Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models.
Hand-foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the molecular biological mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatological and biological abnormalities induced by sunitinib. On the basis of the results of microarray analysis using the three-dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal-type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochemical staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated p38 mitogen-activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib-induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase-3β by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathology of HFSR.


The rbcL gene sequence from chestnut indicates a slow rate of evolution in the Fagaceae.
The nucleotide sequence was obtained for the chloroplast gene coding for the large subunit of the ribulose 1,5-bisphosphate carboxylase (rbcL) of chestnut (Castanea sativa Mill.), a member of the woody family Fagaceae. Amplification primers downstream and upstream the rbcL open reading frame are also described. By comparing with other angiosperm sequences, we show that the rate of evolution of rbcL in the family Fagaceae is much slower than that observed for the families of annuals analyzed.


Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure.
It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons. There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.


[The analysis of association between multiple sclerosis and genetic markers identified in genome-wide association studies].
Our aim was to analyse the association with multiple sclerosis of the genetic markers of autoimmune disorders identified in genome-wide association studies in ethnically homogenous groups of Russians and Tatars residing in the Republic of Bashkortostan. We performed genotyping of the genetic variants rs2069762 in IL2 gene, rs759648 in PVT1 gene, rs1800682 in FAS gene and rs12708716 in CLEC16A gene in the study group consisting of 1724 people (547 patients with multiple sclerosis, 1177 representatives of the control group). We analysed the association of the studied genetic markers with multiple sclerosis using logistic regression under additive genetic model implemented in PLINK program with sex a covariate. In the group of Tatars, we detected an association of PVT1 rs759648*Callele with multiple sclerosis (OR=1.42, p=0,023). Meta-analysis of the study results in the two ethnic groups we confirmed the association of the PVT1 rs759648*C allele with the disease (random effects model and fixed effect model: OR=1.29, p=0,018). Our results provide an evidence of an association between multiple sclerosis and the PVT1 rs759648 allele in the populations of Russian and Tatars from the Republic of Bashkortostan. No association with any other studied polymorphic variant was found in the two ethnic groups.


Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression.
Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.


Socioeconomic status, parenting investments, and negative personality traits over time and across generations.
The current investigation tested predictions from the interactionist model (IM) of socioeconomic influences on the development of negative personality traits with respect to feelings of alienation and low well-being. The model tested proposed that lower family socioeconomic status would lead to fewer parenting and material investments in the next generation adolescent, which in turn would be associated with higher levels of adolescent negative personality traits. The IM also predicted a transactional process in which adolescent negative personality attributes would then deter future socioeconomic success during adulthood which, in turn, would hinder adult development in terms of greater feelings of alienation and diminished well-being. Analyses with a cohort of 347 adolescents followed for over 20 years produced findings consistent with these predictions. Moreover, additional analyses with 282 of the third generation children of these cohort members demonstrated that this same process was being replicated in the third generation. The findings suggest reciprocal or transactional influences that promote the development of negative personality attributes and accumulating personal, economic and social advantages over time and generations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Non-surgical endodontic treatment for dens invaginatus type III using cone beam computed tomography and dental operating microscope: a case report.
Dens invaginatus is a morphological abnormality of the tooth in which the coronal tooth enamel and dentin fold inwards towards the pulp cavity. Dens invaginatus type III (Oehlers: 1957) is characterized by infolding of the enamel and dentin as far as the root apex. This report describes a case of surgical and non-surgical endodontic therapy for a maxillary lateral incisor with type III dens invaginatus, necrotic pulp, and an associated large periradicular lesion. The patient was a 16-year-old man. Periapical radiographs suggested the presence of an untreated area of invagination. Cone beam computed tomography (CBCT) was then used for three-dimensional observation of the morphological details of this area. The CBCT scans revealed invagination and its relationship with the pulp chamber. A dental operating microscope was used to access two primary root canals and the area of invagination. The root canals were then localized, negotiated, enlarged, and filled with calcium hydroxide. Two months later, the canal and invagination were obturated with core-based gutta-percha (FlexPoint Neo: FP core-carrier technique) and restored. Cone beam computed tomography and microscopic techniques allow even complicated cases of dens invaginatus to be diagnosed and treated using non-surgical root canal management.


Reflections on an interview with the late Prof Maria Antonia Modolo Considerazioni su di un'intervista alla Prof Maria Antonia Modolo, recentemente scomparsa.
The Author, now a Research Assistant at the Department of Public Health of the University of Milan, Italy, in the period she was a Resident of the School of Public Health of the University of Perugia, had the occasion to interview Prof Maria Antonietta Modolo, one of the most significant pioneers of Health Education and Health Promotion both in Europe and in this Country, and her mentor at that time. Prof Modolo, who recently passed away, in that occasion explained in detail all the goals of these disciplines, and the impact they can show on the life of the population of developed and developing countries, if applied within a robust public health framework.


Analysis of primary gingivoperiosteoplasty in alveolar cleft repair. Part I: Facial growth.
The primary gingivoperiosteoplasty by Millard consists of presurgical active orthognathic treatment ('Latham device') of the alveolar margins at the age of 3 months and of surgical closure of the alveolar cleft with local gingivoperiosteal flaps at the age of 5 months. The aim of this investigation was to analyse the facial growth following this treatment. The following material was studied: lateral head X-rays and plaster casts from 146 patients with unilateral (UCLP) and bilateral (BCLP) clefts of lip and palate from birth to 16 years of age. Ninety-one of these patients formed the control group, who received neither gingivoperiosteoplasty nor pre-surgical active orthognathic treatment. The same surgeon and orthodontist treated all 146 patients. A three-dimensional growth disturbance after gingivoperiosteoplasty was observed: 42% patients with UCLP and 40% patients with BCLP had an 'open bite' following closure of the alveolar cleft (control group 5%/10%). The length of the upper jaw in patients who underwent gingivoperiosteoplasty was shorter than in the control group. The frequency of posterior cross bite was also higher in the gingivoperiosteoplasty group. These results demonstrate that treatment with a 'Latham device' disturbs facial growth. Therefore, this treatment should be abandoned.


Reptilian and avian ovarian cycles and the evolutionary origin of volant birds.
The first birds probably evolved from a line of theropod dinosaurs in the late Jurassic or early Cretaceous. The "trees down" theory proposes that avian ancestors were arboreal, whereas the "ground-up" (cursorial) theory suggests that they were terrestrial, and ran and jumped for prey. We present suggestive evidence from reptilian and avian female reproductive biology that supports the arboreal theory, although neontological evidence can never authenticate a paleontological event. The "law of follicular constancy" is an empirical observation that the number of ovulations per female per ovulatory cycle (instantaneous fecundity, or IF) is the same regardless of the amount of ovarian tissue present. In vertebrates with an IF of two or more, surgical removal of one of the paired ovaries (unilateral ovariectomy, or ULO) leads to a doubling of ovulations from the remaining ovary (compensatory ovarian hypertrophy, or COH), this ovary cycling at the same frequency as it did before surgery. In vertebrates that produce one egg alternately from each ovary (an IF of one), however, ULO leads to a form of COH in which the remaining ovary still ovulates one egg at a time but twice as frequently. In most birds, only the left ovary is present; it ovulates a single egg every 1-2 days until the species-specific clutch size is reached. Inasmuch as this avian ovulatory pattern is similar to an accelerated version of that occurring after ULO in a species that alternates ovulation, we propose that birds evolved from dinosaurs with such a pattern. A great majority of extant reptiles with an IF of one are either anoline or gekkonid lizards, and many of these ovulate several times a year. Furthermore, most species in these tropical groups are arboreal. Even considering phylogenetic constraints within anoline and gekkonid lizards, we propose that correlations of arboreality and an IF of one in these groups are implied as adaptive relationships and represent ecological parallelisms. Therefore, we propose that the ancestors of birds were arboreal. Furthermore, they probably were of small size, as are all lizards with an IF of one.


The development and evolution of a tertiary pancreaticobiliary endoscopic ultrasound service: lessons learned.
This article reviews the development of the hepatopancreatobiliary (HPB) endoscopic ultrasound (EUS) service at Freeman Hospital and seeks to identify from our experience learning points for good practice and pitfalls to avoid. The Freeman HPB EUS service has expanded rapidly over the past 10 years in response to the consolidation of cancer care and aligned to the needs of the cancer network. Effective multidisciplinary teamwork and increased subspecialisation by the endosonographers has allowed the efficient use of capacity and development of skills. Mechanisms for monitoring diagnostic performance put in place at the outset of the EUS-fine needle aspiration programme have helped to identify interventions that have led to improved test performance. An excellent working relationship between all stakeholders is critical to the success of such a service as is a preparedness to seek and respond to the views of patients and referrers.


Role of articulation in speech perception: clues from production.
The relative roles played by signal properties and nonsignal information in speech perception are first examined. The evidence strongly suggests that phonetic percepts are never knowledge-innocent records of the raw signal. That conclusion is drawn not only about "higher" levels of language processing, but is seen to apply also to the perception of elementary phonetic stimuli. A review of a broad range of facts about production highlights the fact that speech production is adaptively organized. That circumstance suggests that the signal does not encode articulatory or acoustic/auditory invariants, but plays the role of supplementing the multimodal information already in place in the listener's speech processing system. It is accordingly proposed that phonetic signals are not invariants wrapped in "noise," but are products of listener-dependent adaptations that transform speech patterns in principled and, therefore, interpretable ways. Do listeners form speech percepts by way of intermediate articulatory representations? There seem to be strong both theoretical and methodological reasons to doubt that they do.


