca2+-dependent outward K+ channel (K(Ca)). The activity of this channel develops between 0.1 and 1.0 microM free cytoplasmic Ca2+ concentration; it is half-blocked by 10 nM charybdotoxin but insensitive to iberiotoxin. Under asymmetrical K+ conditions, this K(Ca) channel does not depend on membrane potential and is characterized by a linear single-current voltage relationship in the voltage range of -100 to +50 mV, giving a unitary conductance of 10 pico-Siemens. Interestingly, ATP/UTP-induced oxygen radicals release was inhibited by charybdotoxin in the same range of concentration as the UTP-induced K(Ca) channel. Furthermore, we show that ATP or UTP fail to enhance oxygen radicals production before K(Ca) channel is expressed (3 days). The electrogenic nature of the NADPH oxidase, i.e., its level of activation, being dependent on the plasmic membrane potential, might provide the causal link between the reactive oxygen intermediates generation and the opening of the K(Ca) channel.


Laboratory testing of the patient with multiple chemical sensitivity.
Multiple diagnostic laboratory tests are frequently used in the clinical evaluation of persons with multiple chemical sensitivity without a clear a priori hypothesis. In addition, many of these tests are performed despite a lack of understanding of the test technical performance characteristics or the clinical significance (test sensitivity and specificity). The result is a plethora of laboratory data that have little clinical relevance and that can be both misleading and misused.


Redistribution of Endosomal Membranes to the African Swine Fever Virus Replication Site.
African swine fever virus (ASFV) infection causes endosomal reorganization. Here, we show that the virus causes endosomal congregation close to the nucleus as the infection progresses, which is necessary to build a compact viral replication organelle. ASFV enters the cell by the endosomal pathway and reaches multivesicular late endosomes. Upon uncoating and fusion, the virus should exit to the cytosol to start replication. ASFV remodels endosomal traffic and redistributes endosomal membranes to the viral replication site. Virus replication also depends on endosomal membrane phosphoinositides (PtdIns) synthesized by PIKfyve. Endosomes could act as platforms providing membranes and PtdIns, necessary for ASFV replication. Our study has revealed that ASFV reorganizes endosome dynamics, in order to ensure a productive infection.


Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer.
Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (∼20 nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices.


N, S, O Self-Doped Carbon Derived from Grapefruit Peel for High-Performance Supercapacitors.
The development of high-capacity carbon for supercapacitors is highly desirable but challenging. In this work, we design a N, S, O self-doped carbon electrode (NSOC-800) with high capacitance and good stability via the carbonization of grapefruit peel via a one-step KOH activation method without extra dopants. The existence of heteroatoms enables the NSOC-800 to have a high specific capacitance of 280 F/g and a great cycling performance, with 90.1% capacitance retention after 5000 cycles. Moreover, the symmetric supercapacitor with NSOC-800 electrodes delivers a maximum energy density of 5 Wh/kg with a power density of 473 W/kg. Such a promising method to achieve carbon materials with self-doping heteroatwoms is of great significance for developing highly efficient electrodes for energy storage devices.


Generation of Large Vortex-Free Superfluid Helium Nanodroplets.
Superfluid helium nanodroplets are an ideal environment for the formation of metastable, self-organized dopant nanostructures. However, the presence of vortices often hinders their formation. Here, we demonstrate the generation of vortex-free helium nanodroplets and explore the size range in which they can be produced. From x-ray diffraction images of xenon-doped droplets, we identify that single compact structures, assigned to vortex-free aggregation, prevail up to 10^{8} atoms per droplet. This finding builds the basis for exploring the assembly of far-from-equilibrium nanostructures at low temperatures.


Molecular cloning and expression of Hedychium coronarium farnesyl pyrophosphate synthase gene and its possible involvement in the biosynthesis of floral and wounding/herbivory induced leaf volatile sesquiterpenoids.
Farnesyl pyrophosphate synthase (FPPS EC 18.104.22.168) catalyzes the production of farnesyl pyrophosphate (FPP), which is a key precursor for many sesquiterpenoids such as floral scent and defense volatiles against herbivore attack. Here we report a new full-length cDNA encoding farnesyl diphosphate synthase from Hedychium coronarium. The open reading frame for full-length HcFPPS encodes a protein of 356 amino acids, which is 1068 nucleotides long with calculated molecular mass of 40.7 kDa. Phylogenetic tree analysis indicates that HcFPPS belongs to the plant FPPS super-family and has strong relationship with FPPS from Musa acuminata. Expression of the HcFPPS gene in Escherichia coli yielded FPPS activity. Tissue-specific and developmental analyses of the HcFPPS mRNA and corresponding volatile sesquiterpenoid levels in H. coronarium flowers revealed that the HcFPPS might play a regulatory role in floral volatile sesquiterpenoid biosynthesis. The emission of the FPP-derived volatile terpenoid correlates with strong expression of HcFPPS induced by mechanical wounding and Udaspes folus-damage in leaves, which suggests that HcFPPS may have an important ecological function in H. coronarium vegetative organ.


