Factor H binding as a complement evasion mechanism for an anaerobic pathogen, Fusobacterium necrophorum.
Fusobacterium necrophorum subspecies funduliforme is an obligate anaerobic Gram-negative rod causing invasive infections such as the life-threatening Lemierre's syndrome (sore throat, septicemia, jugular vein thrombosis, and disseminated infection). The aim of our study was to understand if and how F. necrophorum avoids C activation. We studied 12 F. necrophorum subsp. funduliforme strains isolated from patients with sepsis. All strains were resistant to serum killing after a 1-h incubation in 20% serum. The bacteria bound, at different levels, the C inhibitor factor H (fH). Binding was ionic and specific in nature and occurred via sites on both the N terminus and the C terminus of fH. Bound fH remained functionally active as a cofactor for factor I in the cleavage of C3b. Interestingly, patients with the most severe symptoms carried strains with the strongest ability to bind fH. An increased C3b deposition and membrane attack complex formation on the surface of a weakly fH-binding strain was observed and its survival in serum at 3.5 h was impaired. This strain had not caused a typical Lemierre's syndrome. These data, and the fact that fH-binding correlated with the severity of disease, suggest that the binding of fH contributes to virulence and survival of F. necrophorum subsp. funduliforme in the human host. Our data show, for the first time, that an anaerobic bacterium is able to bind the C inhibitor fH to evade C attack.


Distinct DNA Damage Spectra Induced by Ionizing Radiation in Normoxic and Hypoxic Cells.
Ionizing radiation induces more cell death under normoxic conditions than under hypoxic conditions. This phenomenon, which is known as the oxygen enhancement effect, occurs primarily because ionizing radiation causes more DNA lesions in the presence of oxygen than in its absence. However, the roles these lesions play in terms of cell survival and chromosome damage have not been fully characterized. We exposed a panel of chicken DT40 mutant cells to ionizing radiation to categorize the type of lesion induced and the DNA-repair pathway involved under both normoxic and hypoxic conditions. Among the mutant panel, RAD54(-/-)/KU70(-/-) cells exhibited the greatest radiosensitivity, which was found to be significantly higher under normoxic conditions. This indicates that double-strand breaks (DSBs) were the major cause of cell death and that ionizing radiation induces more DSBs under normoxic condition. Interestingly, the sensitivity of the REV3(-/-) cells increased under hypoxic conditions. Indeed, the REV3(-/-) mutant exhibited a greater number of chromosomal aberrations under hypoxic conditions than under normoxic conditions. These results suggest that the Rev3-mediated translesion-synthesis pathway is more critical for cellular tolerance to ionizing radiation in hypoxic cells than in normoxic cells, and that more chemically modified DNA might be induced under hypoxic conditions. In this study, we identify a previously unappreciated radiation-induced pattern of DNA damage under hypoxic conditions.


Organizational environment of outpatient drug treatment services in Hungary: a pilot study.
Organizations engaged in drug addiction treatment started their activities only recently in Hungary. This paper examines the organisational environment in drug outpatient treatment using the example of Blue Point Foundation (BPF), a non-governmental organization (NGO). The authors describe BPF's organizational structure and functioning related to its effectiveness. BPF staff members anonymously completed a 59-item questionnaire about its organizational characteristics and functioning. The questionnaire covered demographic data, 50 items of the Quality Control questionnaire and a SWOT (Strengths, Weakness, Opportunities, Threats) analysis. Policy and strategy were considered BPF's best feature, while the management of funds received the lowest rating. The assessment of the staff and that of the organization as a whole was closer to the midpoint of the scale. High risk of staff burnout and unstable organizational environment are the most important threats on the NGOs working in addictology in Hungary.


Sister chromatid exchange in dyskeratosis congenita lymphocytes.
Sister chromatid exchange (SCE) frequency in chromosomes from lymphocytes of a patient with dyskeratosis congenita was 12-2 per mitosis. Our 33 normal controls had a mean of 5-4 SCE per mitosis and 5 patients with Fanconi's anaemia averaged 7-6 SCE per mitosis. The rate of chromosome breakage was only 0-5% in the dyskeratosis congenita patient and 0 to 2-5% in controls, while the Fanconi's anaemia patients showed higher values.


Effect of trehalose on the biocontrol efficacy of Pichia caribbica against post-harvest grey mould and blue mould decay of apples.
The influence of adding trehalose to the culture medium on the efficacy of Pichia caribbica (JSU-1) in controlling post-harvest grey mould and blue mould decay of apples and the possible mechanisms involved were investigated. The antagonistic activity of P. caribbica harvested from nutrient yeast dextrose broth (NYDB) amended with trehalose at 5 mg mL(-1) to post-harvest grey mould and blue mould decay was improved greatly compared with that without trehalose. The intracellular trehalose content of P. caribbica harvested from NYDB amended with trehalose at 5 mg mL(-1) was higher than that of P. caribbica harvested from NYDB. The population of P. caribbica could rapidly colonise and grow in apple wounds. Moreover, the application of P. caribbica cultivated in the culture medium of the trehalose supplement (5 mg mL(-1) ) induced higher polyphenoloxidase (PPO) and peroxidase (POD) activity of apples compared with that cultivated by P. caribbica in the NYDB. SEM results suggested that P. caribbica harvested from NYDB amended with trehalose at 5 mg mL(-1) showed stronger inhibition efficacy to Botrytis cinerea than P. caribbica harvested from NYDB. The antagonistic activity of P. caribbica can be enhanced by adding trehalose to the medium.


Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7 years.
Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7 years (n = 164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12 months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development.


Metastatic melanoma - a review of current and future treatment options.
Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.


Nutritional requirements of Staphylococcus aureus S-6.
A synthetic medium was devised for growth of Staphylococcus aureus strain S-6. The growth yield in synthetic medium was compared to that in complex medium containing an equivalent amount of protein hydrolysate. Enterotoxin B formation in the two media was also compared. The defined medium was composed of inorganic salts, 11 amino acids (glycine, valine, leucine, threonine, phenylalanine, tyrosine, cysteine, methionine, proline, arginine, and histidine), and three vitamins (thiamine, nicotinic acid, and biotin). Biotin was a growth factor requirement of S-6 when glutamic acid but not glucose was used as a carbon source. The quantity of enterotoxin B produced in the defined medium was about one-seventh of that produced in complex medium, even though the growth yields were similar.


Enhanced anti-tumor effect of trastuzumab in combination with cisplatin.
The oncogenenic transmembrane tyrosine kinase receptor HER-2/neu is a promising target for treatment of HER-2-overexpressing cancers. The humanized anti-HER-2/neu antibody Trastuzumab is under clinical evaluation in combination with chemotherapy against breast cancer. The combination of Trastuzumab and cisplatin is expected to be active against HER-2 / neu-expressing tumors. We examined the mechanisms of this combination effect against human solid tumor cells in the presence of human peripheral blood mononuclear cells (PBMCs) using an in vitro MTT assay. The growth-inhibitory effects of cisplatin (CDDP) on the tumor cells were not significantly affected by Trastuzumab in the absence of effector cells. CDDP alone at a dose of less than 12.5 mM did not affect the viability of PBMCs, as determined by MTT assay, suggesting that PBMCs could exert antibody-dependent cell-mediated cytotoxicity (ADCC) at this CDDP concentration. The combination of Trastuzumab and CDDP showed higher cytotoxic effects against the tumor cells in the presence of PBMCs. The CDDP concentration required to inhibit tumor cell growth by 50% was reduced to approximately 20% by Trastuzumab in the presence of PBMCs at an effector/target ratio of 10. It may be important to select combined chemotherapeutic agents which do not diminish the ADCC activity of Trastuzumab via PBMCs. Both the expression of HER-2 / neu and the ADCC activity may be important determinants of the therapeutic benefit of the Trastuzumab/CDDP combination.


The mystery of coronary artery spasm.
Coronary artery spasm is an important cause of chest pain and myocardial ischaemia. It can be defined as an exaggerated contractile response of epicardial coronary artery smooth muscle to various stimuli but the underlying mechanism is not well understood. Recent studies have shown that the loss of endothelial vasodilatory function in conjunction with an increase in vascular smooth muscle constrictor sensitivity to calcium are the likely predisposing conditions for coronary spasm. This review highlights current understanding of the pathophysiology, predisposing factors, diagnostic and therapeutic approaches for coronary spasm.


Cholesterol metabolism in cultured fibroblasts in adrenoleukodystrophy.
The basic biochemical defect of X-linked adrenoleukodystrophy (sudanophilic leukodystrophy, Schilder's disease) is unknown. To investigate reported abnormalities in cholesterol metabolism in vitro, we examined cultured skin fibroblasts of four patients and four normal control subjects. The kinetics of retention and accumulation of [14C]cholesterol by these cells was studied. After 3 days of exposure to tracer amounts of [14C]cholesterol, an apparent steady state between the medium and cellular cholesterol was established. The specific radioactivity expressed per mg of protein was similar for both Schilder and control fibroblasts. tafter labeling the pre-existing cellular cholesterol pool, the rate of loss of label was followed up for a 6-day period. About 23% and 14%, respectively, of the cellular radioactivity in both Schilder's disease and control cells were released into the medium after the consecutive change with fresh nonlabeled medium. No significant differences in [14C]cholesterol rates of uptake or release were observed between control and Schilder's disease fibroblasts. About 44% of the labeled cholesterol was present in an esterfied form after incubation in the presence of unheated serum in both Schilder's and control cultures.