In silico modelling of aortic valve implants - predicting in vitro performance using finite element analysis.
The competing structural and hemodynamic considerations in valve design generally require a large amount of in vitro hydrodynamic and durability testing during development, often resulting in inefficient "trial-and-error" prototyping. While in silico modelling through finite element analysis (FEA) has been widely used to inform valve design by optimising structural performance, few studies have exploited the potential insight FEA could provide into critical hemodynamic performance characteristics of the valve. The objective of this study is to demonstrate the potential of FEA to predict the hydrodynamic performance of tri-leaflet aortic valve implants obtained during development through in vitro testing. Several variations of tri-leaflet aortic valves were designed and manufactured using a synthetic polymer and hydrodynamic testing carried out using a pulsatile flow rig according to ISO 5840, with bulk hydrodynamic parameters measured. In silico models were developed in tandem and suitable surrogate measures were investigated as predictors of the hydrodynamic parameters. Through regression analysis, the in silico parameters of leaflet coaptation area, geometric orifice area and opening pressure were found to be suitable indicators of experimental in vitro hydrodynamic parameters: regurgitant fraction, effective orifice area and transvalvular pressure drop performance, respectively.


Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease.
The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very diverse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid diversification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.


Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation.
Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fy(a), Fy(b), Jk(a), Jk(b), and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported. Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved. A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs. Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens-matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs.


So-called primitive neuroectodermal tumor in aborted previable fetuses.
We have described the gross anatomic and histopathologic characteristics of 36 tumorlike lesions found in previable fetuses. Although these lesions appear to be invasive, metastasizing, and likely contributing to the death of the fetus, they represent a frequent finding only among severely macerated retained fetuses of 9-16 developmental weeks and have never been found in fresh nonretained fetuses. No family history of neurofibromatosis could be elicited in any of these cases to support the suggestion in the literature that these tumors may represent fetal manifestations of neurofibromatosis. The most likely explanation is that they represent an artifact owing to squeezing of brain tissue into the spinal canal and along the spinal nerves into retroperitoneal and retropleural spaces or the neck area. As this artifact appears to be confined to a specific developmental period (9-16 weeks), it may be related to certain developmental characteristics such as a very soft consistency of brain tissue or incomplete development of vertebral foramina. A higher incidence of these lesions among heteroploid fetuses remains unexplained.


The Importance of Visual Feedback Design in BCIs; from Embodiment to Motor Imagery Learning.
Brain computer interfaces (BCIs) have been developed and implemented in many areas as a new communication channel between the human brain and external devices. Despite their rapid growth and broad popularity, the inaccurate performance and cost of user-training are yet the main issues that prevent their application out of the research and clinical environment. We previously introduced a BCI system for the control of a very humanlike android that could raise a sense of embodiment and agency in the operators only by imagining a movement (motor imagery) and watching the robot perform it. Also using the same setup, we further discovered that the positive bias of subjects' performance both increased their sensation of embodiment and improved their motor imagery skills in a short period. In this work, we studied the shared mechanism between the experience of embodiment and motor imagery. We compared the trend of motor imagery learning when two groups of subjects BCI-operated different looking robots, a very humanlike android's hands and a pair of metallic gripper. Although our experiments did not show a significant change of learning between the two groups immediately during one session, the android group revealed better motor imagery skills in the follow up session when both groups repeated the task using the non-humanlike gripper. This result shows that motor imagery skills learnt during the BCI-operation of humanlike hands are more robust to time and visual feedback changes. We discuss the role of embodiment and mirror neuron system in such outcome and propose the application of androids for efficient BCI training.


The Nursing Research Committee: the James A. Haley Veterans' Hospital.
Nursing research has been a part of the culture at the James A. Haley Veterans' Hospital for many years. A Nursing Research Committee (NRC) has been an integral part of this success. The emphasis remains on involving the staff nurse in nursing research. By defining clear-cut goals and objectives, leadership of the NRC reaps substantial professional results.


An aeronautic suicide attempt (3). Suicide and self-destructive behavior in aviation.
Approximately 2-3% of all fatal air accidents may be attributed to suicide, and in many other accidents in aviation there are grounds for inferring that self-destructive or suicidal behavior was involved. Narcissistic personality traits are of paramount importance for the choice of this suicide method. Precursors include undetected depressions, alcoholism, and family problems of pilots.


The Chain Length Distribution of an Ideal Reversible Deactivation Radical Polymerization.
The chain length distribution (CLD) of a reversible deactivation radical polymerization at full conversion is shown to be a negative binomial distribution with parameters that are simple functions of the number-average degree of polymerization and either the chain transfer constant (in the case of polymerizations that incorporate a reversible chain transfer step) or the concentrations of dormant polymer chains and deactivating agent and the rate constants of propagation and deactivation (other types of RDRP). Expressions for the CLD at intermediate conversions are also derived, and shown to be consistent with known expressions for the number-average degree of polymerization and dispersity. It is further demonstrated that these CLDs are well-approximated by negative binomial distributions with appropriate choice of parameters. The negative binomial distribution is thus a useful model for CLDs of reversible deactivation radical polymerizations.


Inhibition of the k-stimulated ATPase of the plasmalemma of pinto bean leaves by ozone.
Three varieties of Phaseolus vulgaris which differ in their sensitivity to ozone were examined for changes in some physiological and structural plasma membrane characteristics. Plasma membrane vesicles were prepared from control and ozone-treated (0.2 to 0.5 microliters per liter ozone for 5 hours) leaf tissue, and the (K(+) + Mg(2+))-ATPase activity determined and compared. No major changes were observed in the resistant varieties. The sensitive variety showed a severe inhibition of ATPase activity which was largely due to a decrease in the K(+)-stimulated component. This inhibition was completely reversed by the addition of sulfhydryl compounds.Ozone-induced plasma membrane permeability changes may be effected by damage to membrane proteins, perhaps by oxidation of amino acid sulfhydryl groups to disulfide and sulfenic moieties.


The CD44 variant isoforms CD44v6 and CD44v7 are expressed by distinct leukocyte subpopulations and exert non-overlapping functional activities.
We have described recently that anti-CD44s, anti-CD44v6 and anti-CD44v7 interfere with delayed-type hypersensitivity (DTH) reactions. Yet, TNBS-induced colitis can be cured only by anti-CD44v7. To clarify the mechanisms underlying the divergent functional activities of CD44v6 and CD44v7 we explored their contribution to lymphocyte activation in vivo and in vitro. CD44v6 and CD44v7 are distinctly expressed on subpopulations of activated lymphocytes. Expression of CD44v6 is mainly restricted to T cell blasts. CD44v7 has been detected on CD4(+) cells, B cells and monocytes. Mitogenic and antigenic stimulation of lymphocytes in vitro was impaired in the presence of anti-CD44v6 and anti-CD44v7. Accordingly, anti-CD44v6 and anti-CD44v7 mitigated the DTH reaction in 2,4-dinitro-1-fluorobenzene-sensitized and challenged mice. However, the seemingly similar effects of CD44v6- and CD44v7-specific antibodies resulted from different activities. Anti-CD44v6 treatment led to a down-regulation of IL-2 and IFN-gamma production predominantly by CD8(+) cells. In anti-CD44v7-treated mice expression of IL-12 was decreased. Elevated levels of IL-10 accompanied this reduction. The latter resulted from an anti-CD44v7-mediated blockade of interactions between CD4(+) cells and monocytes as well as an active triggering of B cells. Thus, anti-CD44v6 and anti-CD44v7 interfere with lymphocyte activation at very specific points. CD44v6 functions predominantly at the T cell level. CD44v7 influences production of proinflammatory cytokines by B cells as well as an interaction between CD4(+) cells and antigen-presenting cells. As CD44 isoforms do not differ in their intracytoplasmatic tail, the distinct activities must result from expression on different leukocyte subsets and interactions with distinct ligands.


Modeling Information Content Via Dirichlet-Multinomial Regression Analysis.
Shannon entropy is being increasingly used in biomedical research as an index of complexity and information content in sequences of symbols, e.g. languages, amino acid sequences, DNA methylation patterns and animal vocalizations. Yet, distributional properties of information entropy as a random variable have seldom been the object of study, leading to researchers mainly using linear models or simulation-based analytical approach to assess differences in information content, when entropy is measured repeatedly in different experimental conditions. Here a method to perform inference on entropy in such conditions is proposed. Building on results coming from studies in the field of Bayesian entropy estimation, a symmetric Dirichlet-multinomial regression model, able to deal efficiently with the issue of mean entropy estimation, is formulated. Through a simulation study the model is shown to outperform linear modeling in a vast range of scenarios and to have promising statistical properties. As a practical example, the method is applied to a data set coming from a real experiment on animal communication.


[Solitary fibrous tumor of the pleura--description of two cases with features of malignancy].
Two cases of solitary fibrous tumor of the pleura with features of malignancy are described. In the first case, the tumor macroscopically showed noncircumscribed growth. Microscopically, on low power examination, the tumor was characteristically "patternless", with alternation of cellular areas and hypocellular, prominently collagenized areas. There was an infiltrative growth present at the margins. Cytological atypias were not present. In the second case, the tumor was macroscopically circumscribed. Microscopically, on low power examination, the tumor had characteristical "patternless" appearance again. Pleomorphic cells with high mitotic activity dominated in cellular areas on high power examination. The infiltrative pattern of growth was not present at the margins. Both tumors were classified as malignant solitary fibrous tumors of the pleura, or fibrosarcomas of the pleura. The criteria of malignancy for solitary fibrous tumor are discussed.


