2HAPI: a microarray data analysis system.
2HAPI (version 2 of High density Array Pattern Interpreter) is a web-based, publicly-available analytical tool designed to aid researchers in microarray data analysis. 2HAPI includes tools for searching, manipulating, visualizing, and clustering the large sets of data generated by microarray experiments. Other features include association of genes with NCBI information and linkage to external data resources. Unique to 2HAPI is the ability to retrieve upstream sequences of co-regulated genes for promoter analysis using MEME (Multiple Expectation-maximization for Motif Elicitation) 2HAPI is freely available at http://array.sdsc.edu. Users can try 2HAPI anonymously with pre-loaded data or they can register as a 2HAPI user and upload their data.


[Epidemiology of domestic accidents of young children in Tunisia: impact of the training of health professionals on data collection quality].
In Tunisia, several studies on domestic injuries have been carried out on children attending care facilities. Nevertheless,there is a lack of data on incidence and kinds of child domestic injuries amongst general population because of absence of a reliable data collect system. To estimate the incidence and kinds of domestic injuries through a prospective survey "here-there" within two cohorts of young children attending two mother and child protection centers (MCPC) in Tunis during the three first years of their life and to analyze the importance of health professional training in improving data collect. A prospective study "here-there" was carried out on two cohorts of children in two mother and child protection centers (MCPC) between January 2007 and December 2009. Only children aged less than 3 months at their first contact with the centers were included and followed up until age of 3 years. In the MCPC2 (cohort2), health personnel have been trained on data collection importance related to child domestic accident and asked to monitor accidents by calling parents while a phone line got available for this aim. In the MCPC1, health personnel was asked to work as they used to do and to collect data on child domestic injuries when children attend the center. 192/435 domestic accidents were recorded within cohort 2 vs only 1/686 within cohort 1. Annual incidence rate was 14.7% for the cohort 2. The kinds of accidents were: falls 78.2% (falls from high plans 84.6%), injuries15.1% (injury by cutting things 58.6%),burns 5.7% (burns by hot liquid 54.5%), intoxications 1%. In terms of damages, we recorded 4 cases of broken bones (thighbone, elbow,handwrist), stitches in 11 cases, broken teeth in 3 cases and nail pulled out in one case. No death was recorded. Training impact on accident prevention was not studied. Child domestic accidents are relatively frequent. Health personnel training allows to improve data. The kinds of recorded accidents indicate the need to educate parents on best practices towards strengthening prevention.


C5a-inhibitory peptide combined with gabexate mesilate prevents the instant blood-mediated inflammatory reaction in a rat model of islet transplantation.
The instant blood-mediated inflammatory reaction (IBMIR), in which the activation of both the coagulation and the complement cascades plays a key role, is one of the main obstacles to successful islet transplantation. At present, however, no useful protocol is clinically available. Therefore the aim of this study was to examine whether complementary peptides against an active region of C5a were safe to suppress IBMIR, owing to their extremely low molecular mass, when combined with a clinically available anticoagulant. Complement receptors on pancreatic tissues and isolated islets were analyzed by immunohistochemical staining and flow cytometry. Two-and-a-half islet equivalents per gram of syngeneic rat islet grafts were transplanted intraportally into 4 groups of 10-13 animals each after streptozotocin induction of diabetes: control, gabexate (Gab), C5a-inhibitory peptide (C5aINH), and C5aINH plus Gab. Recipients injected with equivalent amounts of saline solution served as control subjects. Plasma samples were collected at 0, 0.5, 1, 3, 6, and 24 h after transplantation for analysis. We also evaluated the curative rate, intravenous glucose tolerance test, and insulin amounts in the liver of the recipients. C3a receptor (C3aR) was scarcely expressed on the isolated islets with relatively strong expression of C5a receptor (C5aR): C3aR: 0.44 +/- 0.38%; C5aR: 7.91 +/- 2.83%). However, C5aR was not expressed on pancreatic tissues before the isolation procedures. Thrombin-antithrombin complex was significantly suppressed in the 3 treated groups (P = .0015). The curative rate was also significantly improved (0% vs 33% vs 67% vs 100%, respectively; P = .03). Glucose tolerance was significantly improved among the 3 treated groups (P < .0005). Insulin amounts in the liver were considerably higher among treated versus control hosts. Notably, the treatment did not affect the increased body weight of the recipient. This study suggested that C5a-inhibitory peptide combined with gabexate mesilate may be a useful approach to control the IBMIR induced in clinical islet transplantation and one that is free of side effects.


Regulatory aspects of modified release dosage forms: clinical studies.
In a recently drafted "Note for guidance" of the European Community it is stated that "The therapeutic objective and rationale for developing the prolonged release product should be provided". This implies that any therapeutic claim should be documented by ad hoc clinical trials. Another "Note for guidance" describes "the studies to be conducted in man, which are specific to new extended release forms containing recognized active and safe medicinal substances so as to ensure a more prolonged action than the conventional pharmaceutical forms already marketed". From this second "Note for guidance" it appears clearly that three situations must be distinguished: a) a modified release dosage form is intended for use with a new active principle; b) the active principle is already available in a conventional pharmaceutical form; and c) the active principle is available as a modified release dosage form with which the new form is not bioequivalent. In case a) drug development clearly proceeds as with any other new clinical entity, but in addition "the therapeutic objectives and rationale for developing" a prolonged release product must be provided. Unless the reasons appear evident, some forms of comparison with a conventional release form or a solution will probably be needed for marketing authorization to be granted. In case b), recommendations contained in the "Note for Guidance" on clinical testing will have to be followed. For case c) no clear recommendations are available and it would probably be more efficacious to develop a new and bioequivalent modified release dosage form rather than to embark into a full clinical program.(ABSTRACT TRUNCATED AT 250 WORDS)


Spinal meningiomas: recurrence in ventrally located individuals on long-term follow-up; a review of 46 operated cases.
Surgical removal of spinal meningiomas is usually not difficult. In neurosurgical practice, their locations and growing patterns may affect surgical results. Ventrally located and en plaque meningiomas may not be removed totally. The aim of this study was to present the results of surgery in cases with spinal meningiomas, and reveal the factors affecting outcome. There were 46 cases operated between January 1995 and December 2009 in single clinic. There were 33 female and 13 male patients. The mean age was 52. All patients underwent microsurgical resection using posterior approach. Total resection was obtained in 38 patients (82%). Twenty-eight (61%) patients experienced clinical improvement after surgery. The tumor was completely dorsal to the spinal cord in 30 cases, dorsolateral in nine and ventral to the spinal cord in seven cases. We experienced eight recurrences (17%). Recurrences were seen most commonly seen in ventrally located tumors (62%). Complete resection of spinal meningiomas seems to produce a good clinical outcome. Recently, advances in microneurosurgery and neuroimaging techniques have resulted in decreases in morbidity and recurrence rates in spinal meningiomas.


Kinetic isolation of a slowly recovering component of short-term depression during exhaustive use at excitatory hippocampal synapses.
This study examines the kinetics of the longest lasting form of short-term depression at excitatory hippocampal synapses. After initial depletion of the readily releasable pool (RRP), continued 20-Hz stimulation was found to be fast enough to maximally drive presynaptic neurotransmitter exocytosis; maximal is defined here as the rate needed to maintain the RRP in a nearly empty steady state. Induction of depression proceeded in two distinct phases. The first was caused by RRP depletion, whereas the second is shown to reflect the progressive reduction of the overall rate at which new vesicles are supplied to the RRP and is termed "supply-rate depression." Supply-rate depression is identified further with the emergence, during heavy use, of a rate-limiting vesicle trafficking step that slows the timing of RRP replenishment by switching from a fast (tau congruent with 7 s) to a slow (tau congruent with 1 min) vesicle supply mechanism. Both mechanisms apparently follow first-order kinetics. After the induction of the maximum amount of depression, individual synapses were able to output only <1 quantum of neurotransmitter per synapse per second, matching previous predictions based on cell biological measurements of synaptic vesicle cycling. Surprisingly, the onset of supply-rate depression occurred with a marked delay, not having a detectable impact on synaptic function until after several seconds of continuous use. The delayed onset is not consistent with traditional vesicle trafficking models, but may be important for limiting the impact of supply-rate depression to pathological episodes and might function as a native antiepilepsy device.


Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources.
Based on variation in nucleotide sequence within restricted regions in the putative C (core) gene of hepatitis C virus (HCV), four groups of HCV have been postulated in a panel of 44 HCV isolates. They were provisionally designated types I, II, III and IV. A method for typing HCV was developed, depending on the amplification of a C gene sequence by polymerase chain reaction using a universal primer (sense) and a mixture of four type-specific primers (antisense). HCV types were determined by the size of the products specific to each of them. Type II was found in HCV samples from 131 (82%) of 159 blood donors, more often than in those from 48 (60%) of 80 patients with non-A, non-B (NANB) liver disease in Japan (P less than 0.01). In 11 haemophiliacs who had received imported coagulation factor concentrates, type I was found in five, as against type II in four. Double infection with two different HCV types was found in two patients with chronic NANB liver disease (types I and II; II and III) and two haemophiliacs (types I and II; I and III). HCV types were identical in mother and baby in each of two examples of perinatal transmission, and were also identical in donor and recipient in a case of accidental needle exposure.