Derivation of a site-specific assessment criterion for benzo[a]pyrene in red shale at a former coking works.
A former coking works in England is being remediated to enable its redevelopment. We have developed site specific human health risk assessment criteria (SSAC) for benzo[a]pyrene (BaP) based on detailed characterisation of red shale proposed for reuse in an area allocated for residential development. Samples of red shale were analysed using the Colon-enhanced Physiologically Based Extraction Test (CEPBET) to estimate the bioaccessibility of BaP. The results indicate that between 5% and 28% of the red shale BaP is bioaccessible. A cautious value of 50% was used in calculating an SSAC. The CLEA human health assessment model was used to calculate the SSAC and any changes to the default input parameters have been discussed and justified. Based on the fact that BaP appears to be a point-of-contact, rather than a systemic, carcinogen in animal studies, individual assessment criteria were estimated for the oral, inhalation and dermal routes of entry in-line with current UK guidance. An overall SSAC of 2.5 mg/kg for BaP in red shale for the residential with home-grown produce land use was then derived as the lowest of the three route-specific assessment criteria. This value is specific to both the site and the material being assessed. The approach adopted however can be applied on other sites and for other materials to inform detailed quantitative risk assessments.


Hepatic fat fraction: MR imaging for quantitative measurement and display--early experience.
The institutional review board approved this HIPAA-compliant study. After all five patients with nonalcoholic fatty liver disease signed a consent, they underwent magnetic resonance (MR) imaging for hepatic fat quantification. The purpose of this study was to develop a fast and accurate method to acquire and display quantitative maps of the percentage of hepatic fat. In-phase and out-of-phase gradient-echo MR imaging was performed with dual flip angles (70 degrees, 20 degrees) to resolve ambiguity of the dominant constituent. T2* corrections were also estimated and applied to generate color-coded maps of the estimated percentage of hepatic fat. MR imaging results were compared with biopsy results in two of five patients, and the technique was validated qualitatively and quantitatively with a water-oil phantom. Results of the phantom study confirmed that the dual-flip angle algorithm can be used to correctly identify the dominant constituent, allowing depiction of 0%-100% of fat content. The estimated liver fat fraction was comparable to quantitative fat measurements at biopsy in both patients (MR imaging, 18.3% +/- 2.8 [standard deviation] and 28.6% +/- 2.4, vs quantitative histopathologic analysis, 11.2% and 28.5%, respectively). radiology.rsnajnls.org/cgi/content/full/2373041639/DC1


Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan.
The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension.


The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function.
The von Willebrand factor (VWF) A2 crystal structure has revealed the presence of a rare vicinal disulfide bond between C1669 and C1670, predicted to influence domain unfolding required for proteolysis by ADAMTS13. We prepared VWF A2 domain fragments with (A2-VicCC, residues 1473-1670) and without the vicinal disulfide bond (A2-DeltaCC, residues 1473-1668). Compared with A2-DeltaCC, A2-VicCC exhibited impaired proteolysis and also reduced binding to ADAMTS13. Circular dichroism studies revealed that A2-VicCC was more resistant to thermal unfolding than A2-DeltaCC. Mutagenesis of C1669/C1670 in full-length VWF resulted in markedly increased susceptibility to cleavage by ADAMTS13, confirming the important role of the paired vicinal cysteines in VWF A2 domain stabilization.