Mechanisms generating bistability and oscillations in microRNA-mediated motifs.
The importance of post-transcriptional regulation by microRNAs (miRNAs) has recently been recognized in almost all cellular processes. When participating in cellular processes, miRNAs mainly mediate mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance of motifs involving miRNAs and transcriptional factors (TFs). The simplest motif is a two-node miRNA-mediated feedback loop (MFL) in which a TF regulates an miRNA and the TF itself is negatively regulated by the miRNA. In this paper we present a general computational model for the MFL based on biochemical regulations and explore its dynamics by using bifurcation analysis. Our results show that the MFL can behave either as switches or as oscillators, depending on the TF as a repressor or an activator. These functional features are consistent with the widespread appearance of miRNAs in fate decisions such as proliferation, differentiation, and apoptosis during development. We found that under the interplay of a TF and an miRNA, the MFL model can behave as switches for wide ranges of parameters even without cooperative binding of the TF. In addition, oscillations induced by the miRNA in the MFL model require neither an additional positive feedback loop, nor self-activation of the gene, nor cooperative binding of the TF, nor saturated degradation. Therefore, the MFL may provide a general network structure to induce bistability or oscillations. It is hoped that the results presented here will provide a new view on how gene expression is regulated by miRNAs and further guidance for experiments. Moreover, the insight gained from this study is also expected to provide a basis for the investigation of more complex networks assembled by simple building blocks.


Spatial velocity profile in mouse embryonic aorta and Doppler-derived volumetric flow: a preliminary model.
Characterizing embryonic circulatory physiology requires accurate cardiac output and flow data. Despite recent applications of high-frequency ultrasound Doppler to the study of embryonic circulation, current Doppler analysis of volumetric flow is relatively crude. To improve Doppler derivation of volumetric flow, we sought a preliminary model of the spatial velocity profile in the mouse embryonic dorsal aorta using ultrasound biomicroscopy (UBM)-Doppler data. Embryonic hematocrit is 0.05-0.10 so rheologic properties must be insignificant. Low Reynolds numbers (<500) and Womersley parameters (<0.76) suggest laminar flow. UBM demonstrated a circular dorsal aortic cross section with no significant tapering. Low Dean numbers (<100) suggest the presence of minimal skewing of the spatial velocity profile. The inlet length allows for fully developed flow. There is no apparent aortic wall pulsatility. Extrapolation of prior studies to these vessel diameters (300-350 microm) and flow velocities (~50-200 mm/s) suggests parabolic spatial velocity profiles. Therefore, mouse embryonic dorsal aortic blood flow may correspond to Poiseuille flow in a straight rigid tube with parabolic spatial velocity profiles. As a first approximation, these results are an important step toward precise in utero ultrasound characterization of blood flow within the developing mammalian circulation.


The burden of disease and health care use among pertussis cases in school aged children and adults in England and Wales; a patient survey.
In 2011-2012 a large pertussis outbreak occurred in England. This provided an opportunity to estimate the disease burden in those aged 5 years and over. As pertussis is likely to be under reported both laboratory-confirmed and non-confirmed cases were included. Laboratory-confirmed cases of pertussis, as well as their coughing but non-confirmed household members, were sent a questionnaire that collected information on clinical features and quality of life for the most severe day of disease and the day the patient filled in the questionnaire. The EuroQol-5 dimension questionnaire (EQ-5D) was used to evaluate quality of life. The duration of symptoms was obtained by contacting the patient every two weeks until symptoms stopped. Data for 535 (out of 1262) laboratory confirmed pertussis patients and 44 (out of 140) coughing household contacts was available for analysis. On the most severe day, 56% of laboratory-confirmed cases reported they had 20+ more paroxysms, 58% reported they had a severe cough and 46% reported disruption of sleep for more than 4 hours. For non-confirmed coughing household contacts there were a similar number of coughing spells per day at the height, though the cough was reported to be less severe and to cause less sleep disruption. The main clinical symptoms on the worst day for both were shortness of breath, tiredness, sore ribs and vomiting. The duration of symptoms for both patient groups was around 160 days (162 and 168 days). Under base case assumptions the overall loss of quality of life was 0.097 QALY (0.089-0.106) for confirmed pertussis cases and 0.0365 QALY (0.023-0.054) for coughing household contacts. Pertussis is a serious disease in those aged 5 years and over, causing disruption of sleep and daily activities over long period of time. The burden of illness due to undiagnosed pertussis is also considerable.


Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients' overall survival was analyzed with the Kaplan-Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.


Management of chest pain in the French emergency healthcare system: the prospective observational EPIDOULTHO study.
The aim of this paper was to describe the epidemiology, and diagnostic and therapeutic strategies that emergency physicians use to manage patients presenting with chest pain at all three levels of the French emergency medical system - that is, dispatch centres (SAMUs: the medical emergency system), which operate the mobile intensive care units (MICUs), and hospitals' emergency departments (EDs), with a focus on acute coronary syndrome (ACS). All patients with chest pain who contacted a SAMU and/or were managed by a MICU and/or were admitted into an ED were included in a 1-day multicentre prospective study carried out in January 2013. Data on diagnostic and therapeutic management and disposition were collected. An in-hospital follow-up was performed. In total, 1339 patients were included: 537 from SAMU, 187 attended by a MICU and 615 in EDs. Diagnosing ACS was the main diagnostic strategy of the French emergency care system, diagnosed in 16% of SAMU patients, 25% of MICU patients and 10% of ED patients. Among patients calling the SAMU, 76 (14%) received only medical advice, 15 (8%) patients remained at home after being seen by a MICU and 454 (74%) were discharged from an ED. Management of chest pain at the three levels of the French medical emergency system is mainly oriented towards ruling out ACS. The strategy of diagnostic management is based on minimizing missed diagnoses of ACS.


GH3 expression and IAA-amide synthetase activity in pea (Pisum sativum L.) seedlings are regulated by light, plant hormones and auxinic herbicides.
The formation of auxin conjugates is one of the important regulatory mechanisms for modulating IAA action. Several auxin-responsive GH3 genes encode IAA-amide synthetases that are involved in the maintenance of hormonal homeostasis by conjugating excess IAA to amino acids. Recently, the data have revealed novel regulatory functions of several GH3 proteins in plant growth, organ development, fruit ripening, light signaling, abiotic stress tolerance and plant defense responses. Indole-3-acetyl-aspartate (IAA-Asp) synthetase catalyzing IAA conjugation to aspartic acid in immature seeds of pea (Pisum sativum L.) was purified and characterized during our previous investigations. In this study, we examined the effect of auxin and other plant hormones (ABA, GA, kinetin, JA, MeJA, SA), different light conditions (red, far-red, blue, white light), and auxinic herbicides (2,4-D, Dicamba, Picloram) on the expression of a putative GH3 gene and IAA-amide synthesizing activity in 10-d-old pea seedlings. Quantitative RT-PCR analysis indicated that the PsGH3-5 gene, weakly expressed in control sample, was visibly induced in response to all plant hormones, different light wavelengths and the auxinic herbicides tested. Protein A immunoprecipitation/gel blot analysis using anti-AtGH3.5 antibodies revealed a similar pattern of changes on the protein levels in response to all treatments. IAA-amide synthetase activity determined with aspartate as a substrate, not detectable in control seedlings, was positively affected by a majority of treatments. Based on these results, we suggest that PsGH3-5 may control the growth and development of pea plants in a way similar to the known GH3 genes from other plant species.


G-protein coupled receptor 83 (GPR83) signaling determined by constitutive and zinc(II)-induced activity.
The G-protein coupled receptor 83 (GPR83) is an orphan G-protein coupled receptor for which the natural ligand(s) and signaling pathway(s) remain to be identified. Previous studies suggest a role of GPR83 in the regulation of thermogenesis and the control of circulating adiponectin. The aim of this study was to gain insights into the molecular underpinnings underlying GPR83 signaling. In particular, we aimed to assess the underlying G-protein activated signaling pathway of GPR83 and how this pathway is affected by mutational activation and zinc(II) challenge. Finally, we assessed the capacity of GPR83 for homodimerization. Our results show for the first time that mouse (m) GPR83 has high basal Gq/11 activity without affecting Gi or Gs signaling. Furthermore, we found that, under physiological conditions, zinc(II) (but not calcium(II) and magnesium(II)) potently activates mGPR83, thus identifying zinc(II) as an endogenous molecule with agonistic capability to activate mGPR83. In line with the observation that zinc(II)-ions activate mGPR83, we identified a cluster of ion-binding sensitive amino acids (e.g. His145, His204, Cys207, Glu217) in an activation sensitive receptor region of mGPR83. The occurrence of a constitutive activating mutant and a zinc(II)-binding residue at the N-terminal part corroborate the importance of this region in mGPR83 signal regulation. Finally, our results indicate that mGPR83 forms homodimers, which extend the current knowledge and molecular facets of GPR83 signaling.


