Investigation of the thermal and tissue injury behaviour in microwave thermal therapy using a porcine kidney model.
Minimally invasive microwave thermal therapies are being developed for the treatment of small renal cell carcinomas (RCC, d<3 cm). This study assessed the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex. Three groups of kidneys were evaluated: (1) in vitro treated, (2) in vivo with 2-h post-treatment perfusion (acute) and (3) in vivo with 7-day post-treatment perfusion (chronic). The kidneys were treated with an interstitial water-cooled microwave probe (Urologix, Plymouth, MN) that created a lesion centered in the renal cortex (50 W for 10 min). The thermal histories were recorded at 0.5 cm radial intervals from the probe axis for correlation with the histologic cellular and vascular injury. The kidneys showed a reproducible 2 cm chronic lesion with distinct histologic injury zones identified. The thermal histories at the edge of these zones were found using Lagrangian interpolation. The threshold thermal histories for microvascular injury and stasis appeared to be lower than that for renal epithelial cell injury. The Arrhenius kinetic injury models were fit to the thermal histories and injury data to determine the kinetic parameters (i.e. activation energy and frequency factor) for the thermal injury processes. The resultant activation energies are consistent in magnitude with those for thermally induced protein denaturation. A 3-D finite element thermal model based on the Pennes bioheat equation was developed and solved using ANSYS (V7.0). The real geometry of the kidneys studied and temperature dependent thermal properties were used in this model. The specific absorption rate (SAR) of the microwave probe required for the thermal modelling was experimentally determined. The results from the thermal modelling suggest that the complicated change of local renal blood perfusion with temperature and time during microwave thermal therapy can be predicted, although a first order kinetic model may be insufficient to capture blood flow changes. The local blood perfusion was found to be a complicated function of temperature and time. A non-linear model based on the degree of vascular stasis was introduced to predict the blood perfusion. In conclusion, interstitial microwave thermal therapy in the normal porcine kidney results in predictable thermal and tissue injury behaviour. Future work in human kidney tissue will be necessary to confirm the clinical significance of these results.


Extraction and analysis of the width, gray scale and radian in Chinese signature handwriting.
Forensic handwriting examination is a relevant identification process in forensic science. This research obtained ideas from the process of features detection and analysis in forensic handwriting examination. A Chinese signature database was developed and comprised original signatures, freehand imitation forgeries, random forgeries and tracing imitation forgeries. The features of width, gray scale and radian combined with stroke orders were automatically extracted after image processing. A correlation coefficient was used to precisely characterize and express the similarities between signatures. To validate the differences between writers, a multivariate analysis of the variance was employed. The canonical discriminant analysis was performed between the original and non-original signatures; the cross-validation estimated the discriminating power of the width, gray scale and radian data. It is suggested that the extraction and analysis of these properties in Chinese signatures is reasonable. Meanwhile, forensic handwriting examination using the quantitative feature extraction and statistical analysis methods in this research could be performed with a satisfactory result in the discriminant analysis.


CAM a special challenge for cardiac care.
Some patients are driven to complementary and alternative medicine because traditional medicine offers no cure. Patients and some physicians may be unaware of potential contraindications. Bleeding is one of the primary concerns in patients using both modalities.


[The adaptive regulation of the nonlinear dynamics of brain electrical activity].
The reinforcing automated stimulation of the emotional positive hypothalamic areas which was contingent upon the multiperiodical events in the EEG structure increased the number of episodes with non-linear dynamics. It resulted in an increase in the frequency of the intracranial self-stimulation. Under conditions of controlled experiment a possibility was shown of the intentional experimental formation of the EEG episodes with different types of non-linear dynamics. At the stages preceding the associative learning, the application of fractal analysis enabled revealing a complex character of non-linearity in the bands of the EEG dominant frequencies with a slight tendency to a dominant process. The associative learning produced one dominant non-linear process which determined the dynamics of the whole system. The neurophysiological characteristics of the given adaptive process were determined as well as the difference between this process and the response to control stimulation.


Preoperative risks predict neurological outcome of carotid endarterectomy related stroke.
The aim of this study was to determine if preoperative risk factors are predictors of poor stroke outcome after carotid endarterectomy. In addition, the effect of other stroke risk factors on stroke severity was determined. A retrospective review of carotid endarterectomy results spanning 10 years, encompassing 561 patients, and reporting the combined results of all surgeons at our institution was performed. Patients were assigned to one of four groups. There were 227 patients with no preoperative risks (Group 1), 61 with angiographic risks (Group 2), 196 with medical risks with or without angiographic risks (Group 3), and 77 with neurological risks with or without medical/angiographic risks (Group 4). Other risks associated with stroke occurrence were recorded including: intraoperative risks (cross-clamp time, use of shunt, use of glucose solutions), surgical complications (carotid occlusion/thrombus or ligation), and medical complications (hypoxia, myocardial infarct). Stroke incidence was 5% with 2% (11 patients) and 3.4% (19 patients) having good and poor outcomes, respectively. Stroke incidence was highest in Groups 2 and 4 (10 and 14%, respectively), and Group 4 had the highest incidence of poor-outcome stroke (12%). Cross-clamp time, intraoperative shunt placement, and intraoperative glucose administration were similar among preoperative risk groups and were not primary determinants of stroke severity. The most common medical complication was myocardial infarction, which had the highest incidence in Groups 3 and 4 (6.1 and 5%, respectively). The highest incidence of surgical complications occurred in Groups 2 and 4, carotid thrombosis being the most common event (16 patients). Surgical complications were more commonly associated with stroke than were medical complications.(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between areca nut usage and heart rate in lactating Bangladeshis.
The betel-nut quid, a piece of areca nut chewed alone or mixed with tobacco and slaked lime wrapped in betel vine leaf, is widely used in Asian populations as a stimulant (due to the cholinergic agent, arecoline) or as a relaxant (due to arecaidine and guvacine). This study, which formed part of a larger project assessing the effect of energy expenditure on the duration of post-partum amenorrhoea, provided the opportunity to assess the role of chronic areca nut usage on heart rate and oxygen consumption during resting periods and during graded stepping tests. The mothers (n = 47), all of whom were lactating, were aged between 19 and 39, of low nutritional status and anaemic and they all chewed betel quid daily. Moderate users of betel quid (defined as more than 3 times a day) were found, on average, to have a significantly lower heart rate at rest and during exercise than low betel quid users (less than 3 times a day) but there was no modification in oxygen consumption. Chronic betel quid use does not seem to affect the assessment of 24h energy expenditure provided that subjects are denied access to betel nut usage before and during calibration.