Genotype Distribution and Prevalence of Human Pegivirus among High-Risk Populations in Tunisia.
A recently discovered non-A-E hepatitis virus has been designated as human Pegivirus (HPgV). HPgV is prevalent in high-risk groups such as patients with hepatitis C virus (HCV), and it is of interest for patients who are at risk for transmitted infections. The aim of this study was to evaluate the prevalence of HPgV as well as the genotype distribution among patients in the Tunisian population who are infected with HCV and also in multitransfused patients. A total of 144 patients were screened using RTPCR/nested PCR of the 5'-untranslated region (UTR); 14 cases were sequenced and phylogenetically analyzed. Seven (14.9%) subjects from the multitransfused group and 7 (7.2%) patients infected with HCV, respectively, were found positive for HPgV RNA. Sequencing and phylogenetic analysis of the 14 cases revealed that genotype 2a was the main genotype circulating in Tunisian patients. Genotype 2b was found in the amplified samples of 2 HCV-infected patients. This study enriches the limited data on HPgV prevalence in Tunisia, and shows, for the first time, the molecular epidemiology of the circulating strains in this country.


Enhancing current-induced torques by abutting additional spin polarizer layer to nonmagnetic metal layer.
Recently, the switching of a perpendicularly magnetized ferromagnet (FM) by injecting an in-plane current into an attached non-magnet (NM) has become of emerging technological interest. This magnetization switching is attributed to the spin-orbit torque (SOT) originating from the strong spin-orbit coupling of the NM layer. However, the switching efficiency of the NM/FM structure itself may be insufficient for practical use, as for example, in spin transfer torque (STT)-based magnetic random access memory (MRAM) devices. Here we investigate spin torque in an NM/FM structure with an additional spin polarizer (SP) layer abutted to the NM layer. In addition to the SOT contribution, a spin-polarized current from the SP layer creates an extra spin chemical potential difference at the NM/FM interface and gives rise to a STT on the FM layer. We show that, using typical parameters including device width, thickness, spin diffusion length, and the spin Hall angle, the spin torque from the SP layer can be much larger than that from the spin Hall effect (SHE) of the NM.


Indoleamine 2,3-dioxygenase. A new, rapid, sensitive radiometric assay and its application to the study of the enzyme in rat tissues.
A simple and convenient assay for indoleamine 2,3-dioxygenase has been developed. This depends on the conversion of D-[ring-2-14C]tryptophan to [14C]formate, excess substrate is removed by adsorption onto charcoal. This assay, which is 20-fold more sensitive than previous procedures, is applicable both to crude extracts and to large numbers of samples. Activity in rat tissues is very much lower than in those of the rabbit; measureable activity is found only in the stomach, spleen, intestine and kidney. Enzyme activity in the rat intestine was increased by 50% in rats pretreated with L-tryptophan.


Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve.
Human keratinocytes show a bystander effect when exposed to low doses of low-LET radiation. In this paper, data are presented showing a method of correcting the overall survival curve to enable analysis of the relative contributions of the bystander effect and the effect attributable to direct interaction of the radiation with the target cell. The technique used is to obtain a standard clonogenic survival curve using the assay of Puck and Marcus and, with a different set of flasks containing cloning densities of unirradiated cells, to assay the cell killing caused by medium harvested from 2 x 10(5) cells irradiated with the same doses. The data show that for this human epithelial cell line, doses of 0.01-0. 5 Gy show clonogenic death by the bystander effect only, if maximum potential bystander killing is assumed. The magnitude of the effect is relatively constant, and it appears to saturate at doses in the range of 0.03-0.05 Gy. After doses greater than 0.5 Gy, the curves for clonogenic death are the result of a dose-dependent non-bystander effect and a dose-independent bystander effect. If these particular dose-response effects occur in epithelial cells in vivo, they may have important consequences for therapy and studies of low-dose risk.


Allelic diversity and gene genealogy at the self-incompatibility locus in the Solanaceae.
The self-incompatibility (S) locus of flowering plants offers an example of extreme polymorphism maintained by balancing selection. Estimates of recent and long-term effective population size (Ne) were determined for two solanaceous species by examination of S-allele diversity. Estimates of recent Ne in two solanaceous species differed by an order of magnitude, consistent with differences in the species' ecology. In one species, the evidence was consistent with historical population restriction despite a large recent Ne. In the other, no severe bottleneck was indicated over millions of years. Bottlenecks are integral to founder-event speciation, and loci that are subject to balancing selection can be used to evaluate the frequency of this mode of speciation.


Commercial complementary food consumption is prospectively associated with added sugar intake in childhood.
Given that commercial complementary food (CF) can contain high levels of added sugar, a high consumption may predispose to a preference for sweet taste later in life. This study examined cross-sectional associations between commercial CF consumption and added sugar intake in infancy as well as its prospective relation to added sugar intake in pre-school and primary-school age children. In all, 288 children of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with 3-d weighed dietary records at 0·5 and 0·75 (infancy), 3 and 4 (pre-school age) and 6 and 7 years of age (primary-school age) were included in this analysis. Individual commercial CF consumption as percentage of total commercial CF (%cCF) was averaged at 0·5 and 0·75 years. Individual total added sugar intake (g/d, energy percentage/d) was averaged for all three age groups. Multivariable logistic and linear regression models were used to analyse associations between %cCF and added sugar intake. In infancy, a higher %cCF was associated with odds for high added sugar intake from CF and for high total added sugar intake (>75th percentile, P<0·033). Prospectively, a higher %cCF was related to higher added sugar intake in both pre-school (P<0·041) and primary-school age children (P<0·039), although these associations were attenuated in models adjusting for added sugar intake in infancy. A higher %cCF in infancy may predispose to higher added sugar intake in later childhood by virtue of its added sugar content. Therefore, offering home-made CF or carefully chosen commercial CF without added sugar might be one strategy to reduce sugar intake in infancy and later on.


Yttrium and lanthanide complexes of β-dialdehydes: synthesis, characterization and luminescence of coordination compounds with the conjugate base of nitromalonaldehyde.
Coordination compounds having formulae [AsPh4][Ln(NMA)4] (1(Ln)), Ln(NMA)3(tppo)2 (2(Ln)), Ln(NMA)3(bipyO2) (3(Ln)), Ln(NMA)3(phen) (4(Ln)) and Ln(NMA)3(terpy) (5(Ln)) (Ln = Y and some lanthanides; NMA = conjugate base of nitromalonaldehyde; tppo = triphenylphosphine oxide; bipyO2 = 2,2'-bipyridine-N,N'-dioxide; phen = 1,10-phenanthroline; terpy = 2,2':6',2''-terpyridine) were synthesized and characterized and X-ray diffraction data were collected for [AsPh4][Y(NMA)4] (1(Y)). The neutral europium derivatives showed appreciable luminescence in the solid state upon excitation with UV light and photoluminescence measurements were carried out. These compounds were used as dopants for the preparation of luminescent poly(methyl methacrylate). Luminescent polyvinylpyrrolidone samples were obtained by reacting the pure polymer with water solutions containing NMA and trivalent europium ions.


A new real-time and precision capnography for human respiration carbon dioxide concentration.
This paper is a description of the designing of a new mainstream device to measure human respiration carbon dioxide concentration, based on non-dispersive infrared (NDIR) absorption technology. The device can be used to accurately monitor the cardiopulmonary status during anaesthesia and mechanical ventilation in real time. This new device can not only make up the error of real-time gas measurement of the side-stream device, but also make up the accuracy of the main-stream device. In the paper, four issues which can affect the measurement accuracy were considered: respiration gas flow, turbulence of the light source with all ranges of wavelength, temperature drift and signal noise. The experimental results showed that the device could produce a stable output signal and deviation of measurement accuracy could be achieved to within 4%.


[The negative effect in patients with varicocele of coincidental didymo-epididymal morpho-pathology on sperm response before and after surgical correction].
In order to assess the relative incidence of varicocele (V) alone and V+ coincidental didymo-epididymal morphological abnormalities (DEMA) and the role of these pathologies on the pre- and post-surgical sperm outcome, 151 selected (previous exclusion of cases with bilateral V, seminal infections, antisperm autoAb) patients (aged 20-41 yrs) affected by left V at Doppler ultrasonography, underwent both ultrasound scrotal content examinations and semen analyses (sperm density, total sperm count, forward motility and normal morphology employing as frequency distribution) before and after varicocelectomy (on months 4-8-12, taking for statistical comparison the maximal post-surgical sperm value registered vs. mean correspective pre-treatment value). One-hundred two (67.5%) patients exhibited V alone (group A), whilst 49 (32.5%) patients showed V+DEMA (group B). As regards V, DEMA lesions (testis size < 12 ml; epididymides abnormalities: increased head (> 11 mm) and/or tail (> 6 mm) diameter, multiple microcysts; large idrocele) were omolaterally in 21/49 (42.8%) eterolaterally in 11/49 (22.5%) or bilaterally in 17/49 (34.7%). An additional group of 25 patients, exhibiting the above ultrasonic DEMA lesions alone without V, served as controls (group C) for semen statistical analysis in the pre-surgical period only. In this phase among groups A vs B, A vs C, B vs C, frequency distributions of all sperm parameters studied (excepted for density not significative only between B and C group patients) were significantly different. The following data were registered from A, B and C patient groups respectively: a) azoospermia was present in 12.7%, 34.8% and 24%; b) oligozoospermia (< 20 mil/ml) in 39.2%, 49% and 48%; c) normozoospermia in 48.1%, 16.3% and 8%; d) total sperm count was < 40 millions/ejaculate in 44.1%, 91.9% and 76%; e) asthenozoospermia (forward motility < 25%) was present in 32.3%, 71.4% e 72%; f) teratozoospermia (oval form <30%) was present in 34.3%, 62.3% and 48%. In the post-surgical follow-up examinations, significative changes with ameliorated frequency distributions of all semen parameters were observed within group A only, while these same parameters remained unmodified within group B patients, thus being together a significative difference between groups A vs B higher than that observed in the pretreatment. The coexistence of DEMA+V seems to determine two important effects on sperm output: a) in the pre-treatment, this selection judgement allowed to distinguish a different frequency distribution of semen parameters between patients affected by V alone and V+DEMA; b) since patients with V alone in comparison with V+DEMA patients groups had a favourable sperm outcome, the assessment of DEMA in patients with V seems to be mandatory for a better sperm prognostic judice.


Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis.
Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-α, RANTES, TLR-2, HIF-1α, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-α were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-β, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.


10-year Temporal Trends of Intravenous Thrombolysis in Acute Ischemic Stroke: Analysis of the China National Stroke Registry I-Ⅲ.
To investigate the 10-year trend in healthcare quality of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator in acute ischemic stroke (AIS) in China. We analyzed 42,188 AIS within 7 days of onset from the China National Stroke Registry (CNSR) Ⅰ-Ⅲ. Primary outcomes were temporal changes in the proportion of patients arriving at the hospital within 3.5 hours (and 2 hours) of onset and receiving IVT within 4.5 hours (and 3 hours), stratified by region and hospital tier. Secondary outcomes included temporal changes in door-to-needle time (DNT), DNT ≤60 min and favorable outcome defined as a 90-day modified Rankin Scale (mRS) of 0-1. Among patients arriving at the hospital within 3.5 hours of onset, 13.5%, 7.1% and 33.4% patients received IVT within 4.5 hours in CNSR Ⅰ, Ⅱ and Ⅲ, respectively, including a higher proportion from eastern China (37.0%) and tertiary hospitals (36.5%). The median DNT was shorter in CNSR Ⅲ (60.0 min) than those in Ⅱ (95.0 min) and I (94.0 min). The proportion of patients with DNT ≤60 min was greater in Ⅲ (53.4%) than those in Ⅱ (26.7%) and Ⅰ (13.4%). The proportion of favorable outcomes was higher in CNSR Ⅲ (72.8%) than those in Ⅱ (49.6%) and Ⅰ (49.4%). Similar trends were observed for patients arriving at the hospital within 2 hours and receiving IVT within 3 hours of onset. The healthcare quality of IVT has improved remarkably in the past decade, notably in eastern China and tertiary hospitals.


Refining the indications for carotid endarterectomy in patients with symptomatic carotid stenosis: A systematic review.
The purpose of this study was to summarize the existing literature on the efficacy of carotid endarterectomy in patients with ipsilateral symptomatic carotid stenosis. Database searching, relevance assessment, methodologic quality assessments, and data extraction were all performed in duplicate with prespecified criteria. Twenty-three publications were identified from the North American Symptomatic Carotid Endarterectomy Trial, the European Carotid Surgery Trial, and the Veterans Affairs Cooperative Studies Program. Stenosis was reported as measured in the North American Symptomatic Carotid Endarterectomy Trial. In patients with >70% stenosis, carotid endarterectomy was associated with a pooled relative risk reduction of 48% (95% confidence interval [CI], 27% to 73%) and an absolute risk reduction of 6.7% (95% CI, 3.2% to 10%) for the outcome of death or major disability from stroke. This translates into a number needed to treat of 15 (95% CI, 10 to 31). For patients with 50% to 69% stenosis, the benefit of surgery was less and the confidence intervals were wider. A relative risk reduction of 27% (95% CI, 5% to 44%), an absolute risk reduction of 4.7% (95% CI, 0.8% to 8.7%), and a number needed to treat of 21 (95% CI, 11 to 125) were observed in this group. The patients with the lowest degrees of stenosis (<50%) were harmed by the intervention (number needed to harm, 45). Increasing degree of stenosis, increasing age, male sex, the presence of other medical risk factors, and the presence of hemispheric rather than retinal antecedent events were factors that increased the benefits from surgery. Carotid endarterectomy reduced death or major disability from stroke in patients with >50% symptomatic stenosis. To maximize the benefits of surgery, careful preoperative risk assessment and the maintenance of low rates of major perioperative complications are mandatory.


Navigating between two cultures: Immigrants' gender attitudes toward working women.
Gender attitudes toward women's employment are of particular importance because they positively influence gender-equal outcomes in the labor market. Our understanding of the mechanisms that promote egalitarian gender attitudes among immigrants, however, remains limited. By studying first- and second-generation immigrants from multiple origins and living in different countries, this article seeks to explain under what conditions the prevalent cultural attitudes toward gender roles at the origin and destination influence immigrants' gender attitudes. We address three main research questions. First, does the country-of-origin gender ideology influence immigrants' views toward working women? Second, does the country-of-destination gender ideology influence immigrants' view toward working women? Are these relationships moderated by (1) the immigrant generation; (2) the age at arrival in the country of destination; (3) the length of residence at destination? Using data from the European Social Survey, we model immigrants' gender attitudes toward working women using linear cross-classified models to account for clustering into the country of origin and destination. The results highlight the importance of the context of early socialization in shaping immigrants' gender attitudes. First-generation immigrants, and more specifically, adult migrants hold gender attitudes that reflect more strongly the country of origin's gender culture. In contrast, the positive association between gender ideology at destination and immigrants' gender attitudes is stronger among second-generation immigrants and child migrants. We add to the literature on gender ideology formation by analyzing the influence of gender ideology at the origin- and destination-levels on the gender attitudes of immigrants from 96 countries of origin and residing across 32 countries of destination.


Breast cancer genetics: family history, heterogeneity, molecular genetic diagnosis, and genetic counselling.
Between 5% and 10% of breast cancer cases can be traced to primary genetic factors. Before the discovery of the BRCA1 and BRCA2 genes, if a first-degree relative in direct genetic lineage had hereditary breast cancer or hereditary breast-ovarian cancer syndrome, the best estimate of family members' genetic risk for breast cancer was 50%. Now the lifetime cancer destiny of a patient who carries a BRCA1 or BRCA2 germ line mutation can be determined with an extraordinary degree of precision. However, a major concern facing clinicians is how to use this powerful genetic knowledge without harming the patient. This presentation focuses on the need for (a) compilation of a detailed family history of cancer of all anatomic sites; (b) understanding of the natural history of hereditary breast cancer and its heterogeneous forms and the pathobiology of hereditary breast cancer; and (c) preparation for performance of genetic counseling that is based on the results of DNA sequencing to detect genes related to cancer susceptibility. The discussion addresses the advantages of this molecular genetic movement, which include the abilities (a) to predict who is and who is not at inordinately high risk for cancer; (b) to provide opportunities for highly targeted disease surveillance and management; (c) to give patients the information they need to make appropriate long-term decisions about matters such as procreation; and (d) to give genetic counselors the information they need to appreciate the emotions patients may encounter, such as fear, anxiety, and apprehension, and the ordeal of being subjected to discrimination by insurance companies and employers.


Study of the allelic variants CYP2C9*2 and CYP2C9*3 in samples of the Peruvian mestizo population
Introduction: CYP2C9 metabolizes approximately 15% of the prescribed drugs. Its gene has alleles whose frequencies differ between ethnic groups and populations. The alleles CYP2C9*2 and CYP2C9*3 account for an enzyme with decreased activity and their frequencies have not been determined in the Peruvian mestizo population. Objective: To characterize the frequencies of the allelic variants *2 (rs1799853) and *3 (rs1057910) of CYP2C9 gen in the Peruvian mestizo population from Lima, Tacna y Junín. Materials and methods: We conducted an observational, prospective cross-sectional study with non-probabilistic, by convenience, and incidental sampling. We included 218 subjects according to the inclusion and exclusion criteria, all of whom had signed the informed consent. We obtained the genomic DNA from oral mucosa swab. For the detection of the CYP2C9*2 and CYP2C9*3 genotypes, we used real-time-polymerase chain reaction with TaqMan® probes. Results: The genotyping revealed that CYP2C9*2 and CYP2C9*3 variants have low frequencies (0.046 and 0.062, respectively). The frequency of intermediate metabolizers was 15.13% (CYP2C9*1/*2: 5.96%; CYP2C9*1/*3: 9.17%) and that of slow metabolizers was 3.22% (CYP2C9*2/*2: 1.38%; CYP2C9*3/*3: 1.38%; CYP2C9*2/*3: 0.46%). Conclusions: It was possible to determine the genotypic and allelic frequencies for the variants *2 and *3 of the CYP2C9 gene in a non-probabilistic sample of the Peruvian mestizo population. The frequencies obtained (0.046 and 0.062, respectively) corresponded to those expected for a South American mestizo population with Amerindian, European, African and Asian ancestry.


The MAPT H1 haplotype is associated with tangle-predominant dementia.
Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3' untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3' UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD.


