Emerging respiratory infections threatening public health in the Asia-Pacific region: A position paper of the Asian Pacific Society of Respirology.
In past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. These emerging infections, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the pandemic influenza A(H1N1) and avian influenza (AI) viruses, have seriously threatened global health and the economy. In particular, MERS-CoV and AI A(H7N9) are still causing infections in several areas, and some clustering of cases of A(H5N1) and A(H7N9) may imply future possible pandemics. Additionally, given the inappropriate use of antibiotics and international travel, the spread of carbapenem-resistant Gram-negative bacteria is also a significant concern. These infections with epidemic or pandemic potential present a persistent threat to public health and a huge burden on healthcare services in the Asia-Pacific region. Therefore, to enable efficient infection prevention and control, more effective international surveillance and collaboration systems, in the context of the 'One Health' approach, are necessary.


Resistance patterns to beta-lactams and quinolones in clinical isolates of bacteria from Cuban hospitals.
The resistance patterns to 26 beta-lactams and 8 quinolones of clinical isolates from Cuban hospitals were evaluated using the disk susceptibility test, according to the NCCLS guidelines (1992). The genera studied were Escherichia sp (320), Enterobacter sp (10), Klebsiella sp (90), Proteus sp (10), Pseudomonas sp (90), Serratia sp (20), and Staphylococcus sp (80). Higher resistance to beta-lactams was observed in the genera Pseudomonas, Escherichia and Klebsiella. For fluoroquinolones we found no significant resistance, with the exception of the genus Klebsiella. The most effective antibiotics were cephalosporins of the second and third generations, fluoroquinolones, and non-classical beta-lactams (cephamycins, moxalactam and monobactams). On the contrary, a pronounced resistance was found to penicillin, oxacillin, ticarcillin, ampicillin, methicillin, nalidixic acid and cinoxacin. These resistance patterns correspond to the high consumption of these antibiotics throughout the country.


Middle cranial fossa approach to the internal auditory Meatus:A Chinese temporal bone study.
Most techniques applied in the middle cranial fossa approach to the internal auditory meatus were based on anatomic studies in Caucasians. As racial differences in the cranium exist, this paper evaluated the applicability of these techniques in Chinese patients. This paper also evaluated the usefulness of the 30-degree-angled rigid endoscope in identifying the superior semicircular canal (SSC). Thirty Chinese temporal bones were dissected. It was found that, like in Caucasian patients, (1) constant relation exists between the geniculate ganglion and SSC, and (2) the internal auditory meatus of each specimen was situated within a 60-degree angle anterior to the SSC. However, the orientation of the arcuate eminence and its relationship to the SSC in Chinese differed from Caucasians. The endoscope was found to be useful in aiding early identification of the SSC and in differentiating it from surrounding air cells. In conclusion, some recommended landmarks used in hearing preservation via the middle cranial fossa approach may not apply to Chinese patients. The endoscope has the potential to enhance the chances of hearing preservation.


Factors affecting stress tolerance in recalcitrant embryonic axes from seeds of four Quercus (Fagaceae) species native to the USA or China.
Quercus species are often considered 'foundation' components of several temperate and/or subtropical forest ecosystems. However, the populations of some species are declining and there is considerable urgency to develop ex situ conservation strategies. In this study, the storage physiology of seeds within Quercus was explored in order to determine factors that affect survival during cryopreservation and to provide a quantitative assessment of seed recalcitrance to support future studies of this complex trait. Water relations and survival of excised axes in response to water loss and cryo-exposure were compared for four Quercus species from subtropical China (Q. franchetii, Q. schottkyana) and temperate USA (Q. gambelii, Q. rubra). Seed tissues initially had high water contents and water potentials. Desiccation tolerance of the embryonic axis was not correlated with the post-shedding rainfall patterns where the samples originated. Instead, higher desiccation tolerance was observed in samples growing in areas with colder winters. Survival following cryo-exposure correlated with desiccation tolerance. Among species, plumule tissues were more sensitive than radicles to excision, desiccation and cryo-exposure, and this led to a higher proportion of abnormally developing embryos during recovery following stress. Quercus species adapted to arid and semi-humid climates still produce recalcitrant seeds. The ability to avoid freezing rather than drought may be a more important selection factor to increase desiccation tolerance. Cryopreservation of recalcitrant germplasm from temperate species is currently feasible, whilst additional protective treatments are needed for ex situ conservation of Quercus from tropical and subtropical areas.


A Clinical Evaluation of Circulating MiR-106a and Raf-1 as Breast Cancer Diagnostic and Prognostic Markers.
MicroRNAs (MiRNAs) regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and serve multiple roles in tumorigenesis and progression. Proto-oncogene serine/threonine-protein kinase (RAF-1) functions as a part of the MAPK/ERK signal transduction pathway. The present study aim was to prospectively evaluate MicroRNA 106a (MiR-106a) and RAF-1 as a diagnostic and prognostic factor in early prediction of breast cancer (BC), recurrence and early detection of distant metastasis as well as to analyses the statistical correlation between MiR-106a and RAF-1 levels and clinical-pathological parameters including tumor size, lymph node, histological type and grading. Sera and plasma of 30 normal women and 50 women with breast carcinoma were assayed for MiR-106a by RT-qPCR as well as levels of Hb, WBCs and platelets count and RAF-1 by solid phase enzyme-linked immunosorbent assay (ELISA). The patients' characteristics, they were classified according to grade into 8% grade I, 66% grade II, 22% grade III and 4% grade IV. The stages were classified according to the TNM system as stage II was the highest percentage 66%, while the lowest percentage was 10% for stage I and 24% for stage III. Also, Hb% and RAF-1 levels were significantly decreased in breast cancer patients as compared with healthy control. On the other hand, MiRNA-106a gene expression was non-significantly increased in positive lymph node metastasis patients (FC=3.66) when compared to patients with negative lymph node metastasis (FC=3.51). In addition, MiR-106a was significantly up-regulated in breast cancer patients with a fold of change 3.63 when compared to control samples. Expression of MiR-106a gene can be used as a diagnostic and prognostic noninvasive biomarker which can stimulates breast cancer cell invasion and proliferation through downregulation of Raf-1 levels.<br />.


When reverse genetics meets physiology: the use of site-specific recombinases in mice.
The use of site-specific recombinases enables the precise introduction of defined genetic mutations into the mouse genome. In theory, any deletion, point mutation, inversion or translocation can be modeled in mice. Because gene targeting is controlled both spatially and temporally, the function of a given gene can be studied in the desired cell types and at a specific time point. This 'genetic dissection' allows to define gene function in development, physiology or behavior. In this review, we focus on the technical possibilities of Cre and other site-specific recombinases but also discuss their limitations.


β1 Integrin induces adhesion and migration of human Th17 cells via Pyk2-dependent activation of P2X4 receptor.
Integrin-mediated T-cell adhesion and migration is a crucial step in immune response and autoimmune diseases. However, the underlying signalling mechanisms are not fully elucidated. In this study, we examined the implication of purinergic signalling, which has been associated with T-cell activation, in the adhesion and migration of human Th17 cells across fibronectin, a major matrix protein associated with inflammatory diseases. We showed that the adhesion of human Th17 cells to fibronectin induces, via β1 integrin, a sustained release of adenosine triphosphate (ATP) from the mitochondria through the pannexin-1 hemichannels. Inhibition of ATP release or its degradation with apyrase impaired the capacity of the cells to attach and migrate across fibronectin. Inhibition studies identified a major role for the purinergic receptor P2X4 in T-cell adhesion and migration but not for P2X7 or P2Y11 receptors. Blockade of P2X4 but not P2X7 or P2Y11 receptors reduced cell adhesion and migration by inhibiting activation of β1 integrins, which is essential for ligand binding. Furthermore, we found that β1 integrin-induced ATP release, P2X4 receptor transactivation, cell adhesion and migration were dependent on the focal adhesion kinase Pyk2 but not FAK. Finally, P2X4 receptor inhibition also blocked fibronectin-induced Pyk2 activation suggesting the existence of a positive feedback loop of activation between β1 integrin/Pyk2 and P2X4 purinergic signalling pathways. Our findings uncovered an unrecognized link between β1 integrin and P2X4 receptor signalling pathways for promoting T-cell adhesion and migration across the extracellular matrix.


[Climate change and health in the Netherlands].
Climate change possibly affects public health in the Netherlands, including changes in (a) temperature-related effects, heat stress and air pollution, (b) allergies, (c) vector borne infectious disease, and (d) food- and waterborne infectious disease. Due to many prevailing uncertainties, opinions differ regarding the exact size of the expected health risks and the speed at which these might occur, as well as regarding to what degree society would need to or could adapt to these potential health effects. Thus, the gaps in our knowledge are substantial. Scientists and experts are clearly concerned about the limited amount of attention being paid to health effects of climate change in the Netherlands. In response, a proposal for a research programme 'Klimaatverandering en Gezondheid' ('Climate change and health') has been developed over the past year.


Naming and knowing in dementia of Alzheimer's type.
We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.


In Situ Resistive Switching Effect Scrutinization on Co-Designed Graphene Sensor.
Resistive switching (RS), an electric property based on the forming and rupture of conductive filaments in metal-insulator-metal structures, has attracted intensive attention due to its potential application in next generation energy-efficient and area-efficient memory devices. In situ studies of the RS effect are urgently needed for its mechanism understanding and memristive performance improvement. Here investigations of both the RS effect as well as the gate tunable conductance quantization effect are realized by co-designing an Ag/SiO2 based memory structure on a graphene local sensor. This design enables self-monitoring of the working states of the memristor in real-time by virtue of the graphene sensor. These findings pave the way for further investigations of on-chip electronics and quantum physics.