[A comparative study of the pharmacokinetics and pharmacodynamics of bonnecor].
The pharmacokinetics and pharmacodynamics of bonnecor were studied simultaneously in animals with experimental arrhythmia. It was shown that irrespective of the animal species and individual features of the drug elimination kinetics the level of bonnecor concentration correlated with the antiarrhythmic effect. The data on the excretion of bonnecor and its metabolites in the urine in the dog and man were obtained. The decrease of bioavailability at oral administration of bonnecor was demonstrated to be related to its intensive conversion in metabolite M-I.


Ubiquitination of the N-terminal region of caveolin-1 regulates endosomal sorting by the VCP/p97 AAA-ATPase.
Caveolin-1 (CAV1) is the defining constituent of caveolae at the plasma membrane of many mammalian cells. For turnover, CAV1 is ubiquitinated and sorted to late endosomes and lysosomes. Sorting of CAV1 requires the AAA+-type ATPase VCP and its cofactor UBXD1. However, it is unclear in which region CAV1 is ubiquitinated and how ubiquitination is linked to sorting of CAV1 by VCP-UBXD1. Here, we show through site-directed mutagenesis that ubiquitination of CAV1 occurs at any of the six lysine residues, 5, 26, 30, 39, 47, and 57, that are clustered in the N-terminal region but not at lysines in the oligomerization, intramembrane, or C-terminal domains. Mutation of Lys-5-57 to arginines prevented binding of the VCP-UBXD1 complex and, importantly, strongly reduced recruitment of VCP-UBXD1 to endocytic compartments. Moreover, the Lys-5-57Arg mutation specifically interfered with trafficking of CAV1 from early to late endosomes. Conversely and consistently, depletion of VCP or UBXD1 led to accumulation of ubiquitinated CAV1, suggesting that VCP acts downstream of ubiquitination and is required for transport of the ubiquitinated form of CAV1 to late endosomes. These results define the N-terminal region of CAV1 as the critical ubiquitin conjugation site and, together with previous data, demonstrate the significance of this ubiquitination for binding to the VCP-UBXD1 complex and for sorting into lysosomes.


A Priori True and False Conditionals.
The theory of mental models postulates that meaning and knowledge can modulate the interpretation of conditionals. The theory's computer implementation implied that certain conditionals should be true or false without the need for evidence. Three experiments corroborated this prediction. In Experiment 1, nearly 500 participants evaluated 24 conditionals as true or false, and they justified their judgments by completing sentences of the form, It is impossible that A and ___ appropriately. In Experiment 2, participants evaluated 16 conditionals and provided their own justifications, which tended to be explanations rather than logical justifications. In Experiment 3, the participants also evaluated as possible or impossible each of the four cases in the partitions of 16 conditionals: A and C, A and not-C, not-A and C, not-A and not-C. These evaluations corroborated the model theory. We consider the implications of these results for theories of reasoning based on logic, probabilistic logic, and suppositions.


Iron chelators inhibit the heme-degradation reaction by HutZ from Vibrio cholerae.
HutZ is a heme-degrading enzyme. We found that the heme-degradation reaction by HutZ is inhibited by the iron chelators. Kinetic analysis of each heme-degradation step suggests that water molecules hydrogen bonded to Thr27 are involved in proton transfer to Fe(iii)-OO-, and that this step is inhibited by iron chelators.


[Endoscopic surgical management of nasal septal schwannoma: a case report].
Although benign tumors arising from the nasal cavity are common, those of the peripheral nerve sheath seen in this localization are unusual. We presented a 45-year-old woman with a nasal septal schwannoma filling the whole nasal cavity. She was treated successfully by transnasal endoscopic surgery. No recurrence was detected within a three-year follow-up period.


[Treatment of carcinoma of the rectum (author's transl)].
620 patients with carcinoma of the rectum treated in the years 1944 to 1966 are compared with 301 patients treated in the years 1967 to 1978. There was an increase of the operations alltogether and of the curative operations in particular. In the same space of time the mortality was reduced remarkably. The 5-year-survival time after resections was 38%, after abdomino perineal excision 48%.


The vibratory stimulus as a neurorehabilitation tool for stroke patients: proof of concept and tolerability test.
Current scientific knowledge reinforces that successful reorganization of surviving nervous tissue supports cognitive and motor recovery after stroke. The development of new neurorehabilitation tools to modulate this physiologic process is needed. In this context, vibratory stimuli are a noninvasive form of proprioceptive stimulation of the nervous system and are freely available and easy to use at a low cost. To access the feasibility and tolerability of targeted vibratory stimuli delivered through a wearable device in an early post-stroke setting. Five stroke patients were recruited from a stroke unit setting having a first ever medial cerebral artery ischemic stroke with motor deficit. The stimulation device developed delivered external vibratory stimuli to major joints at preprogrammed arrays of intensity, duration and interval of actuation. The tolerability test was set for five-hour duration and during that period data on vital parameters, cognitive, motor and sensitive performance as well as anxiety scores were recorded. The device remained in place throughout and none of the patients or relatives asked to interrupt the tolerability test. There were no major complications during the trial or the ensuing days. Attention to the affected side during stimulation was increased in four patients, and two were reported as clearly more awake during the test. This is the first tolerability test focused on the use of targeted vibratory stimulus as a neurorehabilitation tool in stroke patients. There were no hazards to report and most interestingly the majority of patients showed increased awareness to the affected side of the body. These findings will be further analyzed under functional MRI control and on long-term ambulatory use trials.


Party Identification, Contact, Contexts, and Public Attitudes toward Illegal Immigration.
Illegal immigration is a contentious issue on the American policy agenda. To understand the sources of public attitudes toward immigration, social scientists have focused attention on political factors such as party identification; they have also drawn on theories of intergroup contact to argue that contact with immigrants shapes immigration attitudes. Absent direct measures, contextual measures such as respondents' ethnic milieu or proximity to salient geographic features (such as borders) have been used as proxies of contact. Such a research strategy still leaves the question unanswered - is it contact or context that really matters? Further, which context, and for whom? This article evaluates the effects of party identification, personal contact with undocumented immigrants, and contextual measures (county Hispanic population and proximity to the US-Mexico border) on American attitudes toward illegal immigration. It finds that contextual factors moderate the effects of political party identification on attitudes toward illegal immigration; personal contact has no effect. These findings challenge the assumption that contextual measures act as proxies for interpersonal contact.


Glutathione-PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first-in-human study.
Intravenous high-dose free methylprednisolone (MP) hemisuccinate is the primary treatment for an acute relapse in relapsing-remitting multiple sclerosis. However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione-PEGylated liposomes, creating a slow-release formulation with reduced toxicity and prolonged peripheral efficacy. This first-in-human study was designed to assess the safety, pharmacokinetics and pharmacodynamics of glutathione-PEGylated liposomes containing MP (2B3-201). The first part was a double-blind, three-way cross over study in 18 healthy male subjects, receiving ascending doses of 2B3-201, active comparator (free MP) or placebo. Part 2 of the study was an open-label infusion of 2B3-201 (different doses), exploring pretreatment with antihistamines and different infusion schedules in another 18 healthy male subjects, and a cross-over study in six healthy female subjects. MP plasma concentrations, lymphocyte counts, adrenocorticotropic hormone, osteocalcin and fasting glucose were determined. Safety and tolerability profiles were assessed based on adverse events, safety measurements and central nervous system tests. The most frequent recorded AE related to 2B3-201 was an infusion related reaction (89%). 2B3-201 was shown to have a plasma half-life between 24 and 37 h and caused a prolonged decrease in the lymphocyte count, adrenocorticotropic hormone and osteocalcin, and a rise in fasting glucose. 2B3-201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3-201 shows a long plasma half-life and prolonged immunosuppressive effects.


Acute and long-term VNS effects on pain perception in a case of treatment-resistant depression.
Vagus Nerve Stimulation (VNS) is approved by the FDA for treatment of both epilepsy and depression. Recent work has shown that VNS acutely affects pain perception in humans, actually increasing pain sensitivity momentarily while the device is firing. It is unclear how this acutely increased sensitivity might change over time with treatment and how it might relate to longer-term therapeutic effects of VNS on pain. We describe a patient with treatment-resistant depression and a history of severe lumbar degenerative disease with resultant chronic low back pain. His depression and pain symptoms both seemed to respond to VNS. He eventually stopped all medications and remained depression and pain free for 35 months with no change in his device settings. Sixty-six months after VNS implantation and 64 months after his initial clinical antidepressant response, under single-blind conditions, we performed quantitative sensory testing with laboratory thermal pain procedures during acute VNS-on and -off conditions. Interestingly, despite a significant and profound anti-nociceptive clinical response for the previous 35 months, he had significant increases in painfulness ratings while the VNS device was actively firing compared with device-off conditions. This case suggests that VNS-induced acute increases in pain sensitivity can coexist with a clinical anti-nociceptive response. If the acutely increased sensitivity sets the stage for the slower chronic anti-pain effects, the increased acute sensitivity does not disappear. Acute and chronic effects of VNS on pain perception merit further research.


Effect of acute administration of delta 1-tetrahydrocannabinol on beta-endorphin levels in plasma and brain tissue of the rat.
Acute treatment with delta 1-tetrahydrocannabinol (delta 1-THC) elevated the concentration of beta-endorphin-like immunoreactivity (beta-ELIR) in plasma and in the hypothalamus, but not in the hippocampus of rats habituated to the injection procedure. These effects were not obtained with the psychotropically inert analog of delta 1-THC, cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal beta-ELIR.