Cooperative RNA polymerase molecules behavior on a stochastic sequence-dependent model for transcription elongation.
The transcription process is crucial to life and the enzyme RNA polymerase (RNAP) is the major component of the transcription machinery. The development of single-molecule techniques, such as magnetic and optical tweezers, atomic-force microscopy and single-molecule fluorescence, increased our understanding of the transcription process and complements traditional biochemical studies. Based on these studies, theoretical models have been proposed to explain and predict the kinetics of the RNAP during the polymerization, highlighting the results achieved by models based on the thermodynamic stability of the transcription elongation complex. However, experiments showed that if more than one RNAP initiates from the same promoter, the transcription behavior slightly changes and new phenomenona are observed. We proposed and implemented a theoretical model that considers collisions between RNAPs and predicts their cooperative behavior during multi-round transcription generalizing the Bai et al. stochastic sequence-dependent model. In our approach, collisions between elongating enzymes modify their transcription rate values. We performed the simulations in Mathematica® and compared the results of the single and the multiple-molecule transcription with experimental results and other theoretical models. Our multi-round approach can recover several expected behaviors, showing that the transcription process for the studied sequences can be accelerated up to 48% when collisions are allowed: the dwell times on pause sites are reduced as well as the distance that the RNAPs backtracked from backtracking sites.


Suppression of rat hepatoma cell growth by expression of phosphatidylethanolamine N-methyltransferase-2.
The expression of rat liver phosphatidylethanolamine N-methyltransferase-2 (PEMT2) in McA-RH7777 rat hepatoma cells resulted in the unexpected inhibition of cell growth. There was a strict correlation (r = 0.973) between the level of expression of the enzyme activity and the generation time for hepatoma cell division. Expression of other foreign proteins via the same vector did not inhibit McA-RH7777 cell growth; thus, retardation of cell division was specific for the methyltransferase. Addition of 1 microM 3-deazaadenosine, which causes inhibition of phosphatidylethanolamine methylation, reversed the PEMT2-mediated inhibition of cell division. Transfection of a line of Chinese hamster ovary cells with PEMT2 had no effect on the division of these cells. Induction of hepatic tumors in rats with N-nitrosodiethylamine coincided with a striking decrease in methyltransferase activity and immunoreactive protein in the tumor nodules. Thus, data from studies in cell culture and intact rats suggest a regulatory role for PEMT2 in hepatocyte cell growth and possibly in the development of liver cancer.


An 85-year-old case with Hashimoto's encephalopathy, showing spontaneous complete remission.
We report an 85-year-old man with Hashimoto's encephalopathy (HE) who showed spontaneous complete remission. The autoantibody against the amino (NH2) terminal region of alpha-enolase was positive in our patient. Neuropsychological manifestations, such as personality change and progressive cognitive impairment, gradually improved over approximately 6 weeks after onset of disease without corticosteroid treatment in parallel with a decrease in the anti-thyroglobulin antibody in the cerebrospinal fluid. HE should be considered as a possible diagnosis even in elderly patients with neuropsychiatric symptoms, particularly when a previous history of thyroid disease is present.


Experimental phase diagram of perpendicularly magnetized ultrathin ferromagnetic films.
We image the domain patterns in perpendicularly magnetized ultrathin Fe films on Cu(100) as a function of the temperature T and the applied magnetic field H. Between the low-field stripe phase and the high-field uniform phase we find a bubble phase, consisting of reversed circular domains in a homogeneous background. The curvature of the transition lines in the H-T parameter space is in contrast to the general expectations. The pattern transformations show yet undetected scaling properties.


Acute effects of glucose tablets on craving, withdrawal symptoms, and sustained attention in 12-h abstinent tobacco smokers.
Glucose administration may decrease desire to smoke in abstinent smokers. Moreover, glucose administration has been associated with improved performance on measures of attention in healthy humans but evidence remains modest. The present study aimed to determine whether reported craving and nicotine withdrawal symptoms can be relieved, and sustained attention on the Rapid Visual Information Processing (RVIP) task improved, with the administration of 12 g oral glucose in nicotine-deprived smokers. Forty-one smokers, abstinent for 12 h, participated in a double-blind, placebo-controlled, randomized study to examine the effect of glucose on desire to smoke, withdrawal symptoms, and attention. Participants completed the RVIP task once and then rated craving and nicotine withdrawal symptoms before chewing four 3 g glucose tablets (experimental group) or four matched placebo tablets (control group). Following tablet consumption participants rated craving and withdrawal symptoms at 5-min intervals for 20 min. Subsequently a second RVIP task was performed, followed by a final rating of craving and withdrawal symptoms. Any effect of glucose across time was not statistically significant on craving, withdrawal symptoms, or performance on the RVIP task. There were no differences between the groups in measures of 'satisfaction' or 'sickness'. The present study failed to find a significant effect of 12 g oral glucose on tobacco craving, withdrawal symptoms, or sustained attention in relatively young tobacco smokers after 12 h of tobacco abstinence.


