Yolk sac tumor with a prominent polyvesicular vitelline pattern: a report of three cases.
We report 3 cases of the rare polyvesicular vitelline variant of ovarian yolk sac tumor (YST). The patients were 23, 29, and 43 years old, and all presented with large unilateral adnexal masses confined to the ovary. One tumor was predominantly cystic, and the other 2 had prominent cystic components; all 3 also had solid components. Microscopic examination of the cystic regions showed dilated cysts that largely effaced the stroma resulting in a honeycomb-like appearance. The solid foci were characterized predominantly by small tubules in a fibrous stroma; the tubules exhibited variably conspicuous cystic dilatation to merge with the microcystic appearance. The tumor cells varied from large and primitive-appearing to flattened and deceptively innocuous when lining large cysts. They were immunoreactive for α-fetoprotein and glypican-3. Non-polyvesicular vitelline components of YST were present focally in 2 cases (hepatoid in one, reticular and endometrioid like in the second). Two patients are disease free after 20 and 26 years, respectively; disease-free follow-up is of short duration in the third case (2 years). The good long-term outcome in 2 cases supports prior evidence that suggests that the natural history of this form of YST may be more indolent than conventional forms of the tumor.


Nerve graft prefabrication: preliminary study.
This study aimed to produce prefabricated nerve graft as effective as autologous nerve graft without donor site morbidity for repairing segmental nerve defects. Thirty rats were used and were separated into three groups. In the first group, vein graft excised from jugular vein was sutured to make a bridge between epineural gaps of tibial and peroneal nerve. In the second group, one-quarter of the nerve diameter was incised after excision of the epineurial sheath, and the vein graft was sutured between epineurial gaps. In the third group, the vein graft was sutured between epineurial gaps, and plasmid including vascular endothelial growth factor (VEGF) gene were injected into muscle next to the nerve. Functional and morphological assessments were performed at the end of the 8 weeks. We prefabricated nerve graft by using autologous vein as a conduit material between two intact nerves and by gene therapy, which increases the VEGF level in the medium.


Usefulness of diffusion tensor tractography in pediatric epilepsy surgery.
This study was conducted to assess the clinical relevance of diffusion tensor tractography (DTT) in pre- and post-operative evaluations of childhood epilepsy surgery. Seventy-two patients who received epilepsy surgery between March 2004 and July 2008 were retrospectively analyzed (M : F=40 : 32, ages of 3 months to 24 years, mean age=8.9 years). DTT was performed using a 3.0 T scanner and single-shot spin-echo echo-planar imaging with 32-different diffusion gradient directions. We reviewed the data focusing on the type of surgery, final pathological diagnosis, and how the DTT data were clinically used. The most common form of childhood epilepsy surgery was complete resection of an epileptogenic lesion (n=52, 72.2%). The reported etiologies included cortical dysplasia (n=32, 44.4%), hippocampal sclerosis (n=9, 12.5%), brain tumors (n=7, 9.7%), and non-pathologic lesions (n=4, 5.6%) in the final diagnoses. Twenty-one dysplastic cortexes and four brain tumors involved an approximal relationship with the corticospinal tract (n=18), optic radiation (n=2), and arcuate fasciculus (n=5). Additionally, although DTT demonstrated white matter tracts clearly, DTT in the hippocampal sclerosis did not provide any additional information. In cases of callosotomy (n=18, 25%), post-operative DTT was utilized for the evaluation of complete resection in all patients. DTT information was not used in functional hemispherectomy (n=2, 2.8%). Preoperatively, DTT was a useful technique in cases of cortical dysplasia and brain tumors, and in cases with callosotomy, postoperatively. DTT should be included among the routine procedures performed in management of epilepsy.


Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.
Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019. We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale. Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8). We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality. Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days. Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty.


Ginsenoside Rb1 Attenuates High Glucose-Induced Oxidative Injury via the NAD-PARP-SIRT Axis in Rat Retinal Capillary Endothelial Cells.
(1) Aims: The present study aimed to observe the effects of Ginsenoside Rb1 on high glucose-induced endothelial damage in rat retinal capillary endothelial cells (RCECs) and to investigate the underlying mechanism. (2) Methods: Cultured RCECs were treated with normal glucose (5.5 mM), high glucose (30 mM glucose), or high glucose plus Rb1 (20 μM). Cell viability, lactate dehydrogenase (LDH) levels, the mitochondrial DNA copy number, and the intracellular ROS content were measured to evaluate the cytotoxicity. Superoxide dismutase (SOD), catalase (CAT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), poly(ADP-ribose) polymerase (PARP), and sirtuin (SIRT) activity was studied in cell extracts. Nicotinamide adenine dinucleotide (NAD+)/NADH, NADPH/NADP+, and glutathione (GSH)/GSSG levels were measured to evaluate the redox state. The expression of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), SIRT1, and SIRT3 was also evaluated after Rb1 treatment. (3) Results: Treatment with Rb1 significantly increased the cell viability and mtDNA copy number, and inhibited ROS generation. Rb1 treatment increased the activity of SOD and CAT and reduced the activity of NOX and PARP. Moreover, Rb1 enhanced both SIRT activity and SIRT1/SIRT3 expression. Additionally, Rb1 was able to re-establish the cellular redox balance in RCECs. However, Rb1 showed no effect on NMNAT1 expression in RCECs exposed to high glucose. (4) Conclusion: Under high glucose conditions, decreases in the reducing power may be linked to DNA oxidative damage and apoptosis via activation of the NMNAT-NAD-PARP-SIRT axis. Rb1 provides an advantage during high glucose-induced cell damage by targeting the NAD-PARP-SIRT signaling pathway and modulating the redox state in RCECs.


QTL Mapping of Adult-Plant Resistance to Leaf and Stripe Rust in Wheat Cross SW 8588/Thatcher using the Wheat 55K SNP Array.
Wheat leaf rust (caused by Puccinia triticina) and stripe rust (caused by Puccinia striiformis f. sp. tritici) cause large production losses in many regions of the world. The objective of this study was to identify quantitative trait loci (QTL) for resistance to leaf rust and stripe rust in a recombinant inbred line population derived from a cross between wheat cultivars SW 8588 and Thatcher. The population and parents were genotyped with the Wheat 55K SNP Array and SSR markers and phenotyped for leaf rust severity at Zhoukou in Henan Province and Baoding in Hebei Province. Stripe rust responses were also evaluated at Chengdu in Sichuan Province, and at Baoding. Seven and six QTL were detected for resistance to leaf rust and stripe rust, respectively. Four QTL on chromosomes 1BL, 2AS, 5AL, and 7BL conferred resistance to both rusts. The QTL on 1BL and 2AS were identified as Lr46/Yr29 and Lr37/Yr17, respectively. QLr.hebau-2DS from Thatcher, identified as Lr22b that was previously thought to be ineffective in China, contributed a large effect for leaf rust resistance. QLr.hebau-5AL/QYr.hebau-5AL, QLr.hebau-3BL, QLr.hebau-6DS, QYr.hebau-4BS, and QYr.hebau-6DS are likely to be new QTL, but require further validation. Kompetitive allele-specific PCR (KASP) markers for QLr.hebau-2DS and QLr.hebau-5AL/QYr.hebau-5AL were successfully developed and validated in a diverse wheat panel from Sichuan Province, indicating their usefulness under different genetic backgrounds. These QTL and their closely linked SNP and SSR markers will be useful for fine mapping, candidate gene discovery, and marker-assisted selection in breeding for durable resistance to both leaf and stripe rusts.


Donepezil increases resistance to induced seizures in a mouse model of Dravet syndrome.
De novo loss-of-function mutations in SCN1A are the main cause of Dravet syndrome, a catastrophic encephalopathy characterized by recurrent early-life febrile seizures, a number of other afebrile seizure types that are often refractory to treatment, and behavioral abnormalities including social deficits, motor dysfunction, and cognitive impairment. We previously demonstrated that the reversible acetylcholinesterase inhibitor, Huperzine A, increases seizure resistance in Scn1a mutants. In the present study, we evaluated the therapeutic potential of donepezil, a reversible acetylcholinesterase inhibitor approved by the Food and Drug Administration, in a mouse model of Dravet syndrome (Scn1a+/- ). We found that donepezil conferred robust protection against induced seizures in Scn1a+/- mutants.


Transcranial alternating current stimulation (tACS) at 40 Hz enhances face and object perception.
Neurophysiological evidence suggests that face and object recognition relies on the coordinated activity of neural populations (i.e., neural oscillations) in the gamma-band (>30 Hz) range over the occipito-temporal cortex. To test the causal effect of gamma-band oscillations on face and object perception we applied transcranial Alternating Current Stimulation (tACS) in healthy volunteers (N = 60). In this single-blind, sham-controlled study, we examined whether the administration of offline tACS at gamma-frequency (40 Hz) over the right occipital cortex enhances performance of perception and memory of face and object stimuli. We hypothesized that gamma tACS would enhance the perception of both categories of visual stimuli. Results, in line with our hypothesis, show that 40 Hz tACS enhanced both face and object perception. This effect is process-specific (i.e., it does not affect memory), frequency-specific (i.e., stimulation at 5 Hz did not cause any behavioural change), and site-specific (i.e., stimulation of the sensory-motor cortex did not affect performance). Our findings show that high-frequency tACS modulates human visual perception, and it is in line with neurophysiological studies showing that the perception of visual stimuli (i.e., faces and objects) is mediated by oscillations in the gamma-band range. Furthermore, this study adds insight about the design of effective neuromodulation protocols that might have implications for interventions in clinical settings.