Treatment-related peripheral small cell lung carcinoma in a Hodgkin lymphoma survivor.
Hodgkin lymphoma (HL) survivors have an increased risk of developing subsequent treatment-related primary malignancies. In the last few decades, advances in knowledge, radiotherapy, chemotherapy and autologous stem cell transplantation have led to the transformation of lethal malignancy into highly curable malignancy, thereby improving outcomes. With prolonged survival, the risk of developing subsequent treatment-related late adverse effects, such as malignancies, steadily increases over time. Herein, we present the first case of a treatment-related second primary stage IV peripheral small cell lung carcinoma in a female HL survivor who was also diagnosed with right breast cancer 13 years after HL treatment and 1 year before her lung cancer diagnosis.


The impact of noise exposure and work posture on job stress in a food company.
In most food companies, workers are constantly exposed to non-standard levels of noise. Also, food production processes require intense manual labor and repetitive movements, which may result in musculoskeletal disorders (MSDs). Noise and awkward posture are considered as two important physical factors in the industrialized world, which can related to perceived stress. This study was conducted among food factory workers to investigate the impact of noise exposure and work posture on occupational stress. A total of 200 workers were examined in this cross-sectional study. Individual noise exposure was measured by TES-1354 dosimeter (TES, TW) according to ISO 9612. Postural risk and job stress levels were assessed using Quick Exposure Check (QEC), and the Osipow occupational stress questionnaire, respectively. The level of noise exposure and awkward posture were significantly associated with work-related stress.The relationship of gender with occupational stress was also statistically significant. Considering that the noise exposure and work posture factors are important determinants of work-related stress, a combined approach to eliminate the levels of non-standard noise and inappropriate posture is essential for promoting psychological health in food companies.


The decline of pharmaceutical psychiatry and the increasing role of psychological medicine.
The increasing influence of the pharmaceutical industry on psychiatric research and practice is leading to an intellectual and clinical crisis. A narrow concept of science attempts to apply oversimplified neurobiological models to the understanding and treatment of mental disorders, and relegates psychiatrists to a marginal role. This paper reviews some emerging trends of renewal that may be subsumed under the rubric of psychological medicine: use of a multidisciplinary approach, emphasis on psychotherapeutic strategies leading to self-management, reliance on repeated assessments, integration of different treatment modalities and independence from the pharmaceutical industry. The concept of psychological medicine, defined as the clinical application of the psychosomatic approach, may provide room for innovative paths in psychiatric research and treatment.


Identification of an ApoA-I ligand domain that interacts with high-affinity binding sites on HepG2 cells.
We have previously described the presence of two (high- and low-affinity) HDL binding sites on the hepatoma cell line (HepG2) (R. Barbaras, X. Collet, H. Chap, and B. Perret (1994) Biochemistry 33, 2335-2340]. Moreover, apoA-I, the major HDL apolipoprotein, interacts with these two binding sites, while lipid-free apoA-I binds only to the high-affinity sites. Using tryptic HDL fragments and HepG2 cell monolayers as an "affinity matrix," we identified an apoA-I peptide of 16 amino acids, spanning between residues 62 and 77, as a ligand domain. The corresponding synthetic peptide displays high-affinity (K(d) approximately 10(-7) M) and low-capacity (B(max) 8 pmol/mg of cell protein) binding components. Competition experiments with this peptide, using (125)I-labeled free apoA-I as a ligand, show that this binding corresponds to the high-affinity binding sites already described. In conclusion, we identified the apoA-I 62-77 region as a specific high-affinity ligand domain of HDL on HepG2 cells.


One-Pot Conversion of Carbohydrates into Pyrrole-2-carbaldehydes as Sustainable Platform Chemicals.
A practical conversion method of carbohydrates into N-substituted 5-(hydroxymethyl)pyrrole-2-carbaldehydes (pyrralines) was developed by the reaction with primary amines and oxalic acid in DMSO at 90 °C. Further cyclization of the highly functionalized pyrralines afforded the pyrrole-fused poly-heterocyclic compounds as potential intermediates for drugs, food flavors, and functional materials. The mild Maillard variant of carbohydrates and amino esters in heated DMSO with oxalic acid expeditiously produced the pyrrole-2-carbaldehyde skeleton, which can be concisely transformed into the pyrrole alkaloid natural products, 2-benzyl- and 2-methylpyrrolo[1,4]oxazin-3-ones 8 and 9, lobechine 10, and (-)-hanishin 11 in 23-32% overall yields from each carbohydrate.


The comparative effects of azathioprine and cyclosporin on some gingival health parameters of renal transplant patients. A longitudinal study.
The periodontal health of 24 adult renal transplant patients was investigated in a longitudinal study. Post-transplant patients were receiving either azathioprine or cyclosporin to prevent graft rejection. No significant difference (P greater than 0.05) was observed for plaque scores on gingival inflammation, either between treatment groups or throughout the investigation period. However, patients on cyclosporin therapy had significantly more gingival hyperplasia and probing sites greater than 3 mm than those on azathioprine (P less than 0.05). In the cyclosporin group, a significant increase in hyperplasia and probing sites greater than 3 mm was observed at 3 and 6 months post-transplant. A significant correlation (rs = 0.55, P less than 0.05) was observed between mean plasma concentrations of cyclosporin throughout the 6-month investigation period and the increase in gingival hyperplasia. The finding from this study would suggest that azathioprine has no unwanted effects on the periodontal health of post-renal transplant patients. Cyclosporin therapy caused an increase in gingival hyperplasia, which may be related to plasma concentrations of the drug.


Different elution modes and field programming in gravitational field-flow fractionation. III. Field programming by flow-rate gradient generated by a programmable pump.
Gravitational field-flow fractionation (GFFF) utilizes the Earth's gravitational field as an external force that causes the settlement of particles towards the channel accumulation wall. Hydrodynamic lift forces oppose this action by elevating particles away from the channel accumulation wall. These two counteracting forces enable modulation of the resulting force field acting on particles in GFFF. In this work, force-field programming based on modulating the magnitude of hydrodynamic lift forces was implemented via changes of flow-rate, which was accomplished by a programmable pump. Several flow-rate gradients (step gradients, linear gradients, parabolic, and combined gradients) were tested and evaluated as tools for optimization of the separation of a silica gel particle mixture. The influence of increasing amount of sample injected on the peak resolution under flow-rate gradient conditions was also investigated. This is the first time that flow-rate gradients have been implemented for programming of the resulting force field acting on particles in GFFF.


Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study.
The susceptibility to rheumatoid arthritis (RA) is partly heritable, but whether the severity of RA is also influenced by genetics has not been determined. The evaluation of the heritability of the severity of RA is basic to further studies on genetic factors. A study was undertaken to determine whether joint destruction is heritable. Iceland has an unique comprehensive genealogy database covering today's population and stretching back to ≥1000 years ago, as well as genome-wide single nucleotide polymorphism data for a large part of the population. Hand and feet x-rays of 325 Icelandic patients with RA were scored according to the Sharp-van der Heijde method. The degree of relatedness between patients was estimated in two ways: (1) kinship coefficients (KC) on the genealogical data were expressed; and (2) the identical-by-descent (IBD) was estimated applying long-range phasing of the genetic profile of the patients. The degree of relatedness was tested against the similarity in joint destruction rates by linear regression analysis and the heritability of joint destruction was calculated. Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (p(KC)=0.018, p(IBD)=0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data. The severity of joint destruction in RA is influenced by genetic factors.


Bevacizumab/docetaxel association is more efficient than docetaxel alone in reducing breast and prostate cancer cell growth: a new paradigm for understanding the therapeutic effect of combined treatment.
Bevacizumab (Bvz), a Vascular Endothelial Growth Factor (VEGF)-targeted humanised monoclonal antibody, provides clinical benefit in combination with docetaxel (DXL), a microtubule-stabilising agent, in the treatment of metastatic breast and prostate cancers. Since VEGF and their receptors are expressed by tumour cells, we hypothesised that Bvz, in addition to its impact on neo-vascularisation, could have an impact on tumour cells and enhance the DXL activity. Hence, we studied the effect of DXL and Bvz on metastatic breast (MDA MB-231) and prostate (PC3) cancer cells lines. Bvz alone did not decrease cell proliferation but in combination with DXL, Bvz enhanced the anti-proliferative activity of DXL. Other anti-angiogenic factors Sunitinib, Sorafenib and Gefitinib enhanced the anti-proliferative effect of DXL. qPCR experiments showed that DXL significantly increased the VEGF and VEGF receptor 2 (VEGF-R2) mRNA levels. Activation of VEGF and VEGF-R2 promoters demonstrated that enhanced mRNA levels are partly due to transcriptional activation. ELISA assays showed that DXL induced accumulation of cytoplasmic VEGF but decreased extracellular levels by 39% (MDA) and 48% (PC3). Cell surface localisation of VEGF-R2 was increased by DXL alone, but decreased after combined treatment of DXL plus Bvz. Abnormal expression of VEGF-R2 was also shown on breast and prostate tumour samples reinforcing the results obtained on cellular models. In conclusion, DXL and Bvz in combination decreased extracellular VEGF and VEGF-R2 levels at the plasma membrane thereby blocking an important growth/survival loop. Thus, the combined therapeutic impact of Bvz and DXL observed in clinical trials is associated with enhanced anti-proliferative activity and inhibition of the vascular network.