An In Vivo Blood-brain Barrier Permeability Assay in Mice Using Fluorescently Labeled Tracers.
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function. Assessment of the BBB permeability is therefore crucial in evaluating the severity of the neurological disease and the success of the treatment strategies employed. We present here a simple yet robust permeability assay that have been successfully applied to several mouse models both, genetic and experimental. The method is highly quantitative and objective in comparison to the tracer fluorescence analysis by microscopy that is commonly applied. In this method, mice are injected intraperitoneally with a mix of aqueous inert fluorescent tracers followed by anesthetizing the mice. Cardiac perfusion of the animals is performed prior to harvesting brain, kidneys or other organs. Organs are homogenized and centrifuged followed by fluorescence measurement from the supernatant. Blood drawn from the cardiac puncture just before perfusion serves for normalization purpose to the vascular compartment. The tissue fluorescence is normalized to the wet weight and serum fluorescence to obtain a quantitative tracer permeability index. For additional confirmation, the contralateral hemi-brain preserved for immunohistochemistry can be utilized for tracer fluorescence visualization purposes.


Comparative modulation transfer functions of the EMI and Delta scanners.
Spatial resolution of the EMI and Delta computed tomographic scanners has been measured by recording the response to a nylon and water sunburst phantom (Siemens star) and calculating the modulation transfer function at radii corresponding to various spatial frequencies. The resolution appears to be related primarily to the size of the matrix element, and exhibits an upper cut-off frequency somewhat in excess of 3 cycles/cm.


DF-2 septicemia following whirlpool spa immersion.
We describe the case of a 31-year-old asplenic man who developed DF-2 bacteremia, septic shock, and pneumonia after recreational immersion in a whirlpool spa. The patient did not have a history of dog bite or contact with canine secretions, although he owned two dogs. DF-2 could not be isolated from the whirlpool spa.


Putrescine bisamides from Aglaia gigantea.
Phytochemical analysis of the leaves of Aglaia gigantea collected in Vietnam yielded three cinnamoyl putrescine bisamide derivatives, which included the known compound dasyclamide ( 1), as well as two new natural products, gigantamide A ( 2) and grandiamide D ( 3). In this study, the structure of dasyclamide ( 1) was confirmed by X-ray crystallography. The structures of the two new alkaloids, gigantamide A ( 2) and grandiamide D ( 3), were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESIMS, HRQTOFMS) data. The absolute configuration of grandiamide D ( 3) was determined via Mosher ester derivatization.


Macro Monte Carlo for dose calculation of proton beams.
Although the Monte Carlo (MC) method allows accurate dose calculation for proton radiotherapy, its usage is limited due to long computing time. In order to gain efficiency, a new macro MC (MMC) technique for proton dose calculations has been developed. The basic principle of the MMC transport is a local to global MC approach. The local simulations using GEANT4 consist of mono-energetic proton pencil beams impinging perpendicularly on slabs of different thicknesses and different materials (water, air, lung, adipose, muscle, spongiosa, cortical bone). During the local simulation multiple scattering, ionization as well as elastic and inelastic interactions have been taken into account and the physical characteristics such as lateral displacement, direction distributions and energy loss have been scored for primary and secondary particles. The scored data from appropriate slabs is then used for the stepwise transport of the protons in the MMC simulation while calculating the energy loss along the path between entrance and exit position. Additionally, based on local simulations the radiation transport of neutrons and the generated ions are included into the MMC simulations for the dose calculations. In order to validate the MMC transport, calculated dose distributions using the MMC transport and GEANT4 have been compared for different mono-energetic proton pencil beams impinging on different phantoms including homogeneous and inhomogeneous situations as well as on a patient CT scan. The agreement of calculated integral depth dose curves is better than 1% or 1 mm for all pencil beams and phantoms considered. For the dose profiles the agreement is within 1% or 1 mm in all phantoms for all energies and depths. The comparison of the dose distribution calculated using either GEANT4 or MMC in the patient also shows an agreement of within 1% or 1 mm. The efficiency of MMC is up to 200 times higher than for GEANT4. The very good level of agreement in the dose comparisons demonstrate that the newly developed MMC transport results in very accurate and efficient dose calculations for proton beams.