Does the pressor response to ischemic exercise improve blood flow to contracting muscles in humans?
The purpose of this study was to determine in humans 1) the gain for the reflex pressor response that occurs when perfusion pressure to rhythmically contracting muscles is reduced and 2) whether the pressor response improves blood flow to the contracting muscles. Six normal subjects performed light, moderate, and heavy rhythmic forearm contractions (30/min) with the forearm enclosed in a Plexiglas box. Pressure in the box was increased 10 mmHg each minute up to 50 mmHg to reduce transmural pressure in the arterial system of the forearm. Mean arterial pressure (MAP) was measured continuously. During light exercise no reflex increase in MAP occurred until box pressure was 50 mmHg. During moderate and heavy exercise MAP began to increase with only 10- to 20-mmHg increases in box pressure. The slope of this increase was 3.5-3.9 mmHg per 10 mmHg of box pressure (approximately 60% of that in dogs). In a further study on six subjects a deep vein draining the active forearm muscles was cannulated and deep venous O2 saturation measured to assess how a 50-mmHg increase in box pressure and subsequent reflex increase in MAP altered blood flow to the contracting muscles during heavy rhythmic exercise. The increase in box pressure reduced blood flow to contracting forearm muscles by 20-25% and was followed by a 19-mmHg increase in MAP that did not appear to improve perfusion of the active muscles. This finding was unexpected, because studies in dogs suggest that the pressor response to rhythmic exercise with restricted muscle blood flow can improve perfusion of the active muscles.(ABSTRACT TRUNCATED AT 250 WORDS)


Noncovalent functionalization of graphene with a Ni(II) tetraaza[14]annulene complex.
The few-layer graphene, produced by exfoliation of graphite in 4-methylanisole, was noncovalently functionalized with the Ni(ii) complex of 5,7,12,14-tetramethyldibenzo-1,4,8,11-tetraazacyclotetradeca-3,5,7,10,12,14-hexaene (Ni(ii)-tetramethyldibenzotetraaza[14]annulene, or NiTMTAA), which is a simple model of more complex porphyrins and phthalocyanines. The resulting hybrid materials with different content of NiTMTAA were characterized by means of thermogravimetric analysis, scanning and transmission electron microscopy (SEM and TEM, respectively), atomic force microscopy (AFM), energy dispersive X-ray, Fourier-transform infrared (FTIR), Raman and UV-visible spectroscopy, as well as fluorescence and conductivity measurements. Additional information on the mechanisms of NiTMTAA interaction with graphene was obtained from density functional theory (DFT) and molecular mechanics (MM) calculations. Both experimental and theoretical results suggest that NiTMTAA forms a full double-sided adsorption layer on the graphene surface. The presence of NiTMTAA molecules in the hybrid materials obtained manifests itself in the appearance of characteristic bands in all types of electromagnetic spectra recorded; in FTIR, they are relatively weak as compared to graphene absorption bands, but dominate in Raman spectra. The morphology of the nanohybrids observed by SEM, TEM and AFM, as well as their electrical conductivity, depends on the NiTMTAA content. According to the results of DFT calculations of NiTMTAA adsorption on different graphene models, flat orientation of the complex with respect to graphene is energetically preferable, with a little difference depending on whether benzo or methyl groups contact the sheet.


Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation.
Nearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario. To establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation. This longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018. Discontinuation of antidepressants. Relapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model. A total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n = 74) compared with controls (n = 34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d = 0.52; P = .02), particularly for those who later relapsed after discontinuation of antidepressants (n = 21) compared with those who did not relapse (n = 39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d = 0.77; P < .001). This slower decision time predicted relapse (accuracy = 0.66; P = .007). Patients invested less effort than healthy controls for rewards (F1,98 = 33.970; P < .001). Computational modeling identified a mean (SD) deviation from standard drift-diffusion models that was more prominent for patients than controls (patients, 0.67 [1.56]; controls, -0.71 [1.93]; Cohen d = 0.82; P < .001). Patients also showed higher mean (SD) effort sensitivity than controls (patients, 0.31 [0.92]; controls, -0.08 [1.03]; Cohen d = 0.51; P = .05). Relapsers differed from nonrelapsers in terms of the evidence required to make a decision for the low-effort choice (mean [SD]: relapsers, 1.36 [0.35]; nonrelapsers, 1.17 [0.26]; Cohen d = 0.65; P = .02). Group differences generally did not reach significance in the smaller replication sample (27 patients and 21 controls), but decision time prediction models from the main sample generalized to the replication sample (validation accuracy = 0.71; P = .03). This study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.


The role of cyclin Y in normal and pathological cells.
The family protein of cyclins, as well as cyclin-dependent kinases (CDKs) cooperating with them, are broadly researched, as a matter of their dysfunction may lead to tumor transformation. Cyclins are defined as key regulators that have a controlling function of the mammalian nuclear cell divides. Cyclin Y (CCNY) is a recently characterized member of the cyclin family and was first identified from the human testis cDNA library. It is an actin-binding protein acting through decreased actin dynamics at a steady state and during glycine-induced long-term potentiation (LTP) and involves the inhibition of cofilin activation. What is more, CCNY is a positive regulatory subunit of the CDK14/PFTK1 complexes affected by the activation of the Wnt signaling pathway in the G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6. The expression of CCNY has been significantly mentioned within the cell migration and invasion activity both in vivo and in vitro. The aim of this review is evaluation of the expression of CCNY in the physiology processes and compare the expression of this protein in cancer cells, taking into account the impact of the level of expression on tumor progression.


Surface plasmon microcavity for resonant transmission through a slit in a gold film.
We demonstrate the use of a compact surface plasmon (SP) microcavity formed in a 300 nm thick gold film to resonantly enhance the optical transmission through a subwavelength slit. Focussed ion beam milling is used to create 200 nm deep SP microcavities, with widths between 800 nm to 1300 nm, each with a 180 nm slit in its center. The experimentally-measured TM polarized optical transmission has a wavelength-dependent peak that has similarities with finite-difference time-domain calculations in terms of peak-position and enhancement factors of peak transmission. The calculations show, by observing the near-field distributions, the interaction between the SP microcavity standing waves and the slit to create enhanced transmission. The SP microcavity demonstrated here is easily fabricated and may be optimized for future applications in surface-enhanced Raman scattering, nonlinear optics and surface plasmon resonance sensors.


Inclement weather and the risk of hip fracture.
An association between inclement weather and hip fractures has been documented, but specific subgroups of the population at particular risk have not been identified. We obtained information that included hospitalization data on all hip fractures in Montreal from 1982 to 1992, and meteorologic data on the amount of snow, rain, and freezing rain and the temperature on each day of study. We used a cross-level design to examine the association between the rate of hip fractures and the meteorologic conditions on the day of the accident in both sexes and five age strata. There were a total of 18,455 hip fractures over the 4,018-day study period. We found a cyclical pattern in occurrence of hip fractures, with the peak occurring in mid-December among women and the first week of January among men. The pattern was less pronounced among women than men, with peak-to-trough ratios of 1.2 and 1.4, respectively. Days with lower temperatures, snow, and freezing rain were associated with increased rates of hip fracture. The meteorologic condition carrying the greatest risk was freezing rain. The association between inclement weather and hip fractures was stronger among younger persons, both women and men. After adjusting for meteorologic variables, there remained increases in winter of 5% among women and 12% among men. The residual effect of winter may be related to cold temperatures or due to an accumulation of ice and snow even on fine days. Other possible mechanisms to explain the residual effect of winter include slower reaction times and winter bone loss, both of which could affect indoor as well as outdoor falls.


BCA2/Rabring7 Interferes with HIV-1 Proviral Transcription by Enhancing the SUMOylation of IκBα.
BCA2/Rabring7 is a BST2 cofactor that promotes the lysosomal degradation of trapped HIV-1 virions but also functions as a BST2-independent anti-HIV factor by targeting Gag for lysosomal degradation. Since many antiviral factors regulate the NF-κB innate signaling pathway, we investigated whether BCA2 is also connected to this proinflammatory cascade. Here, we show for the first time that BCA2 is induced by NF-κB-activating proinflammatory cytokines and that upregulation of BCA2 provides regulatory negative feedback on NF-κB. Specifically, BCA2 serves as an E3 SUMO ligase in the SUMOylation of IκBα, which in turn enhances the sequestration of NF-κB components in the cytoplasm. Since HIV-1 utilizes NF-κB to promote proviral transcription, the BCA2-mediated inhibition of NF-κB significantly decreases the transcriptional activity of HIV-1 (up to 4.4-fold in CD4+ T cells). Therefore, our findings indicate that BCA2 poses an additional barrier to HIV-1 infection: not only does BCA2 prevent assembly and release of nascent virions, it also significantly restricts HIV-1 transcription by inhibiting the NF-κB pathway.IMPORTANCE Understanding the interactions between HIV-1 and its host cells is highly relevant to the design of new drugs aimed at eliminating HIV-1 from infected individuals. We have previously shown that BCA2, a cofactor of BST2 in the restriction of HIV-1, also prevents virion assembly in a BST2-independent manner. In this study, we found that BCA2 negatively regulates the NF-κB pathway-a signaling cascade necessary for HIV-1 replication and infectivity-which in turn detrimentally affects proviral transcription and virus propagation. Thus, our results indicate that, besides its previously described functions as an antiviral factor, BCA2 poses an additional barrier to HIV-1 replication at the transcriptional level.


[Present-day sociomedical problems of orphans].
The specific features of physical and mental development, health status, and lifestyle were found in orphans of sensitive age under the present socioeconomic conditions. The specific features of the adaptive capacities were first studied in these children. Abnormalities in the physical development and health status of orphans were shown to form under their institutional conditions of life, nutrition, and education, and upbringing. Guidelines for medical workers of orphan's institutions and for workers of sanitary-and-epidemiological service are substantiated.


