Prospective randomized evaluation of FOOT gel pads for operating room staff COMFORT during laparoscopic renal surgery.
We evaluated the comfort level of our laparoscopy team during and after laparoscopic renal surgery, with or without the use of gel footpads. Between September 2008 and April 2009 we prospectively randomized 100 consecutive laparoscopic renal procedures to examine whether the use of a foot gel pad altered the surgical team's comfort level. A questionnaire was used to measure the discomfort in 18 different subjects before and during surgery, and one day postoperatively. The procedures performed with or without the foot gel pads were compared. One hundred laparoscopic procedures were randomized to being performed with and without gel pads. In 50 procedures, the foot gel pad was used. The mean age of the subjects was 36 years (range 25-52). The mean surgical experience was 7 years. The characteristics of the participants in procedures with and without the gel pad were similar. In the immediate postoperative period, there were significantly more breaks taken (P = .001), number of stretches (P = .001), foot pain (P = .003), knee pain (P = .001), back discomfort (P = .001), overall discomfort (P = .001), and diminished level of energy (P = .049) in the group not using the gel pad. Of the 24-hour postoperative time point, evaluation significantly favored the gel pads regarding foot pain (P = .004), overall amount of discomfort (P = .001), and energy level of the participants (P = .044). The use of foot gel pads improves surgeon comfort and ergonomics during laparoscopy. The pads have been incorporated into our routine operating room set-up and may improve surgical performance by diminishing fatigue and discomfort.


Incidence of Non-Immunological Defenses of Soil White Grubs on Parasitism Success of Mallophora ruficauda Larva (Diptera: Asilidae).
White grubs are larvae of Coleoptera of the family Scarabaeidae. They are known because of their intensive feeding habits on crop roots. Mallophora ruficauda (Diptera: Asilidae) is a dipteran parasitoid whose larva is a natural enemy for white grubs. This species is a solitary ectoparasitoid, where both female and larva realize different steps in the host location process. Female place its eggs in high grasslands and then, the larva finds and parasitizes the host in the ground. There are nine potential hosts in the area of action of this parasitoid; however a high preference for Cyclocephala signaticollis has been observed (87% of field parasitism). It is known that many insects have developed defensive and immunological mechanisms when attacked by a parasitoid, which can be behavioral, physiological, chemical or genetic. The objectives of this work were to investigate what kind of defense and non-immunological associated mechanisms the white grubs have against this parasitoid and to understand why M. ruficauda have such a high preference for masked chafer grubs or Cyclocephala species. In particular, for each white grub species, we asked: (1) If there is a differential behavioral reaction when a parasitoid attack is simulated; (2) If body attributes of white grubs species have influence on defense behavior, and particularly for the masked chafer C. signaticollis; and (3) Why this species is the most selected by M. ruficauda. It was found that behavioral defenses of white grubs would explain the parasitism pattern of M. ruficauda larvae and its preference for C. signaticollis.


Towards Quantitative Precision for ECG Analysis: Leveraging State Space Models, Self-Supervision and Patient Metadata.
Deep learning has emerged as the preferred modeling approach for automatic ECG analysis. In this study, we investigate three elements aimed at improving the quantitative accuracy of such systems. These components consistently enhance performance beyond the existing state-of-the-art, which is predominantly based on convolutional models. Firstly, we explore more expressive architectures by exploiting structured state space models (SSMs). These models have shown promise in capturing long-term dependencies in time series data. By incorporating SSMs into our approach, we not only achieve better performance, but also gain insights into long-standing questions in the field. Specifically, for standard diagnostic tasks, we find no advantage in using higher sampling rates such as 500 Hz compared to 100 Hz. Similarly, extending the input size of the model beyond 3 seconds does not lead to significant improvements. Secondly, we demonstrate that self-supervised learning using contrastive predictive coding can further improve the performance of SSMs. By leveraging self-supervision, we enable the model to learn more robust and representative features, leading to improved analysis accuracy. Lastly, we depart from synthetic benchmarking scenarios and incorporate basic demographic metadata alongside the ECG signal as input. This inclusion of patient metadata departs from the conventional practice of relying solely on the signal itself. Remarkably, this addition consistently yields positive effects on predictive performance. We firmly believe that all three components should be considered when developing next-generation ECG analysis algorithms.


Hydatid cyst in tail of pancreas.
The authors present a case of hydatid cyst in tail of pancreas in a 35-year-male who presented with 6-month history of dull aching pain in abdomen. Radiologically, a differential diagnosis of cystic pancreatic neoplasm and pseudocyst was made which was confirmed after histopathological examination.


Esophageal Stricture: An Uncommon Complication of Cervical Inlet Patch.
Esophageal heterotopic gastric mucosal patches (HGMP), also known as cervical inlet patches (CIP), is a rare but underdiagnosed condition characterized by the presence of salmon-colored, velvety mucosa located in the proximal esophagus, distal to the upper esophageal sphincter. The incidence of CIP ranges from 3% to 10% in adults, and its endoscopic appearance is characterized by a flat or slightly raised salmon-colored patch. In this case, we report a 78-year-old man who presented with symptoms of laryngopharyngeal reflux and dysphagia. An esophagogastroduodenoscopy showed a flat area of salmon-colored patch between 17 and 20 cm from the incisors, suggestive of a CIP complicated by stricture. The biopsy results showed an oxyntic-type mucosa lined with columnar cells consistent with an inlet patch. Esophageal dilation was done with a savory dilator with no resistance at 18 mm. The patient was placed on maintenance acid suppression therapy with proton-pump inhibitors and reported complete resolution of symptoms at the 1-month follow-up.


Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population.
Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity-associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the 'A' allele carriers had 2.46 times increased risk of obesity than those with 'CC' genotype (P = 3.0 × 10(-5)) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3(rd) tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with 'T' allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the 'A' allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with 'CC' genotype (P = 4.0 × 10(-5)). This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.


[The frequency of cardiovascular disease-associated risk factors in a university student population].
Estimating the frequency of cardiovascular disease-associated risk factors in a university student population in Cartagena, Bolívar. A cross-sectional survey was conducted to establish the frequency of being overweight, obesity, dyslipidaemia, physical inactivity and smoking habits in 301 students from the University of Cartagena. Simple random sampling was carried out without replacement. The International Physical Activity Questionnaire-short form (IPAQ-sf) was applied in addition to lab tests for evaluating total cholesterol, triglycerides, HDL and LDL cholesterol. The main analysis was carried out for establishing the possible risk factors associated with heart diseases; a 0.05 statistical significance level was used. 34.2 % of the students in the survey had alterations regarding their body mass index. 64.1 % of the sample population were physically inactive and 23.9 % stated that they smoked. Triglycerides had the highest lipid prevalence (24.6 %). Statistically significant differences were found regarding gender, recorded statistically significant differences when were related to physical activity levels, smoking and HDL cholesterol and triglyceride levels (p<0.05). Cardiovascular risk factors in this student population revealed similar patterns to those found in the Caribbean region which have shown epidemiological and demographic transition, as reported by national and local health services. These findings thus strongly suggest the need for implementing opportune health promotion and prevention models for reducing the burden of non-communicable disease and chronic disease-associated death.


Paramfit: automated optimization of force field parameters for molecular dynamics simulations.
The generation of bond, angle, and torsion parameters for classical molecular dynamics force fields typically requires fitting parameters such that classical properties such as energies and gradients match precalculated quantum data for structures that scan the value of interest. We present a program, Paramfit, distributed as part of the AmberTools software package that automates and extends this fitting process, allowing for simplified parameter generation for applications ranging from single molecules to entire force fields. Paramfit implements a novel combination of a genetic and simplex algorithm to find the optimal set of parameters that replicate either quantum energy or force data. The program allows for the derivation of multiple parameters simultaneously using significantly fewer quantum calculations than previous methods, and can also fit parameters across multiple molecules with applications to force field development. Paramfit has been applied successfully to systems with a sparse number of structures, and has already proven crucial in the development of the Assisted Model Building with Energy Refinement Lipid14 force field.


Benefit finding and resilience in child caregivers.
A substantial number of children are involved in informal caregiving and make a significant contribution to health care delivery. While this places high levels of demand on their coping resources, there is some evidence that these children find benefit in their caring role. A survey design using questionnaire data collection was used with a sample of 442 children (174 boys and 268 girls) between the ages of 12 and 16. The role of benefit finding and resilience was explored within a stress and coping model of the impact of caregiving. Hierarchical multiple regression analysis (HMRA) identified resilience and benefit finding as accounting for significant amounts of variance in positive health and mediating the impact of caregiving. In regard to negative health, only benefit finding played a significant role. Young caregivers do experience benefit finding and exhibit resilience although the relationship with caregiving burden was inverse. Benefit finding seems to be related to social recognition of the caregiving role and to family support. What is already known on this subject? There is some emerging evidence that child caregivers experience some positive effects or benefits from their caring in spite of the demands of the role. However, the main focus has been on reducing negative outcomes rather than on building resilience. What this study adds? This study provides evidence that young caregivers do experience benefit finding in situations where the role demand is not overly excessive and where the role is socially recognized.