Reference values for the bilateral heel-rise test.
The bilateral heel-rise test is an instrument that evaluates the performance of the triceps surae. Normative parameters need to be established for the use of the heel-rise test in clinical practice. To determine the reference values for the bilateral heel-rise test. This cross-sectional study assessed healthy subjects using the bilateral heel-rise test. We analyzed the number of repetitions, time (in seconds), and repetition rate (repetitions/second) during execution of the heel-rise test, until the point of voluntary fatigue. The estimates were stratified by age and gender. Multiple linear regression was performed to define the reference equation for the bilateral heel-rise test. A total of 147 individuals were included. The median age was 37 years (IQR 28-46). It was observed that the number of repetitions decreases with age, with a higher number of repetitions in male participants compared to female participants. Gender, body mass index, and maximum activity scores predict 14% of the number of plantar flexions performed in the bilateral heel-rise test. Age and adjusted activity scores predict 18% of the repetition rate in the bilateral heel-rise test. The bilateral heel-rise test reference values for an adult population were defined as scores above the 25th percentile for number of repetitions, time, and repetition rate. The number of heel-rise test repetitions that corresponds to the 25th percentile, according to age and gender, is as follows: age 20-29, 65 repetitions for men and 45.5 for women; age 30-39, 62.75 men and 41.5 women; age 40-49, 67.25 men and 45 women; and age 50-59, 54 men and 39.25 women.


The incidence and distribution of mediastinal lymph node metastasis and its impact on survival in patients with non-small-cell lung cancers 3 cm or less: data from 2292 cases.
Our goal was to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in non-small-cell lung cancers (NSCLC) 3 cm or less, with the purpose of guiding mediastinal lymph node dissection. A total of 2292 cases seen between January 2001 and December 2014 were included. These patients were grouped according to the lobes with the primary tumours. The incidence and distribution of pathological MLNM were compared among the groups. The impact of MLNM on overall survival was also compared. The most common mediastinal metastatic sites for different primary tumour lobes were as follows: right upper lobe, 17.7% (87/492) for level 4R; right middle lobe, 14.9% (28/188) for level 7; right lower lobe, 19.8% (82/414) for level 7; left upper lobe, 18.2% (96/528) for level 5; and left lower lobe, 16.6% (42/253) for level 7. For patients with tumours in the upper lobe, the median survival time was 32 months for those with MLNM in the subcarinal zone or lower zone compared with 83 months for those with MLNM only in the upper zone (P < 0.01). When the tumours were 1 cm or less, the incidence of MLNM to the lower zone for upper lobe tumours and of MLNM to the upper zone for lower lobe tumours was zero. Different primary NSCLC lobe locations have a different propensity to be sites of MLNM for those tumours that are 3 cm or less. For tumours no larger than 1 cm, a lower zone mediastinal lymph node dissection might be unnecessary for upper lobe tumours and an upper zone mediastinal lymph node dissection might be unnecessary for lower lobe tumours.


Rapid diagnosis of Pneumocystis carinii infection in AIDS by cytocentrifugation and rapid hematoxylin-eosin staining.
Pneumocystis carinii pneumonia (PCP) is the major pulmonary complication in patients with the acquired immunodeficiency syndrome. While fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBX) is regarded as the procedure of choice to identify PCP, these techniques, particularly TBBX, pose potential risks to the already compromised patient. To reduce the duration of bronchoscopy and, hence, lessen the chance for complications, we describe a rapid technique to identify PCP in BAL fluid by cytocentrifugation and hematoxylin-eosin staining. By this method, PCP can be easily diagnosed within 10 min. The sensitivity of this rapid diagnostic procedure is 95.7%, and the specificity is 100%.


[Problems of hearing loss in aviation engineers (professional and ecological aspects)].
Health standards for noise were exceeded 3 times when noise characteristics were measured at jobs and in apartments of engineers engaged in maintenance of modern aircraft. These specialists were exposed to noise in working hours and at night. Audiometry registered hearing problems in 69% of the examinees. 20% of them had hearing loss of the second degree. In engineers living closer to airports hearing was damaged more seriously, especially at frequencies 1000-8000 Hz. This fact demonstrates ecological implication of non-occupational acoustic load. Relevant regression levels were derived from correlation of noise doses with tonal hearing. Natural and experimental investigations proved efficacy of impedancemetry in objective assessment of noise-induced affection of the organ of hearing and hearing restoration in subjects occupationally exposed to noise.


Acute lymphoblastic leukemia presenting with gross hematuria.
A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient's hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thrombocytopenia potentially caused by acute leukemia should be considered in a child presenting with gross hematuria.


Brain perfusion SPECT abnormalities in neuronal ceroid lipofuscinoses.
Brain perfusion was studied with the Tc-99m-HMPAO SPECT method in 19 INCL patients, 21 JNCL patients and 5 patients with Jansky-Bielschowsky variant disease (JBVD). The typical SPECT findings at an early stage of INCL were bilateral anterior frontal, posterior temporoparietal and occipital hypoperfusion, whereas reduction in cerebellar perfusion appeared later. However, perfusion of basal ganglia and thalami, although atrophic on MRI, was usually well preserved up to the terminal stage. All JNCL patients except one had at least one hypoperfused area. Mild hypoperfusion was usually located in the parietal and occipital lobes and cerebellum, whereas more severe hypoperfusion was observed in the temporal lobes. In JNCL, SPECT revealed lesions not detected on CT. All JBVD patients had supra- and infratentorial hypoperfusion, which was usually bilateral. This study shows that although in NCLs brain hypoperfusion can appear prior to structural abnormalities seen on MRI or CT, such abnormalities are not always associated with significant hypoperfusion.


[Gallbladder polyps: correlation between ultrasonographic and histopathological findings].
Gallbladder polyps are becoming a common finding. The management of these polyps is complicated considering that they can bear malignant lesions. To analyze the ultrasonographic and histopathologic findings of patients operated due to gallbladder polyps. The records of patients with ultrasonographic diagnosis of gallbladder polyp and that underwent cholecystectomy in a thirteen years period were reviewed, collecting their demographic, ultrasonographic and histopathological data. One hundred and twenty three patients were operated. The mean age was 44+/-13 years, and 69% were women. The mean size of polyps in ultrasonography was 7.3+/-5 mm. Histopathology confirmed the presence of polyps in 79% of patients, with a mean size and number of lesions of 5.1+/-3.8 mm and 2.1+/-2, respectively. Nine percent of polyps were greater than 10 mm, and single polyps were significantly larger than the multiple ones (p =0.003). Four cases of adenoma (3.2%) were diagnosed; one of them had in situ carcinoma. All were single and larger than 10 mm. We found a significant correlation between ultrasonographic and histopathological polyp size determination (r =0.47; p =0.002). Polyp size was also a predictor of the presence of adenoma (p =0.043; confidence intervals: 1.006-1.424). There is a good correlation between the size of the gallbladder polyp in ultrasonography and the size in the histopathology report. Gallbladder adenoma is uncommon and it correlates with the size of the polyp. In this series, size was the only predictor of the presence of adenoma.


Effects of the naked-neck gene on traits associated with egg laying in a dwarf stock at two temperatures.
Naked-neck (NaNa and Nana+) and normal hens, all dwarf (dw), were compared for laying performance in two groups at 15 to 20 or 30 degrees C. Naked-neck hens, especially homozygotes, weighed less only at the cooler temperature. Body fatness was not different. Normal, but not naked-neck birds, showed a depression in food intake and egg output at 30 degrees C. In the hot environment mean egg weight and egg mass output were highest for naked-neck homozygotes. At the cooler temperature mean egg weight was also higher for this genotype, at fixed body weight. The decline in egg mass with time seemed greater for fully-feathered layers at high temperature. At moderate temperature residual food intake was slightly increased by the naked-neck gene, but owing to the reduced body weight, food utilisation was not poorer for the NaNa or Nana+ genotypes. At higher temperature Nana+ and especially NaNa hens utilised food more efficiently. An increase in wattle size and a slight decrease in body temperature were associated with the Na allele.


Effects of glossopharyngeal insufflation in ankylosing spondylitis: a pilot study.
In Ankylosing Spondylitis (AS), thoracic range of motion is often greatly limited. The objective of the study was to describe the effects of 12 weeks of Glossopharyngeal Insufflation (GI) training in patients with AS. Dynamic spirometry included vital capacity, forced expiratory volume, and peak expiratory flow. Thoracic and lumbar range of motion was assessed by tragus-to-wall distance, modified Schober test, and tape measure. Disease activity, activity limitation, and health perception were assessed using the BAS-Indices, and tension in the thoracic region during GI was assessed using the Borg CR-10 scale. Adherence to training was recorded in an activity log, along with any remarks on the training. Ten patients were recruited and six male patients fulfilled the study protocol. Three patients were able to learn GI by exceeding their maximal vital capacity with 5% using GI. A significant increase in thoracic range of motion both on costae IV (P = 0.04) and at the level of the xiphoid process (P = 0.04) was seen. Thus, patients with AS can practice GI, it is safe if maximal exertion is avoided, and patients with some mobility in the chest can increase their lung function substantially by performing GI during 12 weeks.