Neutral and charged excitations in carbon fullerenes from first-principles many-body theories.
We investigate the accuracy of first-principles many-body theories at the nanoscale by comparing the low-energy excitations of the carbon fullerenes C(20), C(24), C(50), C(60), C(70), and C(80) with experiment. Properties are calculated via the GW-Bethe-Salpeter equation and diffusion quantum Monte Carlo methods. We critically compare these theories and assess their accuracy against available photoabsorption and photoelectron spectroscopy data. The first ionization potentials are consistently well reproduced and are similar for all the fullerenes and methods studied. The electron affinities and first triplet excitation energies show substantial method and geometry dependence. These results establish the validity of many-body theories as viable alternative to density-functional theory in describing electronic properties of confined carbon nanostructures. We find a correlation between energy gap and stability of fullerenes. We also find that the electron affinity of fullerenes is very high and size independent, which explains their tendency to form compounds with electron-donor cations.


The appearance and distribution of mature T and B cells in the developing immune tissues of the stripe-faced dunnart (Sminthopsis macroura).
This paper describes the initial appearance and distribution of mature T and B cells in the developing immune tissues of the stripe-faced dunnart (Sminthopsis macroura) based on the use of species cross-reactive antibodies to the lymphocyte cell surface markers CD3, CD5 and CD79b. At birth no mature T or B cells were detected in the liver or bone marrow using anti-CD3, anti-CD5 or anti-CD79b antibodies. T cells were detected in the thymus with anti-CD3 by day 12 and anti-CD5 by day 50 postpartum, and T cells in the spleen were detected by day 43 and day 80 postpartum using anti-CD3 and anti-CD5, respectively. B cells were observed in the dunnart spleen by 43 days after birth. CD3- and CD79b-positive cells were detected in the lymph nodes by 50 days and CD5 by day 15 after birth, and in the gut-associated lymphoid tissues by day 50 and anti-CD5 by day 57 postpartum. The development and distribution of T and B cells in the immune tissues of dunnart pouch young is similar to that described in other marsupial species. Low numbers or absence of mature lymphocytes in immune tissues of early pouch young dunnarts further support the proposition that young marsupials are reliant on non-specific defence strategies and/or maternal strategies for a significant period of their time of development in the pouch.


The neuropsychology of antisocial personality disorder.
The literature on executive function in antisocial populations is unclear due to variation in diagnostic criteria and variation in the inclusion of healthy control comparison groups. Some studies suggest prototypical psychopathy is associated with specific deficits in ventromedial prefrontal (VMPFC) function rather than dorsolateral prefrontal (DLPFC). Meta-analytical studies, however, suggest that antisocial personality disorder may be associated with a broader range of executive deficits. This study assessed DLPFC and VMPFC function in antisocial personality disorder subjects and controls using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a Go/NoGo task respectively. All subjects were screened for Axis I pathology, substance misuse and prescribed medication. The performance of 29 subjects with antisocial personality disorder DSM-IV and 20 male right-handed controls (matched for age and IQ) on the neuropsychological test battery was compared. Subjects with antisocial personality disorder displayed impairments on DLPFC executive function tasks of planning ability and set shifting. Impairments were also seen in VMPFC Go/NoGo tasks and in visual memory tasks. Antisocial personality disorder is associated with a broad range of deficits in DLPFC and VMPFC function. Future studies need to examine relationships between the interpersonal and behavioural components of antisocial personality disorder and neuropsychological function.


[Design and development of hydroxypropyl methycellulose (HPMC) based polymeric films of methotrexate: physicochemical and pharmacokinetic evaluations].
The present investigation was aimed to evaluate the possibility of using different concentrations and polymeric grades of hydroxypropyl methylcellulose (K4M, K15M and K100M) for transdermal delivery of methotrexate, an immunosuppressant drug for rheumatoid arthritis. The matrix films were evaluated for their physicochemical characterization followed by in vitro and in vivo evaluation. Selected formulations were subjected for their in vivo studies on healthy rabbits following balanced incomplete block design. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2), K(el), and MRT) were evaluated statistically. The thickness and weight of the patch increased with the increase in polymeric grade and content. Fourier transform infrared spectroscopy and differential scanning calorimetry results confirm that there is no interaction between drug and polymer used. X-ray diffraction study reveals an amorphous state of drug in the matrix films. The in vitro drug release followed Higuchi kinetics (r=0.972-997; p<0.001) as its coefficient of correlation values predominates over zero order and first order release kinetics. In vitro dissolution profiles and pharmacokinetic parameters showed a significant difference between test products (p<0.01), but not within test products. A quantitatively good correlation was found between per cent of drug absorbed from the transdermal patches and AUC((s)). A significant in vitro/in vivo correlation was observed when per cent drug released was correlated with serum drug concentration. Out of the various formulations made, the selected formulations are better in their in vitro dissolution and pharmacokinetic characteristics and thus hold potential for transdermal delivery.