Expanded Hemodialysis: A New Therapy for a New Class of Membranes.
A wide spectrum of molecules is retained in end-stage kidney disease, normally defined as uremic toxins. These solutes have different molecular weights and radii. Current dialysis membranes and techniques only remove solutes in the range of 50-15,000 Da, with limited or no capability to remove solutes in the middle to high molecular weight range (up to 50,000 Da). Improved removal has been obtained with high cut-off (HCO) membranes, with albumin loss representing a limitation to their practical application. Hemodiafiltration (HDF) at high volumes (>23 L/session) has produced some results on middle molecules and clinical outcomes, although complex hardware and high blood flows are required. A new class of membrane has been recently developed with a cut off (MWCO) close to the molecular weight of albumin. While presenting negligible albumin loss, these membranes have a very high retention onset (MWRO), allowing high clearances of solutes in a wide spectrum of molecular weights. These membranes originally defined (medium cut off) are probably better classified as high retention onset. The introduction of such membranes in the clinical routine has allowed the development of a new concept therapy called "expanded hemodialysis" (HDx). The new therapy is based on a special hollow fiber and dialyzer design. Its simple set-up and application offer the possibility to use it even in patients with suboptimal vascular access or even with an indwelling catheter. The system does not require a particular hardware or unusual nursing skill. The quality of dialysis fluid is, however, mandatory to ensure a safe conduction of the dialysis session. This new therapy is likely to modify the outcome of end-stage kidney disease patients, thanks to the enhanced removal of molecules traditionally retained by current dialysis techniques.


[The role of AP-1 and NF-kappaB in glucocorticoid resistance].
Glucocorticoid exerts its anti-inflammatory effect mainly through the suppression of both AP-1 and NF-kappaB by its receptor, glucocorticoid receptor(GR). AP-1 and NF-kappaB are also supposed to be involved in glucocorticoid resistance. Here we describe the role of AP-1 and NF-kappaB in glucocorticoid resistance.


The Utility of Point-of-Care Ultrasound for Post-Bronchoscopy Pneumothorax Evaluation.
We present a case of a 65-year-old female with a prior history of B-cell lymphoma with new CT chest findings of a nodule requiring an electromagnetic navigational bronchoscopy with transbronchial biopsies. Post-bronchoscopy, the patient complained of dyspnea and left scapular pain despite two normal anterior-posterior chest X-rays. Point-of-care ultrasound of the lung demonstrated a lack of lung sliding, which was confirmed via a right lateral decubitus chest X-ray. This case illustrates the utility and superiority of lung point-of-care ultrasound while highlighting the limitations of conventional imaging modalities in a post-bronchoscopy evaluation.


PyCGTOOL: Automated Generation of Coarse-Grained Molecular Dynamics Models from Atomistic Trajectories.
Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of internal coordinates directly from atomistic molecular dynamics simulation trajectories. The derivation of bespoke parameters from atomistic simulations improves the quality of the CG model compared to the use of generic parameters derived from other molecules, while automation greatly reduces the time required. The ease of configuration of PyCGTOOL enables the rapid investigation of multiple atom-to-bead mappings and topologies. Although we present PyCGTOOL used in combination with the GROMACS molecular dynamics engine its use of standard trajectory input libraries means that it is in principle compatible with other software. The software is available from the URL https://github.com/jag1g13/pycgtool as the following doi: 10.5281/zenodo.259330 .


Spatial and social sexual segregation patterns in indo-pacific bottlenose dolphins (Tursiops aduncus).
Sexual segregation seems to be common in bottlenose dolphins, whereby males and females live in different pods that mix mainly for mating. Male dolphins often use aggressive behaviour to mate with females, while females with calves may have different activity and dietary requirements to males and different susceptibility to predation. We investigated the degree of spatial and social sexual segregation in Indo-Pacific bottlenose dolphins (Tursiops aduncus) in a subtropical estuary in Australia. Based on surveys completed over three years, dolphin groups were mostly mixed-sex or female. Mixed-sex groups were found in larger groups in mostly deeper water, whereas, female groups were foraging across all water depths in smaller groups. Aggressive coercive behaviour by males towards females was high, occurring mainly in deeper water, at higher tides, and outside the breeding season. Habitat use by female dolphin groups suggests that shallow tributaries may provide a sanctuary from aggressive males, access to suitable prey items and density for mothers and their calves, or a combination of these factors.


Effects of lysed Enterococcus faecalis FK-23 on allergen-induced peritoneal accumulation of eosinophils and serum total IgE concentration in inbred mice.
Recent clinical trials have shown the possibility of probiotics in prevention and treatment of allergic diseases. The purpose of this experimental study was to assess the influence of lysed Enterococcus faecalis FK-23 (LFK) on allergic responses in different mouse strains. We performed a comparative study on the effects of LFK for allergen-induced peritoneal accumulation of eosinophils and serum total IgE concentration by using BALB/c, C57BL/6, C3H/HeN and C3H/HeJ mice. There was no significant difference in total number of peritoneal accumulated cells induced by cedar pollen allergen between the control and LFK groups in any strain of mice (p > 0.05); however, the ratio of eosinophils to total accumulated cells was significantly decreased in LFK-treated mice of BALB/c (p = 0.016), C3H/HeN (p = 0.010) and C3H/HeJ (p = 0.004), but not C57BL/6 (p > 0.05). No significant difference in serum total IgE concentration was found between the control and LFK groups of different mouse strains (p > 0.05). These results reveal a different effect of LFK on suppressing allergen-induced local eosinophila in inbred strains of mice, suggesting the effectiveness of probiotics on limiting allergy might be under the influence of individual genetic background.


Genetic parameters of coat colour in golden fox (Vulpes vulpes L.).
Genetic parameters (heritability, genetic and phenotypic correlations) of chosen coat colour traits of golden fox were estimated. 1013 animals, born on the Sniaty fox farm (Poland) in 1985-1999 were evaluated. In 1993-1999 colour type was additionally assessed for 833 animals, by detailed evaluation of coat colour on the back and sides of the body, throat colour, belly colour and the amount of silver hair. The REML method was used to estimate genetic (co)variance components. Data were transformed using the probit transformation. Heritability estimates for coat traits were low (0.04 to 0.22). Values of most of the estimated genetic parameters (h2, rG, rP) were comparable to those frequently reported for other colour types of silver fox.


Cancer survivors. Work related issues.
New and more effective treatments for cancer have resulted in individuals living longer with a better quality of life. Many more survivors are employed in the workplace. Cancer is no longer only an issue for survivors and their families; it has become an issue for the employer and the workplace. This article describes survey results of 4,364 long term cancer survivors in which they were asked to respond to items describing their ability to work, job discrimination, and quality of life. Thirty-five percent of survivors were working at the time they completed the survey, and 8.5% considered themselves unable to work. This research has shown that age, gender, ethnic group, and cancer type affected the working status of the survivors. Of survivors continuing to work, 7.3% indicated they had experienced job discrimination. The results indicate most cancer survivors do not perceive employment related problems, and are readily assimilated into the work force. Job discrimination and the ability to work is a quality of life issue.


Syncope.
Syncope is common representing approximately 3% of ED visits and up to 6% of hospital admissions, with a cost close to 2 billion dollars per year. Diagnostic testing is often poorly sensitive and evaluations commonly lack a standardized approach. A mindful and systematic approach can increase sensitivity and improve diagnostic accuracy. A thorough history and physical exam is paramount, as conclusions drawn from the history and exam will guide further assessment. Developing a strategy for the first and, if necessary, subsequent tests will improve the accuracy of identifying the etiology of syncope and reduce cost. Although syncope has a favorable prognosis, identification of patients with structural heart disease is critical, as these patients are at greatest risk for mortality. Several risk scoring systems have been developed to help separate high risk from low risk patients.


Membrane potential defect in hygromycin B-resistant pma1 mutants of Saccharomyces cerevisiae.
The proton transport properties of hygromycin B-resistant pma1 mutants which show kinetic defects in the plasma membrane H+-ATPase were examined. It was found that net proton efflux, as measured by whole cell medium acidification in the presence of 25 mM KCl, was similar for normal and pma1 mutant cells. However, in the absence of added KCl, the extent of net proton efflux was considerably less in wild type than in pma1 mutant cells. The cellular membrane potential was implicated as an important factor in regulating net proton transport and was determined from [14C]tetraphenylphosphonium uptake studies to be considerably depolarized in the pma1 mutants. The growth of wild type cells, which is normally inhibited by hygromycin B at 200 micrograms/ml, was found to be resistant to the antibiotic by the addition of 50 mM KCl to the growth medium. These results suggest that the electrogenic behavior of proton transport by the H+-ATPase may be altered in pma1 mutants and that resistance to hygromycin B may be mediated via depolarization of the cellular membrane potential.