Molecularly Heterogeneous Structure of a Nonionic Deep Eutectic Solvent Composed of N-Methylacetamide and Lauric Acid.
Deep eutectic solvents (DES) are a new class of designer solvents with a wide range of possible applications. DESs are typically made from an ionic compound and a hydrogen bond donor, but lately DESs made of nonionic compounds with interesting properties have started to appear. This study focuses on describing the structure, dynamics, and interactions of a nonionic DES composed of N-methylacetamide (NMA) and lauric acid (LA). Linear IR and time-resolved IR experiments show that LA-NMA DES is the result of hydrogen bond interaction between the two molecular components, though the interaction energy is only favored by ∼1 kJ/mol with respect to the pure components. The IR experiments also reveal the presence of molecular heterogeneities produced by the nanosegregation of polar and nonpolar domains formed by N-methylacetamide and lauric acid, respectively. In addition, it is observed that the hydrogen bond interaction between components occurs at the interface of the two distinct polarity domains. The proposed molecular picture is also supported by the observation of nanodomains with the approximate size of two lauric acids via small-angle X-ray scattering.


Selective antenatal screening for toxoplasmosis and the latex agglutination test.
Recent publicity concerning congenital toxoplasmosis has generated a demand for serological assessment of pregnant women. Many laboratories are requested to undertake primary screening in these cases. We assessed the latex agglutination test (LAT) findings in 158 specimens with detectable toxoplasma specific IgM derived from pregnant women. The LAT titres ranged from 16 to greater than or equal to 4000 reflecting the variable antibody response observed in acute toxoplasmosis. We recommend that non-reference laboratories test specimens from pregnant women using the LAT at a screening dilution of 1:16 and select all reactive samples for detailed investigation.


Type IV collagen in the basal membrane of human papillomavirus associated premalignant and malignant squamous cell lesions of the uterine cervix.
In the present study, the expression of type IV collagen associated with the basal membrane (BM) was studied histochemically (indirect immunoperoxidase-antiperoxidase) in cervical human papillomavirus (HPV) lesions (diagnosed using in situ DNA hybridization) of different grades. The expression of type IV collagen in premalignant epithelial lesions (HPV with and without cervical intraepithelial neoplasia) was identical with that in the BM of normal exocervical epithelium, in contrast to 60% (3/5) of carcinoma in situ lesions and 90% (10/11) of invasive carcinomas, where the staining pattern was interrupted and the staining intensity reduced. Thus, the expression of type IV collagen seems to remain unchanged during the entire spectrum of premalignant stages of cervical HPV lesions. This suggests that the squamous epithelial cells responsible for the formation of the BM are not affected by this virus at early stages of the disease, and immunohistochemical recognition of an intact staining pattern of type IV collagen may signify well-preserved basal cell function (confined to nonmalignant?) HPV-infected squamous epithelium.


Viable spore counts in biological controls pre-sterilization.
The aim of the present study was to evaluate the total count of viable spores in standardized inoculated carriers pre-sterilization. Samples of "Bacterial Spore Sterilization Strip" (R Biological Laboratories) (well before their expiry date) were divided into Group A (B. subtilis) and Group B (B. stearothermophylus). Twenty-four strips were tested per group. The strips were minced in groups of three, placed in chilled sterile water and vortexed for 5 minutes to obtain a homogenous suspension. Ten ml of the homogenous suspension were transferred to two sterile jars, i.e. one jar per group. The samples were then heated in a water bath at 95 degrees C (Group A) or 80 degrees C (Group B) for 15 minutes and cooled rapidly in an ice bath at 0- 4 degrees C during 15 minutes. Successive dilutions were performed until a final aliquot of 30 to 300 colony-forming units (CFU) was obtained. The inoculums were placed in Petri dishes with culture medium (soy extract, casein agar adapted for spores, melted and cooled to 45-50 degrees C) and incubated at 55 degrees C or 37 degrees C. Statistical analysis of the data was performed. A larger number of spores were found at 48 hours than at 24 hours. However, this finding did not hold true for all the groups. The present results show that monitoring viable spores pre-sterilization would guarantee the accuracy of the data. Total spore counts must be within 50 and 300% of the number of spores indicated in the biological control. The procedure is essential to guarantee the efficacy of the biological control.


[The analysis of hantavirus S gene in Apodemus agrarius in Changbai area].
To gain more insights into epidemiologic characteristics and genotype of hantavirus in Apodemus agrarius in Changbai Area. Complete hantavirus S segment sequences were amplified by RT-PCR and sequenced. The phylogenetic trees were constructed for analysis of genetic characters of hantavirus. A total of 58 Apodemus agrarius were trapped in the epidemic areas, and complete hantavirus S segment sequences were obtained from 4 lung samples of these rodents (6. 90%0). Phylogenetic analysis of the four S segment sequences indicated that all viruses isolated from Apodemu sagrarius were closely related to genotype 6 of Hantaan virus (95. 8%-96. 3%, nucleotide identity; 98. 6%-99. 5%, amino acid identity), all of them had a specific S387 different from other genotypes of Hantaan virus.


The study of kinematic transients in locomotion using the integrated kinematic sensor.
A system based on the integrated kinematic sensor (IKS) was used to study the three-dimensional (3-D) kinematics of human lower limb during walking and running. The linear displacement, angular velocity, and linear acceleration of the foot, shank, and thigh segments were directly measured using three IKS's. The results clearly showed the heel strike impact in both walking and running, illustrating the high frequency components that exist in those activities. This paper illustrates the limitations of standard position measurements to capture transients associated with phase transitions, not only in acceleration estimates, but also in the determination of segmental angular velocities. An error analysis was conducted to determine the relative contribution of the accelerometer and the angular rate sensor to the determination of the segmental center of mass (COM) acceleration. The results suggest that in practical kinesiological applications, adding either an accelerometer or an angular rate sensor can remarkably increase the accuracy of segmental COM acceleration estimates.


Cystic Echinococcosis of Camels: 12S rRNA Gene Variation Revealed Changing Pattern of Genetic Diversity Within Echinococcus granulosus sensu lato in the Middle East and North/Sub-Saharan Africa.
Cystic echinococcosis (CE) is one of the most widespread zoonotic diseases, with considerable public health and economic importance. Camels play a significant role in transmission cycle of Echinococcus granulosus especially, in the Middle East and North Africa (MENA). The present study aimed to identify the genetic variation and haplotype distribution of camel isolates of E. granulosus sensu lato using all existing E. granulosus mitochondrial DNA data from camels in different parts of the world. Sequence data from 1,144 camel isolates of E. granulosus s.l. available in the NCBI GenBank including 57 camel hydatid cysts collected in central Iran were used to analyze the nature of genetic variation within the camel isolates of E. granulosus s.l. in MENA region. Fifty-seven camel isolates were also PCR-sequenced on mitochondrial 12S rRNA gene. Haplotype network analysis revealed seven different haplotypes clustered into four major groups. E. intermedius G6 was identified as the most commonly represented genotype in camels followed by G1. Mitochondrial 12S rRNA gene sequence analysis on 57 camel isolates identified three different genotypes, including E. intermedius/G6 (35/57, 61.4%), E. granulosus sensu stricto/G1-G3 (21/57, 36.8%) as well as one isolate identified as E. ortleppi/G5 (1/57, 1.8%). The number of base substitutions per site over 420 positions of partial 12S rRNA gene sequences were shown as 0.000 and 0.004 for E. intermedius (G6) corresponding to the Middle East and sub-Saharan isolates, respectively. Camel isolates of E. granulosus in the MENA region present moderate genetic diversity (Hd = 0.5540-0.6050). The Middle East isolates demonstrated a more diverse population than the North/sub-Saharan isolates, where six out of seven 12S rRNA haplotypes were identified in the former region. E. intermedius (G6 genotype) was shown to be the most common species in the world camel population. In conclusion, camels showed to be an important intermediate host species in the MENA region with different patterns of genetic variation between the Middle East and Africa.


Symptomatic multifocal osteonecrosis. A multicenter study. Collaborative Osteonecrosis Group.
Osteonecrosis of the femoral head frequently occurs in a young population (mean age, approximately 35 years) and may lead to disabling arthritis requiring hip arthroplasty surgery. This disease is compounded when it has concurrent involvement of other joints. Multifocal osteonecrosis is defined as disease involving three or more anatomic sites. The purpose of this study was to review the demographic, clinical, radiographic staging patterns, and treatment options in patients with multifocal osteonecrosis to facilitate earlier diagnosis and optimize treatment. Twenty-one centers participated by submitting completed data forms on patients under their care after review of their databases. One hundred one patients were identified. Patient demographics, associated diseases, corticosteroids and other medications used, presenting joints, and symptomatology were evaluated. Radiographs and magnetic resonance imaging scans or both were used to diagnose and stage osteonecrotic lesions. Ninety-two of the 101 (91%) patients had a history of corticosteroid therapy. Twelve patients (of 14 tested) were found to have a coagulation disorder. All 101 patients had femoral head involvement. Osteonecrosis also was seen in the knee (96%), shoulder (80%), ankle (44%), and seven other sites. Overall, 631 joints were involved (6.2 lesions per patient). Bilaterality was common: hips, 98%; knees, 86%; and shoulders, 83%. Most lesions (69%) were in a precollapse stage at the time the patients presented for treatment. In eleven patients, the knee was the sole presenting symptomatic joint, and the shoulder and ankle were the sole presenting symptomatic joints in five and four patients, respectively. An improved understanding of the epidemiology, pathogenesis, and etiology of multifocal osteonecrosis will facilitate the diagnosis and treatment of this disease. In patients with osteonecrosis of the hip, all symptomatic joints should be evaluated with radiographs. In patients with osteonecrosis presumably not involving the femoral head, the patient's femoral heads should be evaluated radiographically, regardless of whether the hips are symptomatic.