Application of intravoxel incoherent motion imaging in the study of migration and movement of cancer cells.
IVIM imaging technology can obtain physiological information of tissue cells and blood perfusion at the same time in one imaging process. Taking female patients in Shenzhen Maternal and Child Health Hospital affiliated to Southern Medical University as an example, the migration and movement of breast cancer cells and hepatocellular carcinoma cells are studied by intravoxel incoherent motion imaging. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f) are measured by the IVIM bi-index model, and statistical analysis is made. The results show that the IVIM bi-index model can truly reflect the diffusion of water molecules in breast mass-like lesions, and reflect the migration and movement of breast cancer cells. Especially D value has important reference significance for the research and diagnosis of breast cancer cells. IVIM bi-index model has limited diagnostic value for the migration and movement of common hepatocellular carcinoma cells, and ADC value may have higher diagnostic efficiency.


Sequence of a bovine herpesvirus type-1 glycoprotein gene that is homologous to the herpes simplex gene for the glycoprotein gB.
The 130-kDa bovine herpesvirus-1 (BHV-1) glycoprotein GVP 6 was found to cross-react immunologically with the herpes simplex glycoprotein gB. Antibodies in polyclonal serum against gB immunoprecipitated GVP 6 and its cleavage products from a lysate of BHV-1-infected cells. Conversely, polyclonal serum against GVP 6 precipitated gB from HSV-1-infected cell lysates. Sera against the other glycoproteins did not demonstrate cross-reactivity. A 3.6-kb Kpnl-Hpal fragment of BHV-1 DNA that hybridized to the gene for gB was cloned and the nucleotide sequence of both strands was determined. The longest codon reading frame in the fragment coded for a protein that showed extensive homology with gB1 and related sequences from pseudorabies virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus. The strongest homologies were observed in two segments of the ectodomain, the transmembrane domain, and sequences adjacent to the transmembrane domain.


Regulation of poly(A) RNA retention in the nucleus as a survival strategy of plants during hypoxia.
Last finding indicates that post-transcriptional processes are significant in low-oxygen conditions, but their nature is poorly understood. Here, we localized poly(A) RNA and mRNA coding proteins involved and not involved with resistance to hypoxia in Lupinus luteus and Arabidopsis thaliana during submergence and after recovery of aerobic conditions. We showed a strong nuclear accumulation of poly(A) RNA and 6 of 7 studied mRNAs with a concurrent strong reduction in RNA polymerase II transcription during hypoxia. In this study, the nucleus did not accumulate mRNA of the ADH1 (alcohol dehydrogenase 1) gene, which is a core hypoxia gene. The RNA accumulation in the nucleus is among the mechanisms of post-transcriptional gene regulation that prevents translation. However re-aeration was accompanied by a strong increase in the amount of the mRNAs in the cytoplasm and a simultaneous decrease in nuclear mRNAs. This finding indicates that the nucleus is a storage site for those of mRNAs which are not involved in the response to hypoxia for use by the plants after the hypoxic stress. In this study, the highest intensity of RNA accumulation occurred in Cajal bodies (CBs); the intensity of accumulation was inversely correlated with transcription. Under hypoxia, ncb-1 mutants of Arabidopsis thaliana with a complete absence of CBs died sooner than wild type (WT), accompanied by a strong reduction in the level of poly(A) RNA in the nucleus. These results suggest that the CBs not only participate in the storage of the nuclear RNA, but they also could take part in its stabilization under low-oxygen conditions.


[Hypercholesterolemia, cardiovascular risk, and hypocholesteremic treatment in the elderly].
The role of cholesterol as a cardiovascular risk factor in the elderly is not completely clear at the moment. Epidemiologic studies show a continuous relation between cholesterol levels and cardiovascular risk even in the elderly, in fact, in spite of a lower Relative Risk, they have a greater Absolute Risk and Absolute Benefit Increase. In patients over 75-80 years old cholesterol loses its role as a risk factor, probably because of comorbidity, typical in this period. Trials show the efficacy of hypocholesterolemic therapy with statins in secondary prevention in the elderly; fewer data are available for primary prevention. Therapeutic attitudes suggest a pharmacologic intervention of secondary prevention in young and old elderly to lower LDL-C levels, which are more closely related to the events. In primary prevention we should use drugs to reach a LDL-C level lower for each additional risk factor, until 75 years old; in the old elderly we should decide on drug therapy according to the biological age and expected lifespan. Statins seem to be the most effective and safest drugs to reach this aim.


HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular and extraarticular disease manifestations.
In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.


Single-stranded DNA-binding proteins PURalpha and PURbeta bind to a purine-rich negative regulatory element of the alpha-myosin heavy chain gene and control transcriptional and translational regulation of the gene expression. Implications in the repression of alpha-myosin heavy chain during heart failure.
The alpha-myosin heavy chain is a principal molecule of the thick filament of the sarcomere, expressed primarily in cardiac myocytes. The mechanism for its cardiac-restricted expression is not yet fully understood. We previously identified a purine-rich negative regulatory (PNR) element in the first intron of the gene, which is essential for its cardiac-specific expression (Gupta, M., Zak, R., Libermann, T. A., and Gupta, M. P. (1998) Mol. Cell. Biol. 18, 7243-7258). In this study we cloned and characterized muscle and non-muscle factors that bind to this element. We show that two single-stranded DNA-binding proteins of the PUR family, PURalpha and PURbeta, which are derived from cardiac myocytes, bind to the plus strand of the PNR element. In functional assays, PURalpha and PURbeta repressed alpha-myosin heavy chain (alpha-MHC) gene expression in the presence of upstream regulatory sequences of the gene. However, from HeLa cells an Ets family of protein, Ets-related protein (ERP), binds to double-stranded PNR element. The ERP.PNR complex inhibited the activity of the basal transcription complex from homologous as well as heterologous promoters in a PNR position-independent manner, suggesting that ERP acts as a silencer of alpha-MHC gene expression in non-muscle cells. We also show that PUR proteins are capable of binding to alpha-MHC mRNA and attenuate its translational efficiency. Furthermore, we show robust expression of PUR proteins in failing hearts where alpha-MHC mRNA levels are suppressed. Together, these results reveal that (i) PUR proteins participate in transcriptional as well as translational regulation of alpha-MHC expression in cardiac myocytes and (ii) ERP may be involved in cardiac-restricted expression of the alpha-MHC gene by preventing its expression in non-muscle cells.


[3-dimensional sonography--technical concept and image-producing possibilities].
An ultrasound-system realizing 3-D-technique is described. Its handling and depicting possibilities are mentioned. This ultrasound equipment gives additional imaging possibilities. These are combinable planes of cuts, adding-up-techniques, corner-like ultrasound cuts and the possibility to trace a process even out of the straight plane and visualize it. Whole 3-dimensional-technique is available through full stereometric pre- and postprocessing of 3-D pictures which are separately depicted and viewed via stereometric optics.


Plasmid-mediated beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to ceftazidime.
Low-level transferable resistance to ceftazidime was detected in seven strains of Klebsiella pneumoniae and one strain of Escherichia coli. Six of the Klebsiella strains and the E. coli strain were shown to produce a novel beta-lactamase (CAZ-lo) with a pI of 5.6 that hydrolyzed broad-spectrum cephalosporins at low but comparable levels. One strain of K. pneumoniae was of a serotype different from that of the other strains and produced a plasmid-encoded cefuroximase (FUR) with a pI of 7.5 that mediated moderate levels of resistance to different broad-spectrum cephalosporins. High-level resistance to ceftazidime was detected in one other strain of K. pneumoniae, which produced a beta-lactamase with a pI of 6.5 (CAZ-hi). Apart from its pI, this enzyme differed from CAZ-lo by a specific and high hydrolytic activity against ceftazidime. The epidemiological context suggested that CAZ-hi may be a mutant of CAZ-lo, and this hypothesis was supported by the isolation of laboratory mutants of CAZ-lo showing properties identical to those of the clinical CAZ-hi enzyme.


Ultrastructural study of eosinophils from patients with the hypereosinophilic syndrome: a morphological basis of hypodense eosinophils.
We investigated the ultrastructural characteristics and the granule major basic protein (MBP) content of hypodense eosinophils from patients with the hypereosinophilic syndrome who had at least 90% hypodense eosinophils in their peripheral blood and compared these cells to normodense eosinophils from normal persons. The hypodense cells (density less than 1.082) contained significantly less MBP than normodense (density greater than 1.082) eosinophils (P less than .001) as measured by radioimmunoassay (RIA). Electron microscopic examination demonstrated a mean of 25.0 +/- 4.4 (X +/- 1 SD) granules per hypodense cell, compared to 30.6 +/- 8.4 granules per cell in the normodense group (P less than .1). The most striking difference between the hypodense and normodense eosinophils was the small individual granule size (X = .14 +/- .05 v .26 +/- .05 micron 2, respectively, P less than .001), and the smaller total granule area (3.2 +/- 1.8 vs 7.7 +/- 3.1 micron 2, respectively, P less than .001). Because the cytoplasmic areas were similar in the two groups, the mean percent area of cytoplasm occupied by granules was significantly lower in the hypodense group (P less than .001). The finding of consistently smaller granules in the presence of equal or fewer granules per cell in the hypodense eosinophils may explain the lower MBP content and thus provide a morphologic basis for the low density of eosinophils in patients with the hypereosinophilic syndrome.