Sleep-Related Painful Erections in a Patient With Obstructive Sleep Apnea Syndrome.
Sleep-related painful erection (SRPE) is a rare sleep disorder characterized by recurrent, painful penile erections occurring when awakening from rapid eye movement sleep, while erections are painless during wakefulness. Almost 35 cases have been reported worldwide, and only two of them had an associated obstructive sleep apnea syndrome (OSAS). We report a new case of a 61-year-old man suffering from SRPE associated with OSAS. The adequate treatment of respiratory events with continuous positive airway pressure did not alleviate the SRPE symptoms and excessive daytime sleepiness. The SRPE diagnosis was made by polysomnography coupled with video surveillance when the patient was referred to the sleep laboratory for residual excessive daytime sleepiness. The patient had 2-4 episodes of SRPE/night. Beta-blocker did not alleviate the SRPE, but a transient improvement was noted when the patient was treated with paroxetine. In contrast with the two previously published cases of SRPE plus OSAS, continuous positive airway treatment did not improve SRPE symptoms in our patient.


Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by necrotizing agents and experimental gastric or duodenal ulcer in rats.
Effects of FRG-8701, a new histamine H2-receptor antagonist, on gastric acid secretion, necrotizing agents-induced gastric lesions and acute gastric or duodenal ulcer in rats were studied. In lumen-perfused rats, intravenous injection of FRG-8701 reduced gastric acid secretion, and its antisecretory effect was almost equipotent to that of famotidine but the duration of action was substantially longer. In pylorus-ligated rats, the antisecretory effect of intraduodenal FRG-8701 administration was about 7 times more potent than that of cimetidine. FRG-8701 effectively inhibited macroscopic gastric hemorrhagic lesions induced by various kinds of necrotizing agents. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ED50 values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand, famotidine failed to reduce these lesions, and the cytoprotective effect of cimetidine was observed only in high doses compared with the doses for antisecretory activity. In addition, the cytoprotective effect of FRG-8701 was not affected by the treatment of indomethacin or N-ethylmaleimide. FRG-8701 showed antiulcer activity against stress and indomethacin gastric ulcer and mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than that of cimetidine. These results indicate that FRG-8701 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.


Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.
A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important milestone toward improving cancer diagnosis and tumor characterization. More importantly, this paper describes a new family of bifunctional agents that combine two modalities into a single cost-effective "see and treat" approach, namely, a single agent that can be used for contrast agent-enhanced MR imaging followed by targeted photodynamic therapy.


Antitumor actions of ruthenium(III)-based nitric oxide scavengers and nitric oxide synthase inhibitors.
The role of endogenous nitric oxide (NO) in the growth and vascularization of a rat carcinosarcoma (P22) has been investigated. Tumor-bearing animals were treated with (i) nitric oxide synthase (NOS) inhibitors, administered via the drinking water, including N(G)-nitro-l-arginine methyl ester (L-NAME), a nonisoform-selective inhibitor, and 2 others that target the inducible (NOS II) enzyme preferentially, namely 1-amino-2-hydroxyguanidine or N-[3-(aminomethyl)benzyl]acetamidine hydrochloride; or (ii) daily injections (intraperitoneally) of 2 Ru(III) polyaminocarboxylates, AMD6221 and AMD6245, both of which are effective NO scavengers. L-NAME, AMD6221, and AMD6245 reduced tumor growth by approximately 60% to 75% of control rates. Tumor sections stained with abs to CD-31/platelet endothelial cell adhesion molecule-1 or NOS III showed that this was associated with a marked reduction (60%-77%) of tumor microvascular densitiy (MVD). Tumors resumed growing promptly when treatment was discontinued, accompanied by partial or complete restoration of MVDs. In contrast, NOS-II selective inhibitors had no effect on tumor growth or vascularization, indicating that both responses require complete blockade of NO production. The results corroborate the view that endogenous NO facilitates tumor development. We suggest that NO deprivation causes tumor feeder vessels to constrict, reducing tumor blood flow. The delivery of oxygen and essential nutrients to the developing tumor is impaired as a consequence, hampering further growth. Normalizing NO levels by withholding treatment causes tumor feeder vessels to dilate, increasing tumor perfusion and reestablishing conditions that allow tumors to begin growing again.