Spectral parameterization for studying neurodevelopment: How and why.
A growing body of literature suggests that the explicit parameterization of neural power spectra is important for the appropriate physiological interpretation of periodic and aperiodic electroencephalogram (EEG) activity. In this paper, we discuss why parameterization is an imperative step for developmental cognitive neuroscientists interested in cognition and behavior across the lifespan, as well as how parameterization can be readily accomplished with an automated spectral parameterization ("specparam") algorithm (Donoghue et al., 2020a). We provide annotated code for power spectral parameterization, via specparam, in Jupyter Notebook and R Studio. We then apply this algorithm to EEG data in childhood (N = 60; Mage = 9.97, SD = 0.95) to illustrate its utility for developmental cognitive neuroscientists. Ultimately, the explicit parameterization of EEG power spectra may help us refine our understanding of how dynamic neural communication contributes to normative and aberrant cognition across the lifespan. Data and annotated analysis code for this manuscript are available on GitHub as a supplement to the open-access specparam toolbox.


Lymphangiogenesis: a new player in cancer progression.
Lymph node metastasis is the hallmark of colon cancer progression, and is considered one of the most important prognostic factors. Recently, there has been growing evidence that tumor lymphangiogenesis (formation of new lymphatic vessels) plays an important role in this process. Here, we review the latest findings of the role of lymphangiogenesis in colorectal cancer progression, and discuss its clinical application as a biomarker and target for new therapy. Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer. In the future, tailored treatments consisting of combinations of chemotherapy, other targeted therapies, and anti-lymphangiogenesis agents will hopefully improve patient outcomes. This progression to the clinic must be guided by new avenues of research, such as the identification of biomarkers that predict response to treatment.


Legalized abortion in Japan.
The enactment of the Eugenic Protection Act in Japan was followed by many changes. The population explosion was stemmed, the birth rate was halved, and while the marriage rate remained steady the divorce rate declined. The annual total of abortions increased until 1955 and then slowly declined. The highest incidence of abortions in families is in the 30 to 34 age group when there are four children in the family. As elsewhere abortion in advanced stages of pregnancy is associated with high morbidity and mortality. There is little consensus as to the number of criminal abortions. Reasons for criminal abortions can be found in the legal restrictions concerning abortion: Licensing of the abortionist, certification of hospitals, taxation of operations and the requirement that abortion be reported. Other factors are price competition and the patient's desire for secrecy. Contraception is relatively ineffective as a birth control method in Japan. Oral contraceptives are not yet government approved. In 1958 alone 1.1 per cent of married women were sterilized and the incidence of sterilization was increasing.


Calcium-sensing receptor mediates Ca(2+) homeostasis by modulating expression of PTH and stanniocalcin.
Regulation of the synthesis and/or secretion of hypocalcemic and hypercalcemic hormones by the calcium-sensing receptor (CaSR) is believed to be a major pathway for maintaining Ca(2+) homeostasis in vertebrates, based primarily on findings in mammals. However, understanding the evolution of this physiological process requires that it be described in nonmammalian species. Here, we describe the use of zebrafish as a model to investigate whether CaSR contributes to body fluid Ca(2+) homeostasis by regulating synthesis of hypercalcemic (PTH1 and PTH2) and hypocalcemic (stanniocalcin [STC]) hormones. We report that PTH1, but not PTH2, increases Ca(2+) uptake through stimulation of the expression of the gene encoding the epithelial Ca(2+) channel (ecac). Furthermore, we demonstrate that CaSR, as a Ca(2+) sensor, may affect stc-1 and pth1 expressions differently, thereby suppressing ecac expression and Ca(2+) uptake. Finally, we show that CaSR knockdown has time-dependent effects on STC-1 and PTH1 expression, and these 2 hormones have mutual effects on the expression, thus forming a possible counterbalance. These findings enhance our understanding of CaSR-PTH-STC control of Ca(2+) homeostasis in vertebrates.


A comparative first-principles study of the structural and electronic properties of the liquid Li-Si and Li-Ge alloys.
We have performed a comparative first-principles study on the structural and electronic properties of the liquid Li1-xSix and Li1-xGex alloys over a range of composition from x = 0.09 to 0.50. Our calculations showed that Si and Ge atoms can exhibit very distinct local bonding characteristics as they were alloyed with the Li atoms in the liquid state, where Si atoms tended to form a variety of covalent bonding configurations while Ge atoms predominantly appeared as the isolated anions in the liquid alloys. These differences in bonding characteristics were reflected in their electronic density of states, in which the liquid Li1-xGex alloys have a lower degree of s-p hybridization with narrower distributions of the 3s and 3p states than the liquid Li1-xSix alloys. Our calculations also showed that the optical conductivities of these two liquid alloys can undergo a transition from the Drude-like metallic nature to the semiconductor-like character as the Si/Ge content increases from 0.09 to 0.22. However, as the Si/Ge content further increases to 0.50, the liquid Li1-xGex alloys may transit to exhibit the Drude-like metallic nature, while the liquid Li1-xSix alloys can still hold the semiconductor-like character. Moreover, our calculations revealed that the dc conductivities of these liquid alloys are predominantly determined by the number of total electronic states at the Fermi level. As the liquid Li1-xSix alloys are within the composition range between 0.20 and 0.50, the increment of the states at the Fermi level with increasing the Si content is nearly identical to the amount of the Li states decreased, leading to an almost unchanged number of total electronic states at the Fermi level. However, since Ge atoms do not favor forming covalent bonding in the liquid alloys to keep the Fermi level at a minimum of the density of states, the liquid Li1-xGex alloys would have more electronic states at the Fermi level and thereby higher dc conductivities than the liquid Li1-xSix alloys within the same composition range.


Comparative genome analysis identifies novel nucleic acid diagnostic targets for use in the specific detection of Haemophilus influenzae.
Haemophilus influenzae is recognised as an important human pathogen associated with invasive infections, including bloodstream infection and meningitis. Currently used molecular-based diagnostic assays lack specificity in correctly detecting and identifying H. influenzae. As such, there is a need to develop novel diagnostic assays for the specific identification of H. influenzae. Whole genome comparative analysis was performed to identify putative diagnostic targets, which are unique in nucleotide sequence to H. influenzae. From this analysis, we identified 2H. influenzae putative diagnostic targets, phoB and pstA, for use in real-time PCR diagnostic assays. Real-time PCR diagnostic assays using these targets were designed and optimised to specifically detect and identify all 55H. influenzae strains tested. These novel rapid assays can be applied to the specific detection and identification of H. influenzae for use in epidemiological studies and could also enable improved monitoring of invasive disease caused by these bacteria.


The Effect of Insulin Resistance on Ovulation Induction With Clomiphene Citrate in Non-polycystic Ovary Syndrome (PCOS) Women.
Objective To study the status of insulin resistance (IR) in non-polycystic ovary syndrome (PCOS) infertile women and to assess its effects on response to ovulation induction (OI) with clomiphene citrate (CC). Methods and materials A prospective cohort study was conducted at the Department of Obstetrics and Gynecology, King George Medical University, Lucknow, India, over a one-year period. One hundred two women who underwent treatment for infertility were enrolled and evaluated for insulin resistance. Insulin resistance was assessed using fasting serum insulin levels and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. All participants were given ovulation induction with clomiphene citrate and were then followed up for the occurrence of ovulation and conception. Results Insulin resistance was found in 20.5% of infertile subjects and 95.4% of anovulatory subjects. Of the subjects with insulin resistance, 80.5% showed monofollicular development. The pregnancy rate was 5.8%, but there was no conception among subjects with insulin resistance. Conclusions Insulin resistance was found to be present in 20.5% of infertile women. Women with insulin resistance are more likely to have monofollicular development on ovulation induction and are less likely to conceive as compared with women without insulin resistance (OR = 0.2079).


Hospital integration and vertical consolidation: an analysis of acquisitions in New York State.
While prior studies tend to view hospital integration through the lens of horizontal consolidation, I provide an analysis of its vertical aspects. I examine the effect of hospital acquisitions in New York State on the distribution of market share for major cardiac procedures across providers in target markets. I find evidence of benefits to acquirers via business stealing, with the resulting redistribution of volume across providers having small effects, if any, on total welfare with respect to cardiac care. The results of this analysis -- along with similar assessments for other services -- can be incorporated into future studies of hospital consolidation.