Multi-Market Impacts of Market-Based Recycling Initiatives.
In 1995 the average tipping fee in the state of New York was $70/ton, with some landfills charging as high as $100.1 In New Jersey, fees reached prices as high as $165/ton.2 With budget crises occurring at all levels of government, economists, environmental scientists, policy-makers, and others are scrambling to find alternatives to waste disposal. Recycling as a solution has risen to the forefront, most likely because it both saves landfill space and may use fewer resources than virgin material processing. At every level of government, policies are being set that encourage recycling. Unfortunately, some of these programs may be resulting in unintended and undesirable side effects. To understand these effects, a broader view of the many factors involved in materials use, waste generation, and disposal is necessary. Within this paper, the broader view is considered, including a discussion of the externalities that exist in the markets affected by waste and an analysis of the effects on all alternatives to recycling, including composting and reuse. Through use of mathematical optimization, this paper shows that a recycling subsidy, or the more complicated tax/subsidy scheme, does not necessarily provide greater environmental benefits compared with disposal taxes.


Error analysis of nonconstant admittivity for MR-based electric property imaging.
Magnetic resonance electrical property tomography (MREPT) is a new imaging modality to visualize a distribution of admittivity γ = σ+iωε inside the human body where σ and ε denote electrical conductivity and permittivity, respectively. Using B1 maps acquired by an magnetic resonance imaging scanner, it produces cross-sectional images of σ and ε at the Larmor frequency. Since current MREPT methods rely on an assumption of a locally homogeneous admittivity, there occurs a reconstruction error where this assumption fails. Rigorously analyzing the reconstruction error in MREPT, we showed that the error is fundamental and may cause technical difficulties in interpreting MREPT images of a general inhomogeneous object. We performed numerical simulations and phantom experiments to quantitatively support the error analysis. We compared the MREPT image reconstruction problem with that of magnetic resonance electrical impedance tomography (MREIT) to highlight distinct features of both methods to probe the same object in terms of its high- and low-frequency conductivity distributions, respectively. MREPT images showed large errors along boundaries where admittivity values changed whereas MREIT images showed no such boundary effects. Noting that MREIT makes use of the term neglected in MREPT, a novel MREPT admittivity image reconstruction method is proposed to deal with the boundary effects, which requires further investigation on the complex directional derivative in the real Euclidian space [Formula: see text].


Breast cancer therapy planning - a novel support concept for a sequential decision making problem.
Breast cancer is the most common carcinosis with the largest number of mortalities in women. Its therapy comprises a wide spectrum of different treatment modalities a breast oncologist decides about for the individual patient case. These decisions happen according to medical guide lines, current scientific publications and experiences acquired in former cases. Clinical decision making therefore involves the time-consuming search for possible therapy options and their thorough testing for applicability to the current patient case.This research work addresses breast cancer therapy planning as a multi-criteria sequential decision making problem. The approach is based on a data model for patient cases with therapy descriptions and a mathematical notion for therapeutic relevance of medical information. This formulation allows for a novel decision support concept, which targets at eliminating observed weaknesses in clinical routine of breast cancer therapy planning.


Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells.
Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysaccharide (LPS) treatment for DC maturation or negative control of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhancement of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, biomaterial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a moderate delayed type hypersensitivity reaction in mice indicative of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation.


The effect of stimulus current pulse width on nerve fiber size recruitment patterns.
There have been theoretical studies presented that postulate a change in the stimulus current amplitude required to recruit nerve fibers with different stimulus current pulse widths. Based on these theoretical predictions, it has been suggested that the stimulus pulse width parameter may be used to selectively recruit fibers of different sizes and that this selectivity should increase with increasing distance from the stimulus electrode. In this paper, a simulation study of the recruitment patterns of a population of motor nerve fibers with a histologically accurate fiber diameter distribution is presented. Nerve fiber excitation simulations coupled with a time varying field simulation suggest that, for surface stimulation, there is only a marginal selectivity achievable in the average nerve fiber diameter that is recruited across the range of commonly used stimulus pulse widths but this selectivity also increases with increased electrode distance. Experimental evidence consisting of estimates of nerve fiber diameter based on motor unit latency studies is also presented that is consistent with the predictions made by the electromagnetic field and nerve fiber excitation simulations.


Writing history: case study of the university of Victoria School of Nursing.
A historical examination of a nursing curriculum is a bridge between past and present from which insights to guide curriculum development can be gleaned. In this paper, we use the case study method to examine how the University of Victoria School of Nursing (UVic SON), which was heavily influenced by the ideology of second wave feminism, contributed to a change in the direction of nursing education from task-orientation to a content and process orientation. This case study, informed by a feminist lens, enabled us to critically examine the introduction of a "revolutionary" caring curriculum at the UVic SON. Our research demonstrates the fault lines and current debates within which a feminist informed curriculum continues to struggle for legitimacy and cohesion. More work is needed to illuminate the historical basis of these debates and to understand more fully the complex landscape that has constructed the social and historical position of women and nursing in Canadian society today.


Synergistic effect of PB2 283M and 526R contributes to enhanced virulence of H5N8 influenza viruses in mice.
Highly pathogenic avian influenza (HPAI) H5N8 virus has caused considerable economic losses to poultry industry and poses a great threat to public health. Our previous study revealed two genetically similar HPAI H5N8 viruses displaying completely different virulence in mice. However, the molecular basis for viral pathogenicity to mammals remains unknown. Herein, we generated a series of reassortants between the two viruses and evaluated their virulence in mice. We demonstrated that 283M in PB2 is a new mammalian virulence marker for H5 viruses and that synergistic effect of amino acid residues 283M and 526R in PB2 is responsible for high virulence of the HPAI H5N8 virus. Analysis of available PB2 sequences showed that PB2 283M is highly conserved among influenza A viruses, while PB2 526R presents in most of human H3N2 and H5N1 isolates. Further study confirmed that the residues 283M and 526R had similar impacts on an HPAI H5N1 virus, suggesting that influenza viruses with both residues may replicate well in mammalian hosts. Together, these results present new insights for synergistic effect of 283M and 526R in PB2 of H5 HPAI virus on virulence to mammalian host, furthering our understanding of the pathogenesis of influenza A virus.


Diffuse sebaceous gland hyperplasia. A case report and an immunohistochemical study with cytokeratins.
We report a 43-year-old woman with sebaceous gland hyperplasia that occurred in a diffuse pattern of aggregated papular lesions involving her entire face, neck, and upper chest. Comedones, pustules, and inflammatory papules were absent. The eruption was accompanied by marked seborrhea. Histopathological examination showed enlargement of sebaceous acini, an increased number of immature sebocytes in foci, and a dilated follicular infundibulum. Immunohistochemical investigation showed cytokeratin 14 (CK 14) expression in the keratinocytes of the infundibulum, the isthmus, and sebaceous duct and in the mature and immature sebocytes; CK 17 expression in the keratinocytes of the sebaceous duct; CK 1 expression in the keratinocytes of the infundibulum; and an enhanced expression of the proliferation cell antigen Ki-67 (MiB1) in the immature sebocytes. With CK 18 and CK 19, no staining was observed. Oral therapy with isotretinoin (13-cis-retinoic acid) resulted in remarkable improvement in < or = 3 months. Histopathological and immunohistochemical examination after therapy showed markedly reduced sebaceous glands, a decrease in the staining of MiB1-positive immature sebocytes, and enhanced expression of CK 19 in immature sebocytes and sebaceous duct cells. Diffuse sebaceous gland hyperplasia is a rare variant of seboglandular proliferative disorders that is distinct from the well-known circumscribed type.


[Acute rectal hemorrhage].
Problems of the diagnosis, tactics and treatment of acute rectal hemorrhage are discussed. A diagnostic-tactical plan for determining the cause, source, localization and degree of bleeding are discussed. A diagnostic-tactical plan for determining the cause, source, localization and degree of bleeding, the acquired temporary or definitive hemostasis and the degree of blood loss is presented. Adequate approach to acute rectal hemorrhage helps to shorten the operation time, to reduce the extent of preoperative resuscitation and decrease total and operative lethality.


Convergence of EGFR glioblastoma mutations: evolution and allostery rationalizing targeted therapy.
EGFR mutations display striking organ-site asymmetry and heterogeneity. We have shown that structurally diverse extracellular mutations, typical of glioblastomas, converge to a similar intermediate conformation, which can be synergistically targeted extra- and intracelullarly by antibody mAb806 and type-II kinase inhibitors. Our findings reveal convergence behind heterogeneity, paving the way for allostery-based co-targeting.


An innovative interprofessional dental clinical learning environment using entrustable professional activities.
Changes in society, new public demands for dental care and contemporary educational insights have influenced dental education worldwide and demand a renewed perspective. Following this perspective, an innovative interprofessional dental Master curriculum was developed at Radboud University Nijmegen in the Netherlands. The curriculum is based on five contemporary educational principles and the core of the curriculum consists of a Student Run Dental Clinic that is fully run by students under professional supervision. In the Student Run Dental Clinic, Master dental students and Bachelor oral hygiene students are responsible for the care of approximately 750 patients. The students work within the same clinic for 3 years and patients receive oral health care from the same students over a long period. The clinic is a longitudinal cross-disciplinary clinic with different dental subdisciplines. Entrustable professional activities (also known as EPAs), to our knowledge not yet widely used in dental education, were introduced to facilitate learning and assessment. Fourteen EPAs have been developed to stimulate interprofessional education and learning. Of these, five EPAs are identical for the dental and oral hygiene curriculum, leading to extended interprofessional education and learning in the Student Run Dental Clinic. Preliminary results show that EPAs are generally well received by supervisors and students. To monitor and investigate the exact effect of the interventions and underlying mechanisms, a research programme on interprofessional learning, practice-based learning and EPAs and entrustment in dental education was recently set up.