Post Market Clinical Follow up Results of the Steady State Coherent Bio-modulator Patch for tinnitus.
To follow up with a survey for the safety and performance of the coherent biomodulator patch as a device for tinnitus when in clinical use. A survey with 20 questions was emailed to device users a few weeks after fulfilled treatment. Collected data from 927 responders from February 2017 to July 2020 was exported and analyzed. The treatment time was 3 weeks, and the patches were changed daily and placed behind one year. The analysis was performed in order to investigate the possibility of subgroups and if the effect of one or more treatments are different, and is the relief dependent on how long the users have had troublesome tinnitus, the age of the user, and the severity of the tinnitus. Most users were 45 years and older with a gender ratio of 1.65 men vs women. In general, the users reported highly bothersome tinnitus with 82% answering frequently to a lot before treatment. This follow up survey showed that 33% experienced any kind of improvement. The majority of those that reported improvement came from the subgroup of 4-10 years suffered from tinnitus. A very low frequency of side-effects was reported with no new risks or unexpected issues. When considering the intended purpose of the steady state coherent biomodulator and the provided information in this survey, the device remains suitable for the intended tinnitus users.


One-step electrodeposition to layer-by-layer graphene-conducting-polymer hybrid films.
One-step fabrication of graphene-polyaniline (graphene-PANI) hybrid film was facilely achieved by cyclic voltammetric electrolysis of a bath containing both graphene oxide (GO) and aniline, where graphene is obtained by electrochemical reduction of GO and PANI is simultaneously obtained by aniline electropolymerization. As there is no strong attraction between aniline and GO under the electrodeposition conditions, the independent depositions of PANI and reduced GO nanosheets at their greatly differed potentials led to alternate layered graphene-PANI films, with the topmost layer being PANI particles or graphene sheets just by changing the initial scan directions. The two kinds of graphene-PANI hybrid films present excellent but different electrical and electrochemical behaviors.


Cytological examination of the thyroid in children and adolescents after the Fukushima Nuclear Power Plant accident: the Fukushima Health Management Survey.
The Fukushima Daiichi Nuclear Power Plant accident occurred on March 11 2011, following the Great East Japan Earthquake and tsunami. Radioactive materials, including I-131, were released into the environment after the accident. Shortly after, the prefectural government initiated the Fukushima Health Management Survey for monitoring the long-term health conditions of the residents of Fukushima Prefecture. In the survey, thyroid ultrasonography was scheduled for all people aged 18 years or younger who were living in Fukushima Prefecture at the time of disaster. The total number of examinees was approximately 370,000 in the Preliminary Baseline Survey (PBLS), and 380,000 in the first Full-scale Survey (FSS). First, thyroid ultrasonography was performed as the Primary Examination. When a thyroid nodule that meets the fine needle aspiration cytology (FNAC) guideline is detected, thyroid FNAC is performed. By the end of June 2017, the cytological specimens of 187 examinees had been interpreted as Malignant or Suspicious for Malignancy (SFM). In this article, the cytological results of whole categories are presented using the criteria of The Bethesda System for Reporting Thyroid Cytopathology. The total numbers of examinees with SFM or Malignant in PBLS and at the first FSS were 106 (62.0%) and 71 (38.0%), respectively. The data of the cytological results of SFM and Malignant were already reported. However, this is the first report of cytological data from categories other than SFM and Malignant. The results of the current study will contribute to future research into the thyroid conditions of children and adolescents.


[Thermodynamic models of binding ligands to nucleic acids].
Models of adsorption were considered, which describe the binding of biologically active ligands on DNA templates. The binding is described most comprehensively and in greatest detail by the distribution function, which determines the probability of detecting the preset number of adsorbed ligands on the template. In the case of noncooperative binding, this function corresponds to the Gaussian distribution and is characterized by two quantities: the mean value of the occupation of the template by ligands and the dispersion of occupation. The accuracy of the occupation of the template by ligands is inversely proportional to dispersion. As the length of the template and the number of reaction sites covered by one ligand upon binding increase, the accuracy of the occupation of the template by ligands increases. An important characteristic of binding is the degree of coverage of the template by ligands. This characteristic represents the portion of template reaction sites covered by all ligands adsorbed on the template. If polycations are bound to nucleic acid molecules, the coverage of the template determines the transition of nucleic acids to a compact state. The degree of template coverage for extended ligands depends only slightly on the binding constant in a wide range of concentrations of a free ligand in solution. Different adsorption models are considered from the unified point of view. The classification of cooperative interactions for a wide class of systems is given, from situations when several ligands are bound on nucleic acid templates to a situation when templates change by the action of ligands and begin to interact with each other.


Cytolethal distending toxin (CDT)-negative Campylobacter jejuni strains and anti-CDT neutralizing antibodies are induced during human infection but not during colonization in chickens.
The cytolethal distending toxin (CDT) of Campylobacter jejuni was detectable, using an in vitro assay, in most but not all of 24 strains tested. The reason for the absence of toxin activity in these naturally occurring CDT-negative C. jejuni strains was then investigated at the genetic level. CDT is encoded by three highly conserved genes, cdtA, -B, and -C. In the CDT-negative strains, two types of mutation were identified. The CDT activities of C. jejuni strains possessing both types of mutation were successfully complemented with the functional genes of C. jejuni 11168. The first type of mutation comprised a 667-bp deletion across cdtA and cdtB and considerable degeneration in the remainder of the cdt locus. Using a PCR technique to screen for this deletion, this mutation occurred in fewer than 3% of 147 human, veterinary, and environmental strains tested. The second type of mutation involved at least four nonsynonymous nucleotide changes, but only the replacement of proline with serine at CdtB position 95 was considered important for CDT activity. This was confirmed by site-directed mutagenesis. This type of mutation also occurred in fewer than 3% of strains as determined using a LightCycler biprobe assay. The detection of two CDT-negative clinical isolates raised questions about the role of CDT in some cases of human campylobacteriosis. To determine if anti-CDT antibodies are produced in human infection, a toxin neutralization assay was developed and validated using rabbit antisera. Pooled human sera from infected patients neutralized the toxin, indicating expression and immunogenicity during infection. However, no neutralizing antibodies were detected in colonized chickens despite the expression of CDT in the avian gut as indicated by reverse transcription-PCR.


NMR Self-Diffusion and Transverse Relaxation Time in Bitumen: The Effect of Aging.
In this investigation the dynamics of two types of bitumens with different penetration grade were tested by using dynamic shear rheometry (DSR) and Nuclear Magnetic Resonance (NMR) at unaged conditions, and upon both short- and long-term artificial aging. The gel-sol transition temperature T g e l → s o l * ${{T}_{gel\to sol}^{^{\ast}}}$ was found to increase with increasing the time of aging treatment. Arrhenius parameters of the viscosity were found, unexpectedly, to be correlated with those of simple liquids, suggesting that the two kinds of systems, although chemically and physically quite different, share the same basic process at the molecular level. The molecular dynamics has been then investigated by NMR Pulsed Field Gradient Stimulated-Echo (PFGSE) and relaxometry (Carr-Purcell-Meiboom-Gill, CPMG, spin-echo pulse sequence) to capture the effect of aging upon dynamics variables such as self-diffusion coefficients D and transverse relaxation times T2 . The translational diffusion at T> T g e l → s o l * ${{T}_{gel\to sol}^{^{\ast}}}$ of the light molecular components of both types of bitumens was characterized by broad distributions of D which were found independent of the experimental time scale up to 0.2 s. Similarly, T2 data could be described as a continuous unimodal distributions of relaxation times determined both at T< T g e l → s o l * ${{T}_{gel\to sol}^{^{\ast}}}$ and T> T g e l → s o l * ${{T}_{gel\to sol}^{^{\ast}}}$ .


[Ultrasound diagnosis of Meckel diverticulitis in adults].
Meckel's diverticulitis is a rare disease. In addition to physical examination, abdominal ultrasound can help to pinpoint the diagnosis. By presenting a case report we would like to demonstrate the typical ultrasonographic findings in acute Meckel's diverticulitis and differentiate it from acute appendicitis. A 60-year-old patient was admitted to our hospital with the diagnosis of acute appendicitis. Abdominal ultrasound was performed and a blind ending, liquid-filled segment of small bowel in the right lower quadrant of the abdomen found. This segment was not compressible, no peristalsis was evident, nor was there any anatomical association with the cecum. Locally we found free fluid and hints of inflamed mesenteric fatty tissue. A perforated Meckel's diverticulum was diagnosed and confirmed intraoperatively. The major ultrasonographic difference between an inflamed Meckel's diverticulum and acute appendicitis is its anatomical location. In contrast to the appendix there is no association with the cecum. A diameter of up to 40 mm and a well-defined wall of small bowel with 3 definite layers visible by ultrasound may help to distinguish between a Meckel's diverticulum and the appendix.


Oral immunotherapy with yolk antibodies to prevent infections in humans and animals.
There is an increasing prevalence of antibiotic-resistant bacteria, which makes traditional antibiotics less effective. It is thus important to find an alternative to the use of antibiotics. Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are good producers of specific antibodies. After immunisation, the specific antibodies are transported to the egg yolk from which the antibodies (IgY) can be purified in large quantities. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent both bacterial and viral infections. We have treated one patient with yolk antibodies against P. aeruginosa daily for more than eight years, which shows that it is possible to use yolk immunotherapy over long treatment periods.


Risk factors for 5-year complications after midurethral sling surgery for stress urinary incontinence: a retrospective cohort study from Taiwan.
Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011-3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.