Time-Of-Flight Mass Spectrometers Made in Switzerland: Examples of Mobile Applications.
Over the past decade, the technical requirements of analytical instrumentation have continuously risen driven by the demand for increasingly complex and demanding applications. TOFWERK, a Swiss company with the headquarters in Thun, has been at the forefront of this development by producing modular and ruggedized Time-Of-Flight Mass Spectrometers (TOFMS). They are often used to replace quadrupole mass analysers with more powerful TOF mass analysers. Starting with first customers in atmospheric sciences, TOFWERK TOFMS are now used across a wide range of research areas and lately also in industry. Here we present an overview of mobile applications in which Tofwerk TOFMS are in operation while moved around in space.


Idiopathic pulmonary haemosiderosis in paediatric patients: how to make an early diagnosis.
Idiopathic pulmonary haemosiderosis (IPH) is a rare but potentially lethal condition in paediatric patients. This condition is considered an immune-mediated disorder, but its pathogenesis is still unknown. Idiopathic pulmonary haemosiderosis is characterized by the classical triad of haemoptysis, iron-deficiency anaemia, and diffuse parenchymal consolidation on chest radiology. Unfortunately, this triad of signs is not frequent in children at the onset of this disease, resulting in a delay in diagnosis and a negative outcome. This case report describes a 4-year-old girl who was admitted for an acute episode of lower respiratory tract infection associated with severe dyspnoea, polypnoea, and severe anaemia (haemoglobin levels, 5.9 g/dL). She had a history of previous similar episodes, with anaemia treated unsuccessfully with iron supplementation and managed through repeated blood transfusions in the acute phase. She did not experience haemoptysis. A computed tomography (CT) scan of the thorax showed ground-glass opacity suggestive of pulmonary haemorrhage. After other causes of intra-alveolar haemorrhage were excluded, IPH was confirmed by the presence of siderophages in bronchoalveolar lavage. Immunosuppressive corticosteroid treatment was immediately started with a good clinical response. This case highlights the fact that IPH should be suspected in children with recurrent lower respiratory tract infections who have a history of iron-deficiency anaemia who shows no signs of improvement with iron supplementation and may require repeated blood transfusions. The absence of haemoptysis does not exclude the diagnosis of IPH in children. An early and prompt diagnosis is recommended in order to start adequate immunosuppressive treatment.


The effects of inhibitory and facilitatory intracortical circuits on interhemispheric inhibition in the human motor cortex.
Inhibitory and facilitatory intracortical pathways regulating motor cortical output can be studied non-invasively in humans with transcranial magnetic stimulation. These circuits include short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Stimulation of the motor cortex also inhibits the contralateral motor cortex (interhemispheric inhibition, IHI) at short (approximately 10 ms, IHI10) or long intervals (approximately 40 ms, IHI40). We investigated how SICI, ICF, and LICI influence IHI10 and IHI40. We hypothesize that intracortical circuits will have similar effects on IHI and cortical output neurons: SICI and LICI will decrease IHI, and ICF will increase it. Motor evoked potentials were recorded from the first dorsal interosseous muscles bilaterally in 10 healthy subjects. We compared IHI10 and IHI40 alone to IHI10 and IHI40 elicited in the presence of SICI, ICF, or LICI. Our results showed that SICI and LICI reduced IHI10, IHI40 and corticospinal output to a similar degree. ICF increased corticospinal output but had no effect on either IHI10 or IHI40. The different effects of ICF on corticospinal excitability and IHI suggest the transcallosal fibres mediating IHI and the corticospinal output system arise from different neuronal populations. SICI and LICI produce more global inhibition with similar effects on the transcallosal and descending corticospinal circuits.


[The physical rehabilitation at a sanatorium of patients wearing aortic valve prostheses].
Methods and results of physical rehabilitation of 81 patients with prostheses of the aortal valve in conditions of a health resort are reported. The authors revealed a 29.2% increase of physical, working capacity and a reduction (8.2%) of oxygen expenditures per unit of work. Increase of intensity of training loads improved the results of physical rehabilitation. The role of health resort treatment in the system of postoperative rehabilitation of patients with heart valve prostheses is emphasized.


[Coma in full-term newborn infants following acute fetal distress: electro-clinical evolution].
Twenty full term infants who had birth asphyxia were studied. These infants were in a comatose state for 4 to 15 days and at least 3 EEG recordings were performed during this period. Six infants recovered without sequelae and in 2 cases there were minor abnormalities. In 7 cases there were major deficits (follow-up: 1 to 9 years) and 5 infants died within 15 days. Abnormal movements were observed in all the babies. Thirteen infants had EEG documented seizures (intermittent in 5 cases and status epilepticus in 8 cases). The prognosis was not correlated with the time of onset or duration of the coma, the time of onset or type of abnormal movements, nor with the presence of intermittent or continuous electrographic seizure activity. The initial tracing on the first day is the most significant prognostic factor. On subsequent days, an inactive EEG always indicated a poor prognosis. An improvement in the EEG on the 2nd on the 3rd day may not correlate with a favourable outcome since 3 such cases had a poor outcome. The clinical and EEG findings during therapy and the value of high levels of anticonvulsant therapy are discussed.


Ceftriaxone-induced immune hemolytic anemia.
To describe a case of ceftriaxone-induced immune hemolytic anemia (CIIHA) in a 6 year-old boy with sickle cell disease (SCD) and perform a systematic literature review to delineate the clinical and laboratory features of this condition. EMBASE (1947-January 2014), MEDLINE (1946-January 2014), and databases from the US Food and Drug Administration and Health Canada were searched, using anemia, hemolytic anemia, hemolysis, and ceftriaxone as search terms. Additional references were identified from a review of literature citations. All case reports and observational studies describing clinical and laboratory features of CIIHA were included. A total of 37 eligible reports of CIIHA were identified, including our index case, and 70% were children. Mortality was 30% in all age groups and 64% in children. The majority of patients had underlying conditions (70%), of which SCD was most commonly reported. Previous ceftriaxone exposure was reported in 65%. Common features included elevated lactate dehydrogenase (70%); early, new-onset hemoglobinuria (59%); acute renal failure (46%); positive direct antibody testing (70%); and anticeftriaxone antibodies (68%). Also, 32% had a preceding, unrecognized, hemolytic episode associated with ceftriaxone. Given the common use of ceftriaxone worldwide, knowledge of CIIHA, which often goes undiagnosed until late in the course, is essential for clinicians. Based on the findings of this review, we suggest obtaining past history of ceftriaxone exposures and screening for new-onset hemoglobinuria during ceftriaxone therapy in selected patients as potential methods for early diagnosis of this rare but potentially fatal condition.


Silencing of a beta-1,3-glucanase transgene is overcome during seed formation.
Expression of a beta-1,3-glucanase transgene (gn1) driven by the CaMV 35S promoter is silenced in the T17 homozygous tobacco transgenic line. This silencing process is post-transcriptionally regulated and subject to developmental control. We have examined this phenomenon to investigate the developmental pathways involved in suppression and reactivation of gn1 expression as well as to identify the plant tissues where these processes occur. Analysis of beta-1,3-glucanase activity and gene expression have allowed us to determine that suppression of gn1 is a very efficient process reducing the steady-state gn1 mRNA level, simultaneously, in all leaves of the plant. Gene silencing occurs a few weeks after seed germination, and is maintained throughout vegetative growth and floral development. Expression of gn1 is restored in the maturing fruit some time after fertilization. In situ hybridization analyses show that expression of gn1 is restored within the developing seeds in tissues derived from meiotically divided cells. In contrast to the high level of expression found in seedlings obtained from germinated T17 homozygous seeds, the expression of gn1 is not reactivated in plantlets regenerated in vitro from leaf explants of suppressed T17 homozygous plants that is, in plant tissues obtained by mitotic division. Thus, reactivation of gn1 expression specifically occurs along the developmental programme controlling sexual reproduction and likely throughout epigenetic modifications affecting the state of gene expression during meiosis.


Atypia and Ki-67 expression from ductal lavage in women at different risk for breast cancer.
Ductal lavage provides adequate material and detects atypical cells from ducts in women at increased risk of breast cancer, but the clinical significance of this finding is unclear. We studied the prevalence and predictors of atypia in addition to the proliferation-associated antigen Ki-67 expression in ductal lavage done in women at different risk of breast cancer. Ductal lavage was attempted in 202 women at increased risk and in 16 at average risk. Lavage could not be done in 20 women at increased risk because of anatomic impediments. Seven average-risk women (44%) had samples with inadequate cytology versus 30 women at higher risk (16%; P = 0.014). Atypia was observed in two average-risk women [22%; 95% confidence interval (95% CI), 3-60%]. The prevalence of atypia was 33% in women with a 5-year risk of > or =1.3% according to the Gail model (25 of 75; 95% CI, 23-45%), 36% in women with an increased probability of or ascertained BRCA mutation (9 of 25; 95% CI, 18-57%), and 52% in women with contralateral breast cancer (27 of 52; 95% CI, 38-66%). Ki-67 expression measured in a consecutive series of 80 women at increased risk was higher in atypical samples (P = 0.0001) and was positively associated with total cell count per slide (P = 0.002). Atypia is frequent in women at increased risk of breast cancer but it can also be found in average-risk women. Ki-67 expression is associated with atypia and cell yield and it might be assessed as a surrogate biomarker in early-phase chemoprevention trials.