Influence of a Cardiac Rehabilitation Program on Renal Function in Patients With Cardiovascular Disease in a One-Year Follow-Up.
Exercise training may improve renal function in patients with chronic kidney disease (CKD). The effect of cardiac rehabilitation (CR) with exercise training on renal function has not yet been established. We evaluated the effects of CR on renal function in patients with cardiovascular disease (CVD). Twenty-three CVD patients in a 1-year CR program (CR group) who had ischemic heart disease (IHD) and/or heart failure were compared with 26 age- and gender-matched CVD patients without CR (non-CR group, standard pharmacological care alone). At baseline and after 1 year, urea nitrogen (UN), creatinine (Cr), potassium (K), estimated glomerular filtration rate (eGFR) and hematocrit (Hct) in blood were assessed. There were no differences in the patient characteristics at baseline between the CR and non-CR groups except for the percentages of heart failure and the use of calcium channel blocker. After 1 year, there were no significant changes in UN, Cr, K, eGFR or Hct in either the CR or non-CR groups. The patients in the CR group were divided into two groups according to the eGFR level at baseline: low (n = 12, eGFR < 51 mL/minute/1.73 m2, indicating mild-to-moderate CKD) and high (n = 11, eGFR ≥ 51 mL/minute/1.73 m2) eGFR groups. Although there were no differences in the patient characteristics at baseline between the low and high eGFR groups, the low eGFR group showed a significant increase in eGFR after the 1-year CR program. CR may improve renal function in patients with mild-to-moderate CKD.


The electron-transfer site of spinach plastocyanin.
Two sites for electron transfer have been proposed for plastocyanin: one near the copper ion and the other close to the acid patch formed by residues 42-45. Calculations of electrostatic properties of spinach plastocyanin and ionic strength dependences of electron-transfer reactions of this protein have been used to distinguish between these two sites. Calculations show that the electric potential field of spinach plastocyanin is highly asymmetric and that the protein has a dipole moment of 360 D. The negative end of the dipole axis emerges between the negative patches formed by residues 42-45, which is though to be the cation binding site, and residues 59-61. The angles between the dipole vector and vectors from the center of mass to the copper ion and to the acid patch are 90 degrees and 30 degrees, respectively. The angle between the dipole vector and a line from the center of mass to the site of electron transfer is evaluated from the ionic strength dependence of electron-transfer rates at pH 7.8 with the help of equations developed by Van Leeuwen et al. [van Leeuwen, J.W., Mofers, F.J.M., & Veerman, E.C.I. (1981) Biochim. Biophys. Acta 635, 434] and Van Leeuwen [van Leeuwen, J.W. (1983) Biochim. Biophys. Acta 743, 408]. The angles found are 85 degrees, 110 degrees, and 75 +/- 15 degrees for reactions with tris(1,10-phenanthroline)cobalt(III), hexacyanoferrate(III), and ferrocytochrome c, respectively. The electric potential field calculations suggest that the hexacyanoferrate(III) interaction angle corresponds to a unique site of minimum repulsion at the hydrophobic region of the protein surface, close to the copper ion.(ABSTRACT TRUNCATED AT 250 WORDS)


Interventricular Septum Hydatid Cyst: Successful Seven-Year Follow Up- Case Report.
Hydatid cyst disease should be considered in differential diagnosis in many doubtful clinical situations as can present with non-specific symptoms especially in the endemic areas. Cardiac involvement should be considered in patients with history of previous hydatid cyst disease.. Cardiac hydatid cysts account for less than 2% of all hydatid diseases. In this report we aimed to present a case of 14-year-old boy with the diagnosis of occlusion of artery of the right lower extremity. Surgical exploration of the femoral artery revealed multiple hydatid cysts. Echocardiography showed a mobile mixed mass lesion. Complete resection of the mass was done from interventricular septum. Histo-pathological examination of the removed tissue revealed a complicated hydatid cyst and complete mass excision was confirmed. In this case a 7 year clinical and serological tests evaluation follow-up after surgical treatment showed no evidence of recurrence. The finding of this case emphasizes that in endemic countries, primary cardiovascular echino-coccosis should be considered in differential diagnosis.


Elevated HbA1c Levels Are Associated with the Blunted Autonomic Response Assessed by Heart Rate Variability during Blood Volume Reduction.
A high glycemic status increases the risk for autonomic dysfunction and cardiovascular failure. The aim of this study was to investigate time-dependent changes in the autonomic response and cardiovascular dynamics and the association between the level of hemoglobin A1c (HbA1c) and autonomic response during blood volume reduction. The study population consisted of 26 preoperative participants who were scheduled for autologous blood donation (200-400 mL of whole blood) for intraoperative or postoperative use. These participants without circulatory, respiratory, or brain disease and diabetes mellitus were grouped according to their HbA1c levels: < 6.5% (n = 18) and ≥ 6.5% (n = 8). We measured blood pressure (BP) and analyzed heart rate variability (HRV) to quantify cardiac autonomic regulation throughout blood donation. During blood volume reduction, which was about 10% of the circulating blood volume, the BP and heart rate varied within normal ranges in both groups. The high-frequency (HF) component, an index of parasympathetic nerve activity, and the ratio of low-frequency (LF) to HF components (LF/HF), an index of sympathetic nerve activity, significantly decreased and increased with the progression of blood volume reduction, respectively, in the HbA1c < 6.5% group. In contrast, in the HbA1c ≥ 6.5% group, the HF component did not significantly change, and the increase in the LF/HF ratio was delayed. Time-dependent changes in HRV were related to blood volume reduction only in the HbA1c < 6.5% group. Thus, elevated HbA1c levels are associated with the decrease in the autonomic response induced by blood volume reduction.


Characterization of the fine specificity of peptide antibodies to HLA-DQ beta-chain molecules.
In an attempt to produce epitope specific antisera which could distinguish two closely associated HLA-DQ beta-chain alleles, we immunized 20 rabbits with synthetic peptides representing sequences from the first domain of the HLA-DQw8 and -DQw7 beta-chain molecules, differing only by one amino acid in position 57. Several of the antisera in immunoblotting specifically recognized either the HLA-DQw7 or the HLA-DQw8 beta-chain allele as previously reported. The fine specificity of the antisera was tested in ELISA using synthetic peptides of varying length as solid phase antigen. Two out of the 20 antisera specifically recognized DQw7 beta peptides and two antisera bound only to DQw8 beta peptides from the region containing the amino acid in position 57. To analyze whether the antisera bound to native HLA-DQ beta-chain molecules, FACS analysis was carried out. Seven of the 20 antisera bound to intact EBV-transformed B-lymphocytes, and one antiserum bound preferentially to HLA-DQw8 positive cells.


Sense of coherence, lifestyle choices and mortality.
Based on data from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) study, we have previously shown a strong sense of coherence (SOC) to be associated with a reduced rate of all-cause mortality. To investigate the extent to which the SOC mortality association can be explained by socioeconomic status and lifestyle choices. Prospective population-based cohort study. 18 287 study participants aged 41-80 years who reported no pre-existing chronic disease at baseline and who completed an assessment of SOC. Based on 1599 deaths during a mean follow-up of 8.3 years, a strong SOC was associated with a 20% reduced risk of all-cause mortality. Measures of lifestyle choice (cigarette smoking, physical activity, dietary intakes of fruit, vegetables and fibre) and socioeconomic status (social class and education) explained 23% of this association. The SOC concept embraces multiple sets of chronic disease risk factors that include lifestyle choices and those associated with socioeconomic status, and is a potential aid in understanding differences in health outcomes in similar individuals.


A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells.
Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among women in the Western world than all other gynecologic malignancies. There is urgent need for new therapeutic targets and a better understanding of EOC initiation and progression. We have previously identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the GalNAc-transferases (GalNAc-Ts) gene family, as hypomethylated and overexpressed in high-grade serous EOC tumors, compared to low malignant potential EOC tumors and normal ovarian tissues. This data also suggested for a role of GALNT3 in aberrant EOC glycosylation, possibly implicated in disease progression. To evaluate differential glycosylation in EOC caused by modulations in GALNT3 expression, we used a metabolic labeling strategy for enrichment and mass spectrometry-based characterization of glycoproteins following GALNT3 gene knockdown (KD) in A2780s EOC cells. A total of 589 differentially expressed glycoproteins were identified upon GALNT3 KD. Most identified proteins were involved in mechanisms of cellular metabolic functions, post-translational modifications, and some have been reported to be implicated in EOC etiology. The GALNT3-dependent glycoproteins identified by this metabolic labeling approach support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as novel EOC biomarkers and/or therapeutic targets. Knowledge of the O-glycoproteome has been relatively elusive, and the functions of the individual polypeptide GalNAc-Ts have been poorly characterized. Alterations in GalNAc-Ts expression were shown to provide huge variability in the O-glycoproteome in various pathologies, including cancer. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has provided a strategy allowing for proteomic discovery of GalNAc-Ts specific functions. Our study supports an essential role of one of the GalNAc-Ts - GALNT3, in EOC dissemination, including its implication in modulating PTMs and EOC metabolism. Our approach validates the use of the applied metabolic strategy to identify important functions of GalNAc-Ts in normal and pathological conditions.


[Complications of abdominal hysterectomy for benign gynecologic lesions. Apropos of 1,000 cases].
The authors present a retrospective study of 1,000 total abdominal hysterectomies performed between 1969 and 1975, and they report the main complications. Early complications are dominated by: rare thrombo-embolic accidents (2.2%) since the advent of prophylactic heparin therapy; infectious complications, dominated by the abscess of the abdominal wall and asymptomatic urinary infections, and for which simple measures prevent resorting to prophylactic antibiotherapy. The role of the hysterectomy seems minimal in the occurrence of a prolapse or a stress-related urinary incontinence: prolapses after hysterectomy (1.4%) seem more related to tissue aging than to the procedure which modifies very little the supporting system of the pelvis. A post-operative urinary incontinence is, most of the time, the result of an incomplete pre-operative work-up: failure to recognize a potential stress-related incontinence, or an incontinence secondary to an unstable bladder. Prolapse and incontinence must always be treated independently. In the psychological and sexual repercussion, age, ovariectomy and the distress related to the procedure, involving the heart of womanhood, seem to be the most important factors.