Azithromycin in the treatment of Plasmodium falciparum gametocytes. Preliminary observation.
Treatment of malaria represents a problem as antimalarial drugs are relatively few, and because of the increasing widespread resistance of Plasmodium falciparum to most of these drugs. A partial efficacy of azithromycin against Pl. falciparum hepatic stage and against trophozoytes in the erythrocytic stages of the disease has been demonstrated. No data concerning the activity against gametocytes are available, and primaquine stands as the only therapy against Pl. falciparum gametocytes. Primaquine causes haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, so primaquine therapy is usually avoided. A better tolerated therapy against gametocytes would be useful to reduce malaria transmission. We present the results of a study concerning the efficacy of azithromycin in the treatment of P. falciparum gametocytes. A prospective study was performed: 4 patients with Pl. falciparum gametocytes (3 children, 1 adult) were treated with azithromycin for concomitant bacterial infections; in the meantime two children with gametocytes were taken as control. Azithromycin was administered as recommended. Gametocytes were detectable in children thick blood smears after 8, 5 and 6 days respectively after the beginning of azithromycin therapy, while they were undetectable in the adult thick blood smear 5 days after the beginning of the therapy. The gametocytes spontaneously disappeared in the two controls 4 to 6 days after the beginning of observation. These data suggest that azithromycin seems ineffective against Pl. falciparum gametocytes. Further studies are needed in order to determine whether azithromycin treated gametocytes are infective to mosquitoes or not, and to confirm this first observation.


Carotenoids/vitamin C and smoking-related bladder cancer.
Previous epidemiological studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with respect to the role of cigarette smoking as a possible modifier of the diet-bladder cancer association. A population-based case-control study was conducted in nonAsians of Los Angeles, California, which included 1,592 bladder cancer patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and race between January 1, 1987 and April 30, 1996. Information on smoking, medical and medication history, and intake frequencies of food groups rich in preformed nitrosamines, vitamins A and C and various carotenoids, were collected through in-person, structured interviews. Beginning in January 1992, all case patients and their matched control subjects were asked for a blood sample donation at the end of the in-person interviews for measurements of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts, and glutathione S-transferases M1/T1/P1 (GSTM1/T1/P1) and N-acetyltransferase-1 (NAT1) genotypes. Seven hundred seventy-one (74%) case patients and 775 (79%) control subjects consented to the blood donation requests. In addition, all case patients and matched control subjects were asked to donate an overnight urine specimen following caffeine consumption for measurements of cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) phenotypes. Urine specimens were collected from 724 (69%) case patients and 689 (70%) control subjects. After adjustment for nondietary risk factors including cigarette smoking, there were strong inverse associations between bladder cancer risk and intake of dark-green vegetables [p value for linear trend (p) = 0.01], yellow-orange vegetables (p = 0.01), citrus fruits/juices (p = 0.002) and tomato products (p = 0.03). In terms of nutrients, bladder cancer risk was inversely associated with intake of both total carotenoids (p = 0.004) and vitamin C (p = 0.02). There was a close correlation (r = 0.58, p = 0.0001) between intakes of total carotenoids and vitamin C in study subjects. When both nutrients were included in a multivariate logistic regression model, only total carotenoids exhibited a residual effect that was of borderline statistical significance (p = 0.07 and p = 0.40 for total carotenoids and vitamin C, respectively). Cigarette smoking was a strong modifier of the observed dietary effects; these protective effects were confined largely to ever smokers and were stronger in current than ex-smokers. Smokers showed a statistically significant or borderline statistically significant decrease in 3- and 4-aminobiphenyl (ABP)-hemoglobin adduct level with increasing intake of carotenoids (p = 0.04 and 0.05, respectively). The protective effect of carotenoids on bladder cancer seemed to be influenced by NAT1 genotype, NAT2 phenotype and CYP1A2 phenotype; the association was mainly confined to subjects possessing the putative NAT1-rapid, NAT2-rapid and CYP1A2-rapid genotype/phenotype. The carotenoid-bladder cancer association was not affected by the GSTM1, GSTT1 and GSTP1 genotypes.


Achieving stable human stem cell engraftment and survival in the CNS: is the future of regenerative medicine immunodeficient?
There is potential for a variety of stem cell populations to mediate repair in the diseased or injured CNS; in some cases, this theoretical possibility has already transitioned to clinical safety testing. However, careful consideration of preclinical animal models is essential to provide an appropriate assessment of stem cell safety and efficacy, as well as the basic biological mechanisms of stem cell action. This article examines the lessons learned from early tissue, organ and hematopoietic grafting, the early assumptions of the stem cell and CNS fields with regard to immunoprivilege, and the history of success in stem cell transplantation into the CNS. Finally, we discuss strategies in the selection of animal models to maximize the predictive validity of preclinical safety and efficacy studies.


Transformation of Arthrobacter and studies on the transcription of the Arthrobacter ermA gene in Streptomyces lividans and Escherichia coli.
We report the development of a plasmid-mediated transformation system for Arthrobacter sp. NRRLB3381, using the Streptomyces cloning vector pIJ702. Our procedure gives a transformation frequency of 10(3)/micrograms of plasmid DNA. In addition we have explored the expression of the Arthrobacter ermA gene in Streptomyces lividans and Escherichia coli, and shown that the ermA promoter is recognized in S. lividans not E. coli. The relationship between Arthrobacter, Streptomyces and E. coli promoters is discussed.


Antiproliferative and apoptotic effects of tocopherols and tocotrienols on normal mouse mammary epithelial cells.
Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on normal mammary epithelial cell growth and viability. Cells isolated from midpregnant BALB/c mice were grown within collagen gels and maintained on serum-free media. Treatment with 0-120 microM alpha- and gamma-tocopherol had no effect, whereas 12.5-100m microM tocotrienol-rich fraction of palm oil (TRF), 100-120 microM delta-tocopherol, 50-60 microM alpha-tocotrienol, and 8-14 microM gamma- or delta-tocotrienol significantly inhibited cell growth in a dose-responsive manner. In acute studies, 24-h exposure to 0-250 microM alpha-, gamma-, and delta-tocopherol had no effect, whereas similar treatment with 100-250 microM TRF, 140-250 microM alpha-, 25-100 microM gamma- or delta-tocotrienol significantly reduced cell viability. Growth-inhibitory doses of TRF, delta-tocopherol, and alpha-, gamma-, and delta-tocotrienol were shown to induce apoptosis in these cells, as indicated by DNA fragmentation. Results also showed that mammary epithelial cells more easily or preferentially took up tocotrienols as compared to tocopherols, suggesting that at least part of the reason tocotrienols display greater biopotency than tocopherols is because of greater cellular accumulation. In summary, these findings suggest that the highly biopotent gamma- and delta-tocotrienol isoforms may play a physiological role in modulating normal mammary gland growth, function, and remodeling.


Pollinarium morphology and floral rewards in Brazilian Maxillariinae (Orchidaceae).
There is strong support for the monophyly of the orchid subtribe Maxillariinae s.l., yet generic boundaries within it are unsatisfactory and need re-evaluation. In an effort to assemble sets of morphological characters to distinguish major clades within this subtribe, the pollinarium morphology and floral rewards of representative Brazilian species of this subtribe were studied. The study was based on fresh material from 60 species and seven genera obtained from cultivated specimens. Variation of pollinarium structure and floral rewards was assessed using a stereomicroscope and by SEM analysis. Four morphological types of pollinaria are described. Type 1 appears to be the most widespread and is characterized by a well-developed tegula. Type 2 lacks a stipe and the pollinia are attached directly to the viscidium. Type 3 also lacks a stipe, and the viscidium is rigid and dark. In Type 4, the stipe consists of the whole median rostelar portion and, so far, is known only from Maxillaria uncata. Nectar, trichomes, wax-like and resin-like secretions are described as flower rewards for different groups of species within the genus Maxillaria. Data on the biomechanics and pollination biology are also discussed and illustrated. In Maxillariinae flowers with arcuate viscidia, the pollinaria are deposited on the scuttellum of their Hymenopteran pollinators. In contrast, some flowers with rounded to rectangular, pad-like viscidia fix their pollinaria on the face of their pollinators. Pollinarium morphology and floral features related to pollination in Brazilian Maxillariinae are more diverse than previously suggested. It is hoped that the data presented herein, together with other data sources such as vegetative traits and molecular tools, will be helpful in redefining and diagnosing clades within the subtribe Maxillariinae.


Receipt of care and depressive symptoms in later life: the importance of self-perceptions of aging.
This study examines the extent to which self-perceptions of aging and perceived loss of control explain the relationship between the receipt of care and depressive symptoms among older adults. The sample consists of individuals aged 51 and older from the 2006, 2008, and 2010 waves of the Health and Retirement Study (n = 5,938). Structural equation modeling was used to test an analytic model that focused on the mediating effects of self-perceptions of aging and perceived loss of control. The respondents' demographic and health characteristics and depressive symptoms at baseline were included as control variables. The results indicated that self-perceptions of aging mediated the relationship between receipt of care and depressive symptoms. That is, older adults who received a greater amount of care perceive their aging more negatively, which, in turn, increased depressive symptoms 2 years later. However, perceived loss of control did not significantly mediate the relationship between the receipt of care and depressive symptoms. These findings suggest that the receipt of care may make frail older adults more vulnerable to negative self-perceptions of aging.


Quantifying the effects of spinal manipulations on gait, using patients with low back pain: a pilot study.
A pilot study was performed to investigate the effects of chiropractic treatment on the gait of one patient with a chronic sacroiliac joint syndrome. Qualitative and quantitative measures were used to describe pain, sacroiliac joint mobility, functional ability and gait patterns of this patient before and after receiving chiropractic treatment, and throughout the rehabilitation period. For this patient, chiropractic treatment reduced the low back pain and was associated with significant changes in selected gait parameters. A study involving 10-20 subjects is under way to possibly generalize the findings of this investigation.