Effect of heme-apoprotein interactions on the activity of horseradish and wheat germ peroxidases.
The apoenzymes of horseradish and wheat germ peroxidases were reconstituted with synthetic hemins that differ from natural heme in the substitution pattern of side chains. Both enzymes show dual peroxidase and oxygenase activity, being the latter the oxidation of porphobilinogen in the presence of oxygen and a reducing agent. The oxygenase activity was almost unaffected in both enzymes reconstituted with synthetic hemes, while peroxidase activities were inhibited to different extents. According to the pattern of activity inhibition it was concluded that there is low flexibility of both apoproteins in the regions of the acid side chain contact which could be a general features of peroxidases.


Quantification of Gait Stability During Incline and Decline Walking: The Responses of Required Coefficient of Friction and Dynamic Postural Index.
This study aims to investigate the gait stability response during incline and decline walking for various surface inclination angles in terms of the required coefficient of friction (RCOF), postural stability index (PSI), and center of pressure (COP)-center of mass (COM) distance. A customized platform with different surface inclinations (0°, 5°, 7.5°, and 10°) was designed. Twenty-three male volunteers participated by walking on an inclined platform for each inclination. The process was then repeated for declined platform as well. Qualysis motion capture system was used to capture and collect the trajectories motion of ten reflective markers that attached to the subjects before being exported to a visual three-dimensional (3D) software and executed in Matlab to obtain the RCOF, PSI, as well as dynamic PSI (DPSI) and COP-COM distance parameters. According to the result for incline walking, during initial contact, the RCOF was not affected to inclination. However, it was affected during peak ground reaction force (GRF) starting at 7.5° towards 10° for both walking conditions. The most affected PSI was found at anterior-posterior PSI (APSI) even as low as 5° inclination during both incline and decline walking. On the other hand, DPSI was not affected during both walking conditions. Furthermore, COP-COM distance was most affected during decline walking in anterior-posterior direction. The findings of this research indicate that in order to decrease the risk of falling and manage the inclination demand, a suitable walking strategy and improved safety measures should be applied during slope walking, particularly for decline and anterior-posterior orientations. This study also provides additional understanding on the best incline walking technique for secure and practical incline locomotion.


Preservation of lymphokine-activated killer activity following T cell depletion of human bone marrow.
T cell depletion has decreased the incidence and severity of graft-versus-host disease following transplantation of allogeneic bone marrow. In the treatment of leukemia, decreased GVHD has often been associated with diminished antileukemia or graft-versus-leukemia (GVL) reactivity resulting in higher relapse rates. However, we have not seen a loss of the GVL effect following transplantation of marrow grafts depleted of CD3+ T cells. This suggests that non-T-cell effectors may play a role in preventing leukemic relapse. To study whether natural killer and lymphokine-activated killer (LAK) activity in BM was compromised by T cell depletion, the effect of T-cell-specific monoclonal antibodies against CD3 and CD6 determinants alone, or in combination, on the generation and expansion of NK/LAK cells was examined in vitro and compared to the effect of T depletion on mitogen-driven T cell proliferation. Limiting dilution analysis revealed that T depletion with CD3 and/or CD6 specific antibodies significantly reduced the number of proliferating T lymphocytes but did not significantly affect the frequency of cells able to expand and mediate LAK activity. Bone marrow, depleted of CD3+ or CD6+ T cells, generated levels of LAK activity equivalent to non-T-cell-depleted bone marrow following long-term culture in recombinant interleukin 2. CD3- NKH-1+ cells were the predominant population in rIL-2 expanded marrow cultures prior to transplant and in the peripheral blood of patients who had received a CD3-depleted marrow graft 21-65 days earlier. These studies show that it is possible to selectively reduce GVH-reactive T cells in allogeneic bone marrow while retaining non-T-effector cells with potential to mediate an antileukemia effect in vivo.


Theoretical study of the transfer integral and density of states in spiro-linked triphenylamine derivatives.
We present a method for calculating the parameters that control hopping transport in disordered molecular solids, i.e., the transfer integrals and the distribution of transport site energies. Average values of these parameters are obtained by performing quantum-chemical calculations on a large ensemble of bimolecular complexes in random relative orientations. The method is applied to triphenylamine (TPA) and three differently substituted spiro-linked phenylamine compounds, 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9'-spirobifluorene (spiro-MeOTAD), 2,2'7,7'-tetrakis-(N,N-diphenylhenylamino)-9,9'-spirobifluorene (spiro-TAD), and 2,2',7,7'-tetrakis-(N,N-di-m-methylphenylamino)-9,9'-spirobifluorene (spiro-m-TTB). In the case of TPA, the dependence of the root-mean-square hole transfer integral J on intermolecular separation r for the ensemble of relative orientations is compared with that obtained by performing the same calculations for a fixed, approximately cofacial, orientation of the two TPA molecules. The calculation for the disordered geometry predicts a larger localization radius r0, where J approximately exp(-r/r0), than the calculation for the fixed orientation and is in better agreement with experiment. In the case of the spiro-linked compounds, results from our method are compared with parameters extracted from time-of-flight mobility measurements analyzed with the Gaussian disorder model (GDM). We find that the highest occupied molecular-orbital (HOMO) energies of the bimolecular complexes are distributed on an asymmetric peak, whose width varies in qualitative agreement with the value of the energetic disorder sigma obtained from experimental data using the GDM. The mean-square hole transfer integral varies in accordance with the experimentally determined value of the mobility prefactor micro0. The differences between the differently substituted compounds are interpreted in terms of differences in the spatial extent of the wave function. Spiro-MeOTAD was found to have a greater localization radius, which leads to both a larger transfer integral and a broader distribution of HOMO energies than either of the other compounds. For these compounds, differences in energetic disorder could not be explained in terms of differences in the permanent dipole moment. Our method is proposed as an approximate means of predicting the effect of chemical structure on the values of transport parameters in disordered molecular films.


FACS-based isolation, propagation and characterization of mouse embryonic cardiomyocytes based on VCAM-1 surface marker expression.
Purification of cardiomyocytes from the embryonic mouse heart, embryonic stem (ES) or induced pluripotent stem cells (iPS) is a challenging task and will require specific isolation procedures. Lately the significance of surface markers for the isolation of cardiac cell populations with fluorescence activated cell sorting (FACS) has been acknowledged, and the hunt for cardiac specific markers has intensified. As cardiomyocytes have traditionally been characterized by their expression of specific transcription factors and structural proteins, and not by specific surface markers, this constitutes a significant bottleneck. Lately, Flk-1, c-kit and the cellular prion protein have been reported to specify cardiac progenitors, however, no surface markers have so far been reported to specify a committed cardiomyocyte. Herein show for the first time, that embryonic cardiomyocytes can be isolated with 98% purity, based on their expression of vascular cell adhesion molecule-1 (VCAM-1). The FACS-isolated cells express phenotypic markers for embryonic committed cardiomyocytes but not cardiac progenitors. An important aspect of FACS is to provide viable cells with retention of functionality. We show that VCAM-1 positive cardiomyocytes can be isolated with 95% viability suitable for in vitro culture, functional assays or expression analysis. In patch-clamp experiments we provide evidence of functionally intact cardiomyocytes of both atrial and ventricular subtypes. This work establishes that cardiomyocytes can be isolated with a high degree of purity and viability through FACS, based on specific surface marker expression as has been done in the hematopoietic field for decades. Our FACS protocol represents a significant advance in which purified populations of cardiomyocytes may be isolated and utilized for downstream applications, such as purification of ES-cell derived cardiomyocytes.


[A case of lymphocytic hypophysitis mimicking pituitary macroadenoma].
Lymphocytic hypophysitis is a rare autoimmune disease of the pituitary gland mimicking pituitary macroadenoma on magnetic resonance imaging (MRI). We encountered a 32-year-old female who presented with a typical pituitary macroadenoma causing sudden on-set of visual disturbance during her second pregnancy. She underwent an endonasal-transsphenoidal resection of the mass diagnosed as a non-secreting pituitary macroadenoma after a cesarean operation. Intraoperatively, the lesion was found to be extremely tough and mucinous, and apparently differed from pituitary adenoma. The frozen section revealed hypophysitis and we performed only a biopsy of the mass. Histopathological examination showed diffuse infiltrate of non-specific lymphocytes. Postoperatively, prednisolone was given for two weeks, her visual disturbance improved with radiologically marked shrinking of the lesion. This case illustrates the difficulty of differentiation of lymphocytic hypophysitis from pituitary macroadenoma, and we discuss the clinical features and the management of this disease.


Adjuvant anthracycline-based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi-institutional retrospective study of the Italian Society of Veterinary Oncology.
Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.