Effect of dimethyl sulfoxide (DMSO) on radiation-induced heteroallelic reversion in diploid yeast.
Dimethyl sulfoxide has cryoprotective and radioprotective properties. It is also an efficient scavenger of radicals produced by raiolysis of water. Gamma-induced reversions of diploid yeast in the presence of this chemical during irradiation have been studied. The dose-modifying factor was in the same range as for survival. When the yeast was irradiated in the frozen state the observed protection by DMSO disappeared. The results are discussed in terms of direct and indirect actions of radiations and the radical-scavenging ability of this chemical.


Knowledge translation: putting the "practice" in evidence-based practice.
Knowledge translation (KT) is an iterative process that involves knowledge development, synthesis, contextualization, and adaptation, with the expressed purpose of moving the best evidence into practice that results in better health processes and outcomes for patients. Optimization of the process requires engaged interaction between knowledge developers and knowledge users. Knowledge users include consumers, clinicians, and policy makers. KT is highly reliant on understanding when research evidence needs to be moved into practice. Social, personal, policy, and system factors contribute to how and when change in practice can be accomplished. Evidence-based practitioners need to understand a conceptual basis for KT and the evidence indicating which specific KT strategies might help them move best evidence into action in practice. Audit and feedback, knowledge brokering, clinical practice guidelines, professional standards, and "active-learning" continuing education are examples of KT strategies.


Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential.
Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g. amygdala, hippocampus, hypothalamus and frontal cortex). Second, the SP content in these areas changes upon application of stressful stimuli. Third, the central administration of SP produces a range of fear-related behaviours. In addition, the SP/NK1R system shows significant spatial overlap with neurotransmitters such as serotonin and noradrenaline (norepinephrine), which are known to be involved in the regulation of stress, mood and anxiety. Therefore, it was hypothesised that blockade of the NK1R might have anxiolytic as well as antidepressant effects. Preclinical studies investigating the effects of genetic or pharmacological NK1R inactivation on animal behaviour in assays relevant to depression and anxiety revealed that the behavioural changes resemble those seen with reference antidepressant or anxiolytic drugs. Furthermore, antagonism or genetic inactivation of the NK1R causes alterations in serotonin and norepinephrine neuronal transmission that are likely to contribute to the antidepressant/anxiolytic activity of NK1R antagonists but that are--at least partially--distinct from those produced by established antidepressant drugs. This underlines the conceivable unique mechanism of action of this new class of compounds. In three independent clinical trials with three different compounds (aprepitant [MK-869], L-759274 and CP-122721), an antidepressant effect of NK1R antagonists could be demonstrated. These results, however, have been challenged by recent failed studies with aprepitant. There are numerous indications from preclinical studies that, in addition to SP and NK1R, other neurokinins and/or neurokinin receptors might also be involved in the modulation of stress-related behaviour and that exclusive blockade of the NK1R might not be sufficient to produce consistent anxiolytic and antidepressant effects. One such candidate is the neurokinin-2 receptor (NK2R), and clinical trials to assess the antidepressant effects of NK2R antagonists are currently underway. Of special interest might also be substances that block more than one receptor type such as NK1/2R antagonists or NK1/2/3R antagonists. These compounds may be more efficacious in antagonising the effects of SP than compounds that only block the NK1R.


The role of genetic variation in Toll-like receptor 4 in prostate cancer susceptibility: a review.
Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response against invading pathogens. Recent association studies have identified genetic variants in TLR4 that appear to influence the risk of prostate cancer. To evaluate critically whether genetic variation in TLR4 influences prostate cancer susceptibility, a systematic review of the literature on TLR4 and prostate cancer is done. All genetic association studies of TLR4 and prostate cancer are evaluated. In particular, issues related to genetic coverage, study heterogeneity and multiple hypothesis testing are examined. Although all three of the published studies suggest that the TLR4 locus itself is associated with prostate cancer, there is no corroboratory evidence for which specific variants influence the risk of disease. Clearly, these studies alone cannot establish TLR4 as a prostate cancer susceptibility locus. By evaluating candidate genes such as TLR4 further in conjunction with other variants identified by genome-wide association studies of prostate cancer, we shall be better poised to develop the appropriate panel of markers to improve prevention and diagnosis.


A new model of foster care for young children: the Bucharest early intervention project.
The Bucharest Early Intervention Project is a randomized controlled trial of foster care as an intervention for young children who have spent most of their lives in institutions in Bucharest, Romania. The authors implemented an attachment-based model of child-centered foster care there, and a team of three Romanian social workers trained and supported foster parents in managing the complex challenges of caring for postinstitutionalized infants and toddlers. They received regular weekly consultation from US-based clinicians designed to guide their work with foster parents and children. From language development to toilet training to encouraging the development of the young child's ability to trust, foster parents received ongoing support to help these young children transition to family life. Developmental outcomes so far indicate significantly better outcomes for young children in this foster care program than children who remained in institutions. For some domains of development, earlier placement was associated with better outcomes but for others, timing of placement did not appear to matter.