A compact symmetric microstrip filter based on a rectangular meandered-line stepped impedance resonator with a triple-band bandstop response.
This paper presents a symmetric-type microstrip triple-band bandstop filter incorporating a tri-section meandered-line stepped impedance resonator (SIR). The length of each section of the meandered line is 0.16, 0.15, and 0.83 times the guided wavelength (λ g ), so that the filter features three stop bands at 2.59 GHz, 6.88 GHz, and 10.67 GHz, respectively. Two symmetric SIRs are employed with a microstrip transmission line to obtain wide bandwidths of 1.12, 1.34, and 0.89 GHz at the corresponding stop bands. Furthermore, an equivalent circuit model of the proposed filter is developed, and the model matches the electromagnetic simulations well. The return losses of the fabricated filter are measured to be -29.90 dB, -28.29 dB, and -26.66 dB while the insertion losses are 0.40 dB, 0.90 dB, and 1.10 dB at the respective stop bands. A drastic reduction in the size of the filter was achieved by using a simplified architecture based on a meandered-line SIR.


Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis.
Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria. As topical drugs might reduce this phenomenon, the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution. The trial was conducted as randomized, parallel group, and single blind. Children, aged 3-6 years, with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine (250 mg: 1/2 vial in the morning and 1/2 vial in the evening) (Group A) or saline solution twice daily (Group B), both of them for 5 days. Both treatments were administered using a new device: Rinowash. The following parameters were assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, cough, sore throat, fever, and cultures. Of 104 patients screened, 90 children, median age 3.7 years (44 females and 46 males), completed the study: 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters, but fewer than the control group. In conclusion, inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children, as it is effective, safe, economic, and simple to use.


Interleukin-35 enhances Lyme arthritis in Borrelia-vaccinated and -infected mice.
Interleukin-35 (IL-35) has been reported to inhibit the production of interleukin-17 (IL-17) as a means of preventing arthritis and other inflammatory diseases. We previously showed that treatment of Borrelia-vaccinated and -infected mice with anti-IL-17 antibody at the time of infection prevented the development of arthritis. The anti-IL-17 antibody-treated mice lacked the extensive tissue damage, such as bone and cartilage erosion, that occurred in the tibiotarsal joints of untreated Borrelia-vaccinated and -infected control mice. We hypothesized that IL-35 would reduce the severity of arthritis by suppressing the production of IL-17 in Borrelia-vaccinated and -infected mice. Here, we show that administration of recombinant IL-35 (rIL-35) to Borrelia-vaccinated and -infected mice augments the development of severe arthritis compared to the results seen with untreated control mice. Borrelia-vaccinated and -infected mice treated with rIL-35 had significantly (P < 0.05) greater hind paw swelling and histopathological changes from day 4 through day 10 than non-rIL-35-treated Borrelia-vaccinated and -infected mice. In addition, the treatment with IL-35 only slightly decreased the production of IL-17 in Borrelia-primed immune cells and did not prevent the development of borreliacidal antibody. Our data do not support a role for IL-35 as a potential therapeutic agent to reduce inflammation in Lyme arthritis.


A beam profile generation algorithm for wedged half-beam blocked asymmetric fields.
A method is presented to predict beam profiles and outputs for wedged asymmetric fields defined by independent collimator jaws allowing fast generation of beam profiles whilst requiring very little additional data to that already used by most treatment planning systems in generating symmetric field isodoses. Symmetric field data are modified by the use of wedged primary off-centre ratios (POCRS) which are obtained from in air measurements of the largest possible wedged field. Beam hardening occurring within the flattening filter and wedge is taken into account by the use of attenuation coefficients measured under each wedge and used to generate the wedged POCR at depth. A full investigation into the comparison between measured and calculated profiles was performed which demonstrates favourable agreement across the whole of the asymmetric field including the penumbra.


Use of compression stockings in chronic venous disease: patient compliance and efficacy.
Compressive stockings are considered the centerpiece of treatment in chronic venous disease (CVD). It is known that stockings fail in some patients for varied reasons: they are ineffective despite wear in some, but more commonly patients are unable or unwilling to use them as prescribed. Detailed statistics regarding stocking compliance have not been available except in a few selected series focused on leg ulcers. This study focuses on use, compliance, and efficacy of compression stockings among a large cohort of patients referred to a tertiary venous practice. A total of 3,144 new CVD patients were seen from 1998 to 2006. As a referral practice, patients had been under the care of primary-care physicians or specialists for variable times before. A detailed history of past and present compressive regimens was part of our initial evaluation of CVD patients. These data were entered into a time-stamped electronic medical record and later analyzed. Only 21% of patients reported using the stockings on a daily basis, 12% used them most days, and 4% used them less often. The remaining 63% did not use the stockings at all or abandoned them after a trial period in the past. The primary reasons given for nonusage were as follows: unable to specify a reason, 30%; not prescribed by the primary physician, 25%; did not help, 14%; binding/"cutting off" of circulation, 13%; "too hot" to wear, 8%; limb soreness, 2%; poor cosmetic appearance, 2%; unable to apply without help, 2%; contact dermatitis or itching, 2%; and other (cost, work situation, etc), 2%. Multiple factors were cited by 8%. Surprisingly, there was no difference in compliance between men and women (39% vs. 38%) or among different decile age groups. Compliance was relatively better at 50% in patients who gave a prior history of deep vein thrombosis (n = 675) compared to 35% in those without such a prior history (n = 2,437) (p < 0.0001). Compliance was poor in CEAP lower (0-2) as well as higher (3-6) clinical classes (p = nonsignificant). Overall compliance with stockings was low and statistically not different in several subsets with significant symptoms: compliance in pain, 39%; swelling, 37%; stasis dermatitis, 46%; and stasis ulceration, 37%. Compliance was relatively better with longer duration of symptoms: <1 year, 25%; 1-5 years, 34%; 6-10 years, 40%; >10 years, 44% (p < 0.003). Symptoms were still persistent in about a third (37%) of the patients despite apparent compliance with prescribed stockings. Compressive stockings are inapplicable in about a quarter of patients due to the condition of the limb or the general health of the patient. They are ineffective despite wear in about a third of patients seen. In the remainder, noncompliance with prescribed compressive stockings is an apparent major cause of treatment failure. Noncompliance is very high in patients with CVD regardless of age, sex, etiology of CVD, duration of symptoms, or disease severity. The reasons for noncompliance can be grouped into two interdependent major categories: (1) wear-comfort factors and (2) intangible sense of restriction imposed by the stockings.


Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder.
To examine the treatment impact of lamotrigine on the neurocognitive profile of patients with pediatric bipolar disorder (PBD). Healthy controls (HC) (n = 24; mean age = 12.4 +/- 3.3 years) and unmedicated PBD patients with manic, mixed, or hypomanic episodes (n = 34; mean age = 13 +/- 3.1 years) were matched for IQ, age, sex, race, and socioeconomic status. A neurocognitive battery was administered at baseline and again after 14 weeks, during which PBD patients were treated with lamotrigine. Clinical symptoms improved with treatment in the patient group with significant change from baseline to follow-up on the Young Mania Rating Scale (p < 0.001) and the Children's Depression Rating Scale-Revised (p < 0.001). Global neurocognitive function improved with lamotrigine in PBD patients over time relative to that in HC, although overall performance remained impaired. Working memory and verbal memory significantly improved with treatment in patients, and deficits in these domains were no longer significantly impaired relative to HC at follow-up. Executive function significantly improved with treatment in the patient group but still lagged behind HC at follow-up. Performance on attention tests did not improve with treatment. There appears to be significant improvement in cognitive abilities in PBD patients treated with lamotrigine that is most prominent in the areas of working memory and verbal memory and that occurs along with mood stabilization.


Physiological response and carcass and meat quality of suckling lambs in relation to transport time and stocking density during transport by road.
To evaluate the effect of stocking density and transport time on physiological responses and meat quality, 72 male suckling lambs were transported by road to the slaughterhouse at three different stocking densities (0.12, 0.20 or 0.25 m2/lamb) and two transport times (5 h or 30 min). Blood samples were collected pre-transport at the farm and after unloading in the slaughterhouse to measure levels of cortisol, creatine kinase (CK) and lactate dehydrogenase (LDH). After slaughter, the weights of the hot carcass, liver and spleen were recorded and pH in Musculus longisimus thoracis et lumborum (L), Musculus semitendinosus (ST) and Musculus psoas major (PM) were determined. Colour, water-holding capacity (WHC), texture and thiobarbituric acid-reactive substances (TBARS) values were measured in samples of L, at 24 h post mortem and after 5 days of ageing. Cortisol and LDH were higher in suckling lambs transported for 30 min than those transported for 5 h. Stocking density did not affect blood parameters studied. Transport time significantly affected some carcass quality parameters, but stocking density had no significant effect. Suckling lambs transported for 5 h had lower liver weights and dressing percentages than those transported for 30 min. Transport time influenced pH values, with lambs subjected to the longer journey showing the lowest pH at 0 h in the three muscles studied, with the lowest final pH in L and PM. The PM lambs transported at high density (0.12 m2/lamb) had the lowest pH at 24 h. Transport time and stocking density did not greatly affect colour and texture parameters. The meat from lambs transported for 30 min had higher WHC than meat from lambs transported for 5 h. Animals transported for longer journeys showed higher lipid oxidation after 5 days of ageing than those transported for 30 min. Loading and initial transport caused significant stress response in suckling lambs, that stress response was reduced over the time course of the journey.