Quality of life, health-state utilities and willingness to pay in patients with psoriasis and atopic eczema.
Skin diseases have been shown to have a significant adverse impact on the health-related quality of life of patients that may be underestimated by objective assessments of clinical severity. The main aim of this study was to measure the health-state utilities on a scale between 0 (dead) and 1 (full health) of patients with psoriasis and atopic eczema, and to measure the willingness to pay for a cure for psoriasis and atopic eczema. A second aim was to analyse how these measures are related to different dimensions of health-related quality of life, as measured by general and disease-specific quality of life instruments and a subjective measure of disability activity. This study was based on data from a questionnaire administered to, and interviews conducted with, 366 patients with psoriasis and atopic eczema aged 17-73 years, attending the dermatology outpatient clinic in Uppsala, Sweden from November 1996 to December 1997. The survey included: a rating scale question, a time trade-off question, a standard gamble question, a dichotomous choice willingness to pay question, a bidding-game willingness to pay question, a generic quality of life instrument (SF-36), a disease-specific quality of life instrument (the Dermatology Life Quality Index) and a subjective measure of disease activity (on a visual analogue scale). The mean health-state utility was 0.69 (rating scale), 0.88 (time trade-off) and 0.97 (standard gamble) for patients with psoriasis. The corresponding health-state utilities for patients with atopic eczema were 0.73, 0.93 and 0.98. On average, patients were willing to pay between 1253 and 1956 Swedish crowns (SEK) per month for a psoriasis cure and between SEK 960 and 1083 per month for an atopic eczema cure ($1 = SEK 8.25 and pound1 = SEK 13.23). The health-state utilities were related to SF-36, the Dermatology Life Quality Index and disease activity in the expected direction and the correlations were strongest for rating scale and weakest for standard gamble. The willingness to pay was correlated with the Dermatology Life Quality Index and disease activity, but not with SF-36. The study indicates that it is feasible to measure health-state utilities and willingness to pay in this patient population, and the sizeable willingness to pay suggests that skin diseases are associated with substantial reductions in quality of life.


Antimony oxide hydroxide ethanedisulfonate: a cationic layered metal oxide for Lewis acid applications.
We have discovered a rare example of a cationically charged inorganic material. The layered structure is an example outside the extensively studied isostructural set of anionic clays/layered double hydroxides and our previously reported lead fluoride nitrate. For the present compound, the antimony oxide hydroxide layers are positively charged and are templated by anionic alkylenedisulfonate. The organic molecules are only bonded electrostatically to the layers with sulfonate oxygen to antimony distances beyond the covalent range. The material catalyzes a ketal formation reaction as a Lewis acid without the need for drying the solvent before the reaction or a nonaqueous medium such as toluene. The catalyst is heterogeneous and is completely recovered after the catalysis for reapplication.


Prostatic acid phosphatase is a possible tumor marker for intravascular large B-cell lymphoma.
Intravascular large B-cell lymphoma (LBCL) is a rare and aggressive subtype of diffuse LBCL characterized by disseminated intravascular proliferation of neoplastic lymphocytes. Obstruction of blood flow by tumor cells in a variety of organs can cause an array of clinical changes, including alteration of the neural and spinal system and the respiratory system, as well as skin lesions. It is usually very difficult to diagnose intravascular LBCL in a patient simply from clinical symptoms or laboratory examinations. We here document our findings that serum prostatic acid phosphatase levels in both males and a female (2.2-24.0 microg/L) reflect the presence of intravascular LBCL, changing synchronously in response to chemotherapy. To determine whether prostatic acid phosphatase (PAP) might be a useful tumor marker for early diagnosis, we reviewed five intravascular LBCLs. Immunohistochemically, tumor cells in all cases were positive for anti-PAP antibody. The results were further confirmed in one case by Western-blot analysis and in another by the detection of amplified messenger RNA for PAP in microdissected tumor cells, respectively. PAP has not been detected in 17 lymphomas (diffuse LBCL, 8 cases; follicular lymphoma, 3 cases; T-cell lymphoma, 3 cases; Hodgkin lymphoma, 3 cases) by Western blot analyses. We conclude that serum PAP is a useful tumor marker for intravascular LBCL and that it deserves further investigation in this context.


Protective effects of nimodipine on cerebrovascular function in chronic alcoholic encephalopathy.
In the present study, we used chronic gavage administration of alcohol with gradual increases in alcohol concentration and volume to generate a rat model of chronic alcohol intoxication. We measured the changes in biological, behavioral, pathological and vascular injury-related molecular biological markers, and explored the effects of nimodipine intervention on alcohol intoxication. We found that chronic alcohol consumption induced a variety of behavioral abnormalities, accompanied by severe pathological changes in cerebral arterioles, prefrontal cortex and cerebellar tissue, as well as an upregulation of vascular endothelial growth factor (VEGF), leptin receptor (ob-R) and endothelin-1 (ET-1). Treatment with mimodipine for 15 days significantly improved behavioral abnormalities, alleviated the pathological changes in blood vessels and brain tissues, increased VEGF expression, decreased ob-R expression, reduced plasma ET-1 leakage and protected vascular and neuronal functions.


Psychoeducation in bipolar disorder: A systematic review.
Bipolar disorder (BD) is a severe psychiatric disorder characterized by mood swings. Psychosocial interventions, such as psychoeducation, play an essential role in promoting social rehabilitation and improving pharmacological treatment. To investigate the role of psychoeducation in BD. A systematic review of original studies regarding psychoeducation interventions in patients with BD and their relatives was developed. A systematic literature search was performed using the Medline, Scopus, and Lilacs databases. No review articles or qualitative studies were included in the analysis. There were no date restriction criteria, and studies published up to April 2021 were included. A total of forty-seven studies were selected for this review. Thirty-eight studies included patients, and nine included family members. Psychoeducation of patients and family members was associated with a lower number of new mood episodes and a reduction in number and length of stay of hospitalizations. Psychoeducational interventions with patients are associated with improved adherence to drug treatment. The strategies studied in patients and family members do not interfere with the severity of symptoms of mania or depression or with the patient's quality of life or functionality. Psychoeducational interventions with family members do not alter patients' adherence to pharmacotherapy. Psychoeducation as an adjunct strategy to pharmacotherapy in the treatment of BD leads to a reduction in the frequency of new mood episodes, length of hospital stay and adherence to drug therapy.


Neuroimaging in epilepsy.
Epilepsy is the most common neurological disease worldwide and is second only to stroke in causing neurological morbidity. Neuroimaging plays a very important role in the diagnosis and treatment of patients with epilepsy. This review article highlights the specific role of various imaging modalities in patients with epilepsy, and their practical applications in the management of epileptic patients.


Differential response to acrylonitrile toxicity in rat primary astrocytes and microglia.
Acrylonitrile (ACN) is a widely used chemical in the production of plastics, resins, nitriles, acrylic fibers, synthetic rubber and acrylamide. While acute high level exposures to ACN are known to be lethal, chronic low dose exposures causes glial cell tumors in rats. Recently, these glial tumors have been characterized as microglial in origin. While effects of ACN on astrocytes, the more numerous glial cell, have been investigated, the effects on microglia are unknown. This study was conducted to compare the responses of astrocytes and microglia to ACN treatment in vitro to address differential sensitivities and adaptive responses to this toxic chemical. Cell viability, ACN uptake, lipid peroxidation byproducts (F2-isoprostanes), glutathione (GSH) levels and expression of NF-E2-related factor 2 (Nrf2) were evaluated in primary rat microglia and astrocytes following ACN treatment. Results indicate that microglia are more sensitive to ACN than astrocytes, accumulating less ACN while demonstrating higher F2-isoprostane levels. GSH levels were up-regulated in both cell types, as a protective mechanism against ACN-induced oxidative stress, while Nrf2 levels were only induced in microglia. Our data suggest that microglia and astrocytes exhibit different sensitivities and responses to ACN, which are linked to the intracellular thiol status inherent to each of these cell types.


Acer tataricum subsp. ginnala Inhibits Skin Photoaging via Regulating MAPK/AP-1, NF-κB, and TGFβ/Smad Signaling in UVB-Irradiated Human Dermal Fibroblasts.
Skin, the organ protecting the human body from external factors, maintains structural and tensile strength by containing many collagen fibrils, particularly type I procollagen. However, oxidative stress by ultraviolet (UV) exposure causes skin photoaging by activating collagen degradation and inhibiting collagen synthesis. Acer tataricum subsp. ginnala extract (AGE) is a herbal medicine with anti-inflammatory and anti-oxidative effects, but there is no report on the protective effect against skin photoaging. Therefore, we conducted research concentrating on the anti-photoaging effect of Acer tataricum subsp. ginnala (AG) in UVB (20 mJ/cm2)-irradiated human dermal fibroblasts (HDF). Then, various concentrations (7.5, 15, 30 µg/mL) of AGE were treated in HDF for 24 h following UVB irradiation. After we performed AGE treatment, the matrix metalloproteinase1 (MMP1) expression was downregulated, and the type I procollagen level was recovered. Then, we investigated the mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) and nuclear factor-κB (NF-κB) pathway, which induce collagen breakdown by promoting the MMP1 level and pro-inflammatory cytokines. The results indicated that AGE downregulates the expression of the MAPK/AP-1 pathway, leading to MMP1 reduction. AGE inhibits nuclear translocation of NF-κB and inhibitor of nuclear factor-κB (IκB) degradation. Therefore, it downregulates the expression of MMP1 and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 increased by UVB. Besides, the TGFβ/Smad pathway, which is mainly responsible for the collagen synthesis in the skin, was also analyzed. AGE decreases the expression of Smad7 and increases TGFβRII expression and Smad3 phosphorylation. This means that AGE stimulates the TGFβ/Smad pathway that plays a critical role in promoting collagen synthesis. Thus, this study suggests that AGE can be a functional material with anti-photoaging properties.