[Influence of amoxicillin combined with clavulanic acid on the fecal flora in children].
The effect of an amoxycillin-clavulanic acid combination on the intestinal bacterial ecosystem was studied by differential quantitative analysis of the fecal flora in 11 hospitalized pediatric patients aged 8 months to 4 years. The antibiotic combination was given orally to 7 patients and intravenously to 4. The modifications in the intestinal flora are more important with oral route than intravenous route. After treatment, an increase in ampicillin-resistant E. coli with overgrowth of Klebsiella were found. Our previous studies have shown that this microbial overgrowth carries a risk of secondary septicemia. A strain of amoxycillin-resistant Serratia marcescens emerged but did not pullulate . The other aerobic or anaerobic bacteria were not significantly modified. Most strains which emerged after therapy remained susceptible to the combination. Yeasts emerged in two patients. Thus, the amoxycillin-clavulanic acid combination results in intestinal Klebsiella overgrowth, requiring monitoring of the intestinal bacterial ecosystem.


Revealing pelvic structures in the presence of metal hip prothesis via non-circular CBCT orbits.
As the expansion of Cone Beam CT (CBCT) to new interventional procedures continues, the burdensome challenge of metal artifacts remains. Photon starvation and beam hardening from metallic implants and surgical tools in the field of view can result in the anatomy of interest being partially or fully obscured by imaging artifacts. Leveraging the flexibility of modern robotic CBCT imaging systems, implementing non-circular orbits designed for reducing metal artifacts by ensuring data-completeness during acquisition has become a reality. Here, we investigate using non-circular orbits to reduce metal artifacts arising from metallic hip prostheses when imaging pelvic anatomy. As a first proof-of-concept, we implement a sinusoidal and a double-circle-arc orbit on a CBCT test bench, imaging a physical pelvis phantom, with two metal hip prostheses, housing a 3D-printed iodine-filled radial line-pair target. A standard circular orbit implemented with the CBCT test bench acted as comparator. Imaging data collection and processing, geometric calibration and image reconstruction was completed using in-house developed software programs. Imaging with the standard circular orbit, image artifacts were observed in the pelvic bones and only 33 out of the possible 45 line-pairs of the radial line-pair target were partially resolvable in the reconstructed images. Comparatively, imaging with both the sinusoid and double-circle-arc orbits reduced artifacts in the surrounding anatomy and enabled all 45 line-pairs to be visibly resolved in the reconstructed images. These results indicate the potential of non-circular orbits to assist in revealing previously obstructed structures in the pelvic region in the presence of metal hip prosthesis.


Effect of process-induced common bean hardness on structural properties of in vivo generated boluses and consequences for in vitro starch digestion kinetics.
In the present study, we evaluated the effect of process-induced common bean hardness on structural properties of in vivo generated boluses and the consequences for in vitro starch digestion. Initially, the impact of human mastication on the particle size distribution (PSD) of oral boluses from common beans with different process-induced hardness levels was investigated through a mastication study. Then the effect of structural properties of selected boluses on in vitro starch digestion kinetics was assessed. For a particular process-induced hardness level, oral boluses had similar PSD despite differences in masticatory parameters between participants of the mastication study. At different hardness levels, a clear effect of processing (P<0·0001) was observed. However, the effect of mastication behaviour (P=0·1141) was not significant. Two distinctive fractions were present in all boluses. The first one was a cotyledon-rich fraction consisting of majorly small particles (40-125 µm), which could be described as individual cells based on microscopic observations. This fraction increased with a decrease in process-induced hardness. The second fraction (>2000 µm) mostly contained seed coat material and did not change based on hardness levels. The in vitro starch digestion kinetics of common bean boluses was only affected by process-induced hardness. After kinetic modelling, significant differences were observed between the reaction rate constant of boluses generated from the hardest beans and those obtained from softer ones. Overall this work demonstrated that the in vitro nutritional functionality of common beans is affected to a greater extent by structural properties induced by processing than by mechanical degradation in the mouth.


Arrested chloride abstraction from trans-RuCl2(DMeOPrPE)2 with TlPF6; formation of a 1-D coordination polymer having unusual octahedral coordination around thallium(I).
An "arrested" chloride abstraction occurs in the reaction of trans-RuCl(2)(DMeOPrPE)(2) with TlPF(6); the product is a 1-D coordination polymer in which the Tl(I) centers have an unusual octahedral coordination geometry with a stereochemically active 6s(2) lone pair.


Parent Involvement in School Conceptualizing Multiple Dimensions and Their Relations with Family and Demographic Risk Factors.
Parent involvement (PI) in school is associated with more positive academic performance and social competence in children. However, there are inadequacies in current measures of PI and a need for a better understanding of predictors of PI. In this study, measures were obtained from a normative sample of 387 children in kindergarten and first grade from high-risk neighborhoods in 4 different sites. First, a confirmatory factor analysis of a theoretical factor model of PI identified 6 reliable multiple-reporter PI factors: Parent-Teacher Contact, Parent Involvement at School, Quality of Parent-Teacher Relationship, Teacher's Perception of the Parent, Parent Involvement at Home, and Parent Endorsement of School. Next, the relations among 3 specific family and demographic risk factors-parental education level, maternal depression, and single-parent status-and these 6 PI factors were examined using path analyses in structural equation modeling. Results indicated that the 3 risk factors were differentially associated with the 6 PI factors: Parental education was significantly associated with 4 PI outcomes, maternal depression was significantly associated with 5 PI outcomes, and single-parent status was significantly associated with 3 PI outcomes. No significant ethnic group differences between African American and Caucasian families were found in these relations.


Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells.
Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.


SEXUAL SELECTION, SPACE, AND SPECIATION.
A Fisherian model of sexual selection is combined with a diffusion model of mate dispersal to investigate the evolution of assortative mating in a sympatric population. Females mate with one of two types of polygynous males according to a male's display of one of two sex-limited, autosomal traits; these male traits may be associated with differential phenotypic mortalities. Through a Fisherian runaway process, female preferences and male traits can become associated in linkage disequilibrium, leading to patterns of assortative mating. Dispersing males, whose rate of movement is dependent on mating success, carry female preference genes with them, and displaced males thereby produce daughters with preference genes for their respective traits in locally higher than average frequencies. The reduced diffusion of the more preferred males permits the success of other male types in adjacent areas. Thus, mating-success dependent diffusion, when coupled with the rapid divergence in phenotypes possible under the Fisher process, can lead to the coexistence of two female preferences and two male traits in sympatry. We argue that many existing approaches to sympatric speciation fail to explain observed male polymorphisms because they exclude explicit spatial structure from their speciation models.


Anticonvulsant-induced rickets and nephrocalcinosis.
Reported here is the case of a severely disabled young girl who developed Fanconi syndrome secondary to long-term valproic acid administration, ultimately leading to hypophosphatemic rickets. Although nephrocalcinosis is not a common feature in patients with proximal tubulopathy, the patient presented also with this condition, and the concomitant use of another anticonvulsant might have potentiated this condition. The purpose of this report is to increase awareness among healthcare providers of such rare but significant complications associated with anticonvulsants.


Performing Intracochlear Electrocochleography During Cochlear Implantation.
Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the residual function of the cochlea. In cochlear implant candidates with residual hearing, the implant electrode can directly measure ECochG responses during the implantation process. Various authors have described the ability to monitor the inner ear function by continuous ECochG measurements during the surgery. The measurement of ECochG signals during surgery is not trivial. There are no interpretable signals in up to 20% of cases. For a successful recording, a standardized procedure is recommended to achieve the highest measurement reliability and avoid possible pitfalls. Therefore, seamless collaboration between the CI surgeon and CI technician is key. This video consists of an overview of the system setup and a stepwise procedure of performing intracochlear ECochG measurements during CI surgery. It shows the surgeon's and the CI technician's roles in the process, and how a smooth collaboration between the two is made possible.


Performance and interpretation of spirometry among Swedish hospitals.
It is unclear to what extent spirometric performance and interpretation is standardized in Sweden. The aim of this study was to find out how spirometry is performed and interpreted in large Swedish hospitals. In telephone interviews, technicians and physicians working with lung function measurements at 21 large Swedish hospitals were interviewed about routines for spirometry. Answers were obtained from 37 of the 42 departments contacted revealing differences in the spirometric routines. Some departments lack a written method description, and three different prediction equations were used among the departments. Different ways of calculating the forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ratio (FEV%) were found and also differences in performance and interpretation of the reversibility test. When diagnosing chronic obstructive pulmonary disease, none of the departments reported using an individualized diagnostic limit of FEV1/VC based on age, sex and height. There is a need for standardization of performance and interpretation of the spirometry test in Sweden and probably also in other countries.


Skewing of the T-cell receptor repertoire in patients receiving rituximab after allogeneic hematopoietic cell transplantation: what lies beneath?
Rituximab is known to affect T cell immune responses. We and others have reported expansions of T large granular lymphocytes (T-LGLs) in lymphoma patients after Rituximab. We report here the immunogenetic profiling of the T cell receptor (TR) gene repertoire in 14 patients who received Rituximab post allo-HCT and explore clinicobiological correlations. All experienced antigenic triggers, CMV, EBV re-activation and chronic GvHD and had been treated with Rituximab. Skewing of TRBV genes was observed: 3 TRBV genes accounted for half of the repertoire. Oligoclonal pattern with expanded clonotypes was common. Patients with oligoclonality exhibited frequently cGvHD. Longitudinal samples in one revealed distinct clonotypes, suggesting clonal drift. T-LGL leukemia of donor origin with mixed chimerism eventually developed. In conclusion, we report development of oligoclonal T-LGLs after Rituximab post allo-HCT, alluding to antigen selection. Persistence of this phenomenon likely reflects strong antigenic stimulation by viruses and/or cGVHD aggravated by Rituximab.