The finite ridgelet transform for image representation.
The ridgelet transform was introduced as a sparse expansion for functions on continuous spaces that are smooth away from discontinuities along lines. We propose an orthonormal version of the ridgelet transform for discrete and finite-size images. Our construction uses the finite Radon transform (FRAT) as a building block. To overcome the periodization effect of a finite transform, we introduce a novel ordering of the FRAT coefficients. We also analyze the FRAT as a frame operator and derive the exact frame bounds. The resulting finite ridgelet transform (FRIT) is invertible, nonredundant and computed via fast algorithms. Furthermore, this construction leads to a family of directional and orthonormal bases for images. Numerical results show that the FRIT is more effective than the wavelet transform in approximating and denoising images with straight edges.


Influence of variations in methodology on populations of Listeria monocytogenes recovered from lettuce treated with sanitizers.
The elimination of Listeria monocytogenes inoculated onto a piece of cut iceberg lettuce (3.8 by 3.8 cm) by treatment with chlorinated water (200 micrograms/ml free chlorine) and a 0.5% (wt/vol) solution of FIT Professional Line Antibacterial Cleaner (FIT) was investigated. The efficacy of the two sanitizers was not influenced by the composition of the medium used to culture the L. monocytogenes used in the inocula, the number of strains in the inoculum, or the recovery medium used to enumerate the pathogen on lettuce after treatment. Drying inoculum on lettuce for 45 min at 37 degrees C caused more cells to die or not be retrieved compared with drying inoculum for 30 min at 25 degrees C. However, the percentage of cells in the inoculum recovered from lettuce treated with chlorine or FIT was not significantly different, regardless of the drying method. Stomaching, homogenizing, or stomaching followed by homogenizing lettuce treated with sanitizers resulted in recovery of similar numbers of L. monocytogenes, indicating that stomaching and homogenizing are equivalent in extracting cells; the sequential use of both processing methods did not substantially increase the efficiency of recovery. Washing lettuce with water or treating lettuce with 200 micrograms/ml chlorine or FIT resulted in decreases in populations of 0.60, 1.76, and 1.51 log CFU per lettuce piece, respectively, regardless of variations in test parameters. Reductions caused by sanitizers were significantly greater (alpha = 0.05) than that observed for water but not significantly different from each other. It is concluded that evaluation of sanitizers for their efficacy in killing L. monocytogenes on lettuce can be determined by spot inoculating 50 microliters of a five-strain mixture of cells from 24-h cultures suspended in 5% horse serum albumen, followed by drying the inoculum for 45 min at 37 degrees C, treatment by submerging in 50 ml of sanitizer for 5 min, stomaching samples in 50 ml of Dey-Engley neutralizing broth for 2 min, and enumerating survivors on modified Oxford medium.


Pearls: myasthenia.
Myasthenia gravis is typically an acquired autoimmune disorder in which antibodies are directed at structural components of the neuromuscular junction, most commonly the nicotinic acetylcholine receptor. The clinical manifestations of skeletal muscle weakness are broad. Patients most often report fatigable muscle weakness. The eyelid levators and extraocular muscles are most commonly affected, resulting in symptoms of ptosis and diplopia. Symptoms may be confined to the eyes (ocular myasthenia) or reflect bulbar, limb, or respiratory muscle weakness (generalized myasthenia). The diagnosis is based on a characteristic history and the finding of fatigable muscle weakness on examination, and may be supported by diagnostic tests such as finding elevated titers of acetylcholine receptor or muscle-specific receptor tyrosine kinase (MuSK) antibodies, a positive Tensilon test, a decremental response on slow repetitive nerve stimulation, and abnormal jitter on single fiber electromyography. This article presents a series of pearls to aid in the clinical and laboratory diagnosis of myasthenia gravis, emphasizing key historical features, common and characteristic findings on examination, and potential pitfalls in the use of ancillary diagnostic studies.


Association between soft drink consumption and osteoporotic fractures among postmenopausal women: the Women's Health Initiative.
High consumption of soft drinks has been associated with lower bone mineral density among postmenopausal women. This study explores the association of soft drink consumption, osteoporosis, and incidental fractures in this population. Cross-sectional (at baseline) and cohort combined designs, over 11.9 years of median follow-up for 72,342 postmenopausal women participating in the Women's Health Initiative Observational Study. Multiple linear regression models were used to examine the cross-sectional associations between soft drink consumption and hip and lumbar spine bone mineral density. Cox proportional hazards regression models were used to examine the association of soft drink consumption with incident hip fractures. There were no associations between soft drink consumption and hip or lumbar spine t scores. During 700,388 person-years of follow-up, 2,578 hip fractures occurred. Adjusted hazard ratios for incident hip fracture for the highest consumption category compared with no consumption were 1.26 (95% confidence interval [CI] 1.01-1.56) for total soda and 1.32 (95% CI 1.00-1.75) for caffeine-free soda. There was no association between caffeinated soda and incident hip fracture (hazard ratio = 1.16; 95% CI 0.86-1.57). There was no apparent linear trend in the risk of hip fracture across categories of soda consumption in the fully adjusted models, suggesting a threshold effect. A sensitivity analysis using adjudicated hip fractures showed significant associations for all three soda exposures in the highest intake groups. Consuming more than two servings of soft drinks per day on average showed potential associations with higher risk of hip fracture among postmenopausal women.


Characterization of the cocaine binding site on the sigma-1 receptor.
The cocaine photoaffinity label 3-iodo-4-azidococaine ([125I]IACoc) binds to the sigma-1 receptor with an affinity that is 2-3 orders of magnitude higher than the parent compound cocaine [Kahoun, J. R., and Ruoho, A. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1393-1397]. In the present study, the binding properties of several cocaine derivatives to the guinea pig liver sigma-1 receptor were determined. The results from assessing the affinity of various derivatives of cocaine which were substituted on the phenyl ring indicated that an important determinant of binding to the guinea pig sigma-1 receptor binding site may be the development of a dipole in the ring in which the pi electron density of the phenyl ring is reduced. This implies that an electron-rich source is present in the sigma-1 receptor binding site, such as the pi system of an aromatic ring or other electron-rich side chains, which interact with the phenyl ring of cocaine. The precise [125I]IACoc derivatization site in the guinea pig sigma-1 receptor was identified using chemical cleavage and purification of the resulting labeled peptides. Cyanogen bromide cleavage of the [125I]IACoc photolabeled sigma-1 receptor followed by radiosequencing identified Asp188, which is located in the putative steroid binding domain-like II (SBDL II) near the carboxyl terminus, as the site of [125I]IACoc insertion. Systematic truncation of the C-terminus indicated the requirement for the last 15 amino acid residues of the receptor for [125I]IACoc photolabeling.


[Afferent impulse of fibers of the vagus nerve of cats using the method of coincidence of outgoing action potentials].
Tonic electrical activity of afferent fibres of intact vagus nerve was studied in cats using the method of coincidence of recorded action potentials. It was found that tonically active afferent fibres of the intact vagus nerve of the cat had conduction velocity 8-65 m/s. Two groups of fibres conducting the most intensive impulsation from the pulmonary stretch receptors were found. At the maximum frequency of the coincident oscillations the average conduction velocities in these two groups was 29.4 plus or minus 1.4 and 41.0 plus or minus 2.5 m/s. The frequency of oscillations was modulated by respiration.


Ribosome profiling and dynamic regulation of translation in mammals.
Protein synthesis is an energy-demanding cellular process. Consequently, a well-timed, fine-tuned and plastic regulation of translation is needed to adjust and maintain cell states under dynamically changing environments. Genome-wide monitoring of translation was recently facilitated by ribosome profiling, which uncovered key features of translation regulation. In this review, we summarize recent ribosome profiling studies in mammals providing novel insight in dynamic translation regulation, notably related to circadian rhythms, diurnal feeding/fasting cycles, cell cycle progression, stress responses, and tRNA landscapes. In particular, recent results show that regulating translation initiation and elongation represent important mechanisms used in mammalian cells to rapidly modulate protein expression in dynamically changing environments.


Properties of self-paced walking in chronic respiratory disease: a patient goal-oriented assessment.
Patients with chronic respiratory diseases often have the simple goal of wanting to walk for longer. We evaluated the properties of a patient goal-oriented, symptom-limited, self-paced walk (SPW). Patients with symptomatic chronic respiratory disease, referred for a 6-week course of pulmonary rehabilitation (PR), were screened for eligibility. Baseline assessments included two SPWs with both time and speed measured, two 6-min walk tests (6MWTs), and the Medical Research Council dyspnea scale. On program completion, two SPWs and one 6MWT were performed. The repeatability, responsiveness, and validity of the SPW were assessed. Two SPWs were completed by 50 and 37 patients before and after rehabilitation, respectively. The speed (r = -0.54, P < .001) but not the time (r = -0.23, P = .19) of the SPW correlated with Medical Research Council dyspnea grade. The mean SPW time increased on the second day of testing from 15.1 ± 8.4 min to 17.9 ± 7.7 min (P = .004), and the effect of test day was unaltered by PR (P = .80). The coefficient of repeatability for SPW time was 16.1 min. Both the mean SPW time (10.6 min; 95% CI, 6.6-14.5 min; P < .001) and the mean speed (3.5 m/min; 95% CI, 1.3-5.7 m/min; P < .01) increased after rehabilitation. The SPW time is an easily understandable, patient goal-oriented assessment with construct validity that is highly responsive to the effects of PR. The variability in SPW time makes it better suited to interpreting group rather than individual changes. ClinicalTrials.gov; No.: NCT00781183; URL: www.clinicaltrials.gov.