Validation of a Predictive Model to Identify Patients at High Risk for Hospital Readmission.
Hospital readmission is an adverse patient outcome that is serious, common, and costly. For hospitals, identifying patients at risk for hospital readmission is a priority to reduce costs and improve care. The purposes were to validate a predictive algorithm to identify patients at a high risk for preventable hospital readmission within 30 days after discharge and determine if additional risk factors enhance readmission predictability. A retrospective study was conducted on a randomized sample of 598 patients discharged from a Southeast community hospital. Data were collected from the organization's database and manually abstracted from the electronic medical record using a structured tool. Two separate logistic regression models were fit for the probability of readmission within 30 days after discharge. The first model used the LACE index as the predictor variable, and the second model used the LACE index with additional risk factors. The two models were compared to determine if additional risk factors increased the model's predictive ability. The results indicate both models have reasonable prognostic capability. The LACE index with additional risk factors did little to improve prognostication, while adding to the model's complexity. Findings support the use of the LACE index as a practical tool to identify patients at risk for readmission.


Seed-induced growing various TiO₂ nanostructures on g-C₃N₄ nanosheets with much enhanced photocatalytic activity under visible light.
In this study, we provide a seed-induced solvothermal method to grow various TiO2 nanostructures on the surfaces of g-C3N4, such as 0D nanoparticles, 1D nanowires 2D nanosheets and 3D mesoporous nanocrystals. We show that the "seeding" endows g-C3N4 with anchoring sites toward the heterogeneous nucleation growth of TiO2, and the distribution of the loaded TiO2 can be controlled by tuning the amount of nucleation in the dispersion. Among synthesized nanostructures, seed-grown Meso-TiO2/g-C3N4 hybrids exhibit the highest photocatalytic activity upon visible light irradiation using methyl orange and phenol as probe organics, which are about 2-4 times and 29-37 times as high as those of direct-grown Meso-TiO2/g-C3N4 without seeding and bare g-C3N4 for degradation of MO and phenol, respectively. The enhancement of photocatalysis can be ascribed to the adequate separation of photogenerated electrons at the heterojunction interfaces and dominant contribution of photoinduced holes mainly caused by the well-constructed nano- architectures.


[Pes anserinus transfer and medial transplantation of the tibial tubercle in the treatment of rotary instability of the knee (author's transl)].
23 cases of rotary instability of the knee have been reviewed with an average follow up of 5 years. They have been treated by a combination of pes anserinus transfer using Slocum's technique with medial transposition of the tibial tubercle. Functionally the results were satisfactory and there was no antero-posterior instability. No secondary patello-femoral arthrosis was seen. All the knees seemed to be more stable but most cases showed some degree of effusion, quadriceps wasting and some pain. It is concluded that this type of surgical procedure may provide a satisfactory knee for lighter sporting activities but not for competitive sport.


Novel therapeutics for melanoma.
Advanced melanoma has the highest per-death loss of years of potential life expectancy except for adult leukemia. Standard therapy with agents such as dacarbazine, temozolomide and IL-2 is associated with notoriously low response rates. The identification of new active agents is, therefore, critical in this disease. In recent years, better understanding of melanoma biology, as well as cancer and immune biology in general has led to the development of a number of new potential therapeutic agents for advanced melanoma. While many of these compounds are being tested in clinical trials, there are more agents in various stages of preclinical development. These novel therapeutics offer hope for this aggressive and so far largely treatment-resistant disease. In this review we will discuss some of the most promising novel therapeutic agents for advanced melanoma.


Healthcare resource utilization and costs for patients with pulmonary arterial hypertension: real-world documentation of functional class.
Pulmonary arterial hypertension (PAH) is a rare medical disease in which patients experience increased pulmonary vascular resistance (PVR) and pulmonary arterial pressure that can result in remodeling of the pulmonary vasculature and heart, and eventually lead to right heart failure and death. As PAH progresses, patients become unable to perform even routine daily tasks without severe shortness of breath (dyspnea), fatigue, dizziness, and fainting (syncope). Treatment strategies largely depend on assessment of an individual patient's WHO Functional Class. The aim of the present study was to determine whether PAH functional decline, as described by the WHO Functional class (FC), is associated with increased healthcare costs for patients. Patients with a prescription for a FDA-approved treatment for PAH and a medical claim indicating chronic pulmonary heart disease or right heart catheterization were identified from an administrative claims database. Provider-reported data from prior authorization forms required for advanced PAH therapies and medical charts were examined for reported FC. Healthcare resource utilization and costs were the primary outcomes of interest. Costs were accounted in 2014 US dollars ($) from a healthcare payer perspective. Patients with a reported FC-IV were observed to have the worst outcomes; averaging significantly more inpatient admissions, longer average lengths of stay, and more emergency department visits than the other FC sub-groups, resulting in higher medical costs. Using administrative data to document disease severity, this study replicates and expands on findings obtained from the registry study; disease severity was associated with higher healthcare resource utilization and costs. Stakeholders' implications for patient management are discussed.


Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration.
Mesenchymal niche cells instruct activity of tissue-resident stem and progenitor cell populations. Epithelial stem cells in hair follicles (HFs) have region-specific activity, which may arise from intrinsic cellular heterogeneity within mesenchymal dermal papilla (DP) cells. Here we show that expression of Hoxc genes is sufficient to reprogram mesenchymal DP cells and alter the regenerative potential of epithelial stem cells. Hoxc gene expression in adult skin dermis closely correlates with regional HF regeneration patterns. Disrupting the region-specific expression patterns of Hoxc genes, by either decreasing their epigenetic repression via Bmi1 loss or inducing ectopic interactions of the Hoxc locus with an active epigenetic region, leads to precocious HF regeneration. We further show that a single Hoxc gene is sufficient to activate dormant DP niches and promote regional HF regeneration through canonical Wnt signaling. Altogether, these results reveal that Hoxc genes bestow mesenchymal niches with tissue-level heterogeneity and plasticity.