Quantification of enantiomers by mass spectrometry based on chemical derivatization and spectral shape deformation quantitative theory.
A facile mass spectrometric kinetic method for quantitative analysis of chiral compounds was developed by integrating mass spectrometry based on chemical derivatization and the spectral shape deformation quantitative theory. Chemical derivatization was employed to introduce diastereomeric environments to the chiral compounds of interest, resulting in different abundance distribution patterns of fragment ions of the derivatization products of enantiomers in mass spectrometry. The quantitative information of the chiral compounds of interest was extracted from complex mass spectral data by an advanced calibration model derived based on the spectral shape deformation quantitative theory. The performance of the proposed method was tested on the quantitative analysis of R-propranolol in propranolol tablets. Experimental results demonstrated that it could achieve accurate and precise concentration ratio predictions for R-propranolol with an average relative predictive error (ARPE) of about 4%, considerably better than the corresponding results of the mass spectrometric method based on chemical derivatization and the univariate ratiometric model (ARPE: about 12%). The limit of detection (LOD) and limit of quantification (LOQ) of the proposed method for the concentration ratio of R-propranolol were estimated to be 1.5% and 6.0%, respectively. The proposed method is complementary to the existing methods designed for the quantification of enantiomers such as the Cooks kinetic method.


Grain boundary sliding in aluminum nano-bi-crystals deformed at room temperature.
Room-temperature uniaxial compressions of 900-nm-diameter aluminum bi-crystals, each containing a high-angle grain boundary with a plane normal inclined at 24° to the loading direction, revealed frictional sliding along the boundary plane to be the dominant deformation mechanism. The top crystallite sheared off as a single unit in the course of compression instead of crystallographic slip and extensive dislocation activity, as would be expected. Compressive stress strain data of deforming nano bicrystals was continuous, in contrast to single crystalline nano structures that show a stochastic stress strain signature, and displayed a peak in stress at the elastic limit of ~ 176 MPa followed by gradual softening and a plateau centered around ~ 125 MPa. An energetics-based physical model, which may explain observed room-temperature grain boundary sliding, in presented, and observations are discussed within the framework of crystalline nano-plasticity and defect microstructure evolution.


Advancement of the cleft maxilla using distraction osteogenesis--surgical and orthodontic considerations.
The distraction osteogenesis principle that was originally developed by orthopedists for purposes of limb lengthening can now be used successfully for bones of the craniofacial region, including cleft palate deformities. Advancement of the cleft maxilla by means of distraction is based on the concept of using stretching forces to separate two bony elements at the midface region. The role of orthodontists in skeletal treatment of the maxilla utilizing distraction osteogenesis should be collaborative and adjunctive as part of a team approach to rehabilitate the patient. Advances over traditional techniques are mainly because of simultaneous adaptation of the surrounding soft-tissue envelope which contributes to the stability of the reconstruction, thus lessening the risk of relapse.


2JHH-resolved HSQC: Exclusive determination of geminal proton-proton coupling constants.
The measurement of two-bond proton-proton coupling constants (2JHH) in prochiral CH2 groups from the F2 dimension of 2D spectra is not easy due to the usual presence of complex multiplet J patterns, line broadening effects and strong coupling artifacts. These drawbacks are particularly pronounced and frequent in AB spin systems, as those normally exhibited by the pair of diastereotopic CH2 protons. Here, a novel 2JHH-resolved HSQC experiment for the exclusive and accurate determination of the magnitude of 2JHH from the doublet displayed along the highly-resolved indirect F1 dimension is described. A pragmatic 2JHH NMR profile affords a fast overview of the full range of existing 2JHH values. In addition, a 2JHH/δ(13C)-scaled version proves to be an efficient solution when severe signal overlapping complicate a rigorous analysis. The performance of the method is compared with other current techniques and illustrated by the determination of challenging residual dipolar 2DHH coupling constants of small molecules dissolved in weakly orienting media.


Role of cell interactions in ascidian muscle and pigment cell specification.
Muscle and brain pigment cell specification was studied by disrupting cell adhesion, cell dissociation, and reaggregation in embryos of the ascidianStyela clava. Treatment of embryos with Ca2+-free sea water between the 2-cell and gastrula stages disrupted blastomere adhesion but did not prevent acetylcholinesterase or muscle actin expression in presumptive muscle cells. Similar treatments initiated between the 2- and 32-cell stages caused more ectoderm cells to express tyrosinase and develop pigment granules than expected from the cell lineage. Whereas 2 pigment cells become the otolith and ocellus sensory organs in normal embryos, up to 33 pigment cells could differentiate in embryos after disruption of cell adhesion. Replacement of Ca2+-free sea water with normal sea water restored cell adhesion and usually resulted in development of embryos containing the conventional number of pigment cells. Dissociation of embryos into single cells between the 2- and 64-cell stages and culture of these cells beyond the fate restricted stage had no effect on the accumulation of muscle actin mRNA and muscle actin synthesis, but blocked pigment cell differentiation. Reaggregation of the dissociated cells did not enhance the number of cells that developed muscle features, but rescued pigment cell development. The results indicate that ascidian muscle cell specification occurs by an autonomous mechanism, whereas pigment cell specification occurs by a conditional mechanism involving cell interactions. In addition, the results suggest that negative cell interactions may restrict the potential for pigment cell development in the ectoderm of cleaving ascidian embryos.


Health Literacy and Demographic Disparities in HIV Care Continuum Outcomes.
Studies evaluating the association between human immunodeficiency virus (HIV) infection continuum of care outcomes [antiretroviral (ART) adherence, retention in care, viral suppression] and health literacy have yielded conflicting results. Moreover, studies from the southern United States, a region of the country disproportionately affected by the HIV epidemic and low health literacy, are lacking. We conducted an observational cohort study among 575 people living with HIV (PLWH) at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee). Health literacy was measured using the brief health literacy screen, a short tool which can be administered verbally by trained clinical personnel. Low health literacy was associated with a lack of viral suppression, but not with poor ART adherence or poor retention. Age and racial disparities in continuum of care outcomes persisted after accounting for health literacy, suggesting that factors in addition to health literacy must be addressed in order to improve outcomes for PLWH.


Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome.
18p deletion syndrome is a rare chromosomal disease caused by deletion of the short arm of chromosome 18. By using cytogenetic and SNP array analysis, we identified a girl with 18p deletion syndrome exhibiting craniofacial anomalies, intellectual disability, and short stature. G-banding analysis of metaphase cells revealed an abnormal karyotype 46,XX,del(18)(p10). Further, SNP array detected a 15.3-Mb deletion at 18p11.21p11.32 (chr18:12842-15375878) including 61 OMIM genes. Genotype-phenotype correlation analysis showed that clinical manifestations of the patient were correlated with LAMA1, TWSG1, and GNAL deletions. Her neuropsychological assessment test demonstrated delay in most cognitive functions including impaired mathematics, linguistic skills, visual motor perception, respond speed, and executive function. Meanwhile, her integrated visual and auditory continuous performance test (IVA-CPT) indicated a severe comprehensive attention deficit. At age 7 and 1/12 years, her height was 110.8 cm (-2.5 SD height for age). Growth hormone (GH) treatment was initiated. After 27 months treatment, her height was increased to 129.6 cm (-1.0 SD height for age) at 9 and 4/12 years, indicating an effective response to GH treatment.


DoGSD: the dog and wolf genome SNP database.
The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼ 19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.


Effect of experimental feed additives on aflatoxin in milk of dairy cows fed aflatoxin-contaminated diets.
Three studies were conducted to determine the potential of experimental feed additives (EFAs), clays or non-digestible yeast oligosaccharides, to reduce milk aflatoxin (AFM1) concentrations in lactating Holstein cows consuming aflatoxin-contaminated diets. All studies included a pre-treatment period and a 2-week experimental period in a randomized block design. During the pre-treatment period, cows received a total mixed ration (TMR) with no aflatoxin contamination. During both experimental weeks, all cows were fed a TMR containing aflatoxin-contaminated corn. During experimental week 1, cows received no EFA's in the TMR, but EFA's were included in the TMR for the second experimental week. In studies 1 and 2, the experimental period consisted of 2 weeks each lasting 7 days with 12 cows per treatment. Aflatoxin M1 concentrations were analysed by HPLC for milk samples collected on days 5-7 and days 11-14. In various experiments, treatments included control (no EFA), 100 g/cow daily of experimental Lallemand(®) product, 10 g/cow daily of MTB-100(®) -2004, (Alltech, Inc.), 10 g/cow daily of MTB-100(®) -2006, (Alltech, Inc.), 10 g/cow daily of experimental Alltech(®) product (Alltech, Inc.) and 227 g/cow daily of Astra-Ben 20(®) (AB-20(®) ; Prince Agri Products, Inc.). In study 3, the experimental period of 2 weeks each lasting 8 days and milk samples were collected from day 4 to 8 and day 11 to 16. Milk samples from study 3 were analysed for AFM1 concentrations by ELISA. For all experiments, changes in AFM1 concentrations because of the addition of EFA's were calculated. Four of the five EFAs tested in this study had no significant effect on AFM1 concentrations. However, the addition of AB-20(®) resulted in a significant decrease in AFM1 concentrations (60.4%). In summary, the addition of AB-20(®) to the diet of cattle appears to be effective for significantly reducing AFM1 concentrations in the milk of cows fed an aflatoxin-contaminated diet.