Muscular proprioception contributes to the control of interceptive actions.
The authors proposed a model of the control of interceptive action over a ground plane (Chardenon, Montagne, Laurent, & Bootsma, 2004). This model is based on the cancellation of the rate of change of the angle between the current position of the target and the direction of displacement (i.e., the bearing angle). While several sources of visual information specify this angle, the contribution of proprioceptive information has not been directly tested. In this study, the authors used a virtual reality setup to study the role of proprioception when intercepting a moving target. In a series of experiments, the authors manipulated proprioceptive information by using the tendon vibration paradigm. The results revealed that proprioception is crucial not only to locate a moving target with respect to the body but also, and more importantly, to produce online displacement velocity changes to intercept a moving target. These findings emphasize the importance of proprioception in the control of interceptive action and illustrate the relevance of our model to account for the regulations produced by the participants.


Genetic Modifications of Icosahedral Plant Virus-based Nanoparticles for Vaccine and Immunotherapy Applications.
Vaccine development is one of the greatest achievements of modern medicine. Vaccines made of live-attenuated pathogens can revert to virulent live strains, which causes safety concerns. On the other hand, the use of purified antigenic components as subunit vaccines is safer, but less effective, as these components induce lower levels of protective immunity. Multiple copy presentation of an antigenic determinant in a well-ordered and well-defined orientation on a nanosized particle can mimic the natural host-pathogen surface interaction to provide antigen stability and immunogenicity similar to that of conventional vaccines with improved safety. The icosahedral symmetry of plant viral capsid based nanoparticles is highly ordered and their multivalent structured protein nanostructures facilitate genetic modifications that result in the display of heterologous epitopes or antigens attached to coat proteins. These recombinant plant virus-based nanoparticles (PVNs) provide platforms for the induction of humoral and cellular immune responses to genetically fused antigens from pathogenic viruses, bacteria, tumors, and toxins in man and animals. Here, we comprehensively review the developments of several recombinant PVNs as prophylactic and/or therapeutic vaccines for the prevention or treatment of several microbial diseases, pathologies, and toxin poisoning.


Role of coprophagy in the cecal microbiome development of an herbivorous bird Japanese rock ptarmigan.
The transgenerational maintenance of symbiotic microbes that benefit host nutrition and health is evolutionarily advantageous. In some vertebrate lineages, coprophagy is used as a strategy for effectively transmitting microbes across generations. However, this strategy has still not been studied in birds. Accordingly, the aim of the present study was to evaluate the role of maternal cecal feces consumption by Japanese rock ptarmigan (Lagopus muta japonica) chicks as a strategy for acquiring essential gut microbes. Both the duration of coprophagy behavior by the chicks and the development process of the chick cecal microbiome (n=20 one- to three-week-old chicks, from three broods) were investigated. In all three broods, coprophagy behavior was only observed from 3 to 18 days of age. Furthermore, there was no significant difference in the number of bacterial operational taxonomic units (OTUs) in 1-week-old chicks (n=651) and adults (n=609), and most of the main OTUs observed in the adults were already present in the 1-week-old chicks. These results indicate that, in this precocial bird species, coprophagy may contribute to the early establishment of cecal bacteria that are essential for food digestion and, thus, chick survival. In fact, Japanese rock ptarmigan chicks consume the same food as their hens from the time of hatching. This behavior may have applications to ex-situ conservation.


Evaluation of Pesticides Found in Oregon Cannabis from 2016 to 2017.
Pesticide use and worker exposures to pesticides in the US cannabis industry have not been studied due to cannabis being illegal at the federal level. Without knowing the types of pesticides being used in this industry, it is difficult to assess whether workers are being exposed to potentially dangerous pesticides. When recreational cannabis became legal in the state of Oregon in 2014, the Oregon Department of Agriculture (ODA) published a list of recommended pesticides for use in the cannabis industry and developed the state's pesticide testing regulations for all cannabis products, medicinal and recreational. Using the state's pesticide testing data, the aim of this study was to investigate the types of pesticides being used in the Oregon cannabis industry and if they present a hazard to cannabis workers. Both recreational and medicinal cannabis samples contained high levels of residual pesticides and pesticides not legally allowed to be used on cannabis products. Medicinal cannabis products were found to have mean levels of residual pesticides that were 3-12 times higher than recreational products. Nine of the 50 pesticides identified were classified highly or extremely hazardous by the World Health Organization.


COVID-19 outbreaks in hospital workers during the first COVID-19 wave.
Health care workers (HCWs) are on the frontline, playing a crucial role in the prevention of infection and treatment of patients. This study was aimed to evaluate the prevalence of hospital-acquired coronavirus disease 2019 (COVID-19) infection at work and related factors at the University Hospital of Trieste workers exposed to COVID-19 patients. From March 1 to May 31, of 4216 employees, 963 were in contact with COVID-19 patients or colleagues and were followed up. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs was determined every 3 days, by RT-PCR. During the follow-up period, 193 workers were positive for COVID-19 (5%), and 165 of these (86%) were symptomatic. We identified five major cluster outbreaks of COVID-19 infection in Trieste Hospitals, four of which occurred before the implementation of universal masking for HCWs and patients (1-14 March 2020). COVID-19 infection was significantly higher in high-risk ward workers (Infectious Diseases, and Geriatric and Emergency Medicine, odds ratio [OR] 13.4; 95% confidence interval [CI] 5.8-31), in subjects with symptoms (OR 5.4; 95% CI 2.9-10) and in those with contacts with COVID-19 patients and colleagues (OR 2.23; 95% CI 1.01-4.9). Hospital workers were commonly infected due to contact with COVID-19 patients and colleagues, mainly in the first 15 days of the pandemic, before the implementation of universal mask wearing of HCWs and patients. Repetitive testing and follow-up permitted the identification of COVID-19 cases before symptom onset, obtaining better infection prevention and control.


Home care assistants' attitudes and perceptions of caring for people at the end of life in their homes in Sweden.
The ageing population is increasing worldwide, with older people often having multimorbidity and a need for help with activities and personal care. Home Care Assistants (HCAs) are central to the provision of care in the home. They meet older people approaching the end of life and their relatives. Little is known about HCAs attitudes towards caring for a dying person and how aspects such as education, age, earlier care experiences, care education and experience of caring for dying older people affect their attitudes. The aim was to describe HCAs' attitudes towards the care of dying persons living in their ordinary homes. This cross-sectional study used the Frommelt Attitude Toward Care of the Dying Scale (FATCOD) for data collection during December 2017 and January 2018, and descriptive statistics and regression analysis for data analysis. The participants were HCAs (n = 127, 96% of those eligible) in a municipality in central Sweden. An overall positive attitude was reported. About 32% lacked formal HCA education although 93% had experience of interacting with a dying person. Age, HCA education, internal palliative care education, number of years' experience and previous experience of caring for a dying person were independently associated with HCAs' attitudes. In the multivariate regression analysis, age and years of experience were the only significant predictors of HCAs' attitudes towards caring for dying care recipients. Young employees without HCA education and experience of a dying person might be vulnerable in situations involving caring for a dying person. Communicating about death and dying, forming a relationship with the care recipient and the family, and providing care when a person is dying can be challenging. Implications: Young employees without HCA education and experience of interacting with a dying person needs to be prepared for the situation. This needs to be considered by stakeholders and social and healthcare organisations.


Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study.
To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period. Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine. Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis.


Cause specific mortality in an Italian pool of asbestos workers cohorts.
Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.


Structural models for host-pathogen protein-protein interactions: assessing coverage and bias.
Recently, we applied structural systems biology to host-pathogen interaction and constructed the human-virus structural interaction network (SIN) based on a combination of solved structures and homology models. Subsequent analysis of the human-virus SIN revealed significant differences between antagonistic human-virus and cooperative within-human protein-protein interactions (PPIs). Although the SIN approach is advantageous due to the complementary nature of 3D structure and network data, integration of these data sources is associated with two potential issues: reduced coverage of the full human-virus PPI network, and the introduction of specific biases from structure determination. In this work, we evaluate the impact of these issues by comparing the growth and properties of human-virus and within-human PPI networks with and without structural models. We find that although the human-virus SIN is small in size, it is largely depleted for false positives, which are common in the full network. In addition, the SIN shows potential for major growth in the near future. Furthermore, compared to the full network, the coverage of viral species in the human-virus SIN is large relative to its size, suggesting that it may be a less biased sampling of the universe of human-virus PPIs. Next, we systematically compare structural versus full networks of human-virus and within-human PPIs in terms of functional, physicochemical, and network properties. We find that although there exist biases inherent to the structural approach, such biases tend to affect both human-virus and within-human PPIs equally. As a result, the significant differences between structured human-virus and within-human PPI networks are never contradicted by the full networks. Collectively, these results suggest that a structural approach to host-pathogen systems biology is not only justified, but also highly complementary to previous approaches. In particular, conclusions drawn from direct comparisons of host-virus and host-host PPIs within the SIN are minimally confounded by the inherent biases of the structural approach.