Mitochondrial genome maintenance: roles for nuclear nonhomologous end-joining proteins in Saccharomyces cerevisiae.
Mitochondrial DNA (mtDNA) deletions are associated with sporadic and inherited diseases and age-associated neurodegenerative disorders. Approximately 85% of mtDNA deletions identified in humans are flanked by short directly repeated sequences; however, mechanisms by which these deletions arise are unknown. A limitation in deciphering these mechanisms is the essential nature of the mitochondrial genome in most living cells. One exception is budding yeast, which are facultative anaerobes and one of the few organisms for which directed mtDNA manipulation is possible. Using this model system, we have developed a system to simultaneously monitor spontaneous direct-repeat-mediated deletions (DRMDs) in the nuclear and mitochondrial genomes. In addition, the mitochondrial DRMD reporter contains a unique KpnI restriction endonuclease recognition site that is not present in otherwise wild-type (WT) mtDNA. We have expressed KpnI fused to a mitochondrial localization signal to induce a specific mitochondrial double-strand break (mtDSB). Here we report that loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs. Furthermore, our data support homologous recombination (HR) as the predominant pathway by which mtDNA deletions arise in yeast, and suggest that the MRX and Ku70/80 complexes are partially redundant in mitochondria.


Identification of a heparin binding peptide on the extracellular domain of the KDR VEGF receptor.
Vascular endothelial growth factor (VEGF), a potent and specific activator of endothelial cells, is expressed as multiple homodimeric forms resulting from alternative RNA splicing. VEGF121 does not bind heparin while the other three isoforms do, and it has been documented that the binding of VEGF165 to its receptor is dependent upon cell surface heparin sulfate proteoglycans. Little is known about the biochemical mechanism that allows for heparin regulation of growth factor binding. For example, it is not clear whether heparin interactions with growth factor or with cell surface receptors or both are essential for VEGF binding to its receptor. In this manuscript we provide results which are consistent with the hypothesis that an interaction between heparin and a site on the KDR receptor subtype is essential for VEGF165 binding. First, we demonstrate that expression of KDR into a CHO cell line deficient in heparan sulfate biosynthesis does not allow VEGF165 binding unless heparin is exogenously added during the binding assay. Secondly, we show that a ten amino acid synthetic peptide, corresponding to a sequence from the extracellular domain of the KDR, both inhibits VEGF165 binding to the receptor and also binds heparin with high avidity. Third, affinity purification of heparin molecules on a KDR-derived peptide affinity column, together with capillary electrophoresis and polyacrylamide electrophoresis analysis, was used to show that the KDR-derived peptide interacts with a specific subset of polysaccharide chains contained in the unfractionated heparin. Taken together, these results are consistent with the hypothesis that interactions between cell surface heparan sulfate proteoglycans and the VEGF receptor contribute to allowing maximal VEGF binding.


Terminating prolonged refractory status epilepticus using ketamine.
Refractory status epilepticus (RSE) is an emergent and difficult neurologic problem that is not uncommon in clinical practice. In this report, we describe a 23-year-old man whose RSE was refractory to standard antiepileptic drugs and barbiturates; it was successfully terminated only with intravenous ketamine. In this report, we evaluated and discuss the clinical and electroencephalographic effects under ketamine. This case and the rare cases of ketamine experience in RSE reported in the literature show that ketamine is potentially effective to use when treating patients with RSE. Further clinical trials are warranted, however.


Microwave and quantum chemical study of propargyl thiocyanate (HC[triple bond]CCH2SC[triple bond]N).
The MW spectrum of propargyl thiocyanate (HC[triple bond]CCH(2)SC[triple bond]N) has been investigated for the first time in the 25-80 GHz spectral region at room temperature or at 0 degrees C. The spectra of the ground vibrational state and of the first excited state of the C-S torsional vibration have been assigned for one conformer. This rotamer, denoted ap, has a symmetry plane (C(s) symmetry) and an antiperiplanar arrangement for the C-C-S-C link of atoms. It has previously been claimed that a conformer that has a synclinal conformation for this chain of atoms is present in the gas in approximately the same concentration as ap (approximately 50% of the gas), but this is not supported by the present experiments, where it is shown that the synclinal rotamer, denoted sc, cannot be present in a concentration exceeding 1/3 of the total. It is therefore concluded that ap must be at least 3.0 kJ/mol more stable than sc. The spectroscopic work has been augmented by quantum chemical calculations at advanced B3LYP/aug-cc-pVQZ, B3LYP/6-311++G(3df,3pd), and MP2/aug-cc-pVTZ levels of theory. These theoretical calculations underestimate the energy difference between ap and sc and predict values for the conformationally important C-C-S-C dihedral angle of the hypothetical synclinal form that deviates by approximately 10 degrees.


Enhancement of enzyme activity in supercritical carbon dioxide via changes in acid-base conditions.
Enzyme performance is often impaired in supercritical carbon dioxide. We were able to enhance enzyme activity in this medium via changes in acid-base conditions by using ion-exchange materials (solid H(+)/Na(+) buffer pairs and a zeolite), which were selected on the basis of the response of an organosoluble acid-base indicator. The concentration of ion-exchange materials had an important effect on the catalytic activity of subtilisin Carlsberg cross-linked enzyme crystals (CLECs), and this was related to the protonation and hydration states of the enzyme. The buffer Na(2)CO(3)/NaHCO(3) gave the highest enhancement in enzyme activity (by a factor of 54), probably as a result of its high basicity and capacity to counteract the deleterious effect of carbonic acid to a greater extent than the other materials tested.


The Pseudomonas aeruginosa Pan-Genome Provides New Insights on Its Population Structure, Horizontal Gene Transfer, and Pathogenicity.
The huge increase in the availability of bacterial genomes led us to a point in which we can investigate and query pan-genomes, for example, the full set of genes of a given bacterial species or clade. Here, we used a data set of 1,311 high-quality genomes from the human pathogen Pseudomonas aeruginosa, 619 of which were newly sequenced, to show that a pan-genomic approach can greatly refine the population structure of bacterial species, provide new insights to define species boundaries, and generate hypotheses on the evolution of pathogenicity. The 665-gene P. aeruginosa core genome presented here, which constitutes only 1% of the entire pan-genome, is the first to be in the same order of magnitude as the minimal bacterial genome and represents a conservative estimate of the actual core genome. Moreover, the phylogeny based on this core genome provides strong evidence for a five-group population structure that includes two previously undescribed groups of isolates. Comparative genomics focusing on antimicrobial resistance and virulence genes showed that variation among isolates was partly linked to this population structure. Finally, we hypothesized that horizontal gene transfer had an important role in this respect, and found a total of 3,010 putative complete and fragmented plasmids, 5% and 12% of which contained resistance or virulence genes, respectively. This work provides data and strategies to study the evolutionary trajectories of resistance and virulence in P. aeruginosa.


Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions.
Macromolecular interactions define many biological phenomena. Although genetic methods are available to identify novel protein-protein and DNA-protein interactions, no genetic system has thus far been described to identify molecules or mutations that dissociate known interactions. Herein, we describe genetic systems that detect such events in the yeast Saccharomyces cerevisiae. We have engineered yeast strains in which the interaction of two proteins expressed in the context of the two-hybrid system or the interaction between a DNA-binding protein and its binding site in the context of the one-hybrid system is deleterious to growth. Under these conditions, dissociation of the interaction provides a selective growth advantage, thereby facilitating detection. These methods referred to as the "reverse two-hybrid system" and "reverse one-hybrid system" facilitate the study of the structure-function relationships and regulation of protein-protein and DNA-protein interactions. They should also facilitate the selection of dissociator molecules that could be used as therapeutic agents.


12-O-tetradecanoylphorbol-13-acetate-induced inhibition of gap junctional communication is differentially regulated in a transformation-sensitive Syrian hamster embryo cell line compared to early passage SHE cells.
The transformation-sensitive cell-line BPNi was more susceptible to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) than early passage Syrian hamster embryo (SHE) cells, while the potency of TPA to down-regulate EGF-binding was similar in the two cell types. The kinetics of TPA-induced inhibition of GJIC suggested that different mechanisms may operate at high and low TPA concentrations. The initial inhibition after exposure to high TPA concentrations was followed by a recovery of GJIC. The recovery was much more pronounced in SHE than in BPNi cells. This effect could not be explained by differences in down-regulation of protein kinase C. Removal of high TPA concentrations also resulted in a faster recovery of GJIC in SHE than in BPNi cells. In addition, although forskolin induced a similar protection against the inhibitory effect of TPA on GJIC, forskolin restored GJIC blocked by TPA much faster in SHE than in BPNi cells. Thus, BPNi cells are more sensitive to TPA induced inhibition of GJIC than SHE cells, and have reduced capability to recover from down-regulated GJIC as compared to SHE cells.


Attitudes of direct care staff towards external professionals, team climate and psychological wellbeing: a pilot study.
Relationships with external professionals may be an important factor in the psychological wellbeing of care staff. A questionnaire to measure team climate and staff wellbeing was developed, tested and revised. Seventy-two direct care staff completed the revised questionnaire, which had acceptable levels of internal consistency. Significant correlations were found between care staff attitudes towards professionals and levels of team climate and psychological wellbeing. The pattern of relationships was explored by path analysis. Further work is needed on the reliability and validity of the questionnaire. There is a clear association between attitudes to professionals and team climate and between some aspects of climate and psychological wellbeing. Professionals should adopt collaborative ways of working based on problem-solving approaches with staff teams, with the aim of delivering improved quality of care to residents.


Epidemiology and diagnosis of peripheral arterial disease in patients with chronic kidney disease.
Chronic kidney disease (CKD) and peripheral arterial disease (PAD) are common and frequently coexist. Among subjects with CKD, arterial disease may be due to atherosclerosis, medial arterial calcification (MAC), or both conditions concomitantly. It is important for clinicians to recognize both conditions because each identifies individuals at higher risk of cardiovascular disease events, and because the presence of MAC complicates interpretation of the ankle brachial index, the most commonly used diagnostic test for artherosclerotic PAD. To that end, we review the epidemiology and diagnosis of atherosclerotic PAD and medical arterial calcification in patients with CKD.