Age-related Changes in Motor Function (I). Mechanical and Neuromuscular Factors.
This two-part narrative review aims to provide an insight into the age-related mechanical and neuromuscular factors contributing to: (1) decreased maximal muscle strength and power; (2) decreased force control; and (3) increased fatigability. Structural and functional changes from the macro-level of the muscle-tendon unit to the micro-level of the single muscle fibre have been reviewed and are described. At the muscle-tendon unit level, muscle volume, thickness and cross-sectional area, as well as pennation angle and fascicle length all decrease as part of the natural ageing process. These changes negatively affect muscle quality, muscle and tendon stiffness and Young's modulus and account for impairment in motor performance. A progressive age-related alteration in neuromuscular function is also well-established, with reduction in number and firing rate of the motor unit, contractile velocity and specific tension of muscle fibres, and stability of neuromuscular junction. These could be the result of structural alterations in the: (i) motor neuron, with number reduced, size and collateral sprouting increased; (ii) neuromuscular junction, with decreased post-synaptic junctional fold and density of active zones and increased pre-synaptic branching and post-synaptic area; and (iii) muscle fibre, with decreased number and size and increased type I and co-expression of myosin heavy chain.


Bilateral widefield calcium imaging reveals circuit asymmetries and lateralized functional activation of the mouse auditory cortex.
Coordinated functioning of the two cortical hemispheres is crucial for perception. The human auditory cortex (ACx) shows functional lateralization with the left hemisphere specialized for processing speech, whereas the right analyzes spectral content. In mice, virgin females demonstrate a left-hemisphere response bias to pup vocalizations that strengthens with motherhood. However, how this lateralized function is established is unclear. We developed a widefield imaging microscope to simultaneously image both hemispheres of mice to bilaterally monitor functional responses. We found that global ACx topography is symmetrical and stereotyped. In both male and virgin female mice, the secondary auditory cortex (A2) in the left hemisphere shows larger responses than right to high-frequency tones and adult vocalizations; however, only virgin female mice show a left-hemisphere bias in A2 in response to adult pain calls. These results indicate hemispheric bias with both sex-independent and -dependent aspects. Analyzing cross-hemispheric functional correlations showed that asymmetries exist in the strength of correlations between DM-AAF and A2-AAF, while other ACx areas showed smaller differences. We found that A2 showed lower cross-hemisphere correlation than other cortical areas, consistent with the lateralized functional activation of A2. Cross-hemispheric activity correlations are lower in deaf, otoferlin knockout (OTOF-/-) mice, indicating that the development of functional cross-hemispheric connections is experience dependent. Together, our results reveal that ACx is topographically symmetric at the macroscopic scale but that higher-order A2 shows sex-dependent and independent lateralized responses due to asymmetric intercortical functional connections. Moreover, our results suggest that sensory experience is required to establish functional cross-hemispheric connectivity.


[The role of amygdala in the inhibitory effect of somatic afferent inputs on the central pressor response].
To investigate the inhibitory effect of the deep peroneal nerve (DPN) on the cardiovascular responses induced by excitation of the paraventricular nucleus of hypothalamus (PVN) and the role of central nucleus of amygdala (CeA) in this effect. CeA was injected by L-glutamate or Kainic acid (KA). The femoral arterial pressure, mean arterial pressure (MAP), electrocardiogram (ECG) and heart rate (HR) of SD rats were recorded while PVN or DPN was electrically stimulated. It showed that MAP increased when PVN was activated by electrical stimulation. Stimulating contralateral DPN inhibited this pressor response. Ten minutes after microinjection of KA(0.02 mol/L, 100 nl) into ipsilateral CeA, MAP increased for (13.8 +/- 3.2) mmHg when PVN was stimulated. Microinjection of KA into CeA could not only reduce the pressor response elicited by stimulation of PVN for (6.6 +/- 1.6) mmHg (P < 0.05), but also the inhibitory effect of DPN from 51.5% to 32.0% . The results suggest that central nucleus of amygdala partly mediate the central pressor response induced by stimulation of PVN. The neurons in central nucleus of amygdala are involved in the inhibitory effect of DPN on the above pressor response.


Significance of CD10 protein expression in the diagnostics of follicular lymphoma: A comparison of conventional immunohistochemistry with flow cytometry supported by the establishment of BCL2 and BCL6 rearrangements.
Histopathological examination and immunohistochemistry (IHC) with a crucial role of CD10 expression remain a standard diagnostic tool in follicular lymphoma (FL). The results of IHC CD10 detection with different primary antibodies are not fully reproducible, but some reports show that flow cytometry (FCM) can be a reliable method of CD10 identification. The aim of the study was to compare results of CD10 expression in FL by IHC and FCM including immunophenotypic features in the context of the BCL2 and BCL6 alterations. Out of 76 histopathologically diagnosed FL, a group of 25 cases had simultaneously FCM. Immunohistochemically 77.6% of cases were CD10-positive with comparable and reproducible results to FCM. Differences between the FCM expression of CD5/CD10/CD11c/CD25/CD43 and BCL2 overexpression (BCL2(+)higher ) correlated with the BCL2 and BCL6 rearrangements (R) status. Lack of CD10 expression corresponded with the absence of BCL2R and higher MUM1 expression by IHC results but had no clinical impact on the long-time outcomes. Immunohistochemistry staining is a comparable method to FCM assessment in the evaluation of CD10 expression and diagnosis of FL. Fine-needle aspiration biopsy/FCM (FNAB/FCM) could be a useful tool for verifying FL diagnosis and CD10 detection. Despite its heterogeneity, FL has a characteristic immunophenotype. BCL2R and BCL6R FL cases differ mainly in levels of BCL2 and CD10 with CD43 co-expression; BCL2(+)higher by FCM correlates with BCL2R. Moreover, FNAB plays an important role in material provision for supportive karyotyping and BCL2R, BCL6R assessed by FISH.


Nutrition, vitamin D, and health outcomes in hemodialysis: time for a feeding frenzy?
The role of nutrition and nutritional supplementation in dialysis recently has been reinvigorated, with small clinical trials exploring surrogate outcomes and larger epidemiologic studies generating treatment hypotheses requiring further study. The present review focuses on major aspects of nutrition and outcomes in hemodialysis patients: protein and calorie intake and nutritional vitamin D supplementation. Building on data from small studies, two large, quasi-experimental cohort studies showed significant mortality benefits associated with oral nutritional supplements provided during dialysis, suggesting potential options for ameliorating the protein-energy wasting that is common in dialysis patients and associated with poor outcomes. Multiple cohort studies suggest, both in the general population and in dialysis, that higher 25(OH) vitamin D levels are associated with improved outcomes; however, no major mortality trials exist in dialysis, and the smaller, surrogate studies conducted to date have been disappointing, showing no consistent benefits in surrogate outcomes including inflammation and anemia, despite appropriate responses of vitamin D levels to repletion. Nutritional interventions are attractive options for improving outcomes in dialysis patients. Nutritional protein supplements have considerable promise, but require further study, preferably in a large, generalizable pragmatic trial. Small nutritional vitamin D supplementation trials in dialysis have had disappointing results. In the absence of new data, there appears to be no role for routine assessment or repletion of 25(OH) vitamin D deficiency or insufficiency in dialysis.


Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters.
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.


Increased beta-endorphin and dynorphin concentrations in discrete hypothalamic regions of genetically obese (ob/ob) mice.
Disturbances in hypothalamic beta-endorphin and dynorphin levels were investigated in non-fasted genetically obese (ob/ob) and homozygous lean mice at 14-15 weeks of age. Eight brain regions were microdissected from fresh, unfixed brain slices, and opioid peptide concentrations were determined in tissue micropunches by radioimmunoassay. A two-fold and five-fold increase in beta-endorphin levels in ob/ob versus lean mice were found in the ventromedial and dorsomedial hypothalamic nuclei respectively. Dynorphin levels were comparable between ob/ob and lean mice in the anterior, lateral, ventromedial and paraventricular hypothalamic areas, but a 5-fold increase in dynorphin concentrations was detected in the dorsomedial hypothalamic nucleus of the ob/ob mouse. These results demonstrate that increased concentrations of beta-endorphin and dynorphin occur in discrete hypothalamic nuclei, which are known to influence food intake and glucose homeostasis. This could signify an important central defect contributing to hyperphagia and glucoregulatory dysfunction in obese mice.