β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates.
The β-lactams are the most widely used antibacterial agents worldwide. These antibiotics, a group that includes the penicillins and cephalosporins, are covalent inhibitors that target bacterial penicillin-binding proteins and disrupt peptidoglycan synthesis. Bacteria can achieve resistance to β-lactams in several ways, including the production of serine β-lactamase enzymes. While β-lactams also covalently interact with serine β-lactamases, these enzymes are capable of deacylating this complex, treating the antibiotic as a substrate. In this tutorial-style review, we provide an overview of the β-lactam antibiotics, focusing on their covalent interactions with their target proteins and resistance mechanisms. We begin by describing the structurally diverse range of β-lactam antibiotics and β-lactamase inhibitors that are currently used as therapeutics. Then, we introduce the penicillin-binding proteins, describing their functions and structures, and highlighting their interactions with β-lactam antibiotics. We next describe the classes of serine β-lactamases, exploring some of the mechanisms by which they achieve the ability to degrade β-lactams. Finally, we introduce the l,d-transpeptidases, a group of bacterial enzymes involved in peptidoglycan synthesis which are also targeted by β-lactam antibiotics. Although resistance mechanisms are now prevalent for all antibiotics in this class, past successes in antibiotic development have at least delayed this onset of resistance. The β-lactams continue to be an essential tool for the treatment of infectious disease, and recent advances (e.g., β-lactamase inhibitor development) will continue to support their future use.


Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells.
Carotenoids have been advocated as potential therapeutic agents in treating age-related macular degeneration (AMD). In ocular tissues carotenoids may undergo oxidation and form carotenoid-derived aldehydes (CDA), which would be toxic to tissues. We have investigated the cytotoxic effects of CDA from beta-carotene, Lutein and Zeaxanthin on human retinal pigment epithelial cells (ARPE-19). The serum-starved ARPE-19 cells were treated with CDA without or with antioxidant, N-acetylcysteine (NAC) and cell viability, apoptosis, reactive oxygen species (ROS) levels, nuclear chromatin condensation as well as fragmentation, change in mitochondrial membrane potential (MMP) and activation of transcription factors NF-kappaB and AP-1 were determined. We observed a dose and time-dependent decline in cell viability upon incubation of ARPE-19 cells with CDA. The CDA treatment also led to elevation in ROS levels in a dose-dependent manner. Upon CDA treatment a significant number of apoptotic cells were observed. Also early apoptotic changes in ARPE-19 cells induced by CDA were associated with change in MMP. Increased nuclear chromatin condensation and fragmentation were also observed in cells treated with CDA. The cytotoxicity of CDA in ARPE-19 cells was significantly ameliorated by the antioxidant, NAC. Furthermore, CDA induced the activation of NF-kappaB and AP-1 which was significantly inhibited by NAC. Thus our results demonstrate that CDA could increase the oxidative stress in ARPE-19 cells by elevating ROS levels that would cause imbalance in cellular redox status, which could lead to cell death. This would suggest that high carotenoid supplementation for treatment of AMD should be used cautiously.


Mercury-Mediated Epitaxial Accumulation of Au Atoms for Stained Hydrogel-Improved On-Site Mercury Monitoring.
Trivalent Au ions are easily reduced to be zerovalent atoms by coexisting reductant reagents, resulting in the subsequent accumulation of Au atoms and formation of plasmonic nanostructures. In the absence of stabilizers or presence of weak stabilizers, aggregative growth of Au nanoparticles (NPs) always occurs, and unregular multidimensional Au materials are consequently constructed. Herein, the addition of nanomole-level mercury ions can efficiently prevent the epitaxial accumulation of Au atoms, and separated Au NPs with mediated morphologies and superior plasmonic characteristics are obtained. Experimental results and theoretical simulation demonstrate the Hg-concentration-reliant formation of plasmonic nanostructures with their mediated sizes and shapes in the presence of weak reductants. Moreover, the sensitive plasmonic responses of reaction systems exhibit selectivity comparable to that of Hg species. As a concept of proof, polymeric carbon dots (CDs) were used as the initial reductant, and the reactions between trivalent Au and CDs were studies. Significantly, Hg atoms prevent the epitaxial accumulation of Au atoms, and plasmonic NPs with decreased sizes were in situ synthesized, corresponding to varied surface plasmonic resonance absorption performance of the CD-induced hybrids. Moreover, with the integration of sensing substrates of CD-doped hydrogels, superior response stabilities, analysis selectivity, and sensitivity of Hg2+ ions were achieved on the basis of the mercury-mediated in situ chemical reactions between trivalent Au ions and reductant CDs. Consequently, a high-performance sensing strategy with the use of Au NP-staining hydrogels (nanostaining hydrogels) was exhibited. In addition to Hg sensing, the nanostaining hydrogels facilitated by doping of emerging materials and advanced chem/biostrategies can be developed as high-performance on-site monitoring routes to various pollutant species.


DL_MG: A Parallel Multigrid Poisson and Poisson-Boltzmann Solver for Electronic Structure Calculations in Vacuum and Solution.
The solution of the Poisson equation is a crucial step in electronic structure calculations, yielding the electrostatic potential-a key component of the quantum mechanical Hamiltonian. In recent decades, theoretical advances and increases in computer performance have made it possible to simulate the electronic structure of extended systems in complex environments. This requires the solution of more complicated variants of the Poisson equation, featuring nonhomogeneous dielectric permittivities, ionic concentrations with nonlinear dependencies, and diverse boundary conditions. The analytic solutions generally used to solve the Poisson equation in vacuum (or with homogeneous permittivity) are not applicable in these circumstances, and numerical methods must be used. In this work, we present DL_MG, a flexible, scalable, and accurate solver library, developed specifically to tackle the challenges of solving the Poisson equation in modern large-scale electronic structure calculations on parallel computers. Our solver is based on the multigrid approach and uses an iterative high-order defect correction method to improve the accuracy of solutions. Using two chemically relevant model systems, we tested the accuracy and computational performance of DL_MG when solving the generalized Poisson and Poisson-Boltzmann equations, demonstrating excellent agreement with analytic solutions and efficient scaling to ∼109 unknowns and 100s of CPU cores. We also applied DL_MG in actual large-scale electronic structure calculations, using the ONETEP linear-scaling electronic structure package to study a 2615 atom protein-ligand complex with routinely available computational resources. In these calculations, the overall execution time with DL_MG was not significantly greater than the time required for calculations using a conventional FFT-based solver.


Is there a role for fondaparinux in perioperative bridging?
A possible role for fondaparinux as a bridging agent in the perioperative setting is explored. Anticoagulation guidelines provide minimal direction on the perioperative use of fondaparinux. Fondaparinux's extended half-life of 17-21 hours complicates its use as a perioperative bridging therapy. The ideal time for discontinuation before surgery is an issue, particularly in surgeries with a high bleeding risk or in which neuraxial anesthesia is used. Guidance for perioperative bridging with fondaparinux must be derived from pharmacokinetic data, surgical prophylaxis trials, case reports, and anesthesia guidelines. Published trials used fondaparinux sodium 2.5 mg daily for venous thromboembolism prophylaxis in surgical patients, and the majority avoided its use before surgery in patients receiving neuraxial anesthesia. Three case reports cited the use of fondaparinux sodium as perioperative bridge therapy; one used a 2.5-mg dose, and the other two used a full treatment dose of 7.5 mg. Furthermore, professional anesthesia guidelines conflict in their recommendations regarding the timing of drug administration with neuraxial catheter use. For these reasons, it may be optimal to avoid fondaparinux use before surgery. In some instances, the use of low-molecular-weight heparin or inpatient use of i.v. unfractionated heparin is not possible, is contraindicated, or has limited efficacy, such as a patient with history of heparin-induced thrombocytopenia or antithrombin III deficiency. Fondaparinux may have a role in bridge therapy for these patients. The role of fondaparinux in perioperative bridge therapy has not been established, and there are some important limitations to its use as a routine bridging agent.


Experimental study on pollutant movement in surf zone.
The experiments on pollutant movement in surf zone were conducted on the two gentle beaches (with slope of 1:100 and 1:40, respectively), for diverse wave cases. The movement contours and direction of pollutants, under the action of regular and random waves with diverse wave amplitudes, were provided and studied in this paper. It was shown that, due to complicated hydrodynamics in surf zone, the pollutant movement state is quite complicated and different from that in pure current zone.


Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells.
Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and "supershift" assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.


A virus with a bisegmented double-stranded RNA genome in rat (Oryzomys nigripes) intestines.
Examination of the intestinal contents of free-living Oryzomys nigripes rats by PAGE revealed two sharply defined bands that could be stained by ethidium bromide or by silver nitrate with comparable intensities. The molecules forming these bands were susceptible to digestion by pancreatic RNase A but not by RNase T1 or by DNase I. Their lengths were estimated to be about 2.6 and 1.5 kbp, respectively, by comparison with rotavirus SA11 genome segments. They cosedimented in CsCl gradients at a density of 1.39 to 1.40 g/ml, together with uniform particles approximately 35 nm in diameter with indistinct surface structure. It is suggested that these particles represent an as yet undescribed virus with a bisegmented double-stranded RNA genome, for which the name 'picobirnavirus' is proposed.