BacMam recombinant baculoviruses in G protein-coupled receptor drug discovery.
With completion of the sequencing of the human and mouse genomes, the primary sequences of close to 400 non-olfactory G protein-coupled receptors (GPCRs) have been determined. There are intensive efforts within the pharmaceutical industry to discover and develop new therapeutic agents acting via GPCRs. In addition, there is a concerted effort to identify potential new drug targets from the remaining 150+orphan GPCRs through the identification of their ligands. Access to functionally expressed recombinant receptors underpins both of these key drug discovery activities. Typically, GPCR drug discovery screening activities are carried out using mammalian cell lines stably expressing the target of interest. The influx of new receptor sequences originating from genomic sequencing efforts has caused a shift toward wider applications of transient rather than stable expression systems, especially in support of assays for orphan receptor ligand screening. Recombinant baculoviruses in which the polyhedrin promoter has been replaced with a mammalian promoter, termed BacMam viruses, were originally designed as potential new gene therapy delivery vehicles. This same technology offers numerous advantages as a transient expression system in the assay of membrane-expressed drug targets, including GPCRs. Data presented show that BacMam can be used rapidly to generate robust and pharmacologically authentic GPCR assays in several formats, with the potential to transform drug discovery screening processes for this gene family.


Effects of dietary galactooligosaccharide on azaserine-induced acinar pancreatic carcinogenesis in male Wistar rats.
In the present study the effects of dietary galactooligosaccharide (GOS) on dietary fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. The aims of this study were to determine 1) whether GOS acts as an inhibitor of pancreatic carcinogenesis and 2) whether GOS interacts with dietary fat-promoted pancreatic tumor development. Four groups of 39 azaserine-treated rats were maintained on different experimental diets that were formulated as follows: 4.3 wt% fat-8.3 wt% GOS (low fat-low GOS), 3.5 wt% fat-27.4 wt% GOS (low fat-high GOS), 15.5 wt% fat-9.5 wt% GOS (high fat-low GOS), and 14.3 wt% fat-28.6 wt% GOS (high fat-high GOS). Autopsies were performed after 6 months (9 animals/group) and 12 months (30 animals/group). Five rats per group were treated with bromodeoxyuridine before autopsy. Parallel sections of the pancreas were stained with hematoxylin and eosin or with hematoxylin and a monoclonal antibody against bromodeoxyuridine and examined by light microscopy. A high-fat diet caused a significant decrease, whereas a diet high in GOS caused a significant increase, in absolute and relative weight of the cecum content. A high level of dietary fat caused a highly significant increase in multiplicity and incidence of pancreatic (pre)neoplastic lesions after 6 and 12 months of feeding. A high level of GOS in the diet did not influence the number of atypical acinar cell nodules or the tumor incidence in comparison with controls. Dietary fat and dietary GOS caused a significant increase in cell proliferation in atypical acinar cell nodules after six months. It was concluded that dietary GOS has no modulating effect on pancreatic carcinogenesis in azaserine-treated rats or on the tumor-promoting effect of a high-fat diet.


Effects of positioning on ankle edema.
The purpose of this study was to determine the effects of positioning on ankle edema during a 20-minute treatment period. Fifty subjects were alternately assigned to one of two groups. Members of group A lay supine with their legs elevated, group B subjects sat with their legs dependent. Pre- and postpositioning volumetric displacements were recorded to determine if a significant change occurred. Analysis of covariance testing showed significant volumetric difference between groups (p < 0.001). Group A had a significant decrease in volume whereas group B had a significant increase in volume. The results of this study suggest that physical therapists and athletic trainers should no longer attempt to reduce edema with high voltage electrical stimulation while their patients sit with their legs dependent. J Orthop Sports Phys The 1986;8(1):30-33.


Animal carcass and eyelid anthrax: a case report.
Anthrax is a worldwide zoonosis of herbivores, which is caused by the spore-forming bacteria Bacillus anthracis, and humans become infected when they are exposed to infected animals and their tissues or the organism directly. In this report, we present a 13-year-old boy who developed eyelid anthrax after contact with a sheep carcass during his summer holiday that resulted in eyelid anthrax and cicatricial ectropion.


A Calix[3]acridan-Based Host-Guest Cocrystal Exhibiting Efficient Thermally Activated Delayed Fluorescence.
A supramolecular strategy to construct thermally activated delayed fluorescence (TADF) materials through host-guest charge transfer interactions was proposed. Consequently, a new class of macrocycle namely calix[3]acridan was conveniently synthesized in 90 % yield. The host-guest cocrystal formed by calix[3]acridan and 1,2-dicyanobenzene exhibited efficient TADF properties due to intense intermolecular charge transfer interactions. Moreover, the spatially separated highest occupied molecular orbital and lowest unoccupied molecular orbital resulted in a very small singlet-triplet energy gap of 0.014 eV and hence guaranteed an efficient reverse intersystem crossing for TADF. Especially, a high photoluminescence quantum yield of 70 % was achieved, and it represents the highest value among the reported intermolecular donor-acceptor TADF materials.


[Léon Monsel and his solution].
Léon Monsel was born on March 13, 1816 in Gironde. He did training courses in chemist's first near of home and then in Paris. He also studied pharmacy in Pharmacy School of Paris where he succeeded on August 12, 1840 and he entered army. He remained in it until his retirement in 1874. He died at Nancy on April 15, 1878. Monsel is overall well known by his publications about coagulation power of ferric sub-sulfate from which he described three preparation ways. Current publications are exclusively foreigner. They point out advantages and disadvantages of Monsel's solution. It is used to day as hemostatic agent in minor surgical procedures such as biopsies in genecology, dermatology, proctology and O.R.L. Besides when he was stationed in Roma he studied Acqua Acetosa (acid salty gaseous water) of this town and later when he was stationed in Bordeaux, he took out a patent about manufacturing varnish from metallic resinates.


Prevelar Vowel Raising and Merger in Manitoba English.
This study examines production of the vowels /æ/, /ɛ/, and /e/ among three different English-speaking ethnic populations in Manitoba, Canada, focusing on patterns of raising and vowel overlap in prevelar contexts. Although raising of /æ/ before /ɡ/ has been documented for the Prairies region of Canada generally, its specific occurrence in Manitoba as well as the occurrence of vowel merger(s) there has not previously been examined in detail. This study finds that pre-velar patterns are distinguished by coda voicing, with voiceless /k/ producing lowering and some retraction while voiced /ɡ/ and /ŋ/ produce similar raising and especially fronting patterns in preceding /æ/ and /ɛ/. Statistical analysis of spatial and temporal qualities shows that, while complete merger is not observed between any of the three vowels, there is much more substantial overlap in their productions before the voiced velars than in other contexts; in contrast, the voiceless velar /k/ is associated with productions which often substantially diverge from these. The results suggest that Manitoba speakers' productions of these vowels share some features of other dialects with velar-affected productions, but the arrangement of these features in Manitoba may represent a unique configuration having a potential, incipient, or early-stage prevelar merger of /æ/ and /ɛ/, mainly without the participation of /e/. Social factors such as conservatism and extra-local affiliation are also found to play a role in production.


Nanomedicines Eradicating Cancer Stem-like Cells in Vivo by pH-Triggered Intracellular Cooperative Action of Loaded Drugs.
Nanomedicines capable of control over drug functions have potential for developing resilient therapies, even against tumors harboring recalcitrant cancer stem cells (CSCs). By coordinating drug interactions within the confined inner compartment of core-shell nanomedicines, we conceived multicomponent nanomedicines directed to achieve synchronized and synergistic drug cooperation within tumor cells as a strategy for enhancing efficacy, overcoming drug resistance, and eradicating CSCs. The approach was validated by using polymeric micellar nanomedicines co-incorporating the pan-kinase inhibitor staurosporine (STS), which was identified as the most potent CSC inhibitor from a panel of signaling-pathway inhibitors, and the cytotoxic agent epirubicin (Epi), through rationally contriving the affinity between the drugs. The micelles released both drugs simultaneously, triggered by acidic endosomal pH, attaining concurrent intracellular delivery, with STS working as a companion for Epi, down-regulating efflux transporters and resistance mechanisms induced by Epi. These features prompted the nanomedicines to eradicate orthotopic xenografts of Epi-resistant mesothelioma bearing a CSC subpopulation.