Sulfate reduction in poorly-drained soils as influenced by organic matter and soil texture.
Investigations of the influence of added organic matter content (rice straw or clover) on the reduction of added sulfate (8 meq/100 g soil) following submergence and incubation of 120 days gave these results: 1. In soils with native organic matter (humus) the rate of sulfate reduction was very low; it slightly increased with increased clay content of the soils. 2. The addition of undecomposed organic matter led to a complete reduction of the added sulfates within 120 days. 3. The varying C/N ratio of the added organic matter appeared to have no influence on the sulfate reduction. 4. As a qualitative indication of the reduction the soil darkened after three weeks of incubation, and an odour of H2S was detected.


Molecular phylogeny and new taxa in the Archaeosporales (Glomeromycota): Ambispora fennica gen. sp. nov., Ambisporaceae fam. nov., and emendation of Archaeospora and Archaeosporaceae.
The AM fungal family Archaeosporaceae and the genus Archaeospora are rendered paraphyletic by the relationship with the Geosiphonaceae. This problem led to a more detailed study of the Archaeosporales. Members of the Archaeosporaceae were described as forming both glomoid and acaulosporoid spores, or solely acaulosporoid spores. However, we found that Glomus callosum fell into the same phylogenetic clade as A. leptoticha and A. gerdemannii, but exclusively formed glomoid spores. To resolve these inconsistencies, a genus, Ambispora gen. nov., typified by Ambispora fennica sp. nov., is erected based on morphological evidence and SSU and ITS region rDNA data. Ambispora contains three species known to produce both acaulosporoid and glomoid spores: A. fennica, A. leptoticha comb. nov. (basionym G. leptotichum), and A. gerdemannii comb. nov. (basionym G. gerdemannii). Another species, A. callosa comb. nov. (basionym G. callosum), is known only from glomoid spores. Ambispora is placed in a new family, the Ambisporaceae fam. nov. The Archaeosporaceae is maintained with the type species, Archaeospora trappei (basionym Acaulospora trappei), along with Intraspora schenckii (basionym Entrophospora schenckii). Acaulospora nicolsonii, known only from acaulosporoid spores, is discussed and is considered likely to belong in the Ambisporaceae, but is retained within its present genus because of inadequate morphological information and a lack of molecular data.


Determination of cortisol in saliva and serum by a luminescence-enhanced enzyme immunoassay.
A new luminescence-enhanced enzyme immunoassay (LEIA) has been developed and validated for the direct measurement of cortisol in saliva and serum. It has been demonstrated that this LEIA has a very good analytical and functional sensitivity. There was a good correlation to a commercial RIA. The assessment of diurnal cortisol profiles of healthy persons are discussed. Cortisol monitoring is indicated in diseases with abnormal glucocorticoid production such as Cushing's syndrome and Addison's disease. Because of the diurnal fluctuation of cortisol levels it is necessary to take several samples for an individual cortisol profile or during dynamic tests like the dexamethasone-suppression or ACTH stimulation. Salivary sample collection is an alternative method without the stress of repeated venipuncture. The measurement of cortisol in saliva is advisable in patients with abnormal cortisol-binding-globulin (CBG) levels such as pregnancy, hypothyroidism, nephrotic syndrome or marked adipositas and during the administration of certain drugs, especially oral contraceptives.


Noninvasive prenatal testing.
Noninvasive prenatal testing (NIPT) refers to recently developed genetic tests of the maternal serum that allow higher detection rates of trisomy 21 and other chromosomal aneuploidies in high-risk pregnancies. Noninvasive prenatal test analyzes cell-free DNA (cfDNA) in the maternal serum. Approximately 3% to 15% of cfDNA in the maternal blood is of fetal origin. Analysis of cfDNA can help identify fetuses affected with trisomy 21 and several other fetal aneuploidies. Testing can be performed after 9 to 10 weeks' gestation and has a higher sensitivity and specificity for trisomy 21 than other aneuploidy screening test. Noninvasive prenatal test has been studied and validated in singleton pregnancies at risk for trisomy 21 secondary to advanced maternal age, an abnormal serum screen, personal or family history of aneuploidy, or abnormal ultrasound findings, if these are suggestive of trisomy 13, 18, or 21. The utilization of NIPT for genetic screening has increased rapidly since introduction of the first clinical test in October 2011. Currently, there are limitations to NIPT including the possibility of test failure (2.6%-5.4%) and the focus on only the common trisomies. Noninvasive prenatal test is a screening test, and both false-positive (0.2%-1%) and false-negative results can occur. As the technology for NIPT is further evaluated, this test is likely to be increasingly used for prenatal screening. This review provides the obstetric clinician with an update of the current issues concerning NIPT.