Premeiotic clusters of mutation and the cost of natural selection.
Haldane stated that there is a cost of natural selection for new beneficial alleles to be substituted over time. Most of this cost, which leads to "genetic deaths," is in the early generations of the substitution process when the new allele is low in frequency. It depends on the initial frequency and dominance value, but not the selection coefficient, of the advantageous allele. There have been numerous suggestions on how to reduce the cost for preexisting genetic variation that goes from disadvantageous, or neutral, to advantageous with a change in the environment. However, the cost of natural selection for new alleles that arise by mutation is assumed to be high, based on the assumption that new mutant alleles arise in natural populations as single events [1/(2N) of the total alleles]. However, not all mutant alleles arise as single events. Premeiotic mutations occur frequently in individuals (germinal mosaics), giving rise to multiple copies of identical mutant alleles called a "cluster" (C) with an initial allele frequency of C/(2N) instead of 1/(2N). These clusters of new mutant alleles reduce the cost of natural selection in direct proportion to the relative size of the cluster. Hence new advantageous alleles that arise by mutation have the greatest chance of going to fixation if they occur in large clusters in small populations.


[Clinico-pathological analysis of vesiculotubular myopathy of adult onset].
The patient was a 50-year-old house wife. There were complicated consanguineous marriages in the family tree. Since 30 years of age, she had suffered from progressive limb muscle weakness, but without myalgia and myasthenia. At present, she was wheelchair-bound. Physical examinations showed obesity, congenital livedo racemosa, epicanthus palpebrae and left renal defect. Neurologically, facial, anterior cervical, and iliopsoas muscles were well preserved, but others were severely involved. Laboratory examinations revealed mildly elevated myogenic serum enzymes, and myogenic changes on needle EMG. In her muscle biopsy from the left rectus femoris muscle, there were no inflammatory changes, but marked variations of the fiber size as well as adipose tissue replacement were recognized. Strickingly, basophilic masses located in the center of the sarcoplasm were present in about 10% of the fibers. Histochemically, the masses were present in both type 1 and 2 fibers, and exhibited almost similar stained patterns to the tubular aggregates, but were dystrophin-, GRP78- and clathrin-positive. Under electron microscopy, the masses consisted of aggregates of the vesiculotubular structure, measuring approximately from 60 nm to more than 6 microns in diameter, which were continuous with T system/sarcoplasmic reticulum and were clearly segregated from myofilaments. This is a chronic progressive muscular disorder of adult onset with the peculiar pathological finding of vesiculotubular structure.


Nucleoside Analogs with Antiviral Activity against Yellow Fever Virus.
Yellow fever virus (YFV) is a human Flavivirus reemerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of an effective antiviral against YFV is crucial, as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with 50% effective concentration (EC50) values between 0.25 and 1 μM with selectivity indices over 100 in culture.


Regulatory principles governing Salmonella and Yersinia virulence.
Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.


Spent hops (Humulus Lupulus L.) extract as modulator of the inflammatory response in lipopolysaccharide stimulated RAW 264.7 macrophages.
Macrophages play important roles in acute and chronic inflammation. Upon their activation, they secrete a variety of mediators, including eicosanoids, nitric oxide and cytokines, which play different roles in the stimulation and resolution of inflammatory processes. There is a continuous search for selective modulators of these processes. Natural polyphenols and polyphenol-rich extracts have been found to possess preventive and therapeutic potential, including by their anti-inflammatory effects. In this study, the inhibition of the formation of inflammatory mediators by the spent hops extract (SHE), a polyphenol-rich extract from Humulus Lupulus L., was examined using lipopolysaccharide (LPS)- activated murine macrophages (RAW 264.7). The SHE suppressed inter alia the interleukin-6 (IL-6) mRNA expression to 32% in LPS-activated macrophages and to 61% at a protein level (at 25 μg/mL). SHE reduced both the cyclooxygenase-2 (COX-2) mRNA expression to 47% and their protein expression to 32%. Not only did SHE inhibit the IL-6 and COX-2 levels but also decreased both inducible nitric oxide synthase (iNOS) protein expression to 2% at 25 μg/mL and nitric oxide (NO) production for all tested concentrations. The inhibited expression of these inflammatory molecules was likely caused by the reduced activity of nuclear factor-κB (NF-κB). Both mRNA and protein expression of NF-κB was decreased to 38% and 42%, respectively. These results provide the first evidence that SHE decreases the expression of proinflammatory cytokines and inflammatory mediators, which merits further studies to investigate the potential of SHE as anti-inflammatory preparation.


Ca2+ sensitization in contraction of human bladder smooth muscle.
The role of Ca2+ sensitization in the contraction of human bladder urinary smooth muscle (UBSM) was investigated. Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension in fura-2 loaded intact strips and receptor coupled strips permeabilized with alpha-toxin were applied. Protein expressions was confirmed by Western blot analysis. In intact fura-2 loaded strips 1 microM carbachol (CCh) induced a greater contraction and a lower [Ca2+]i elevation than that induced by 60 mM K depolarization. In alpha-toxin permeabilized strips 1 microM CCh induced contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips the application of 3 microM Y-27632, a ROCK inhibitor, or 3 microM bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the sustained phase of contraction induced by 1 microM CCh induced relaxation without changing [Ca2+]i. In alpha-toxin permeabilized strips the application of 3 microM Y-27632 or 3 microM GF109203X during the sustained contraction induced by 0.3 microM Ca plus 10 microM guanosine triphosphate and 1 microM CCh induced relaxation at constant [Ca2+]i. These results indicate that in human UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.


The predictive power of trajectory motion.
When the central region of an obliquely oriented line is bisected by a wide, vertical opaque occluder, observers misperceive the two line segments as being misaligned (the Poggendorff illusion). If the oblique line segment is replaced with a spot moving on an oblique trajectory, little if any misalignment is perceived. This accurate alignment of oblique segments depends upon the consistent motion of the dot along the oblique trajectory and not other temporal or spatial characteristics of the motion-defined segments since random plotting of the dot along each oblique segment resulted in robust misalignment. The nullification of the Poggendorff illusion was also obtained if only one of the segments was defined by a moving spot so long as the spot moved in a direction that 'pointed' to the static segment. Moreover, if the occluder boundary was defined by rows of vertically moving dots, was filled with vertically moving dots or was a real (cardboard) occluder, the motion-defined oblique segments were still perceived to be aligned with little error, consistent with the unimpaired detection of a trajectory dot in noise interrupted by similar occluders [Watamaniuk, S. N. J. & McKee, S. P. (1995). 'Seeing' motion behind occluders. Nature, 377, 729-730]. The results are interpreted as evidence that trajectory motion produces a cascade of activity in appropriately aligned motion detectors, in the direction of motion, that continues after the moving object has been occluded to produce a prediction of where the moving object should reappear.


Delayed closure technique using the ventral hernia repair prosthesis for a ruptured abdominal aortic aneurysm: report of a case.
In spite of modern advances in medical care, the operative mortality of ruptured abdominal aortic aneurysm remains high at 40%-50%. Multiple organ failure is one of the reasons for the high mortality rates. An acute increase in intra-abdominal pressure and abdominal compartment syndrome are common causes of multiple organ failure.It is important to prevent abdominal compartment syndrome to improve the outcome of ruptured abdominal aortic aneurysm. Delayed abdominal closure is effective in preventing abdominal compartment syndrome in patients with ruptured abdominal aortic aneurysm. We successfully achieved delayed abdominal closure using the ventral hernia repair prosthesis for a ruptured abdominal aortic aneurysm, in a straightforward and rapid manner. No infection was seen, secondary closure was readily performed, and wound healing was good. We conclude that our delayed closure technique is useful for the treatment of ruptured abdominal aortic aneurysm.


Experimental simulation of A-bomb gamma ray spectra: revisited.
It has been reported recently that the A-bomb gamma ray spectra received by the colon of the average Japanese survivor of Hiroshima and Nagasaki may be experimentally simulated using a hospital-based Philips SL15 linear accelerator. The simulated A-bomb gamma radiation may be used in radiobiology experiments to determine, amongst other things, the biological effectiveness of the A-bomb gamma radiation. However, in that study, the electron beams from the linear accelerator were poorly defined and photon contamination was ignored. In the study reported here, a Varian Clinac 2100C linear accelerator has been used for the same purpose but with photon contamination included in better defined output electron beams. It is found that the A-bomb gamma radiation can still be matched to an acceptable degree (<10%). The cause of the slightly poorer fit was due mainly to the different ranges of energies available from the linear accelerators used. The absorbed dose received by model breasts was also estimated in this study for the same situations as in the previous study. The ratio of the breast to colon doses was found to be only (3.9 +/- 4.0)% low compared with the expected values of 1.17 and 1.16 for Hiroshima and Nagasaki, respectively. These results provide further confirmation of the acceptability of the simple cylindrically symmetrical body models employed in these studies to represent the average Japanese survivor.