Ricinus communis L. (castor bean) as a potential candidate for revegetating industrial waste contaminated sites in peri-urban Greater Hyderabad: remarks on seed oil.
Ricinus communis L. (castor bean or castor oil plant) was found growing on metal-contaminated sites (4) of peri-urban Greater Hyderabad comprises of erstwhile industrial areas viz Bollaram, Patancheru, Bharatnagar, and Kattedan industrial areas. During 2013-2017, about 60 research papers have appeared focusing the role of castor bean in phytoremediation of co-contaminated soils, co-generation of biomaterials, and environmental cleanup, as bioenergy crop and sustainable development. The present study is focused on its use as a multipurpose phytoremediation crop for phytostabilization and revegetation of waste disposed peri-urban contaminated soils. To determine the plant tolerance level, metal accumulation, chlorophyll, protein, proline, lipid peroxidation, oil content, and soil properties were characterized. It was noticed that the castor plant and soils have high concentration of metals such as cadmium (Cd), lead (Pb), iron (Fe), manganese (Mn), and zinc (Zn). The soils have high phosphorous (P), adequate nitrogen (N), and low concentration of potassium (K). Iron (Fe) concentrations ranged from1672±50.91 to 2166±155.78 mg kg-1 in the soil. The trend of metal accumulation Fe>Zn>Mn>Pb>Cd was found in different plant parts at polluted sites. The translocation of Cd and Pb showed values more than one in industrial areas viz Bollaram, Kattedan, and Bharatnagar indicating the plants resistance to metal toxicity. Chlorophyll and protein content reduced while proline and malondialdehyde increased due to its tolerance level under metal exposure. The content of ricinoleic acid was higher, and the fatty acids composition of polluted areas was almost similar to that of the control area. Thus, R. communis L. can be employed for reclamation of heavy metal contaminated soils.


Differential distribution of excitatory amino acid receptors on embryonic rat spinal cord neurons in culture.
1. Excitatory amino acid (EAA) receptors mediate synaptic transmission in many areas of the vertebrate CNS. To map the distribution of the EAA receptors, three agonists selective for EAA receptor subtypes [kainate, quisqualate, and N-methyl-D-aspartate (NMDA)] were applied by pressure to the cell bodies and neurites of voltage-clamped, embryonic rat spinal cord neurons in culture. 2. Current loss along the neurite between the site of activation and the recording electrode at the soma was estimated independently of variations in receptor density by focal application of high [K+] solution. This estimate was used to compensate agonist-evoked responses for current loss due to leak. K(+)-evoked current amplitudes progressively decreased as applications were made at more distal positions along the neurite. 3. Response amplitudes to EAAs showed a monotonic decay, similar to that with high [K+] solution, in only a few of the cells tested with each agonist. The majority of neurons had areas of high agonist sensitivity along the neurites, implying a nonuniform density of receptors. Such regions sometimes occurred at the most proximal segment of the neurite. Most neurites had distal regions of agonist sensitivity that ranged from 40 to 300% higher than at the soma. 4. The relative distributions of the three EAA receptors were compared by applying two agonists to the same sites along neurites and observing variations in normalized response amplitudes. When comparing NMDA versus non-NMDA receptor distributions on the same neurite, approximately 40% of the cells had similar patterns to two agonists, and the remaining 60% had different patterns. When sensitivity to the two non-NMDA agonists kainate and quisqualate were compared, about one-half of the cells tested had different patterns of agonist sensitivity. 5. Areas of high sensitivity persisted after block of calcium channels by addition of La3+ to the bath solution and after prevention of evoked transmitter release by a low [Ca2+]/high [Mg2+] solution. 6. These results show that spinal cord neurons can have regions of high agonist sensitivity to NMDA, kainate, and quisqualate along their neurites and that the sensitivity to any one of the EAA receptor subtypes can be elevated independently of the others.