[Priorities in anaesthesiology].
On the basis of an analysis of published data, the authors draw the attention of medical circles to generally- and little-known facts of using a variety of general and local anesthesia types by Russian doctors. It is pointed out that not the very first application based on a calendar date of using a method but the first contribution made into the medical science and supported by efforts promoting such method should be regarded as genuine priority. Prominent medical figures are listed, i.e. N.I. Pirogov, S.K. Klikovich, N.P. Kravkov, S.P. Fyodorov, V.K. Anrep, I.N. Katsaurov, A.V. Vishnevsky, whose priority in certain anesthesia variations, as the authors believe it, is indisputable.


[Movement, play and sports in the treatment of drug addicts].
In 1992 a campaign was initiated to bring to attention new ways for drug prevention in adolescents for health promotion in addicts and for therapy and follow-up of ex-addicts. By this broad base the Swiss Health Authority and the Federal Sports Institute at Magglingen together with partners from Swiss sport and addiction-care organizations try to contribute to a reduction of drug-related problems in Switzerland. The following article bases mainly on experiences with long-term therapy of the 'Drogenhilfe Aebihus' in Leubringen.


Examining suicide assessment measures for research use: Using item response theory to optimize psychometric assessment for research on suicidal ideation in major depressive disorder.
Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need. We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome. All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation. The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores.


[Antithrombotic therapy after iliac vein stenting].
Stenting for iliac vein stenosis or compression has become a common therapeutic approach in recent years. The antithrombotic therapy after the stent deployment, however, reaches no consensus. Medications strategies and patients' prognoses differ in non-thrombotic, acute thrombotic and chronic thrombotic these three circumstances. Non-thrombotic patients usually possess satisfactory stent patency whatever antithrombotic therapy is used. Anticoagulant is the basic medication for acute thrombotic patients, benefits from additional antiplatelet drug remains to be clarified. In terms of chronic thrombotic patients, their prognoses are unsatisfactory under all antithrombotic therapies. In this review, we outlined the recent progress of antithrombotic therapy after iliac vein stenting, aiming to provide feasible medication plans for each circumstance.


Increased bone strength in coop-reared broilers provided flouridated water.
Four experiments were conducted to determine the feasibility of using fluoride to mitigate bone fragility (osteoporosis) that develops in cage-reared broilers. The treatments consisted of adding sodium fluoride to the drinking water at the levels of 100, 150, 200, and 200 p.p.m. of fluoride in the four experiments, respectively. Birds were transferred from starting batteries at four weeks of age into six coops. Birds in three coops served as controls; birds in the other three coops were provided the fluoridated water ad libitum from four to eight weeks of age. No significant differences were observed in the final body weights between treated and control birds in the four experiments. The percentage of bone ash was usually greater from the treated birds than from the controls. These differences were significant (P less than or equal to 0.01) in the 150 and 200 p.p.m. treatments. At all levels of fluoridation, the strengths of humeri were significantly (P less than or equal to 0.01) increased. However, at the lowest level of fluoridation, 100 p.p.m., the increase was significant only in the females. Tibia strength was significantly (P less than 0.01) increased only at the 200 p.p.m. level. The increase in bone strength from fluoridation may be sufficiently great enough to result in a decrease in the incidence of bone breakage during the processing of coop-reared boilers.


[(C5H5)Co(P(O)(OH)2)3H]: a novel organometallic tris-phosphonic acid that dissolves glass to form a six-coordinate silicon complex.
The sodium salt of the tripodal oxygen ligand Na[(C5H5)Co(P(O)(OMe)2)3] (1) reacts with gaseous hydrogen chloride in dichloromethane to give sodium chloride and [(C5H5)Co(P(O)(OMe)2)3H2]Cl (2). Addition of an equimolar amount of 1 leads to precipitation of sodium chloride again to yield the acid form of the ligand [(C5H5)Co(P(O)(OMe)2)3H] (3). Its solid-state structure contains a very short intramolecular OH.O hydrogen bond. The compound hydrolyses in boiling water to give methanol and the title complex [(C5H5)Co(P(O)(OH)2)3H] (4). This complex is a rather strong tris-phosphonic acid (pK(a1) 2.0, pK(a2) 4.0, pK(a3) 6.3, and pK(a4) 9.6). Attempts to grow single crystals of this highly water-soluble yellow crystalline compound lead to the silicon complex [((C5H5)Co[P(O)(OH)2]2[P(O)2(OH)])(2)Si].8 H2O (5). The crystal structure determination shows that it is a molecular complex of two tris-phosphonic acids that each act as a tris-chelating ligand. Additional water molecules form a complex net of hydrogen bonds between the complexes of 5. The SiO6 octahedron is only insignificantly distorted with Si-O bond lengths of 1.78 A. Complex 4 reacts with stoichiometric amounts of potassium carbonate to yield the potassium salt K[(C5H5)Co(P(O)(OH)2)3] (6). The crystal structure of 6 has also been determined. In the solid state it is a two-dimensional coordination polymer with each potassium ion being coordinated by twelve oxygen atoms of six tris-phosphonic acids.


[Degradation of endocrine disrupting chemicals(EDCs)-BP by combination of UV/ micro-aeration process and impact factors].
The removal performances of EDCs 4-tert-butylphenol (BP) in water using a new process UV/micro-aeration was introduced. The results show that UV/micro-aeration process is also an advanced oxidation and BP can be effectively degraded by UV/micro-aeration process; the degradation of BP by UV/micro-aeration process is greatly influenced by TOC value, BP initial concentrations, intensity of UV radiation, and initial pH of solution. The k1 value of BP degradation increases with TOC values decreasing,or with intensity of UV radiation increasing. The effect of different BP initial concentrations on removal of BP has also been investigated. The k1 value of BP degradation increases with increasing BP initial concentrations in the range of 189 - 410 microg/L, while decreases with increasing initial BP concentrations in the range of 410 - 971 microg/L. The degradation of BP has been investigated under UV/micro-aeration over a wide pH range (2.77 - 8.16), and BP degradation rate in UV/micro-aeration process was significantly enhanced by the initial pH in the range of 2.77 - 4.01, while decreases in the pH range of 4.70 - 8.16.


A note on estimating the posterior density of a quantitative trait locus from a Markov chain Monte Carlo sample.
We provide an overview of the use of kernel smoothing to summarize the quantitative trait locus posterior distribution from a Markov chain Monte Carlo sample. More traditional distributional summary statistics based on the histogram depend both on the bin width and on the sideway shift of the bin grid used. These factors influence both the overall mapping accuracy and the estimated location of the mode of the distribution. Replacing the histogram by kernel smoothing helps to alleviate these problems. Using simulated data, we performed numerical comparisons between the two approaches. The results clearly illustrate the superiority of the kernel method. The kernel approach is particularly efficient when one needs to point out the best putative quantitative trait locus position on the marker map. In such situations, the smoothness of the posterior estimate is especially important because rough posterior estimates easily produce biased mode estimates. Different kernel implementations are available from Rolf Nevanlinna Institute's web page (http://www.rni.helsinki.fi/;fjh).


An unusual case of abdominal pain.
Renal calyceal rupture is a usual etiology of abdominal pain in the emergency department. We present a case of unexpected renal calyx rupture in a patient with symptomatology of renal colic. A discussion and review are provided.


Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg.
Chronic venous insufficiency (CVI) of the lower limbs is a complex and fluctuating disease by its pathogenic mechanisms and its clinical symptoms. Although symptoms are subjective, they affect the quality of life and socio-professional activity of many patients. This is why convincing demonstration of therapeutic activity of a venotropic drug should be carried out according to strict methodology. Only randomized double-blind controlled trials versus placebo (no reference drugs being available) could demonstrate the activity on condition that they are set up in a protocol, the statistical design of which, is adapted and defined "a priori". Inclusion, non inclusion and judgement criteria must be rigorous, taking into account many exogenous and endogenous factors which could have influence on the severity or the change in CVI and on the comparability of groups at the beginning and at the end of the study. Thus, the main risk factors of CVI (heredity, obesity, obstetrical and gynecological history, estroprogestogen treatment, profession, environment, etc.) and the season when the patient is recruited should be taken into account. With respect to all these restraints on methodology, the venotrotopic activity of a flavonoid Daflon 500 mg (2 tablets daily) was demonstrated in 200 patients (174 women, 26 men) with organic CVI (n = 83) or functional CVI (n = 117) treated for two months in two double-blind randomized trials versus placebo. The venotropic activity of Daflon 500 mg, was shown by a significant reduction of CVI signs and symptoms, whether organic or functional, and a significant improvement in venous hemodynamics according to plethysmographic parameters. Good acceptability was observed after medium and long term trials.