Implications of the BIA-102474-101 study for review of first-into-human clinical trials.
Over the past 10 years, thousands of first-into-human (FIH) clinical trials have been performed in Europe, with few severe adverse events (SAEs). Each has received detailed prior safety review at both the local clinical research facility and at national drug regulatory authority level. The recent fatal SAE in the BIA-102474-101 clinical trial shows the limitations of this process. Although criticized for not sequentially dosing subjects both within and between cohorts - as recommended by the European Medicines Agency for high-risk compounds after the TeGenero clinical trial disaster in 2006 - BIA-102474-101 was not considered to be high risk. Indeed, compounds with similar mechanisms of action had previously been taken through phase I and II trials without incident, and higher doses had been safely given for longer durations to nonhuman primates. If the available data are comprehensive and accurate, and further investigation does not reveal unreported warning signs, this study has serious implications for ongoing and future review of FIH clinical trials. All preclinical study documents and clinical data collected during the BIA-102474-101 trial should be made available urgently so that lessons can be learnt. In the meantime, reviewers and clinical researchers should always ask for information on drug and target interactions and full reports of preclinical toxicity studies, and plan sequential dosing with longer delays between patients and cohorts, particularly if late SAEs might be anticipated. The use of individual patient pharmacokinetic and dynamic data should guide sequential dosing. A process for systematic risk assessment, like that currently used in the Netherlands, should be applied routinely to all trials with novel compounds.


Oncolytic viruses for the therapy of brain tumors and other solid malignancies: a review.
In spite of significant advances in the understanding of molecular processes in tumor biology that have led to the development of oncologic therapeutic strategies, the prognosis for several types of tumors (such as brain, pancreas, or hepatic malignancies) remains dismal. Without question, a strong need exists for continued investigations in new agents and new therapeutic regimens. The realization that several genes used by viruses in their lytic life cycle interact and/or complement the function of genes employed by cells in cellular events linked to cell cycle progression, apoptosis, and/or metabolism immediately suggests the development of treatment strategies wherein viral mutants could be employed as selective anticancer agents. Such viruses (designated as oncolytic viruses) can selectively grow in tumor cells, produce viral progeny in those cells, lyse them and release this progeny that can then infect additional cells in the tumor mass. A theoretical advantage of oncolytic viruses (OV) is that their numbers should augment within the tumor mass, a property that is lacking with drugs or radiation treatments. Additionally, Ovs' mode of tumor killing differs from standard anticancer agents, providing the possibility for synergistic interactions in multimodal tumor therapies. In this review, we will describe the development of OVs and briefly review the life cycle of their wild-type (wt) counterparts. We will also summarize published results from OV clinical trials and attempt to provide a perspective on research in this area.


Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner.
Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.5 and then returned to normoxic conditions for the remainder of pregnancy. A control group was housed under normoxic conditions throughout pregnancy. Offspring were studied at 2 weeks (juveniles) and 8 weeks (adults), where lung volume was assessed by plethysmography, airway responsiveness to methacholine determined by the forced oscillation technique and lungs fixed for morphometry. IUGR offspring were lighter at birth, exhibited "catch-up growth" by 2 weeks, but were again lighter in adulthood. IUGR males were "hyper-responsive" at 2 weeks and "hypo-responsive" as adults, in contrast with IUGR females who were hyper-responsive in adulthood. IUGR males had increased inner and total wall thickness at 2 weeks which resolved by adulthood, while airways in IUGR females were structurally normal throughout life. There were no differences in lung volume between Control and IUGR offspring at any age. Our data demonstrate changes in airway responsiveness as a result of IUGR that could influence susceptibility to asthma development and contribute to sexual dimorphism in asthma prevalence which switches from a male dominated disease in early life to a female dominated disease in adulthood.


Dry mouth and dietary quality in older adults in north Carolina.
To quantify prevalence of dry mouth, association between dry mouth and beverage intake and dietary quality, and association between dry mouth and self-reported dietary accommodations to oral health deficits. Cross-sectional study; data from self-reports. Rural North Carolina counties with substantial African-American and American Indian populations. Six hundred twenty-two participants aged 60 and older. Data included the 11-item Xerostomia Inventory (higher scores connote greater effect from dry mouth), a food frequency questionnaire (converted into Health Eating Index-2005 scores), and survey items on foods modified before consumption or avoided because of oral health problems. Dry mouth was associated with being female, lower education, and income below the poverty level. Although overall beverage consumption did not vary with dry mouth, consumption of certain sugar-sweetened beverages was positively associated with dry mouth. Overall dietary quality did not differ with dry mouth, but more-severe dry mouth was associated with lower intake of whole grains and higher intakes of fruits. Dry mouth was strongly associated with self-reported modification and avoidance of foods. Those in the highest tertile of dry mouth were more likely to modify several foods than those in the lowest tertile and were more likely to avoid three or more foods. Older adults appear to modify foods or selectively avoid foods in response to perceived dry mouth. Despite these behaviors, dry mouth does not result in poorer dietary quality.


The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the Treatment of Uveitis.
Purpose: To detect any correlation between race and sex and the side effects of methotrexate in uveitis treatment. Methods: Retrospective review of patients seen at Northwestern Memorial Hospital between August 2012 and September 2014 with a history of MTX treatment for uveitis. Demographic, treatment, and side-effect data were collected for each patient. Results: Ninety-seven patients were included (25 males, 72 females). Twenty-eight patients reported African American race, 60 reported Caucasian race, and the remaining 9 reported Asian, Hispanic, or Arabic ethnicity. Males experienced more gastrointestinal upset than females (24% versus 13.8%). Caucasians had more gastrointestinal complaints (20% versus 8%) while African Americans developed more hair loss (14% versus 6.6%), although the numbers were too small to detect a statistical difference. Conclusion: While our sample was small, these findings suggest racial and gender disparities in the side effects experienced by patients treated with methotrexate. This information may be useful to clinicians counseling patients on risk profile.


Biosecurity in poultry production: where are we and where do we go?
An overview is given about the importance of biosecurity in the poultry industry, and a comparison is made with other systems of disease control such as vaccination and medication. Different measures considered to be important in bio-security are reviewed and some expectations for the future are given. Furthermore, some attention is paid to the animal welfare aspects.


Of rough starts and smooth finishes: correlations between post-anesthesia care unit and postoperative days 1-5 pain scores.
The goal of this project was to explore the association between post-anesthesia care unit (PACU) pain scores recorded within the first and second hour of the end of surgery with maximum and median pain scores recorded on postoperative days (PODs) 1 through 5. This study was a retrospective cohort study of clinically documented pain scores in a mixed surgical population. This study was set in a single tertiary-care teaching hospital over a 1-year time period. All patients were adult patients undergoing a single, non-ambulatory, non-obstetric surgical procedure. Pain scores, measured using the numerical rating scale, from PODs 0 through 5 were obtained from an integrated data repository. Kendall's Tau-b correlations were then calculated between maximum pain scores occurring within each of the two PACU time periods and maximum and median pain scores in each of the five ensuing PODs. A total of 349,797 pain scores from 8,332 patients were reviewed. Correlations between maximum pain score by time period demonstrated a significant and high correlation at Tau-b = 0.86, between 1-hour PACU pain scores and 2-hour PACU pain scores. However, the correlation of maximum pain scores recorded in the PACU with those recorded on PODs 1 through 5 was significantly lower, ranging from 0.19 to 0.27. The correlation of maximum PACU pain score with median pain scores recorded on PODs 1 through 5 ranged from 0.22 to 0.29. The correlation structures of the PODs 1 through 5 median pain scores may be consistent with an autoregressive pattern. Maximum scores measured within the PACU likely reflect a set of circumstances distinct from those experienced on PODs 1 through 5.


Comparison of the peripheral blood eosinophil count using near-patient testing and standard automated laboratory measurement in healthy, asthmatic and COPD subjects.
Near-patient testing (NPT) allows clinical decisions to be made in a rapid and convenient manner and is often cost effective. In COPD the peripheral blood eosinophil count has been demonstrated to have utility in providing prognostic information and predicting response to treatment during an acute exacerbation. For this potential to be achieved having a reliable NPT of blood eosinophil count would be extremely useful. Therefore, we investigated the use of the HemoCue® WBC Diff System and evaluated its sensitivity and specificity in healthy, asthmatic and COPD subjects. This method requires a simple skin prick of blood and was compared to standard venepuncture laboratory analysis. The HemoCue® WBC Diff System measured the peripheral blood eosinophil count in healthy, asthma and COPD subjects with very close correlation to the eosinophil count as measured by standard venepuncture. The correlations were unaffected by disease status. This method for the measurement of the peripheral blood eosinophil count has the potential to provide rapid near-patient results and thus influence the speed of management decisions in the treatment of airway diseases.


The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.
Dim1 is a small evolutionarily conserved protein essential for G2/M transition that has recently been implicated as a component of the mRNA splicing machinery. To date, the mechanism of Dim1 function remains poorly defined, in part because of the absence of informative sequence homologies between Dim1 and other functionally defined proteins or protein domains. We have used a combination of molecular modeling and NMR structural analysis to demonstrate that approximately 125 of the 142 amino acids of human Dim1 (hDim1) define a novel branch of the thioredoxin fold superfamily. Mutational analysis of Dim1 based on the predicted fold indicates that alterations in the region corresponding to the thioredoxin active site do not affect Dim1 activity. However, removal of a very short carboxy-terminal extension generates a dominant negative form of the protein [hDim1-(1-128)] that when overproduced induces cell cycle arrest in G2, via a mechanism likely to involve alteration of Dim1 association with partner molecules. In sum, this study identifies the Dim1 proteins as a novel sixth branch of the thioredoxin superfamily involved in cell cycle.