Fluorescent treponemal antibody-absorption double-staining procedure.
The fluorescent treponemal antibody-absorption double-staining step-by-step procedure and proposed reference reagents for the test are described. The test and reagents were evaluated in two separate laboratories on 265 fresh sera, and test results were compared with the reference fluorescent treponemal antibody-absorption test results performed in a third laboratory. The data indicate that the tests are comparable in the areas where the test is recommended for use. Problems with inadequate light filtration occurred, but these could be resolved. This test is recommended for use with microscopes equipped with incident illumination.


A modified electronic key feature examination for undergraduate medical students: validation threats and opportunities.
The purpose of our study was the development and validation of a modified electronic key feature exam of clinical decision-making skills for undergraduate medical students. Therefore, the reliability of the test (15 items), the item difficulty level, the item-total correlations and correlations to other measures of knowledge (40 item MC-test and 580 items of German MC-National Licensing Exam, Part II) were calculated. Based on the guidelines provided by the Medical Council of Canada, a modified electronic key feature exam for internal medicine consisting of 15 key features (KFs) was developed for fifth year German medical students. Long menu (LM) and short menu (SM) question formats were used. Acceptance was assessed through a questionnaire. Thirty-seven students from four medical schools voluntarily participated in the study. The reliability of the key feature exam was 0.65 (Cronbach's alpha). The items' difficulty level scores were between 0.3 and 0.8 and the item-total correlations between 0.0 and 0.4. Correlations between the results of the KF exam and the other measures of knowledge were intermediate (r between 0.44 and 0.47) as well as the learners' level of acceptance. The modified electronic KF examination is a feasible and reliable evaluation tool that may be implemented for the assessment of clinical undergraduate training.


Efficacy of Oral Recombinant Methioninase and Eribulin on a PDOX Model of Triple-negative Breast Cancer (TNBC) Liver Metastasis.
The aim of the present study was to identify effective drugs for a highly-aggressive liver-metastasis of triple-negative breast cancer (TNBC) in a patient-derived orthotopic xenograft (PDOX) mouse model. Drugs tested were oral recombinant methioninase (o-rMETase), low-dose eribulin and their combination. Patient-derived TNBC was implanted in the liver of nude mice by surgical hepatic implantation. Two weeks after transplantation, 32 mice were randomized (n=8 per group) into a phosphate-buffered saline vehicle-control group; o-rMETase-treatment group (100 units, o-rMETase, oral, daily for 2 weeks); eribulin-treatment group (0.05 mg/kg intraperitoneally once per week for 2 weeks); or combination-treatment group (100 units r-METase, oral, daily for 2 weeks + 0.05 mg/kg eribulin intraperitoneally once per week for 2 weeks). After 2 weeks, the three treatment groups exhibited significantly-inhibited TNBC growth in the liver compared to the vehicle-control group (p≤0.05). o-rMETase and low-dose eribulin monotherapy and their combination were efficacious against the highly-aggressive TNBC PDOX growing in the liver. The TNBC PDOX model can be used to identify highly-effective drugs for therapy of TNBC with liver metastasis.


Longitudinal changes of cardiotocographic parameters throughout pregnancy: a prospective cohort study comparing small-for-gestational-age and normal fetuses from 24 to 40 weeks.
To compare longitudinal trends of cardiotocographic (CTG) parameters between small-for-gestational-age (SGA) and normal fetuses, from 24 to 41 weeks of pregnancy. A prospective cohort study was carried out in singleton pregnancies without fetal malformations. At least one CTG was performed in each of the following intervals: 24-26 weeks+6 days, 27-29 weeks+6 days, 30-32 weeks+6 days, 33-35 weeks+6 days, 36-38 weeks+6 days and ≥39 weeks. Tracings were analyzed using the Omniview-SisPorto® 3.6 system. Cases with a normal pregnancy outcome, including a birthweight ≥10th percentile for gestational age, were compared with two groups of SGA fetuses: with birthweight <10th percentile (SGA<p10) and <3rd percentile (SGA<p3; a subgroup of the latter). Generalized linear mixed-effects models were used for analysis. A total of 176 fetuses (31 SGA) and 1256 tracings (207 from SGA fetuses) were evaluated. All CTG parameters changed significantly throughout pregnancy in the three groups, with a decreasing baseline and probability of decelerations, and an increasing average long-term variability (LTV), average short-term variability (STV) and accelerations. Baseline showed a more pronounced decrease (steeper slope) in SGA fetuses, being higher in these cases at earlier gestational ages and lower later in pregnancy. Average LTV was significantly lower in SGA<p3 fetuses, but a parallel increase occurred in all groups. There was a considerable inter-fetal variability within each group. A unique characterization of CTG trends throughout gestation in SGA fetuses was provided. A steeper descent of the baseline was reported for the first time. The findings raise the possibility of clinical application of computerized CTG analysis in screening and management of fetal growth restriction.