Correlation between zeta-potential of a cell in a new cationic disinfectant solution and minimum inhibitory concentration of the disinfectant.
In the previous paper, we described the synthesis of new quaternary ammonium slats with antimicrobial activity: N-alkyl-N-2-hydroxyethyl-N,N-dimethylammonium butyl phosphate (4) and N-alkyl-N-(2-hydroxy-3-phenoxy)-propyl-N,N-dimethylammonium butyl phosphate (5). In this study, we examined the relationship between the MIC (minimum inhibitory concentration) of these new cationic disinfectants, 4 (six compounds) and 5 (three compounds), and the xi-potential against Escherichia coli in solutions of these compounds. The MIC values of these disinfectants against E. coli were highly correlated with the concentration that induced electric charge inversion (xi-potential=0) of E. coli from negative to positive.


Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease.
Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote AD-like pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-beta protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-beta precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of Abeta, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.


Polycyclic aromatic hydrocarbons (PAHs) in traditionally harvested bivalves in northern British Columbia, Canada.
Butter clams, blue mussels, and Nuttall's cockle are important traditional food of the Gitga'at First Nation in Canada. Samples were collected and analyzed for polycyclic aromatic hydrocarbon (PAH) from the Gitga'at harvest sites from 2006 to 2015 to: 1) establish baseline conditions; 2) determine the likely source; 3) understand species specific response to spills; and 4) evaluate health risk associated with consumption. Baseline lipid normalized-total PAH in mussels was 2.36 (±2.86, 95%CI) μg/g in mussels, 3.26(±4.14) μg/g in clams and 3.98 (±4.98) μg/g in cockles. PAHs varied according to proximity to point sources and became less petrogenic through time. Concentrations of PAHs were elevated in all three species following diesel spills but returned to baseline levels within 5months. However, Gitga'at harvesters avoided bivalves from spill-affected habitats for several years because of their detection of reduced quality and palatability, highlighting the importance of incorporating local knowledge into future monitoring programs.


Lipoprotein-associated phospholipase A2: a potential therapeutic target for atherosclerosis.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme that is produced by inflammatory cells, is bound to circulating LDL, and is involved in hydrolyzing polar phospholipids, including those found in oxidized low-density lipoproteins. To date, the biological role of Lp-PLA(2) in atherogenesis has been controversial, with initial reports purporting an atheroprotective effect attributable to the degradation of platelet activating factor and similar molecules. However, more recent studies suggest a proatherogenic role for this enzyme, which is attributed to Lp-PLA(2)-mediated hydrolysis of oxidatively modified low-density lipoproteins that results in the accumulation of proinflammatory products. The liberation of lysophosphatidylcholine and oxidized nonesterified fatty acids from oxidized phospholipids by the action of Lp-PLA(2) results in diverse inflammatory effects on various cell types involved in atherogenesis. This concept is further supported by a number of recently published epidemiology studies suggesting that plasma levels of the enzyme predict future cardiovascular events independent of conventional risk factors. The development of selective inhibitors of Lp-PLA(2) that inhibit enzyme activity in the circulation as well as within human atherosclerotic lesions opens the possibility of therapeutic manipulation of vascular inflammatory processes to reduce residual cardiovascular events in high risk individuals who continue to suffer fatal and nonfatal events despite the current standard of care.


Eccentric calf muscle training in non-athletic patients with Achilles tendinopathy.
Achilles tendinopathy is prevalent in athletes, but can also affect sedentary patients. We studied the effects of eccentric exercises in sedentary non-athletic patients with Achilles tendinopathy. Thirty-four sedentary patients (18 males, average age 44 years, range 23-67; 16 females, average age 51 years, range 20-76; average BMI: 28.6+/-4.7, range 22.1-35.4) with a clinical diagnosis of unilateral tendinopathy of the main body of the Achilles tendon completed the VISA-A questionnaire at first attendance (39+/-S.D. 22.8) and at their subsequent visits. The patients underwent a graded progressive eccentric calf strengthening exercises programme for 12 weeks. Fifteen patients (44%) did not improve with eccentric exercise regimen. Three patients improved after perintendinous injections aprotinin and local anaesthetic. Surgery was performed in seven patients as 6 months of conservative management failed to produce improvements. The overall average VISA-A scores at latest follow up was 50 (S.D. 26.5). Eccentric exercises, though effective in nearly 60% of our patients, may not benefit sedentary patients to the same extent reported in athletes.


Increased lectin-like oxidized low-density lipoprotein receptor-1 expression in the maternal vasculature of women with preeclampsia: role for peroxynitrite.
Preeclampsia is a hypertensive disorder unique to pregnancy, in which the placenta may release factors into the maternal circulation resulting in systemic effects. Small dense low-density lipoprotein (LDL; which is susceptible for oxidation) is increased in preeclampsia. Lectin-like oxidized LDL receptor-1 (LOX-1) is a receptor for oxidized LDL. However, the expression levels and the regulation of LOX-1 in the maternal vasculature of women with preeclampsia are unknown. We hypothesized that there is an increased LOX-1 expression in arteries from women with preeclampsia. We further hypothesized that circulating factors in the plasma of women with preeclampsia would upregulate the LOX-1 expression in vascular endothelial cells and contribute to vascular endothelial oxidative stress. We observed abundant LOX-1 expression and the presence of oxidized LDL in arteries from women with preeclampsia, which was negligible in arteries from normotensive pregnant women. Human umbilical vein endothelial cells treated for 24 hours with 2% plasma from preeclamptic women increased LOX-1 expression and oxidized LDL uptake, as well as induced oxidative stress, as evidenced by increased NADPH oxidase activity and superoxide and peroxynitrite levels. These effects were significantly reduced by pretreatment with blocking antibody or small interfering RNA to LOX-1, as well as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III), chloride (FeTPPS), a peroxynitrite scavenger. Exogenous peroxynitrite and 3-morpholino sydnonimine (SIN-1) increased LOX-1 protein and mRNA expression. In conclusion, increased LOX-1 expression in the systemic vasculature of preeclampsia women provides a fundamental insight into the pathology of preeclampsia and likely contributes to the induction and maintenance of vascular oxidative stress.


Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L.
The ubiquitin-like modifier FAT10 targets proteins for degradation by the proteasome, a process accelerated by the UBL-UBA domain protein NEDD8 ultimate buster 1-long. Here, we show that FAT10-mediated degradation occurs independently of poly-ubiquitylation as purified 26S proteasome readily degraded FAT10-dihydrofolate reductase (DHFR) but not ubiquitin-DHFR in vitro. Interestingly, the 26S proteasome could only degrade FAT10-DHFR when NUB1L was present. Knock-down of NUB1L attenuated the degradation of FAT10-DHFR in intact cells suggesting that NUB1L determines the degradation rate of FAT10-linked proteins. In conclusion, our data establish FAT10 as a ubiquitin-independent but NUB1L-dependent targeting signal for proteasomal degradation.


[Aeromonas spp. as the causative agent of acute diarrhoea in children under 1 year of age].
To establish whether there is a link between cases of acute watery diarrhoea and a specific Aeromonas species. Eight strains studied were identified as aeromonads and were further characterized by biochemical tests, fatty acid analysis and ribotyping. Aeromonads were isolated repeatedly from stool specimens of four children under one year of age with acute diarrhoea, two of whom were admitted to hospital. Of eight isolated aeromonads strains six were identified as A. caviae, one was classified into A. veronii bv. sobria and one could not be identified to the species level. Only two A. caviae strains from one patient were found to be identical by ribotyping while the Aeromonas species (strains) isolated from the other cases differed from one another. Contaminated fresh water, contaminated food and contact with travellers with imported diarrhoea were identified as probable sources of infection. Four cases of acute gastroenteritis in small children document that aeromonads are not rare and can cause serious health problems. However, epidemiological links remain unclear. We did not prove correlation between the four serious cases of acute diarrhoea and specific Aeromonas species but the results suggest the predominant role of A. caviae.


Perception of initial moving target signals: support for a cumulative lateral inhibition theory.
The cumulative lateral inhibition (CLI) theory of the Fröhlich effect (perceptual mislocalization of the starting position of a moving target in the direction of movement) proposes that the target is difficult to see early in its trajectory because inhibitory feedback from later target views weakens initial target representations. In contrast, attention shift explanations contend that a phenomenal representation of the target is unavailable until attention has shifted to the vicinity of the target. Experiments 1-3 demonstrated that instructing naive undergraduate participants to accept different degrees of target clarity before making their response can alter the magnitude (and presence) of the Fröhlich effect. Experiments 2-4 showed that increasing movement distance by adding target presentations reduced the visibility of the target at early positions. These results are difficult to reconcile with an attention shift account.


Sticking Around: Short-Range Activity of Wnt Ligands.
Wnt ligands are secreted lipid-modified proteins that are essential for development and homeostasis. Published recently in Nature, Farin et al. (2016) report that Wnt3 acts at a short distance during growth of mouse intestinal organoids, suggesting that Wnt proteins remain membrane-bound to activate signaling at a short range from their source.


A real time Taqman RT-PCR for the detection of rabbit hemorrhagic disease virus 2 (RHDV2).
A specific real time RT-PCR for the detection of RHDV2 was developed and validated using RHDV and RHDV2 RNA preparations from positive field samples. The system was designed to amplify a 127 nucleotide-long RNA region located within the vp60 gene, based on the alignment of six sequences originated in Portugal, obtained in our laboratory, and 11 sequences from France and Italy. The primers and probe target sequences are highly conserved in the vast majority of the RHDV2 sequences presently known. In the sequences showing variability, only one mismatch is found per strain, usually outlying the 3' end of the primer or probe hybridization sequences. The specificity of the method was demonstrated in vitro with a panel of common rabbit pathogens. Standardization was performed with RNA transcripts obtained from a recombinant plasmid harboring the target sequence. The method was able to detected nine RNA molecules with an efficiency of 99.4% and a R(2) value of 1. Repeatability and reproducibility of the method were very high, with coefficients of variation lower than 2.40%. The assay was proven a valuable tool to diagnose most of RDVH2 circulating strains, and may be also useful to monitor viral loads, and consequently, disease progression and vaccination efficacy.


In vivo study of trace elements in leprous skin.
The skin of leprous patients at various stages of the disease was investigated by diagnostic x-ray spectrometry, In the active stage raised iron and slightly raised zinc levels were found. The usefulness of the method in skin investigation is foreseen.


Bactericidal activity of amikacin and gentamicin.
Using the membrane filtration method bactericidal activity of amikacin and gentamicin as a function of time and concentrations was determined. Amikacin was bactericidal against all Pseudomonas aeruginosa (n = 7) and Klebsiella pneumoniae strains (n = 8) tested. In 5 of the 7 P. aeruginosa and 3 of the 8 K. pneumoniae strains we saw a secondary regrowth at 24h. There was no difference between amikacin and gentamicin. The experiments to determine the effect of concentration on bactericidal activity showed that higher concentrations lead to a faster kill rate.