An approach for mapping the number and distribution of Salmonella contamination on the poultry carcass.
Mapping the number and distribution of Salmonella on poultry carcasses will help guide better design of processing procedures to reduce or eliminate this human pathogen from poultry. A selective plating media with multiple antibiotics (xylose-lysine agar medium [XL] containing N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) and the antibiotics chloramphenicol, ampicillin, tetracycline, and streptomycin [XLH-CATS]) and a multiple-antibiotic-resistant strain (ATCC 700408) of Salmonella Typhimurium definitive phage type 104 (DT104) were used to develop an enumeration method for mapping the number and distribution of Salmonella Typhimurium DT104 on the carcasses of young chickens in the Cornish game hen class. The enumeration method was based on the concept that the time to detection by drop plating on XLH-CATS during incubation of whole chicken parts in buffered peptone water would be inversely related to the initial log number (N0) of Salmonella Typhimurium DT104 on the chicken part. The sampling plan for mapping involved dividing the chicken into 12 parts, which ranged in average size from 36 to 80 g. To develop the enumeration method, whole parts were spot inoculated with 0 to 6 log Salmonella Typhimurium DT104, incubated in 300 ml of buffered peptone water, and detected on XLH-CATS by drop plating. An inverse relationship between detection time on XLH-CATS and N0 was found (r = -0.984). The standard curve was similar for the individual chicken parts and therefore, a single standard curve for all 12 chicken parts was developed. The final standard curve, which contained a 95% prediction interval for providing stochastic results for N0, had high goodness of fit (r2 = 0.968) and was N0 (log) = 7.78 +/- 0.61 - (0.995 x detention time). Ninety-five percent of N0 were within +/- 0.61 log of the standard curve. The enumeration method and sampling plan will be used in future studies to map changes in the number and distribution of Salmonella on carcasses of young chickens fed the DT104 strain used in standard curve development and subjected to different processing procedures.


The actin-bundling protein L-plastin: a critical regulator of immune cell function.
L-plastin is a leukocyte-specific protein that cross-links actin filaments into tight bundles, increasing the stability of actin-based structures such as podosomes and lamellipodia. While first identified as an abundant cytoplasmic protein in hematopoietically derived cells over 25 years ago, the requirement for L-plastin in multiple functions critical for immunity, such as antigen receptor signaling, adhesion, and motility, has only recently become clear. L-plastin has been identified as an important component in cellular processes critical for neutrophil, macrophage, osteoclast, eosinophil, and T- and B-lymphocyte biology. Following a brief description of the structure and function of L-plastin, the regulation of immune cell functions by L-plastin will be reviewed in detail.


Basic fibroblast growth factor induces interleukin-6 synthesis in osteoblasts: autoregulation by protein kinase C.
We previously reported that basic fibroblast growth factor (bFGF) stimulates both phospholipases C and D via independent pathways in osteoblastlike MC3T3-E1 cells. In this study, we investigated the effect of bFGF on interleukin-6 (IL-6) synthesis in these cells. bFGF stimulated the IL-6 synthesis dose-dependently in the range between 1 and 30 ng/ml. The depletion of extracellular Ca2+ by EGTA suppressed the bFGF-induced IL-6 synthesis. TMB-8, an inhibitor of intracellular Ca2+ mobilization, also inhibited the IL-6 synthesis by bFGF. bFGF stimulated the Ca2+ influx from extracellular space. Genistein, a tyrosine kinase inhibitor, suppressed the bFGF-induced Ca2+ influx. Staurosporine, an inhibitor for protein kinases, enhanced the bFGF-induced IL-6 synthesis. Calphostin C, a highly potent and specific inhibitor for protein kinase C (PKC), also enhanced the IL-6 synthesis by bFGF. The bFGF-induced IL-6 synthesis was amplified in PKC down-regulated cells. U-73122, a phospholipase C inhibitor, enhanced the bFGF-induced IL-6 synthesis. Propranolol, a phosphatidic acid phosphohydrolase inhibitor, also enhanced the IL-6 synthesis by bFGF. These results strongly suggest that bFGF stimulates IL-6 synthesis, which depends on intracellular Ca2+ mobilization in osteoblastlike cells, and that the IL-6 synthesis by bFGF is autoregulated due to PKC activation.


3,4-Dimethoxycinnamic Acid as a Novel Matrix for Enhanced In Situ Detection and Imaging of Low-Molecular-Weight Compounds in Biological Tissues by MALDI-MSI.
Low-molecular-weight (low-MW) compounds have many essential functions in biological processes, and the molecular imaging of as many low-MW compounds as possible is critical for understanding complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an emerging molecular-imaging technology that enables determination of the spatial distributions and the relative abundances of diverse endogenous compounds in tissues. New matrices suitable for the imaging of low-MW compounds by MALDI-MSI are important for the technological advancement of tissue imaging. In this study, 3,4-dimethoxycinnamic acid (DMCA) was evaluated as a new matrix for enhanced low-MW compound detection by MALDI-MSI because of its strong ultraviolet absorption, low matrix-ion related interferences below m/ z 500, and high ionization efficiency for the analysis of low-MW compounds. DMCA was successfully used for improved in situ detection of low-molecular-weight metabolites ( m/ z < 500) and lipids in rat liver, rat brain, and germinating Chinese-yew seed tissue sections. The use of DMCA led to the successful in situ detection of 303, 200, and 248 low-MW compound ion signals from these three tissues, respectively. Both MALDI-MS/MS and LC-MS/MS were used to identify these ion signals, leading to the identification of 115 low-MW compounds from rat liver (including 53 lipids, 29 oligopeptides, and 33 metabolites), 130 low-MW compounds from rat brain (including 104 lipids, 5 oligopeptides, and 21 metabolites), and 111 low-MW compounds from germinating Chinese-yew seeds (including 77 lipids, 22 oligopeptides, 8 flavonoids, and 4 alkaloids). A larger number of low-MW compounds could be detected and imaged when DMCA was used as the MALDI matrix than with other commonly used MALDI matrices such as 2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, 2-mercaptobenzothiazole, graphene oxide, and silver nanoparticles. Our work provides a new and powerful matrix for enhanced MALDI-MS profiling of low-MW compounds in both animal and plant tissues.


Feasibility of detecting prostate cancer by ultraperformance liquid chromatography-mass spectrometry serum metabolomics.
Prostate cancer (PCa) is the second leading cause of cancer-related mortality in men. The prevalent diagnosis method is based on the serum prostate-specific antigen (PSA) screening test, which suffers from low specificity, overdiagnosis, and overtreatment. In this work, untargeted metabolomic profiling of age-matched serum samples from prostate cancer patients and healthy individuals was performed using ultraperformance liquid chromatography coupled to high-resolution tandem mass spectrometry (UPLC-MS/MS) and machine learning methods. A metabolite-based in vitro diagnostic multivariate index assay (IVDMIA) was developed to predict the presence of PCa in serum samples with high classification sensitivity, specificity, and accuracy. A panel of 40 metabolic spectral features was found to be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy. The performance of the IVDMIA was higher than the prevalent PSA test. Within the discriminant panel, 31 metabolites were identified by MS and MS/MS, with 10 further confirmed chromatographically by standards. Numerous discriminant metabolites were mapped in the steroid hormone biosynthesis pathway. The identification of fatty acids, amino acids, lysophospholipids, and bile acids provided further insights into the metabolic alterations associated with the disease. With additional work, the results presented here show great potential toward implementation in clinical settings.


A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days.
Perillyl alcohol (POH) has been shown to have both chemopreventative and chemotherapeutic activities in preclinical studies. The underlying mechanism(s) of action of POH have yet to be delineated but may involve effects on the transforming growth factor beta (TGFbeta) and/or the Ras signaling pathways. A phase I study of POH for 14 days out of every 28 days in subjects with advanced malignancies was performed to evaluate dose escalation, toxicity, pharmacokinetics, and effects on TGFbeta and Ras. POH was administered orally (500 mg capsules containing 250 mg POH) to 20 patients four times a day on a continuous basis for 14 days followed by a 14-day rest period, for up to three courses. The starting dose was 1200 mg/m(2) per dose. A minimum of three patients were treated and evaluated at each escalating POH dose. Pharmacokinetic analysis was performed on days 1 and 14 of course 1 and day 1 of selected later courses. Plasma TGFbeta levels were measured on days 1 and 14. Peripheral blood lymphocyte (PBLs) Ras levels were assayed on days 1 and 2 of the first course. The 20 patients, of whom 15 were evaluable, received doses between 1200 and 2000 mg/m(2) per dose for a total of 43 courses. The most common observed toxicities were nausea, gastrointestinal distress, and fatigue. Other toxicities included diarrhea or constipation, hypokalemia, and one incidence of acute pancreatitis. Due to these toxicities, four of the patients declined further treatment either during or after the second course. While POH was not detected in plasma, perillic acid (PA) and dihydroperillic acid (DHPA) were detected in plasma, and the peak levels at 2000 mg/m(2) per dose were approximately 600 micro M (PA) and 50 micro M (DHPA). There was some evidence for linearity in the peak plasma levels and area under the concentration-time curve of the metabolites from the starting dose to the highest dose. Metabolite pharmacokinetics were not significantly affected by ingestion in the fed or fasting state, or repeated exposure to POH. No evidence for an effect of POH on plasma TGFbeta or PBL Ras protein was observed. No objective responses were observed. In adults with advanced malignancies, an interrupted administration schedule of POH did not reveal significant advantages over continuous dosing schedules.