Affordable sensor based gaze tracking for realistic psychological assessment.
Eye movement analysis finds tremendous usefulness in various medical screening applications and rehabilitation. Infrared sensor based eye trackers are becoming popular but these are expensive and need repeated calibration. Moreover, with multiple calibration also, there persists some noises called, variable and systematic, resulting in inaccurate gaze tracking. This study aims to build an one time calibration module to avoid the overhead of multiple calibration and to design an algorithm to remove both the types of errors effectively. The proposed approach is used for correcting the gaze tracking data for Digit Gazing task and standard recall-recognition test, where an accuracy of 90% and 82% are achieved respectively for detecting the gaze positions against the raw eye gaze data. Results also show that it is possible to perform accurate gaze tracking with one-time calibration method provided the experimental setup is not altered.


Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.
Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.


Integrin beta 3 cDNA transfection into a highly metastatic alpha v beta 3-negative human melanoma cell line inhibits invasion and experimental metastasis.
Even though integrin alpha v beta 3 is thought to play a role in invasive growth of melanomas, some metastatic melanoma cell lines lack alpha v beta 3, and downmodulation of alpha v beta 3, expression can enhance the invasive capacity of certain melanoma cells. To further investigate this apparent dualistic role of alpha v beta 3, we transfected beta 3 cDNA into the highly metastatic, beta 3-negative human melanoma cell line MV3. MV3 cells adhered to fibronectin but not to fibrinogen or a synthetic RGD peptide, while MV3-beta 3 adhered to all three RGD-containing adhesive ligands, and this adhesion was inhibited by LM609 alpha v beta 3 mAb. Expression of alpha v beta 3 did not affect MV3 in vitro proliferation or in vivo tumorigenicity upon subcutaneous inoculation into nude mice. In contrast, it strongly reduced invasion in matrigel and lung colonization in nude mice of MV3 cells. Thus, certain melanoma cell lines have adopted a metastatic strategy in the absence of alpha v beta 3, and in such cells expression of this integrin leads to a less aggressive phenotype.


Association of clinical parameters with periodontal bacterial haemolytic activity.
To determine whether haemolytic activity of subgingival bacteria is associated with periodontitis clinical parameters and to identify which bacteria produce the haemolysins. Subgingival plaque samples from 22 untreated chronic periodontitis patients were investigated by culture and identified with matrix assisted laser desorption/ionisation time-of-flight mass spectrometry. Total aerobic and anaerobic bacterial viable counts, percentage distribution of α- and β-haemolytic bacteria were significantly elevated in diseased sites in relation to healthy sites (p < 0.001). Periodontal pathogens were more frequently detected at diseased sites: Porphyromonas gingivalis, Tannerella forsythia, Treponema sp., Prevotella sp., Parvimonas micra, Fusobacterium sp., Campylobacter sp., Capnocytophaga sp., and Selenomonas sp. Haemolytic unidentifiable species and Gram-positive anaerobes such as Slackia exigua, Solobacterium moorei, and Bulledia extructa were also more frequently detected at diseased sites. In diseased sites, the presence of different haemolytic characteristics was more strongly correlated with clinical measures of disease than the mere absence or presence of specific species. The strongest correlation with probing pocket depth was observed for overall β-haemolytic toxicity (r = 0.73, p < 0.001). A strong association was observed between subgingival bacterial haemolytic activity and clinical parameters in patients with chronic periodontitis. Further investigations are warranted to delineate the role of haemolysins in the pathogenesis of periodontitis.


COOH-terminal domain of p53 modulates p53-mediated transcriptional transactivation, cell growth, and apoptosis.
The tumor suppressor protein p53 contributes to the control of cell cycle checkpoints and stress-induced apoptosis and is frequently mutated in many different types of human cancers. The COOH terminus of p53 modulates the transcriptional and apoptotic activities of the protein. Although COOH-terminal mutants of p53 are uncommon, we proposed that these p53 mutants nevertheless contributed to the selective clonal expansion of the cancer cells. Therefore, we analyzed the tumor-derived p53 COOH-terminal domain (CTD) mutants (352D/H, 356G/W, 342-stop, 360-del, and 387-del) functionally. The results have revealed that all mutants have impaired apoptotic activity when compared with wild-type p53. However, some of these mutants still transcriptionally transactivate p21Waf/Cip1 and inhibit cell growth. Interestingly, of the tumor-derived CTD mutants, oligomerization-defective mutant 342-stop was the only one that did not exhibit sequence-specific DNA binding or failed to transactivate p21Waf1/Cip1, Bax, and IGF-BP3 transcriptionally. The failure to inhibit cell growth by this tumor-derived CTD mutant supports the hypothesis that p53 sequence-specific transcriptional transactivity to p21Waf1/Cip1 is correlated with induction of cell cycle arrest and that the p53 transcriptional transactivity requires oligomerization of the p53 protein. These and other data indicate that the CTD of p53 is an important component of p53-mediated apoptosis and cell growth arrest and that inactivation of the apoptotic function, but not the inhibition of growth, is an important step during human tumorigenesis.


Novel demonstration of amyloid-β oligomers in sporadic inclusion-body myositis muscle fibers.
Accumulation of amyloid-β (Aβ) within muscle fibers has been considered an upstream step in the development of the s-IBM pathologic phenotype. Aβ42, which is considered more cytotoxic than Aβ40 and has a higher propensity to oligomerize, is preferentially increased in s-IBM muscle fibers. In Alzheimer disease (AD), low-molecular weight Aβ oligomers and toxic oligomers, also referred to as "Aβ-Derived Diffusible Ligands" (ADDLs), are considered strongly cytotoxic and proposed to play an important pathogenic role. ADDLs have been shown to be increased in AD brain. We now report for the first time that in s-IBM muscle biopsies Aβ-dimer, -trimer, and -tetramer are identifiable by immunoblots. While all the s-IBM samples we studied had Aβ-oligomers, their molecular weights and intensity varied between the patient samples. None of the control muscle biopsies had Aβ oligomers. Dot-immunoblots using highly specific anti-ADDL monoclonal antibodies also showed highly increased ADDLs in all s-IBM biopsies studied, while controls were negative. By immunofluorescence, in some of the abnormal s-IBM muscle fibers ADDLs were accumulated in the form of plaque-like inclusions, and were often increased diffusely in very small fibers. Normal and disease-controls were negative. By gold-immuno-electron microscopy, ADDL-immunoreactivities were in close proximity to 6-10 nm amyloid-like fibrils, and also were immunodecorating amorphous and floccular material. In cultured human muscle fibers, we found that inhibition of autophagy led to the accumulation of Aβ oligomers. This novel demonstration of Aβ42 oligomers in s-IBM muscle biopsy provides additional evidence that intra-muscle fiber accumulation of Aβ42 oligomers in s-IBM may contribute importantly to s-IBM pathogenic cascade.


Intracoronary ethanol ablation for the treatment of recurrent sustained ventricular tachycardia.
The selective infusion of ethanol into the coronary circulation supplying the site of origin of incessant ventricular tachycardia has been demonstrated to abolish this arrhythmia in selected patients. The present study was designed to evaluate the efficacy and safety of the intracoronary ethanol ablation technique in patients with paroxysmal ventricular tachycardia related to prior myocardial infarction. Twenty-three patients with sustained monomorphic ventricular tachycardia that was refractory to conventional antiarrhythmic drug therapy were prospectively studied. After induction of ventricular tachycardia by programmed electrical stimulation, the response of the arrhythmia to the infusion of radiographic contrast medium or saline solution into the ostia of the native coronary arteries and coronary artery bypass grafts was assessed. If ventricular tachycardia was reliably interrupted by injections into the proximal coronary artery or bypass graft, the vessel was cannulated with a steerable guide wire and 2.7F infusion catheter to determine the smallest arterial branch that would result in termination of the arrhythmia with selective injections. If reliable interruption of ventricular tachycardia was observed with saline or contrast injections, ethanol (2 ml) was then delivered through the infusion catheter. Ventricular tachycardia could be terminated by injections of saline solution or contrast medium in 11 of 21 patients in whom the protocol could be completed. Ethanol was infused in 10 of these patients. Ventricular tachycardia was inducible in only 1 of 10 patients immediately after ethanol infusion. At a follow-up electrophysiologic study performed 5 to 7 days after ablation, ventricular tachycardia became inducible in two other patients, in one of whom the arrhythmia substrate was successfully ablated after three sessions. The mean left ventricular ejection fraction was 0.33 +/- 0.1 before and 0.35 +/- 0.11 after ablation. Complications of the procedure included complete atrioventricular block in four patients and pericarditis in one patient. Thus, intracoronary ethanol ablation is associated with a moderate degree of efficacy but the potential for important complications. Despite these limitations, this technique may provide effective long-term control of ventricular tachycardia for some patients.