Pseudohypoparathyroidism versus signaling disorder: A case report.
Pseudohypoparathyroidism is a terminology used to describe a group of metabolic disorders characterized by parathyroid hormone resistance. Patients with pseudohypoparathyroidism have hypocalcemia, hyperphosphatemia, and elevated serum parathyroid hormone. This methylation defect leads to signaling abnormalities in the parathyroid hormone and parathyroid hormone-related peptide receptor. We present a 40-year-old African American male who was referred to our endocrinology clinic for hypocalcemia. On physical examination, his body mass index was 34.3 kg/m2 and he was found to have a round face, and several subcutaneous nodules on his scalp, hands, and legs. Laboratory findings revealed hypocalcemia, hyperphosphatemia, and elevated levels of intact parathyroid hormone and thyroid stimulating hormone (TSH). His hand X-ray showed brachydactyly of all metacarpal bones, and soft tissue calcifications. Brain CT indicated dense calcifications in the subcortical region, bilateral basal ganglia, bilateral thalami, bilateral cerebellum and vermis, and soft tissue calcifications in the scalp. The "inactivating parathyroid hormone/parathyroid hormone-related peptide signaling disorder" diagnostic approach suggested by the Euro pseudohypoparathyroidism network was applied to the patient, who was diagnosed with parathyroid hormone signaling disorder. Compared to the old pseudohypoparathyroidism classification and the 2018 Pseudohypoparathyroidism International Consensus Statement Report, the inactivating parathyroid hormone/parathyroid hormone-related peptide signaling disorder cluster classification appears to be more flexible, and easier to use. It also accommodates future inclusion of genetic mutations associated with hormonal signaling disorders. Adoption of the inactivating parathyroid hormone/parathyroid hormone-related peptide signaling disorder classification remains limited, and further larger studies are needed to compare the three approaches.


Defective production of reactive oxygen intermediates by tumor-associated macrophages exposed to phorbol ester.
Macrophages were isolated from poorly immunogenic metastatic sarcomas (mFS6 and MN/MCA1) of C57BL/6 origin. Tumor-associated macrophages (TAM) showed little release of superoxide when exposed to phorbol myristate acetate. When exposed to a phagocytic stimulus (zymosan), TAM released appreciable amounts of superoxide. TAM had a lower number of specific binding sites for phorbol esters than resident or caseinate-elicited peritoneal macrophages, but had normal NADPH-cytochrome C reductase. The tumor environment, possibly through previously demonstrated products of neoplastic cells, may influence the functional status of in situ macrophages and, thus, impair host anti-tumor and anti-microbial defense mechanisms.


Nuclear Envelope-Associated Chromosome Dynamics during Meiotic Prophase I.
Chromosome dynamics during meiotic prophase I are associated with a series of major events such as chromosomal reorganization and condensation, pairing/synapsis and recombination of the homologs, and chromosome movements at the nuclear envelope (NE). The NE is the barrier separating the nucleus from the cytoplasm and thus plays a central role in NE-associated chromosomal movements during meiosis. Previous studies have shown in various species that NE-linked chromosome dynamics are actually driven by the cytoskeleton. The linker of nucleoskeleton and cytoskeleton (LINC) complexes are important constituents of the NE that facilitate in the transfer of cytoskeletal forces across the NE to individual chromosomes. The LINCs consist of the inner and outer NE proteins Sad1/UNC-84 (SUN), and Klarsicht/Anc-1/Syne (KASH) domain proteins. Meiosis-specific adaptations of the LINC components and unique modifications of the NE are required during chromosomal movements. Nonetheless, the actual role of the NE in chromosomic dynamic movements in plants remains elusive. This review summarizes the findings of recent studies on meiosis-specific constituents and modifications of the NE and corresponding nucleoplasmic/cytoplasmic adaptors being involved in NE-associated movement of meiotic chromosomes, as well as describes the potential molecular network of transferring cytoplasm-derived forces into meiotic chromosomes in model organisms. It helps to gain a better understanding of the NE-associated meiotic chromosomal movements in plants.


Early effect of Mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages.
Effect of M. tuberculosis infection was studied on the expression of intercellular adhesion molocule-1 (ICAM-1) and Mac-1 markers on murine peritoneal macrophages. Intraperitoneal administration of M. tuberculosis resulted in a marked increase in the proportion of Mac-1(+) cells whereas the proportion of ICAM-1(+) cells declined sharply 4 h post infection. Absolute numbers of Mac-1(+) and ICAM-1(+) cells however increased at all time points after the infection. Comparison of kinetics of changes observed in Mac-1(+) and ICAM-1(+) cell populations with differential leukocyte counts in peritoneal cells indicated that these alterations could be due to cellular influx, especially that of neutrophils, or up regulation of these markers on macrophages and other peritoneal cells. In adherent peritoneal macrophages infected in vitro with M. tuberculosis, proportion of Mac-1(+) and ICAM-1(+) cells increased markedly within 24 h of infection. Mean expression of these markers on per cell basis also increased significantly. Similar results were obtained by using RAW 264.7 mouse macrophage cell line, suggesting that the enhanced expression of Mac-1 and ICAM-1 markers was a direct effect of M. tuberculosis infection and not mediated by contaminating cell types present in adherent macrophage preparations. Mac-1 and ICAM-1 expression was further studied on macrophages that had actually engulfed M. tuberculosis and compared with bystander macrophages without intracellular M. tuberculosis. For this purpose M. tuberculosis pre-stained with DilC18 fluorescent dye were used for infecting adherent peritoneal macrophages. Mac-1 and ICAM-1 expression on gated DilC18 positive and negative cell populations was analyzed. Our results indicate that the expression of Mac-1 and ICAM- 1 markers was significantly enhanced on all macrophages incubated with M. tuberculosis but was more pronounced on macrophages with internalized mycobacteria. Taken together, our results suggest that the expression of Mac-1 and ICAM-1 markers is significantly up regulated as a result of exposure and infection with M. tuberculosis. Since these markers play important role in the uptake of mycobacteria as well as in the process of antigen presentation by macrophages, their upregulation may be beneficial for generation of a protective immune response to M. tuberculosis.


Glycyrrhizic acid ameliorates the kynurenine pathway in association with its antidepressant effect.
Our previous study implied the role of central high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-induced depressive-like behaviors that could partially abrogate by glycyrrhizic acid (GZA). Here, we considered the potential mechanism underlying GZA ameliorating chronic stress-induced depression both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS) mice. Sucrose preference test, tail suspension test and open field test were performed to reflect depressive-like behaviors. Enzyme activity of indoleamine-2,3-dioxygenase (IDO) was recorded with the ratio of kynurenine (KYN) / tryptophan (Trp). Transcription of gene was evaluated by RT-PCR. Along with depressive-like behaviors, IDO, the rate-limiting enzyme of the kynurenine pathway (KP), was upregulated at the level of mRNA expression, and enzyme activity was also elevated in stressed hippocampi and LPS/HMGB1-treated hippocampus slices. Treatment of mice with GZA, the inhibitor of HMGB1, prevented the activated enzymes in KP and the development of depressive-like behaviors. These experiments demonstrate that GZA may restrain HMGB1 thus improving chronic stress-induced depressive behavior through regulating KP.


Early discharge and home treatment of patients with acute pulmonary embolism in the tertiary care setting.
Acute pulmonary embolism (PE) is a potentially life-threatening disease. Current guidelines suggest risk-adapted management. Hospitalization is required for intermediate- and high-risk patients. Early discharge and home treatment are considered safe in the majority of low-risk patients. In this study, we describe characteristics, discharge, and outcome of outpatients diagnosed with acute PE at a tertiary care center. All outpatients undergoing computed tomography pulmonary angiography or ventilation/perfusion lung scan between 01.01.2016 and 31.12.2019 at the University Hospital Vienna, Austria, were screened for a PE diagnosis. Electronic patient charts were used to extract characteristics, clinical course, and outcomes. Within the 4-year period, 709 outpatients (median age: 62 years, 50% women) were diagnosed with PE. Thirty-three (5%) patients were classified as high-risk, 159 (22%) as intermediate-high, 332 (47%) as intermediate-low, and 185 (26%) as low-risk PE according to the European Society of Cardiology risk stratification. In total, 156 (22%) patients (47% with low-risk and 20% with intermediate-low-risk PE) were discharged as outpatients and received home treatment. Rates for home treatment increased 2.4-fold during the study period. Thirty-day mortality in the entire population was 4.9%. All low-risk patients and all but one patient with home treatment survived the first 30 days. Home treatment significantly increased over time and seems to be safe in routine clinical practice. Notably, one in five intermediate-low-risk patients was discharged immediately, suggesting that a subpopulation of intermediate-low-risk patients may also be eligible for home treatment.


Website Use and Effects of Online Information About Tobacco Additives Among the Dutch General Population: A Randomized Controlled Trial.
As a legal obligation, the Dutch government publishes online information about tobacco additives to make sure that it is publicly available. Little is known about the influence this website ("tabakinfo") has on visitors and how the website is evaluated by them. This study assesses how visitors use the website and its effect on their knowledge, risk perception, attitude, and smoking behavior. The study will also assess how the website is evaluated by visitors using a sample of the Dutch general population, including smokers and nonsmokers. A randomized controlled trial was conducted, recruiting participants from an online panel. At baseline, participants (N=672) were asked to fill out an online questionnaire about tobacco additives. Next, participants were randomly allocated to either one of two experimental groups and invited to visit the website providing information about tobacco additives (either with or without a database containing product-specific information) or to a control group that had no access to the website. After 3 months, follow-up measurements took place. At follow-up (n=492), no statistically significant differences were found for knowledge, risk perception, attitude, or smoking behavior between the intervention and control groups. Website visits were positively related to younger participants (B=-0.07, 95% CI -0.12 to -0.01; t11=-2.43, P=.02) and having a low risk perception toward tobacco additives (B=-0.32, 95% CI -0.63 to -0.02; t11=-2.07, P=.04). In comparison, having a lower education (B=-0.67, 95% CI -1.14 to -0.17; t11=-2.65, P=.01) was a significant predictor for making less use of the website. Furthermore, the website was evaluated less positively by smokers compared to nonsmokers (t324=-3.55, P<.001), and males compared to females (t324=-2.21, P=.02). The website did not change perceptions of tobacco additives or smoking behavior. Further research is necessary to find out how online information can be used to effectively communication about the risks of tobacco additives. Nederlands Trial Register NTR4620; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4620 (Archived by WebCite at http://www.webcitation.org/6oW7w4Gnj).