Recurrent varicoceles: causes and treatment using angiography and magnification assisted subinguinal varicocelectomy.
To investigate the causes of varicocele recurrence and assess the use of embolization and subinguinal varicocelectomy in its treatment in patients with angiography and subinguinal varicocelectomy. The present study involved 15 patients with recurrent varicoceles. The mean patient age was 21.2 years (range: 12-42 years). Preoperative angiography was performed in 11 patients. Embolization was used in patients with patent internal spermatic veins (ISVs). Patients without patent ISVs or preoperative angiography underwent magnification-assisted subinguinal varicocelectomy which included testicular retrieval and ligation of all collateral veins except arteries and deferential veins. Seven among 11 patients (64%) which had preoperative angiography had patent ISVs and underwent embolization and 8 patients underwent subinguinal varicocelectomy. Of those 8 patients, 6 had dilated ISVs and external spermatic veins (ESVs), one had dilated ISVs and gubernacular veins, and one had dilated ISVs, ESVs and gubernacular veins. No patient experienced recurrence or testis atrophy. Patent ISVs or collateral veins may be the cause of recurrence after varicocelectomy. Angiographic embolization was successful in 64% of recurrent varicoceles patients with patent ISVs. However, microscope-assisted subinguinal varicocelectomy may be the best overall treatment for patients with recurrent varicoceles.


Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death.
Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2'-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.


Mining and environmental change in Sierra Leone, West Africa: a remote sensing and hydrogeomorphological study.
This paper evaluates the environmental changes in southwestern Sierra Leone, West Africa from rutile (titanium dioxide) between 1967 and 1995. Mining in peripheral parts of the world economy is a consequence of larger global economic interests. Historically, long-distance trade and export production of minerals and other natural resources primarily for the benefit of core countries are responsible for transforming the natural environment and landscapes of peripheral sectors of the world economy. Tracking environmental change in developing countries such as Sierra Leone is challenging because of financial and infrastructural constraints on the use of ground methods of evaluation and monitoring. Remote sensing data are invaluable in assessing the human dimensions of Land Use and Land Cover Change (LULCC) with implications for political ecology. Using available multi-date infrared Landsat images supplemented with field hydrological and biophysical data, we monitored the rapid temporal and spatial dynamic characteristic of mining areas in the study area with a focus on physical changes to the landscape. Reservoir construction for mining has caused flooding of alluvial lowlands, deforestation, and the creation of tailings and stockpiles over mined-out portions of the lease. Although the study was conducted at a local scale, it represents the broad, regional, past-to-present manner by which global economic interests exploit natural resources and impact the environment in distant places.


[Erection disorders: the value, significance and limits of various examinations].
Erection, a complex physiological phenomenon, is the result of numerous simultaneously interacting mechanisms. A defect of one of these mechanisms can induce erectile dysfunction. In this paper, the authors define the various tests used to investigate the principal pathways governing erection, taking into account their respective value in view of the increasing pressure of budget restrictions on health systems.


Economic assessment of the secondary prevention of ischaemic stroke with dipyridamole plus aspirin (Aggrenox/Asasantin) in France.
To assess the cost effectiveness of aspirin 25 mg plus dipyridamole 200 mg twice daily in the secondary prevention of ischaemic stroke, according to the French social security perspective, using efficacy data from the second European Stroke Prevention Study (ESPS-2). The ESPS-2 was a double-blind, placebo-controlled clinical trial which assessed the efficacy of four secondary prevention strategies: (i) placebo; (ii) aspirin (acetylsalicylic acid) 25 mg twice daily; (iii) dipyridamole 200 mg twice daily; and (iv) aspirin 25 mg plus dipyridamole 200 mg twice daily. We performed a cost-effectiveness analysis with Monte Carlo simulations to compute confidence intervals. We combined data from various sources including the Dijon Stroke Registry, Institut National de la Statistique et des Etudes Economiques, Etude du Coût de l'Infarctus Cérébral (Study of the Cost of Cerebral Infarction [ECIC]) study and the ESPS-2 trial. According to our findings, a preventive strategy with aspirin 25 mg plus dipyridamole 200 mg twice daily is associated with net benefits per avoided stroke recurrence amounting to USD 23,932 (95% CI -USD 32,609, USD 35,772) compared with aspirin 25 mg twice daily alone, and USD 31,555 (95% CI USD 4921, USD 74,515) compared with dipyridamole alone (1997 values). Sensitivity analysis demonstrated that dipyridamole plus aspirin was still cost effective when the average cost of adverse effects per episode (ignored in the original estimation of the cost-effectiveness ratios due to a lack of data) was assumed to be USD 8600 (50,000 French francs); this cost is unlikely as most of the adverse effects associated with aspirin plus dipyridamole are only slight to moderate in severity. In the secondary prevention of stroke in France, this study suggests, given its underlying assumptions and data, that aspirin 25 mg plus dipyridamole 200 mg twice daily is likely to be a cost-effective strategy from the social security perspective, when compared with other relevant strategies that were evaluated in the ESPS-2 trial.


A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting.
Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue.


[How to carry out high quality clinical trial].
Evidence-based medicine derived from large-scale clinical trials has been widely accepted by clinicians, which strongly motivates the clinicians in medical institutions to conduct or participate in clinical trials. However, how to improve the clinical trial quality and management to achieve worldwide acceptance still remains challenging. By analyzing the difficulties faced by the majority of large Chinese clinical institutions and the opportunities during the evolvement of research modes, this paper proposes to improve the quality of clinical trial by closely following the domain development, raising clinical research thinking, ensuring rigorous research design, standardizing the steps and details of each operational session, as well as establishing a collaborative and well-communicated team. So far there is limited data support in therapeutic standards and guidelines in China. We have systematically designed and rigorously operated the research program based on the actual situation, whereby we have derived a set of high-quality disease guidelines that are adapted to the national disease characteristics in China.


[Experimental studies on cryochemotherapy (author's transl)].
The combination effect of chemotherapy and cryosurgery on solid tumor have been evaluated using Ehrlich tumor implanted in hind-limbs of ddN mice. Following regimens were performed. 1) Mitomycin C (MMC) lmg/kg i.p. as a chemotherapeutic agent. 2) cryosurgery -60 degree C for 1.5 minutes. 3) various combination of MMC and cryosurgery. Each average life-span was A) without therapy: 23.8 +/- 4.3 days, B) MMC: 28.0 +/- 4.0 days, C) cryosurgery: 29.5 +/- 6.1 days. Combination therapy which cryosurgery was first performed and then MMC was administered was most effective among various combinations. And the life-span was significantly extended to 38.7 +/- 5.2 days compared with that of each single therapy. When PSK, a immunopotentiator, was added to this regimen, the life-span was extended to 45.0 +/- 9.3 days. The immunological aspects of these regimens were examined by radioisotopic foot-pad assay. Transient increase of cellular immunity was observed in cryosurgery group. The effect of cryosurgery on uptake of anti-tumor agent into tumor tissue were also studied using 3H-labelled 5FU and 14C-labelled 5FU. It was revealed that the uptake rate was significantly increased in tumor margin, but not in tumor center. When the uptake in tumor margin was examined at serial time after cryosurgery, peak of increased uptake was observed at 6 and 12 hours after cryosurgery. Satisfactory response was obtained in clinical application of cryochemotherapy based on these experimental findings.U


The fate of the unconscious in the human sciences.
In this essay the author seeks to answer some of the criticisms of Freud's central concepts, theories, and methods that have been raised by twentieth century philosophy. He argues that many of these concepts and theories, particularly the concept of the unconscious, represent indispensable assumptions shared by the human sciences, even when they are not directly addressed by them. Further, he argues that in Freud's ideas we find one of the most advanced positions in our understanding of culture, its illusions and discontents, and a profound attempt to bridge the distance between a description of social reality and its critical appraisal.


[Acquired von Willebrand syndrome].
Two patients, a man aged 69 and a woman aged 64, were diagnosed with Von-Willebrand syndrome caused by monoclonal gammopathy. The man, who was admitted for hip surgery, had a history of long episodes of epistaxis. The patient was treated with immunoglobulin and the hip operation was carried out with no complications. The woman suffered from haemorrhagic diathesis. She was advised that should she undergo an invasive procedure then treatment with a prophylactic with intravenous immunoglobulin or Von-Willebrand factor (VWF)/factor-VIII-concentrates must be administered. Acquired Von-Willebrand syndrome is a rare condition with an estimated prevalence of 0.04-0.13%. It is linked to a large number of underlying diseases such as paraproteinaemia, multiple myeloma (Kahler's disease), myeloproliferative disease, lymphoproliferative disease, auto-immune disease, solid tumours and hypothyroidism. Recognition depends on a careful case-history and identification of the underlying disease. For its diagnosis VWF antigen. VWF propeptide, activated partial thromboplastin time and factor VIII are of importance. Technically, it is difficult to show the presence of VWF antibodies as it concerns a heterogeneous group of antibodies. There are two pillars of treatment: symptomatic treatment of the bleeding tendencies using desmopressin, VWF-concentrate or intravenous gammaglobulin, and treatment of the underlying disease. The latter form of treatment can lead to acquired Von-Willebrand-syndrome disappearing altogether.