Identification of Chromosome Segment Substitution Lines of Gossypium barbadense Introgressed in G. hirsutum and Quantitative Trait Locus Mapping for Fiber Quality and Yield Traits.
Chromosome segment substitution lines MBI9804, MBI9855, MBI9752, and MBI9134, which were obtained by advanced backcrossing and continuously inbreeding from an interspecific cross between CCRI36, a cultivar of upland cotton (Gossypium hirsutum) as the recurrent parent, and Hai1, a cultivar of sea island cotton (G. barbadense) as the donor parent, were used to construct a multiple parent population of (MBI9804×MBI9855)×(MBI9752×MBI9134). The segregating generations of double-crossed F1 and F2 and F2:3 were used to map the quantitative trait locus (QTL) for fiber quality and yield-related traits. The recovery rate of the recurrent parent CCRI36 in the four parental lines was from 94.3%-96.9%. Each of the parental lines harbored 12-20 introgressed segments from Hai1across 21 chromosomes. The number of introgressed segments ranged from 1 to 27 for the individuals in the three generations, mostly from 9 to 18, which represented a genetic length of between 126 cM and 246 cM. A total of 24 QTLs controlling fiber quality and 11 QTLs controlling yield traits were detected using the three segregating generations. These QTLs were distributed across 11 chromosomes and could collectively explain 1.78%-20.27% of the observed phenotypic variations. Sixteen QTLs were consistently detected in two or more generations, four of them were for fiber yield traits and 12 were for fiber quality traits. One introgressed segment could significantly reduce both lint percentage and fiber micronaire. This study provides useful information for gene cloning and marker-assisted breeding for excellent fiber quality.


String formation and demixing in monolayers of dipolar colloidal mixtures.
Employing hypernetted chain (HNC) integral equations and a stability analysis we investigate the structure and phase behavior of bidisperse mixtures of dipolar hard spheres with different size ratios s=σ(S)/σ(L) confined to a plane. The dipole moments of the particles are perfectly ordered along an in-plane direction, yielding anisotropic interactions favoring chain formation. Exploring a range of size ratios and compositions, our study predicts a complex interplay between aggregation phenomena, on the one hand, and volume phase transitions, on the other hand. In dilute, strongly asymmetric systems (s = 0.5), our HNC analysis indicates chain formation of the large particles, while the small particles act as a weakly correlated background. According to our fluctuation analysis, this aggregation behavior results in combined condensation-demixing transitions, with a trend towards pure demixing when the concentration of the large particles, c(L), becomes small. In dense systems, the most interesting results are found for intermediate size ratios, s ~ 0.7-0.8. Here we find signatures of a concentration-driven transition from pure chains of large particles (large c(L)) to mixed chains with alternating order of large and small particles (small c(L)). The two regimes are separated by a characteristic "jump" in the HNC non-solution line.


Modulation of CD4(+)CD28null T lymphocytes by tumor necrosis factor-alpha blockade in patients with unstable angina.
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that favors the expansion of CD4(+)CD28null T cells, an aggressive and unusual proinflammatory lymphocyte subset frequently observed in patients with unstable angina (UA). The purpose of the present ex vivo study was to evaluate whether inflammation in patients with UA may be modulated by selective blockade of TNF-alpha. Peripheral blood samples were collected from 17 patients with UA (Braunwald's class IIIB). CD4(+)CD28null T cells were assessed by flow cytometry and expressed as a percentage of all CD4+ T cells after 24 hours of incubation of whole blood with and without increasing doses (0.1, 1, 10, and 100 microg/mL) of infliximab, an anti-TNF-alpha monoclonal antibody. In addition, CD28 expression was assessed and expressed as mean fluorescence intensity (geometric mean of the CD28 fluorescence value on all CD4+ T cells). CD4(+)CD28null T-cell percentage decreased from a median of 6.2% (range, 1.2% to 23.9%) to 4.9% (range, 1.1% to 21.9%), 4.5% (range, 1.1% to 21.6%), and 4.1% (range, 0.4% to 21.4%) after incubation with 1, 10, and 100 microg/mL of infliximab (P for trend=0.043). Analysis of CD28 mean fluorescence intensity showed that the expression of CD28 on cell surface significantly increased after incubation with increasing doses of infliximab (P for trend=0.03). The findings of this ex vivo study show that CD4(+)CD28null T-cell expansion in patients with UA may be reduced by selective TNF-alpha blockade. Further studies are warranted to evaluate the clinical benefit of CD4(+)CD28null T-cell modulation.


Endophytic Diaporthe sp. LG23 Produces a Potent Antibacterial Tetracyclic Triterpenoid.
A new lanostanoid, 19-nor-lanosta-5(10),6,8,24-tetraene-1α,3β,12β,22S-tetraol (1), characterized by the presence of an aromatic B ring and hydroxylated at C-1, C-3, C-12, and C-22, was isolated from an endophytic fungus, Diaporthe sp. LG23, inhabiting leaves of the Chinese medicinal plant Mahonia fortunei. Six biosynthetically related known steroids were also isolated in parallel. Their structures were confirmed on the basis of detailed spectroscopic analysis in conjunction with the published data. Compound 1, an unusual fungus-derived 19-nor-lanostane tetracyclic triterpenoid with an aromatic B-ring system, exhibited pronounced antibacterial efficacy against both Gram-positive and -negative bacteria, especially the clinical isolates of Streptococcus pyogenes and Pseudomonas aeruginosa as well as a human pathogenic strain of Staphylococcus aureus. Our results reveal the potential of endophytes not only in conferring host fitness but also in contributing toward traditional host plant medicines.


Species- and tissue-specific expression of the C-terminal alternatively spliced form of the tumor suppressor p53.
Alternative splicing of the p53 transcript which so far has been demonstrated only in the murine system has been proposed as a general regulatory mechanism for the generation of functionally different p53 proteins. We analyzed by RT-PCR the pattern of p53 mRNAs within the region spanning exons 10 and 11 of the p53 gene in 13 different tissues from two independent mouse strains, in 10 different rat tissues and in six different human tissues. PCR products of the expected sizes, corresponding to the normally spliced and the alternatively spliced p53 mRNAs, were detected in mice. Alternatively spliced mRNA was found at approximately 25-20% the level of the normally spliced p53 mRNA in most tissues analyzed. In spleen and kidney the proportion of alternatively spliced p53 mRNA was much lower. Surprisingly, examination of p53 mRNAs isolated from 10 different rat tissues and six human tissues within the same region of the p53 gene showed only products of normal size. Although a potential homologous alternative 3' splice site within intron 10 of the human p53 gene is present in the genomic sequence of human p53, the expected corresponding alternatively spliced p53 mRNA was undetectable. These findings imply that the generation of functionally different forms of p53 by alternative splicing of p53 transcripts is a species-specific event, possibly indicating species-specific mechanisms for regulating p53 activities.


CLINICAL AND HAEMATOLOGICAL CHANGES AMONG HIV PATIENTS.
This is an article about anemia of chronic diseases in HIV patients. It follows a study of the nature of red blood cells changes in patients with HIV infection and the features of anemia of chronic diseases (ACD) in the particular group of patients. In addition, connection was established between changes in oral cavity and peripheral blood parameters. The study identified clinical signs of anemia in maxillofacial area and oral cavity in HIV-infected people. During the analysis of red blood cell indicators in patients with HIV a number of changes were observed. The problem of anemia in this group was complicated by the patients taking highly active antiretroviral therapy (ART). The study revealed significant changes in red blood cell count in people with HIV status, who were either taking or not taking highly active ART. We also analyzed the studied parameters of red blood cells in patients with HIV infection, depending on level of blood lymphocytes with CD4 cluster differentiation in plasmolemma, and depending on the stage of the main disease. We also analyzed and studied parameters depending on the state of periodontal tissues. Identified results can be interesting in terms of establishing pathogenetical relationships in development of inflammatory and degenerative changes in periodontal tissues and anemia of chronic diseases associated with HIV infection. These findings require further investigation and more comprehensive analysis.


[Outcomes of Clostridium difficile enterocolitis after administration of antibiotics along with probiotic supplement].
Clostridium difficile enterocolitis is a potentially fatal disease showing increasing incidence in hospital environment. Therapeutic approach in the management of Clostridium difficile enterocolitis is highly complex, particularly because of its tendency to relapse and reinfection. The study was aimed at investigating the factors influencing the development of Clostridium difficile enterocolitis and outcomes of enterocolitis after administration of standard antimicrobial therapy combined with probiotic supplement. A non-comparative prospective observational study encompassed 42 patients (22 males and 20 females) diagnosed with Clostridium difficile enterocolitis and treated at the Department of Infectious Diseases in Novi Sad in the period October 2011 - April 2012. Higher incidence of the disease was found in elderly patients (78.6% of them were over 60 years of age), after antimicrobial therapy (83.8%), after hospitalization (83.3%) and in comorbid conditions (85.7%). The clinical picture revealed predominantly mild to moderate symptoms. A good clinical response to the standard antimicrobial therapy (metronidazole, vancomycin) combined with probiotic given for 10 days was observed in all patients, and the improvement in parameters such as the number and appearance of stools, abdominal distension and pain was recorded. Statistically significant changes in laboratory parameters (leukocyte count, C-reactive protein level) were recorded on day 5 after the onset of disease. Recurrent infection after successful therapy was observed in 9.5% of the patients. Administration of probiotic bacteria Lactobacillus acidophilus Rosell-52, Lactobacillus rhamnosus Rosell-11 and Bifidobacterium longum Rosell-175 alongside the standard antimicrobial therapy in the patients with Clostridium difficile enterocolitis demonstrated positive effects on the severity or clinical picture and normalization of laboratory parameters. Recurrent infection after successful therapy was observed in only a small number of patients as compared with the literature data.