Effect of dietary antibiotics on chickens infected with Eimeria tenella.
Two experiments were performed to study the effect of dietary antibiotics on percent daily weight change, mortality and gross cecal pathology in chickens during the critical phase of Eimeria tenella infection. In the first experiment, chickens were continuously fed ration containing thiopeptin, 2 mg/kg.; bacitracin, 20 mg./kg.; penicillin, 12 mg./kg.; or chlortetracycline, 22 mg./kg. One day after antibiotic fed was given, each bird received an oral inoculation of 30,000 sporulated oocyts. In the second experiment, chickens were consecutively fed ration containing amprolium plus ethopabate, 125 plus 8 mg./kg., and a combination of the coccidiostat and one of 4 antibiotics; thiopeptin, bacitracin, penicillin, or chloretracycline. One day after medicated feed was given, birds were each given an oral inoculation of 30,000 amprolium plus ethopabate-resistant E. tenella oocysts. The experiments were terminated 7 days after coccidia exposure. In both experiments, E. tenella infection resulted in depression in all birds of infected groups. Average percent weight change of infected birds was significantly lower than that of uninfected unmedicated control between 4 and 5 days after infection. Significantly greater number of birds died of cecal coccidiosis in group fed dietary bacitracin than that of other infected groups. Dietary antibiotics did not reduce gross cecal lesions.


Pseudolymphoma of the tongue mimicking Hodgkin's disease. (A case report).
We have presented a case of what we believe to be pseudolymphoma arising on the dorsal aspect of the anterior part of the tongue in a middle-aged male with histological features initially suggestive of Hodgkin's disease. The nature and significance of pseudolymphoma have been discussed, together with a critical review of the relevant literature and a suggested outline of management for patients with this type of lesion.


Reaction of Cd7-metallothionein with cis-dichlorodiammine platinum (II).
The reaction of Cd7-metallothionein with cis-dichlorodiammine platinum (II) has been examined in titration and kinetic experiments. Titrations followed by 111Cd NMR spectroscopy and analysis of cadmium and platinum in the products indicated that platinum displaced cadmium in approximate 1:1 fashion, producing Pt7-metallothionein. According to NMR analysis, the overall reaction involved cooperative exchange of platinum for 111Cd in each domain of the protein. There was a modest preference for the reaction of the drug with the Cd3-containing beta-domain of the protein. The product had an apparent molecular weight that was nearly the same as that of Cd7-metallothionein as determined by Sephadex G-75 chromatography. Kinetic analysis also supported a cooperative displacement mechanism. The reaction was biphasic; neither step could be identified solely with the reaction of one cluster as indicated by the biphasic reaction of the Cd4-containing alpha-domain with the platinum complex.


Quantification of Clostridium botulinum type A toxin and organisms in the feces of a case of infant botulism and examination of other related specimens.
Bacteriological examinations were performed on the first case of infant botulism in Japan (an infant boy aged 79 days at onset of illness). Clostridium botulinum type A toxin and organisms were detected continually in the stools of the infant for at least 31 days and 39 days, respectively. The highest levels of the toxin and of the population of the organisms, 7.8 X 10(4) LD50/g and 1.3 X 10(6) colony forming units (cfu)/g, were detected in the stool specimen taken on the 20th day of illness. Type A organisms were detected also in the honey fed to the infant before onset of illness, teats of his feeding bottle, soil specimens taken at the house entry and the vacuum-cleaner dust. Fecal excretion of the toxin and organisms was no longer detected from the 68th day of illness and he recovered.


Studies of self-organized nanostructures on InP(111) surfaces after low energy Ar+ ion irradiation.
We report formation of self organized InP nano dots using 3 keV Ar+ ion sputtering, at 15 degrees incidence from surface normal, on InP(111) surface. Morphology and optical properties of the sputtered surface, as a function of sputtering time, have been investigated by Scanning Probe Microscopy and Raman Scattering techniques. Uniform patterns of nano dots are observed for different durations of sputtering. The sizes and the heights of these nano dots vary between 10 to 100 nm and 20 to 40 nm, respectively. With increasing of sputtering time, t, the size and height of these nano dots increases up to a certain sputtering time t(c). However beyond t(c), the dots break down into smaller nanostructures, and as a result, the size and height of these nanostructures decrease. The uniformity and regularity of these structures are also lost for sputtering beyond t(c). The crossover behavior is also observed in the rms surface roughness. Raman investigations of InP nano dots reveal optical phonon softening due to phonon confinement in the surface nano dots.


Economist intelligence unit democracy index in relation to health services accessibility: a regression analysis.
The relationship between political environment and health services accessibility (HSA) has not been the focus of any specific studies. The purpose of this study was to address this gap in the literature by examining the relationship between political environment and HSA. This relationship that HSA indicators (physicians, nurses and hospital beds per 10 000 people) has with political environment was analyzed with multiple least-squares regression using the components of democracy (electoral processes and pluralism, functioning of government, political participation, political culture, and civil liberties). The components of democracy were represented by the 2011 Economist Intelligence Unit Democracy Index (EIUDI) sub-scores. The EIUDI sub-scores and the HSA indicators were evaluated for significant relationships with multiple least-squares regression. While controlling for a country's geographic location and level of democracy, we found that two components of a nation's political environment: functioning of government and political participation, and their interaction had significant relationships with the three HSA indicators. These study findings are of significance to health professionals because they examine the political contexts in which citizens access health services, they come from research that is the first of its kind, and they help explain the effect political environment has on health.


Prospective comparison of noninvasive, bedside ultrasound methods for assessing central venous pressure.
To prospectively evaluate the accuracy of noninvasive central venous pressure (CVP) assessment by compression ultrasound of a forearm vein (CUS), inferior vena cava (IVC-C) and internal jugular vein collapsibility (IJV-C) compared to invasive CVP measurement (invCVP) as the gold standard. CUS, IVC-C and IJV-C were performed in a random sequence in 81 consecutive intensive care patients with simultaneous invCVP monitoring. Examiners were blinded to invCVP and previous examinations. Median invCVP was 12.0 mmHg (range 1 - 23). CUS, IVC-C and IJV-C could be obtained in 89 %, 95 % and 100 % of cases, respectively, within a median time of 188 sec [IQR 125; 270], 133 sec [IQR 100; 211] and 60 sec [IQR 50; 109], respectively. The Spearman correlation coefficient between invCVP and CUS, IVC-C, and IJV-C was 0.485 95 %-CI [0.25; 0.65], -0.186 [-0.42; 0.07], and -0.408 [-0.59; -0.18], respectively. The median absolute difference between CUS and invCVP was 3 mmHg [IQR 2; 6.75]. CVP was categorized as low (< 7 mmHg; collapsibility > 0.6), normal (7 - 12 mmHg; collapsibility 0.6 - 0.2) and high (> 12 mmHg; collapsibility < 0.2) as prespecified. The proportions of identical CVP classifications compared to invCVP were 61.4% 95%-CI [49.3%; 72.4%] with CUS, 48.7% [37.4%; 60%] with IVC-C and 51.3% [40.3%; 62.3%] with IJV-C (p > 0.10 for all pair-wise comparisons). The overall ability of CUS, IVC-C and IJV-C to assess invCVP was only moderate. CUS seems to be the preferable method if absolute CVP values are needed. IJV-C seems to be the fastest and most easily acquirable method, and thus may be especially valuable in emergency rooms.


[Fluorescence spectroscopy and imaging for optical biopsy].
In the past few years extensive attention has turned toward optical biopsy, because of its ability to perform noninvasive, real time and accurate diagnosis of tissue pathologies, especially precancer. Fluorescence spectroscopy is one of a series of techniques widely developed for optical biopsy, and can be generally divided into two categories: fluorescence spectroscopy and imaging. This paper reviews the applications of autofluorescence and exogenous fluorescence to optical biopsy, and the principle and advantages as well as the clinic applications of various steady-state and time-resolved fluorescence spectroscopy and imaging techniques. Furthermore, the development perspectives of optical biopsy by using fluorescence spectroscopy and imaging are also briefly discussed.