Activation of microglia reveals a non-proteolytic cytokine function for tissue plasminogen activator in the central nervous system.
Tissue plasminogen activator mediates excitotoxin-induced neurodegeneration and microglial activation in the mouse hippocampus. Here we show that tissue plasminogen activator (tPA) acts in a protease-independent manner to modulate the activation of microglia, the cells of the central nervous system with macrophage properties. Cultured microglia from tPA-deficient mice can phagocytose as efficiently as wild-type microglia. However, tPA-deficient microglia in mixed cortical cultures exhibit attenuated activation in response to lipopolysaccharide, as judged by morphological changes, increased expression of the activation marker F4/80 and the release of the pro-inflammatory cytokine tumor necrosis factor-(&agr;). When tPA is added to tPA deficient cortical cultures prior to endotoxin stimulation, microglial activation is restored to levels comparable to that observed in wild-type cells. Proteolytically-inactive tPA can also restore activation of tPA-deficient microglia in culture and in vivo. However, this inactive enzyme does not restore susceptibility of tPA-deficient hippocampal neurons to excitotoxin-mediated cell death. These results dissociate two different functions of tPA: inactive enzyme can mediate microglial activation, whereas proteolytically-competent protein also promotes neuronal degeneration. Thus tPA is identified as a new cytokine in the central nervous system.


Pulmonary Kaposi Sarcoma without Mucocutaneous Involvement: The Role of Sequential Thallium and Gallium Scintigraphy.
Kaposi sarcoma (KS) is a vascular-related tumor that has been associated with human immunodeficiency virus (HIV). It commonly involves the skin and lymph nodes, and infrequently involves the lungs. In very rare instances, pulmonary KS can be found in the absence of endobronchial and mucocutaneous involvement. Utilization of sequential thallium and gallium scintigraphy can aid in the diagnosis of pulmonary KS in the absence of mucocutaneous and endobronchial involvement. In this report, we discuss a case of a patient with acquired immunodeficiency syndrome who presented with dyspnea and cough and was found to have subtle pulmonary parenchymal nodular airspace opacities. He underwent negative infectious evaluation, including bronchoscopy. Despite the absence of mucocutaneous findings, sequential positive thallium and negative gallium scintigraphy led to an early diagnosis of pulmonary KS. Pulmonary KS in the absence of mucocutaneous involvement is a rare finding that is exceedingly difficult to diagnose. However, pulmonary KS should be considered in patients with HIV who present with respiratory symptoms even if the typical mucocutaneous manifestations of KS are absent. In such circumstances, sequential thallium and gallium scintigraphy can help differentiate pulmonary KS from other processes such as infections and lymphoma, and assist in establishing an earlier diagnosis.


The brain-derived neurotrophic factor prompts platelet aggregation and secretion.
Brain-derived neurotrophic factor (BDNF) has both autocrine and paracrine roles in neurons, and its release and signaling mechanisms have been extensively studied in the central nervous system. Large quantities of BDNF have been reported in circulation, essentially stored in platelets with concentrations reaching 100- to 1000-fold those of neurons. Despite this abundance, the function of BDNF in platelet biology has not been explored. At low concentrations, BDNF primed platelets, acting synergistically with classical agonists. At high concentrations, BDNF induced complete biphasic platelet aggregation that in part relied on amplification from secondary mediators. Neurotrophin-4, but not nerve growth factor, and an activating antibody against the canonical BDNF receptor tropomyosin-related kinase B (TrkB) induced similar platelet responses to BDNF, suggesting TrkB could be the mediator. Platelets expressed, both at their surface and in their intracellular compartment, a truncated form of TrkB lacking its tyrosine kinase domain. BDNF-induced platelet aggregation was prevented by inhibitors of Ras-related C3 botulinum toxin substrate 1 (Rac1), protein kinase C, and phosphoinositide 3-kinase. BDNF-stimulated platelets secreted a panel of angiogenic and inflammatory cytokines, which may play a role in maintaining vascular homeostasis. Two families with autism spectrum disorder were found to carry rare missense variants in the BDNF gene. Platelet studies revealed defects in platelet aggregation to low concentrations of collagen, as well as reduced adenosine triphosphate secretion in response to adenosine diphosphate. In summary, circulating BDNF levels appear to regulate platelet activation, aggregation, and secretion through activation of a truncated TrkB receptor and downstream kinase-dependent signaling.


Three-dimensional optical profilometry analysis of surface states obtained after finishing sequences for three composite resins.
The operating protocols used for finishing composite resins are numerous and affect the success of filling from a mechanical, biological, and aesthetic point of view. The study determined the most favorable finishing for each of the composites considered. The three-dimensional optical profilometry examination was used to obtain qualitative and quantitative measurements of three hybrid composites. Tungsten carbide burs left irregularities harder to eliminate than those caused by diamond burs. Sof-Lex disks and the Enhance System gave good results for the three materials. Charisma presented a good surface regardless of polishing method used. Finishing Z100 and Prisma TPH required a special operating protocol as specified by the manufacturers. This study demonstrated that the finishing procedure for composite materials must be strictly followed to obtain optimal results. Profilometry proved to be an excellent method to study the surface roughness of samples.


Automatic detection of unattended changes in room acoustics.
Previous research has shown that the human auditory system continuously monitors its acoustic environment, detecting a variety of irregularities (e.g., deviance from prior stimulation regularity in pitch, loudness, duration, and (perceived) sound source location). Detection of irregularities can be inferred from a component of the event-related brain potential (ERP), referred to as the mismatch negativity (MMN), even in conditions in which participants are instructed to ignore the auditory stimulation. The current study extends previous findings by demonstrating that auditory irregularities brought about by a change in room acoustics elicit a MMN in a passive oddball protocol (acoustic stimuli with differing room acoustics, that were otherwise identical, were employed as standard and deviant stimuli), in which participants watched a fiction movie (silent with subtitles). While the majority of participants reported no awareness for any changes in the auditory stimulation, only one out of 14 participants reported to have become aware of changing room acoustics or sound source location. Together, these findings suggest automatic monitoring of room acoustics.


[Age-specific stages of pneumatization of the spenoidal sinus in children based on the results of computed and magneto-resonance tomography].
The present study had the objective to evaluate specific features of pneumatization along with the growth rate of the sphenoid bone and the size of the sphenoidal sinus in children of different age. To this effect, computed and magneto-resonance tomograms of paranasal sinuses taken from 100 patients at the age from 2 to 15 years were analysed retrospectively. The data thus obtained included the size (length, height, and width) and anatomic position of the canals for the internal carotid artery and optic nerve with respect to the walls of the sphenoidal sinus as well as age-specific growth dynamics of this sinus. Its formation was followed up from the age of 1 year till 3-5 years. Pneumatization of the sphenoidal sinus was evaluated. It is recommended that the results of the study should be taken into consideration when carrying out endonasal diagnostic procedures and surgical endoscopic interventions during the childhood period.


Learned fear of "unseen" faces after Pavlovian, observational, and instructed fear.
This study compared fear learning acquired through direct experience (Pavlovian conditioning) and fear learning acquired without direct experience via either observation or verbal instruction. We examined whether these three types of learning yielded differential responses to conditioned stimuli (CS+) that were presented unmasked (available to explicit awareness) or masked (not available to explicit awareness). In the Pavlovian group, the CS+ was paired with a mild shock, whereas the observational-learning group learned through observing the emotional expression of a confederate receiving shocks paired with the CS+. The instructed-learning group was told that the CS+ predicted a shock. The three groups demonstrated similar levels of learning as measured by the skin conductance response to unmasked stimuli. As in previous studies, participants also displayed a significant learning response to masked stimuli following Pavlovian conditioning. However, whereas the observational-learning group also showed this effect, the instructed-learning group did not.


Environmental sustainability assessment of biodiesel production from Jatropha curcas L. seeds oil in Pakistan.
According to IPCC Annual Report (AR-5), environmental impact assessment of any product prototype is recommended before its large-scale commercialization; however, no environmental profile analysis of any biodiesel prototype has been conducted in Pakistan. Therefore, objective of this study was to conduct a comprehensive life cycle assessment (LCA), water footprint and cumulative energy demand (CED) of biodiesel production from Jatropha curcas L. (JC) seeds oil in Pakistan. A cradle-to-gate LCA approach was applied for 400 liter (L) JC biodiesel produced in Pakistan. JC biodiesel production chain was divided into three stages i.e., 1). cultivation of JC crop 2). crude oil extraction from JC seeds and 3). crude oil conversion to biodiesel. Primary data for all the stages were acquired through questionnaire surveys, field visits and measurements in the field. Potential environmental impacts were calculated in SimaPro v.9.2 software using Eco-indicator 99 methodology. Results showed that crude oil extraction stage accounted for highest emissions (77%) to the overall environmental impact categories evaluated, followed by oil conversion stage (21%) and JC cultivation stage (02%), respectively. The three stages of JC biodiesel production chain are major contributor to ecotoxicity with a contribution of 57% to this impact category. Higher contribution to ecotoxicity was due to agrochemicals used in the JC cultivation. Similarly, fossil fuels impact category was responsible for 38% of overall environmental impacts. In addition, water footprint of JC biodiesel production chain was 2632.54 m3/reference unit. Cumulative energy required for 400L JC biodiesel production chain was 46745.70 MJ in Pakistan. Fossil diesel consumption, synthetic fertilizers use and purchased electricity were major hotspot sources to environmental burdens caused by JC biodiesel production in Pakistan. By performing sensitivity analysis at 20% reduction of the baseline values of fossil diesel used, synthetic fertilizers and purchased electricity, a marked decrease in environmental footprint was observed. It is highly recommended that use of renewable energy instead of fossil energy would provide environmental benefits such as lower greenhouse gases and other toxic emissions as compared to conventional petroleum fuels. It is also recommended that JC as a biofuel plant, has been reported to have many desired characteristics such as quick growth, easy cultivation, drought resistance, pest and insect resistance, and mainly great oil content in JC seeds (27-40%). Therefore, JC plant is highly recommended to Billion Tree Afforestation Project (BTAP) for plantation on wasteland because it has multipurpose benefits.