Physics of Transcranial Direct Current Stimulation Devices and Their History.
Transcranial direct current stimulation (tDCS) devices apply direct current through electrodes on the scalp with the intention to modulate brain function for experimental or clinical purposes. All tDCS devices include a current controlled stimulator, electrodes that include a disposable electrolyte, and headgear to position the electrodes on the scalp. Transcranial direct current stimulation dose can be defined by the size and position of electrodes and the duration and intensity of current applied across electrodes. Electrode design and preparation are important for reproducibility and tolerability. High-definition tDCS uses smaller electrodes that can be arranged in arrays to optimize brain current flow. When intended to be used at home, tDCS devices require specific device design considerations. Computational models of current flow have been validated and support optimization and hypothesis testing. Consensus on the safety and tolerability of tDCS is protocol specific, but medical-grade tDCS devices minimize risk.


Tm3+ Ion Blue Emission Quenching by Pd2+ Ions in Barium Phosphate Glasses: Fundamental Analysis toward Sensing Applications.
The quenching effect of Pd2+ ions on the blue emission from Tm3+ was investigated for the first time using barium phosphate glass as model matrix. Glasses containing fixed Tm2O3 at 0.5 mol % and PdO up to 0.3 mol % (added relative to P2O5) were prepared by melting and first characterized for basic structural properties by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. Thermal properties were then evaluated by differential scanning calorimetry (DSC). The focus was thereafter on evaluating the optical properties by absorption and photoluminescence (PL) spectroscopy with decay kinetics assessment. XRD confirmed the amorphous nature of the glasses synthesized. The vibrational spectroscopy assessment consistently exhibited the IR- and Raman-active bands characteristic of phosphate glasses, showing no significant variation with PdO codoping. The DSC analysis revealed all glasses possessed high thermal stability assessed by the differences (ΔT = Tg - Tx ≥ 154 °C) between glass transition temperatures (Tg) and onset of crystallization (Tx). A tendency of the Tg values to increase with PdO contents was however exhibited. In addition, specific enthalpies of crystallization showed magnitudes decreasing with increasing PdO concentration, thus suggesting crystallization suppression by Pd2+. Concerning the optical properties, it was observed that codoping the glasses with PdO (0.1-0.3 mol %) led to the development of the visible Pd2+ d-d absorption band (peak ≈415-410 nm). In addition, drastic PL quenching of the Tm3+ blue emission around 452 nm (1D2 → 3F4 transition) was induced by Pd2+. Analyzing PL decay curves obtained by exciting Tm3+ ions at 359 nm while monitoring 452 nm emission revealed decreased 1D2 state lifetimes. Thus, a potential of Tm3+ for analytical sensing of Pd2+ in various matrices was suggested. Ultimately determining quenching constants from the PL data and based on the comparison of results from emission intensity and decay rates, likely Tm3+ → Pd2+ energy transfer processes underlying the PL quenching were proposed.


Endoscopic ultrasonography in pancreatic disease.
Endoscopic ultrasound has emerged as an important modality for management of pancreatic disease because of its ability to provide high frequency images of the pancreatic ducts and the parenchyma. Development of interventional techniques under endosonographic guidance has further advanced the potential use of this technique in pancreatic disorders. This paper shows and reviews the current knowledge on endoscopic ultrasound in pancreatic imaging.


Effects of pentoxifylline on inflammatory cytokine expression and acute pleuropneumonia in swine.
Pentoxifylline, a methylxanthine derivative and nonspecific type 4 phosphodiesterase inhibitor, has been used to improve survival of animals with sepsis and to attenuate lung injury in acute lung inflammation. The purpose of this study was to examine whether pentoxifylline would inhibit the expression of inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae--induced elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in vitro. Pentoxifylline therapy in vivo significantly reduced the number of band neutrophils in swine but did not reduce the pathology associated with pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline and its metabolites in pig sera suggested that efficacious doses of pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and tremors. These results suggest that pentoxifylline is an effective pharmacological tool for the dissection of cytokine regulation in vitro, but inhibitory concentrations may not be achievable for in vivo pharmacological use in swine.