Structure and regulation of the cellulose degradome in Clostridium cellulolyticum.
Many bacteria efficiently degrade lignocellulose yet the underpinning genome-wide metabolic and regulatory networks remain elusive. Here we revealed the "cellulose degradome" for the model mesophilic cellulolytic bacterium Clostridium cellulolyticum ATCC 35319, via an integrated analysis of its complete genome, its transcriptomes under glucose, xylose, cellobiose, cellulose, xylan or corn stover and its extracellular proteomes under glucose, cellobiose or cellulose. Proteins for core metabolic functions, environment sensing, gene regulation and polysaccharide metabolism were enriched in the cellulose degradome. Analysis of differentially expressed genes revealed a "core" set of 48 CAZymes required for degrading cellulose-containing substrates as well as an "accessory" set of 76 CAZymes required for specific non-cellulose substrates. Gene co-expression analysis suggested that Carbon Catabolite Repression (CCR) related regulators sense intracellular glycolytic intermediates and control the core CAZymes that mainly include cellulosomal components, whereas 11 sets of Two-Component Systems (TCSs) respond to availability of extracellular soluble sugars and respectively regulate most of the accessory CAZymes and associated transporters. Surprisingly, under glucose alone, the core cellulases were highly expressed at both transcript and protein levels. Furthermore, glucose enhanced cellulolysis in a dose-dependent manner, via inducing cellulase transcription at low concentrations. A molecular model of cellulose degradome in C. cellulolyticum (Ccel) was proposed, which revealed the substrate-specificity of CAZymes and the transcriptional regulation of core cellulases by CCR where the glucose acts as a CCR inhibitor instead of a trigger. These features represent a distinct environment-sensing strategy for competing while collaborating for cellulose utilization, which can be exploited for process and genetic engineering of microbial cellulolysis.


[Occurrence of intestinal parasites among first grade students in Poland in years 2002/2003].
In the school year 2002/2003 there were examined in Poland some of the population of 7-year-old children for the presence of intestinal parasites, continuing countrywide operation launched in 1988. The studies were based on the examination of a single faecal specimen and a cellophane swab using the following methods: wet mount preparations in 0.9% NaCl and diluted Lugol's ioine, zinc sulphate centrifugal flotation and decantation. The studies included 31 504 children from 15 provinces of Poland. The parasites most frequently encountered in the examinations included: Enterobius vermicularis (in 3 827 of the examined, i. e. 12, 15%), Ascaris lumbricoides (in 263; 0.83%), Giardia intestinalis (in 217: 0.69%), Entamoeba coli (n 189; 0.60%) and Trichuris trichiura (in 39; 0.12%) The overall percentage of the infected children was 15.4%. The highest number of infected children was found in the province warmińsko-mazurskie (29.6%0), the smallest in slaskie (8.8%). The number of infected among children inhabiting country (19%) was significantly higher than among those from the towns (10.4%). The obtained results confirmed hitherto existing views that in Poland the epidemiological situation of infections with intestinal parasites is steadily improving.


Anti-progesterone effects on maternal recognition and behaviour imprinted during first pregnancy in mice.
Anti-progesterone treatment using specific anti-progesterone antibodies or a progesterone receptor (PR) antagonist during first pregnancy impairs postpartum maternal behaviour in mice. This effect is demonstrable only if the treatment is given during pregnancy but not immediately after parturition. The purpose of the present studies was to investigate if maternal behaviour is also impaired by anti-progesterone treatment in subsequent pregnancies. Studies with a monoclonal antibody to progesterone (DB3; 4.5 nmol/mouse) showed that injection of females on day 17 of second pregnancy did not cause maternal rejection but the latency of pup retrieval was prolonged especially during the first 3 days of lactation. This phenomenon was not observed in animals that had previous experience of full length lactation. Experiments were carried out with mifepristone (RU486; 10 micrograms/mouse) injected at day 17 of first, second or third pregnancies. Pup rejection (22.5% vs 12.3%) and prolongation of the retrieval latency (62.3 +/- 13.3 vs 19.7 +/- 6.5 s; P < 0.02) were observed following the first pregnancy. No abnormal behavioural effects were found in mothers treated in second or third pregnancy who had prior full length lactation experience. Control females subjected to only one pup retrieval test after first delivery rejected their pups if treated in their second pregnancy (27.3% vs 4.4%; P < 0.001) and displayed a marginal prolongation of the retrieval latency period (20.9 +/- 7.0 vs 7.4 +/- 2.6 s). Anti-progesterone treatment had no negative influence when administered during third pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)


Blockade of postsynaptic alpha 2-adrenoceptors enhances responses to mixed alpha 1/alpha 2-agonists in rat submaxillary gland.
The effects of selective blockade of alpha 2-adrenoceptors with idazoxan on salivary secretion elicited by several alpha-adrenoceptor agonists known to differ in their alpha 1/alpha 2 potency ratios were studied in the submaxillary gland. Doses of idazoxan ranging between 0.01 to 10 000 micrograms/kg did not produce secretion in anaesthetized rats. Idazoxan (3 micrograms/kg) effectively blocked the inhibitory action of clonidine, 10 micrograms/kg, on the responses to methacholine but did not change the sialagogic responses to either phenylephrine or isoprenaline. On the other hand, idazoxan enhanced the secretion elicited by other agonists known to have mixed alpha 1/alpha 2-agonistic properties. The degree of augmentation of the responses observed after alpha 2 blockade was: clonidine much greater than alpha-methyl-norepinephrine greater than norepinephrine. Guanabenz did not elicit secretory responses in either the presence or absence of idazoxan. These results argue that two components determine the magnitude of the sialagogic response induced by agonists with mixed alpha 1/alpha 2 activity: (a) an alpha 1-mediated secretory effect and (2) an alpha 2-mediated inhibitory effect, both being localized at postsynaptic level.


Carotenoids in the sea urchin Paracentrotus lividus: occurrence of 9'-cis-echinenone as the dominant carotenoid in gonad colour determination.
Regular sampling of wild Paracentrotus lividus was carried out over a 12-month period to examine seasonal effects on the pigment profile and content of the gonads, especially in comparison to gonad colour. The major pigments detected in the gut wall were breakdown products of fucoxanthin, namely fucoxanthinol and amarouciaxanthin A. Lower levels of other dietary carotenoids (lutein and beta-carotene) together with some carotenoids not found in the diet, namely isozeaxanthin and echinenone ( approximately 20% total carotenoid) were also detected in the gut wall. The presence of echinenone in the gut wall demonstrates that this organ acts as a major site of carotenoid metabolism. Echinenone is the dominant carotenoid in the gonads, accounting for approx. 50-60% of the total pigment. Both all-trans and 9'-cis forms of echinenone were detected in both the gut wall and in the gonad, with levels of the 9'-cis form typically 10-fold greater than the all-trans form in the gonad. The detection of large levels of 9'-cis-echinenone in wild sea urchins is unexpected due to the absence of 9- or 9'-cis forms of carotenoids in the natural, algal, diet. Whilst echinenone clearly contributes towards gonad pigmentation, levels of this carotenoid, cannot be directly linked to a qualitative assessment of gonad colour in terms of market acceptability. Indeed, unacceptable gonad colouration can be seen with both very low and high levels of echinenone and total carotenoid. The presence of 9'-cis-echinenone as the major carotenoid contributing to the pigmentation/colour of the gonad is an important observation in terms of developing artificial diets for urchin cultivation.


Changes in the volatile compounds and in the chemical and physical properties of snake fruit (Salacca edulis Reinw) Cv. Pondoh during maturation.
During the maturation of snake fruit (Salacca edulis Reinw) Pondoh, the contents of sucrose, glucose, fructose, and volatile compounds changed drastically. The glucose, fructose, and volatile compounds contents showed their maximum levels at the end of maturation; however, the sucrose content decreased. During maturation, the flesh firmness tended to increase; however, at the end of maturation (6 months), the flesh became soft. The major volatile aroma in solvent-assisted flavor evaporation (SAFE) and solvent extracts were identified to be methyl esters of butanoic acids, 2-methylbutanoic acids, hexanoic acids, pentanoic acids, and the corresponding carboxylic acids. Furaneol (4-hydroxy-2,5-dimethyl-3(2H)-furanone) was also identified as a minor aroma constituent in the SAFE residue. The methyl esters were found to increase dramatically during stages 4-6 (5-6 months after the pollination) to exceed the amounts of carboxylic acids, whereas the acid amount increased gradually until stage 5 (5.5 months after the pollination) to reach the maximum at stage 6 (6 months after the pollination).


Pleiotropic effects of transforming growth factor-β in hematopoietic stem-cell transplantation.
Transforming growth factor (TGF)-β is a pleiotropic cytokine with beneficial and detrimental effects posthematopoietic stem-cell transplantation. TGF-β is increased in specific sites postengraftment and can suppress immune responses and maintain peripheral tolerance. Thus, TGF-β may promote allograft acceptance. However, TGF-β is also the central pathogenic cytokine in fibrotic disease and likely promotes pneumonitis. Although TGF-β can enhance leukocyte recruitment and IgA production, it inhibits both innate and adaptive immune cell function and antiviral host defense posthematopoietic stem-cell transplantation. This review will focus on the current understanding of TGF-β biology and the numerous ways it can impact outcomes posttransplant.


Vessel wall injury and arterial thrombosis induced by a photochemical reaction.
Arterial thrombosis may be initiated in an experimental animal by a photochemical reaction between transmural green light and i.v. administered Rose Bengal, a photosensitizer dye. In this study, scanning electron microscopy has been used to reveal the nature of vessel injury and the cellular composition of the photochemically induced thrombus. A 5 mm segment of the guinea pig femoral artery was occluded by a thrombus about 10 min after irradiation with green light in the presence of systemically administered Rose Bengal. Electron microscopy revealed that following photochemical reaction, endothelial cells first contract and, with further irradiation, become detached from the vessel wall, with their cell membrane being destroyed at the irradiated site where an occlusive platelet-rich thrombus was formed. Endothelial cell injury and vessel occlusion could be completely inhibited by the aminothiol, DL-cysteine administered i.v. 1 min after Rose Bengal. The mechanism of endothelial injury in this model appears to be by singlet molecular oxygen, 1O2 formed by energy transfer from the photo-excited dye to O2.