Determining the optimal forensic DNA analysis procedure following investigation of sample quality.
Crime scene traces of various types are routinely sent to forensic laboratories for analysis, generally with the aim of addressing questions about the source of the trace. The laboratory may choose to analyse the samples in different ways depending on the type and quality of the sample, the importance of the case and the cost and performance of the available analysis methods. Theoretically well-founded guidelines for the choice of analysis method are, however, lacking in most situations. In this paper, it is shown how such guidelines can be created using Bayesian decision theory. The theory is applied to forensic DNA analysis, showing how the information from the initial qPCR analysis can be utilized. It is assumed the alternatives for analysis are using a standard short tandem repeat (STR) DNA analysis assay, using the standard assay and a complementary assay, or the analysis may be cancelled following quantification. The decision is based on information about the DNA amount and level of DNA degradation of the forensic sample, as well as case circumstances and the cost for analysis. Semi-continuous electropherogram models are used for simulation of DNA profiles and for computation of likelihood ratios. It is shown how tables and graphs, prepared beforehand, can be used to quickly find the optimal decision in forensic casework.


Quantitative Determination and Validation of Four Ketones in Salvia miltiorrhiza Bunge Using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy.
Salvia mltiorrhiza Bunge (SMB) is native to China, whose dried root has been used as medicine. A few chromatographic- or spectrometric-based methods have already been used to analyze the lipid-soluble components in SMB. However, the methodology of qNMR on the extracts of fresh SMB root has not been verified so far. The purpose of this study was to establish a fast and simple method to quantify the tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh Salvia Miltiorrhiza Bunge root without any pre-purification steps using 1H-NMR spectroscopy. The process is as follows: first, 70% methanol aqueous extracts of fresh Salvia Miltiorrhiza Bunge roots were quantitatively analyzed for tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone using 1H-NMR spectroscopy. Different internal standards were tested and the validated method was compared with HPLC. 3,4,5-trichloropyridine was chosen as the internal standard. Twelve samples of Salvia Miltiorrhiza Bunge were quantitatively analyzed by qNMR and HPLC respectively. Then, the results were analyzed by chemometric approaches. This NMR method offers a fast, stable, and accurate analysis of four ketones: tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh roots of Salvia Miltiorrhiza Bunge.


Estimation of arterial arrival time and cerebral blood flow from QUASAR arterial spin labeling using stable spline.
QUASAR arterial spin labeling (ASL) permits the application of deconvolution approaches for the absolute quantification of cerebral perfusion. Currently, oscillation index regularized singular value decomposition (oSVD) combined with edge-detection (ED) is the most commonly used method. Its major drawbacks are nonphysiological oscillations in the impulse response function and underestimation of perfusion. The aim of this work is to introduce a novel method to overcome these limitations. A system identification method, stable spline (SS), was extended to address ASL peculiarities such as the delay in arrival of the arterial blood in the tissue. The proposed framework was compared with oSVD + ED in both simulated and real data. SS was used to investigate the validity of using a voxel-wise tissue T1 value instead of using a single global value (of blood T1 ). SS outperformed oSVD + ED in 79.9% of simulations. When applied to real data, SS exhibited a physiologically realistic range for perfusion and a higher mean value with respect to oSVD + ED (55.5 ± 9.5 SS, 34.9 ± 5.2 oSVD + ED mL/100 g/min). SS can represent an alternative to oSVD + ED for the quantification of QUASAR ASL data. Analysis of the retrieved impulse response function revealed that using a voxel wise tissue T1 might be suboptimal.


Circulating microRNAs as Potential Biomarkers of Infectious Disease.
microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease.


Immunoglobulin M antibodies to hepatitis B core antigen: evaluation of enzyme immunoassay for diagnosis of hepatitis B virus infection.
In acute and chronic hepatitis B, antibodies of the immunoglobulin M (IgM) class against the hepatitis B core antigen (anti-HBc IgM) have been demonstrated. For the determination of anti-HBc IgM, a sensitive enzyme immunoassay with anti-mu-coated flat-bottomed microtiter plates is described and evaluated. The specificity of the anti-HBc IgM test system was proven by pretreatment of presumed anti-HBc IgM-positive samples with anti-mu to block anti-HBc IgM. The test system was highly sensitive. In the acute stage of hepatitis B, anti-HBc IgM could be demonstrated in serum dilutions up to 10(-7) (mean titer, 10(-5)), and in sera from patients with chronic hepatitis B, the mean titer was 10(-3). In a study of unselected patients whose sera were sent at irregular intervals for testing, anti-HBc IgM persisted in a high percentage (52%) for at least 13 to 18 months after onset of illness despite the fact that these patients eliminated hepatitis B surface antigen (HBsAg) and produced antibodies to HBsAg (anti-HBs). By using the anti-HBc IgM test as an additional aid in the diagnosis of acute HBsAg-negative hepatitis, the hepatitis B etiology could be established in 13 of 42 patients (31.4%). Investigations of the prevalence of anti-HBc IgM in different groups of patients with chronic hepatitis B infection showed 89.4% anti-HBc IgM-positive results in patients with chronic active hepatitis B, 60% in patients with HBsAg-negative chronic active hepatitis, 58.2% in patients with primary liver carcinoma and markers of hepatitis B infections, and 34.9% in healthy carriers of HBsAg.


Two unsung heroes of closed-chest cardiac pacing: Green and McWilliam.
In the latter half of the last century, cardiorespiratory arrest was not uncommon due to the anesthetic used (chloroform). Animal studies showed that the heart could be paced. One physician (Green) resuscitated 5 of 7 cardiac arrest patients with single stimuli applied to body surface electrodes. Another (McWilliam) issued a proposal for adoption of closed-chest pacing and provided information on the procedure. The following historical footnote describes these pioneering events in the history of cardiac pacing.


Electrolyte Engineering on Performance Enhancement of NiCo2 S4 Anode for Sodium Storage.
NiCo2 S4 is an attractive anode for sodium-ion batteries (SIBs) due to its high capacity and excellent redox reversibility. Practical deployment of NiCo2 S4 electrode in SIBs, however, is still hindered by the inferior capacity and unsatisfactory cycling performance, which result from the mismatch between the electrolyte chemistry and electrode. Herein, a functional electrolyte containing 1.0 m NaCF3 SO3 in diethylene glycol dimethyl ether (DEGDME) (1.0 m NaCF3 SO3 -DEGDME) is developed, which can be readily used for NiCo2 S4 anode with high initial coulomb efficiency (96.2%), enhanced cycling performance, and boosted capacities (341.7 mA h g-1 after 250 continuous cycles at the current density of 200 mA g-1 ). The electrochemical tests and related phase characterization combined with density functional theory (DFT) calculation indicate the ether-based electrolyte is more suitable for the NiCo2 S4 anode in SIBs due to the formation of a stable electrode-electrolyte interface. Additionally, the importance of the voltage window is also demonstrated to further optimize the electrochemical performance of the NiCo2 S4 electrode. The formation of sulfide intermediates during charging and discharging is predicted by combining DFT and verified by in situ XRD and HRTEM. The findings indicate that electrolyte engineering would be an effective way of performance enhancement for sulfides in practical SIBs.


Patterns of cardiovascular and ventilatory response to maximal cardiopulmonary test in elite basketball players.
The aim of this study was to investigate patterns of cardiovascular and ventilatory response during cardiopulmonary exercise stress test and determine standard values of physical capacity during cardiopulmonary exercise stress tests for professional basketball players. Materials of the study were collected during a ramp exercise test of 33 professional athletes using an electronically braked bike ERGOLINE 9000. Power output and heart rate samples were collected. Ventilation and gas exchange indices were measured during the tests using VMAX229 metabolic card and Sensor Medics gas flow analyzer. Scattergrams of power, oxygen uptake, heart rate and pulmonary ventilation with 95% mean prediction intervals were presented. Data of European champions as example of successful conditioning were compared with other athletes. The typical values of oxygen uptake, power output, hear rate and pulmonary ventilation are presented. We found statistically significant correlations between heart rate, oxygen uptake and power output at anaerobic threshold. Statistically significant correlations between heart rate, oxygen uptake and power output disappeared at peak of exercise. The data of incremental exercise tests gives valid information about physical capacity of basketball players. The collected data could become referential source for the sport and might be useful for monitoring and evaluating current and future players. European champions developed relative high peak oxygen consumption despite "early" anaerobic threshold. Other advantages of European champions during cardiopulmonary testing were not determined.


Cholesteatoma of the external ear canal: etiological factors, symptoms and clinical findings in a series of 48 cases.
To evaluate symptoms, clinical findings, and etiological factors in external ear canal cholesteatoma (EECC). Retrospective evaluation of clinical records of all consecutive patients with EECC in the period 1979 to 2005 in a tertiary referral centre. Main outcome measures were incidence rates, classification according to causes, symptoms, extensions in the ear canal including adjacent structures, and possible etiological factors. Forty-five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of 12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4), hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms were found in secondary EECC, but less pronounced. In total the temporomandibular joint was exposed in 11 cases, while the mastoid and middle ear was invaded in six and three cases, respectively. In one primary case the facial nerve was exposed and in a posttraumatic case the atticus and antrum were invaded. In primary EECC 48% of cases reported mechanical trauma. EECC is a rare condition with inconsistent and silent symptoms, whereas the extent of destruction may be pronounced. Otalgia was the predominant symptom and often related to extension into nearby structures. Whereas the aetiology of secondary EECC can be explained, the origin of primary EECC remains uncertain; smoking and minor trauma of the ear canal may predispose.


Efficacy of aprepitant for nausea in patients with head and neck cancer receiving daily cisplatin therapy.
Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy). Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron (40 μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80 mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group). For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant. This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.