Assessment of competence in clinical practice: a phenomenological approach.
Using a phenomenological approach, this study explores the different dimensions of student nurse assessment in clinical practice from the perspective of 10 experienced practitioners. Phenomenology, one of the various types of qualitative research methods, is used to discover and understand the meaning of human life experiences through an analysis of the subjects' descriptions of situations. It is therefore of particular value when addressing the questions posed in the present study: (a) what attributes characterize competence and non-competence in learner nurses, (b) how they recognize these attributes in practice, and (c) how they measure competence at different levels of preparation. Rather than provide answers, the phenomenologist explores the meaning of the language used in determining competence in practice. Through this contribution to the understanding of the notion of competence and its measurement by these experienced practitioners, it may be possible in some way to unravel the confusion that surrounds the meaning of competence represented in the literature. It is hoped that, through the discovery of the lived world of these clinicians, others may be better facilitated for and within their role as assessors in the future.


DentaCT for evaluating mandibular and maxillary invasion in cancer of the oral cavity.
We used a retrospective analysis of charts, imaging studies, and histologic findings when available in 17 patients with cancer of the oral cavity to define the value of DentaCT or multiplanar reformation software in assessing bony involvement by malignant tumors of the oral cavity. From two academic tertiary-referral medical centers, the 17 patients had a mean age of 63 years and suspected maxillary (2) or mandibular (15) invasion. All patients had conventional computed tomography scanning and multiplanar reformation scans with several additional imaging studies obtained. Two patients demonstrated no bony involvement by imaging and histologic studies. Twelve of the remaining 15 patients had surgically documented bony involvement also correctly detected by DentaCT. DentaCT was found to be a valuable tool in defining extent of bony invasion by tumor. Although not compared to other imaging modalities, our experience supports the use of DentaCT where available for this purpose.


Peripheral blood neutrophil granulocytes from patients with head and neck squamous cell carcinoma functionally differ from their counterparts in healthy donors.
Solid tumors such as head and neck squamous cell carcinoma (HNSCC) display an intense interaction between tumoral factors and the immune system. Functional modulation of tumor-infiltrating and peripheral blood immune cells plays an important role during tumor progression. In this pilot study we compared biological functions of polymorphonuclear granulocytes (PMN) from the peripheral blood of HNSCC patients and healthy subjects. PMN were simultaneously isolated from the peripheral blood of HNSCC patients and healthy donors for functional analysis (apoptosis, production of reactive oxygen species (ROS), cytokine release and immunophenotyping). PMN from HNSCC patients showed a significantly lower inducible production of ROS (P = 0.02) and reduced spontaneous apoptosis (P= 0.008) compared with PMN from healthy donors. Under standard culture conditions, there was no significant difference regarding the release of inflammatory cytokines between PMN from HNSCC patients and PMN from healthy donors. Confirming previous observations, serum concentrations of PMN-related cytokines were significantly higher in the peripheral blood of HNSCC patients than in that of controls. Importantly, immunophenotyping revealed an increased number of immature PMN in PMN fractions isolated from HNSCC patients. Peripheral blood PMN from HNSCC patients and healthy donors show distinct functional differences. The presence of increased numbers of immature stages of PMN in HNSCC patients may partly contribute to the changes observed. After recruitment to and infiltration of the tumor, PMN may be further modulated in the local tumor microenvironment. This pilot study justifies functional analyses of myeloid cells in larger cohorts of patients with HNSCC.


Transition state models for probing stereoinduction in Evans chiral auxiliary-based asymmetric aldol reactions.
The use of chiral auxiliaries is one of the most fundamental protocols employed in asymmetric synthesis. In the present study, stereoselectivity-determining factors in a chiral auxiliary-based asymmetric aldol reaction promoted by TiCl(4) are investigated by using density functional theory methods. The aldol reaction between chiral titanium enolate [derived from Evans propionyl oxazolidinone (1a) and its variants oxazolidinethione (1b) and thiazolidinethione (1c)] and benzaldehyde is examined by using transition-state modeling. Different stereochemical possibilities for the addition of titanium enolates to aldehyde are compared. On the basis of the coordination of the carbonyl/thiocarbonyl group of the chiral auxiliary with titanium, both pathways involving nonchelated and chelated transition states (TSs) are considered. The computed relative energies of the stereoselectivity-determining C-C bond formation TSs in the nonchelated pathway, for both 1a and 1c, indicate a preference toward Evans syn aldol product. The presence of a ring carbonyl or thiocarbonyl group in the chiral auxiliary renders the formation of neutral TiCl(3)-enolate, which otherwise is energetically less favored as compared to the anionic TiCl(4)-enolate. Hence, under suitable conditions, the reaction between titanium enolate and aldehyde is expected to be viable through chelated TSs leading to the selective formation of non-Evans syn aldol product. Experimentally known high stereoselectivity toward Evans syn aldol product is effectively rationalized by using the larger energy differences between the corresponding diastereomeric TSs. In both chelated and nonchelated pathways, the attack by the less hindered face of the enolate on aldehyde through a chair-like TS with an equatorial disposition of the aldehydic substituent is identified as the preferred mode. The steric hindrance offered by the isopropyl group and the possible chelation are identified as the key reasons behind the interesting stereodivergence between Evans and non-Evans products normally reported for the title reaction. The application of an activation strain model on the critical TSs has been effective toward rationalizing the origin of stereoselectivity. Improved interaction energy between the reactants is found to be the key stabilizing factor for the lowest energy TS in both chelated and nonchelated pathways. The present study provides newer insights on the role of titanium(IV) toward modulating stereoselectivity in aldol reactions.


Somatostatin receptor subtype 2 gene therapy inhibits pancreatic cancer in vitro.
Most human pancreatic adenocarcinoma cells do not express somatostatin receptors and somatostatin does not inhibit the growth of these cancers. We have demonstrated previously that somatostatin inhibits the growth of pancreatic cancers expressing somatostatin receptor subtype 2 (SSR2) but not receptor-negative cancers. SSR2 expression may be an important tumor suppressor pathway that is lost in human pancreatic cancer. We hypothesized that SSR2 gene transfer would restore the growth inhibitory response of human pancreatic cancer to somatostatin. We created adenoviral constructs containing the SSR2 or Lac-Z gene and transfected somatostatin receptor-negative human pancreatic cancer cells (Panc-1). Presence of functional cell surface SSR2 protein was assessed by whole-cell competitive binding assays. Parental cells, Lac-Z-transfected, and SSR2-transfected cells were cultured in the presence and absence of somatostatin. The rate of cell growth was determined by direct cell counting using a hemacytometer (n = 8 wells/group). Cells were analyzed for expression of tumor suppressor proteins by Western blot. Panc-1 cells transfected with the SSR2 transgene demonstrated high-affinity specific binding of (125)I-somatostatin at physiologic concentrations. Expression of somatostatin receptors caused 60% inhibition of cell growth compared with the Lac-Z virus-treated controls (P < 0.05 by Kruskal-Wallis/Bonferroni). There was no additional inhibition of cell proliferation with exogenous somatostatin. Furthermore, addition of somatostatin ligand antibody did not diminish the effect of SSR2 expression on cell proliferation. Western blot analysis revealed an upregulation of the cyclin-dependent kinase inhibitor p27 in the SSR2-transfected cells. Expression of SSR2 by human pancreatic cancer causes significant slowing of cell division by a mechanism independent of somatostatin. The mechanism may involve upregulation of known tumor suppressor proteins. Restoration of SSR2 gene expression deserves further study as a potential gene therapy strategy in human pancreatic cancer.


A DNA barcode library for 5,200 German flies and midges (Insecta: Diptera) and its implications for metabarcoding-based biomonitoring.
This study summarizes results of a DNA barcoding campaign on German Diptera, involving analysis of 45,040 specimens. The resultant DNA barcode library includes records for 2,453 named species comprising a total of 5,200 barcode index numbers (BINs), including 2,700 COI haplotype clusters without species-level assignment, so called "dark taxa." Overall, 88 out of 117 families (75%) recorded from Germany were covered, representing more than 50% of the 9,544 known species of German Diptera. Until now, most of these families, especially the most diverse, have been taxonomically inaccessible. By contrast, within a few years this study provided an intermediate taxonomic system for half of the German Dipteran fauna, which will provide a useful foundation for subsequent detailed, integrative taxonomic studies. Using DNA extracts derived from bulk collections made by Malaise traps, we further demonstrate that species delineation using BINs and operational taxonomic units (OTUs) constitutes an effective method for biodiversity studies using DNA metabarcoding. As the reference libraries continue to grow, and gaps in the species catalogue are filled, BIN lists assembled by metabarcoding will provide greater taxonomic resolution. The present study has three main goals: (a) to provide a DNA barcode library for 5,200 BINs of Diptera; (b) to demonstrate, based on the example of bulk extractions from a Malaise trap experiment, that DNA barcode clusters, labelled with globally unique identifiers (such as OTUs and/or BINs), provide a pragmatic, accurate solution to the "taxonomic impediment"; and (c) to demonstrate that interim names based on BINs and OTUs obtained through metabarcoding provide an effective method for studies on species-rich groups that are usually neglected in biodiversity research projects because of their unresolved taxonomy.


Initiation of Postmeiotic beta-Galactosidase Synthesis during Microsporogenesis in Oilseed Rape.
The synthesis of beta-galactosidase during Brassica campestris pollen development results from the transcription of the haploid genome. A quantitative cytochemical method has been developed in which 5-bromo-4-chloro-3-indoxyl-beta-d-galactoside is used as substrate giving a blue-green final reaction product. We have recently detected oilseed rape plants which are heterozygous for the beta-galactosidase locus, in which 50% of the pollen grains produced are Gal (having enzyme activity), while the other 50% are gal (enzyme deficient). The gal pollen grains served as a built-in control during microspectrophotometric determinations of enzyme activity. The present study has identified the developmental phase at which synthesis of the enzyme commenced. Activity is absent in microsporocytes, tetrads, and at microspore release. Enzyme activity is first detected in the young microspores and, by early vacuolate period, there is an increase in the rate of enzyme activity. A second period of increased enzyme synthesis occurred prior to generative cell division, although the rate is reduced in mature pollen.


Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function.
The incidence of high blood pressure with advancing age is notably high, and it is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders. Although age-related hypertension is an established phenomenon, current treatments are only palliative but not curative. Thus, there is a critical need for a curative therapy against age-related hypertension, which could greatly decrease the incidence of cardiovascular disorders. We show that overexpression of human thioredoxin (TRX), a redox protein, in mice prevents age-related hypertension. Further, injection of recombinant human TRX (rhTRX) for three consecutive days reversed hypertension in aged wild-type mice, and this effect lasted for at least 20 days. Arteries of wild-type mice injected with rhTRX or mice with TRX overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxation, increased nitric oxide production, and decreased superoxide anion (O2•-) generation compared to either saline-injected aged wild-type mice or mice with TRX deficiency. Our study demonstrates a potential translational role of rhTRX in reversing age-related hypertension with long-lasting efficacy.


Kinesin spindle protein inhibitors in cancer: from high throughput screening to novel therapeutic strategies.
Bringing to a halt the cell cycle in mitosis and interfering with its normal progression is one of the most successful anti-cancer strategies used nowadays. Classically, several kinds of anti-cancer drugs like taxanes and vinca alkaloids directly inhibit microtubules during cell division. These drugs exhibit serious side effects, most importantly, severe peripheral neuropathies. Alternatively, KSP inhibitors are grasping a lot of research attention as less toxic mitotic inhibitors. In this review, we track the medicinal chemistry developmental stages of KSP inhibitors. Moreover, we address the challenges that are faced during the development of KSP inhibitor therapy for cancer and future insights for the latest advances in research that are directed to find active KSP inhibitor drugs.


Dietary habits in Greek children with functional constipation based on Rome III criteria: a school-based, cross-sectional multivariate analysis.
Functional constipation (FC) is the most common gastrointestinal disorder of childhood and has a multifactorial etiology. We aimed to assess dietary habits in Greek children with FC compared to the general population (control group, CG). This was a subgroup analysis of a school-based, cross-sectional study carried out in children 6-18 years of age, between January and June 2014, using the Rome III criteria for the diagnosis of FC. Dietary parameters, as well as socioeconomic and demographic data and their association with the likelihood of FC, were analyzed through multivariate logistic regression analysis and expressed as odds ratios (OR). A total of 1439 children (1218 CG, 221 FC) were included in the analysis. The final model showed that consumption of was the only dietary parameter significantly related to FC; higher frequency of consumption was inversely related to the likelihood of FC (OR: 0.98, 95% CI: 0.96, 0.99, P=0.048). Significant socioeconomic confounders with a positive association with FC were: parental educational level, victimization, physical activity and number of adults at home. Increased frequency of fiber consumption is significantly associated with higher odds of FC irrespective of socioeconomic background and lifestyle parameters. Interventional studies are required to validate these cross-sectional observations.


Orchid-fungus fidelity: a marriage meant to last?
The characteristics of plant-mycorrhizae associations are known to vary in both time and space, but the ecological consequences of variation in the dynamics of plant-fungus interactions are poorly understood. For example, do plants associate with single fungi or multiple fungi simultaneously, and do the associations persist through a plant's lifetime or do plants support a succession of different fungi? We investigated these and other questions related to plant-fungus interactions in Goodyera pubescens, an evergreen terrestrial orchid of the eastern United States, that interacts with closely related fungi in the genus Tulasnella. Unlike the mycorrhizal associations of other plants, orchid-mycorrhizal associations only benefit the orchid, based on current evidence. Many terrestrial orchids have been found to associate with specific groups of fungi. This characteristic could potentially limit orchids to relatively narrow ranges of environmental conditions and may be a contributing factor in the decline of many orchids in the face of changing environmental conditions. We found that G. pubescens protocorms (developing embryos prior to leaf production) and adults associated with only one fungal individual at a time. The orchid-fungus association persists for years, but during a drought period that was associated with the death of many plants, surviving plants were able to switch to new fungal individuals. These results suggest that G. pubescens interacts with the same fungal partner during periods of modest environmental variation but is able to switch to a different fungal partner. We hypothesize that the ability to switch fungi allows G. pubescens to survive more extreme environmental perturbations. However, laboratory experiments suggest that switching fungi has potential costs, as it increases the risk of mortality, especially for smaller individuals. Our findings indicate that it is unlikely that switching fungi is a common way to improve tolerance of less severe environmental fluctuations and disturbances. These findings may have important implications for plant responses to severe climatic events or to more gradual environmental changes such as global warming.


[Intestinal sensitivity disorders and irritable bowel syndrome].
Long neglected in the past, the study of visceral sensitivity (interoception) has progressed in recent years because of advances in neurobiological techniques. Dealing with the structure or the function of single neurons, these techniques have profoundly increased our knowledge about the sensitive mechanisms in the digestive tract. According to recent data, the visceral sensitivity organs are richer and more complex than imagined previously. Microphysiological techniques have shown that intestinal sensitive terminations are capable of transmitting information concerning visceral activity and physicochemical modifications of intestinal contents directly to the central nervous system. This means that visceral sensitivity intervenes under physiological as well as pathological conditions. This notion is new and of great interest. As progress was being made concerning the morphologic and electrophysiologic aspects and contemporaneous studies were establishing the richness of visceral, and particularly, intestinal, sensitive receptors, basic science research in humans and animals have emphasized the diversity of the implication of the extrinsic nervous system in pain, regulation of digestive motility, homeostasis and alimentary behaviour. Our present knowledge on the nervous and neurohumoral mechanisms has shed new light on the determinisms in digestive tract pathology. This is especially true in the irritable bowel syndrome which can be considered as an extrinsic nervous system derangement. Due to abnormal sensitivity by modification of the threshold values of sensitivity to distension, and/or to stimulation by substances such as cholecystokinin, for example, motor disorders occur. Other factors, such as stress, can be responsible for revelation or exacerbation of neurohumoral disorders.


Engineering a mineralocorticoid- to a glucocorticoid-synthesizing cytochrome P450.
Site-directed mutagenesis of a domain (amino acids 299-338) aligning to the I-helix region of P450cam, P450BM3 and P450terp was used to investigate the different regioselectivities displayed in the hydroxylation reactions performed by human aldosterone synthase (P450aldo) and 11beta-hydroxylase (P45011beta). The two enzymes are 93% identical and are essential for the synthesis of mineralocorticoids and glucocorticoids in the human adrenal gland. Single replacement of P450aldo residues for P45011 beta-specific residues at positions 296, 301, 302, 320, and 335 only gave rise to slightly increased 11beta-hydroxylase activities. However, a L301P/A320V double substitution increased 11beta-hydroxylase activity to 60% as compared with that of P45011 beta. Additionally substituting Ala-320 for Val-320 of P45011 beta further enhanced this activity to 85%. The aldosterone synthase activities of the mutant P450aldo proteins were suppressed to a varying degree, with triple replacement mutant L301P/E302D/A320V retaining only 10% and double replacement mutant L301P/A320V retaining only 13% of the P450aldo wild type activity. These results demonstrate a switch in regio- and stereoselectivities of the engineered P450aldo enzyme due to manipulation of residues at three critical positions, and we attribute the determination of these features in P450aldo to the structure of a region analogous to the I-helix in P450cam.


Great gerbil burrowing-induced microbial diversity shapes the rhizosphere soil microenvironments of Haloxylon ammodendron in temperate deserts.
In the Gurbantunggut Desert of northwest China, the main habitat of Rhombomys opimus (great gerbil) is under the thickets of Haloxylon ammodendron, the main construction species. In the long-term coexistence, continuous gerbil activities (burrowing, defecating, and gnawing) limited the growth of H. ammodendron, affected the root microenvironment under the H. ammodendron forest, and weakened the desert ecosystem. However, there is a lack of general understanding about the response of desert soil microhabitats to such gerbil disturbance. Accordingly, this study examined the effects of different intensities of gerbil disturbance (none, mild, moderate, or severe disturbances) on soil nutrients content and used high-throughput sequencing to explore the change in diversity and structure of microbial communities (bacteria and fungi) in H. ammodendron rhizosphere at different soil depths (0-20, 20-40, and 40-60 cm). In the arid desert ecosystem, compared with the soil fungal community, the alpha diversity of the soil bacterial community was significantly affected by gerbil disturbance. Meanwhile, both soil depth and gerbil disturbance significantly impacted the beta diversity and relative abundance of soil bacterial and fungal communities. In addition, gerbil disturbance significantly altered the soil characteristics affecting the distribution and composition of soil microbial communities in H. ammodendron rhizosphere, especially the soil bacterial community. This survey provides evidence that remold impact of gerbil disturbance on soil microenvironment of H. ammodendron rhizosphere in desert ecosystems in northwest China, which helps to further understand the potential correlations with changes in the microbial community at a regional scale.


Placement of implants in an ossifying fibroma defect obliterated with demineralized, freeze-dried bone allograft and Plasma-rich growth factor.
There has been considerable clinical interest in combining the grafts, particularly bone allografts for support for dental implants, soft-tissue support, periodontal maintenance, and ovate pontic formation. The use of demineralized, freeze-dried bone allograft (DFDBA) offers certain advantages over other graft materials and can avoid the need for a second-site surgery for autogenous donor bone. The advantages of DFDBA include handling properties, osteoinductivity, membrane tenting, and less susceptibility to migration after placement. This article will review available grafting materials and demonstrate a case of ossifying fibroma of the mandible, which was treated by curettage and hollow cavity filled with DFDBA. Six months follow-up period showed successful graft result and this grafted bone form was utilized for implant supported prosthesis.