Selective affinity of dimethyl sulphoxide (DMSO) and 2-amino-4-phenylsulphonylbenzenesulphonamide (NSD 3004) for the large intestinal mucosa of mice.
Whole-body autoradiography of 14C-labelled dimethyl sulphoxide and 35S-labelled 2-amino-4-phenylsulphonylbenzenesulphonamide revealed a selective accumulation of labelled substance in the large intestinal mucosa of mice. The mechanism of accumulation is discussed with regard to previous results on sulphone-containing compounds with tissue-specific distribution patterns.


Dissociation of pure korean words and Chinese-derivative words in phonological dysgraphia.
Phonological dysgraphia is a writing impairment, characterized by marked disability to spell pronounceable pseudo-words as opposed to relatively mild reduction in ability to spell real words. Within the realm of Korean vocabulary, there are two categories of real words: pure Korean words and Chinese-derivative words. We present a patient with a history of CVA, resulting in phonological dysgraphia and, further, a dissociated performance in the aforementioned two categories of real words. It is suggested that the lexicon for pure Korean words is segregated from that for Chinese-derivative words.


Sonographic prediction of viability in testicular torsion: preliminary observations.
This study was performed to determine if sonography can assist in predicting testicular viability in the setting of testicular torsion. Sixteen patients with sonographically diagnosed and surgically proved testicular torsion were studied. The preoperative sonograms were reviewed retrospectively to determine testicular echogenicity and homogeneity, testicular size and vascularity, scrotal skin thickness and vascularity, and the presence or absence of a hydrocele. These findings were correlated with the viability of the testis at surgery. All nine patients with normal homogeneous testicular echogenicity had viable testes at surgery. All seven patients with hypoechoic or inhomogeneous testes had nonviable testes at surgery and pathologic evidence of necrosis. The other findings were less helpful in predicting viability. In the setting of testicular torsion, normal testicular echogenicity is a strong predictor of viability. Immediate surgical detorsion in these patients carries a very high likelihood of salvaging the affected testis.


Gallbladder adenocarcinomas in two captive African lions (Panthera leo).
Gallbladder adenocarcinomas in two captive African lions (Panthera leo), an 18-yr-old male and a 17-yr-old female, are described in this report. Grossly, both lions had hemoperitoneum with thickened and sclerotic gallbladder walls. Histopathologically, the male's tumor was well differentiated and the female's was poorly differentiated with multinucleate giant cells. Both tumors were highly invasive and involved the gallbladder serosa. The male also had a tumor in the liver, and the female's tumor had disseminated to the serosal surfaces of abdominal organs. In both cases, neoplastic cell cytoplasm stained diffusely for cytokeratin AE-1/AE-3 and cytokeratin 7 and granularly for lysozyme on immunohistochemical staining.


Influence of 2-substituent on the activity of imidazo[1,2-a] pyridine derivatives against human cytomegalovirus.
The synthesis of various 2-substituted imidazo[1,2-a]pyridine bearing a thioether side chain in position 3 was reported. The new compounds were characterized by 1H and 13C NMR spectra. A conformational study was obtained by X-ray crystallographic analysis for 2-biphen-4-ylimidazopyridine 7. The antiviral activity against human cytomegalovirus (HCMV) was investigated. It was strongly influenced by the nature of C-2 substituent.


Evaluation of the lateral collateral ligament after fibular head transposition in dogs.
Cranial transposition of the fibular head stabilizes the stifle joint by displacing the distal attachment of the lateral collateral ligament (LCL). The forces applied to the LCL after displacement may cause ligamentous elongation. This investigation evaluated the morphological, histological, and biomechanical changes of the LCL after fibular head transposition (FHT) in dogs. Unilateral cranial cruciate ligament (CCL) excision and FHT were performed on 25 dogs. Cross-sectional area, length, histological, and structural properties of the LCL were evaluated 3 weeks, 4 months, and 10 months after surgery. Ligament length means were significantly increased at week 3, month 4, and month 10 compared with intraoperative length means. No significant changes in elongation were observed after week 3. Fibrovascular proliferation within the LCL increased the cross-sectional area and associated structural properties.


The functional genomics of noncoding RNA.
Large numbers of noncoding RNA transcripts (ncRNAs) are being revealed by complementary DNA cloning and genome tiling array studies in animals. The big and as yet largely unanswered question is whether these transcripts are relevant. A paper by Willingham et al. shows the way forward by developing a strategy for large-scale functional screening of ncRNAs, involving small interfering RNA knockdowns in cell-based screens, which identified a previously unidentified ncRNA repressor of the transcription factor NFAT. It appears likely that ncRNAs constitute a critical hidden layer of gene regulation in complex organisms, the understanding of which requires new approaches in functional genomics.


Effects of hydrothermal pre-treatments on Giant reed (Arundo donax) methane yield.
Twelve hydrothermal pre-treatment combinations of temperature (150 and 180 °C), time (10 and 20 min) and acid catalyst (no catalyst; H2SO4 at 2% w/w immediately before steam cooking or in 24-h pre-soaking) were tested to assess their effects on methane yield of Giant reed biomass vs. untreated control. A batch anaerobic digestion was conducted with 4 g VS l(-1) at 53 °C for 39 days. Untreated biomass exhibited a potential CH4 yield of 273 ml g(-1) VS; the four pre-treatments without acid catalyst achieved a 10%, 7%, 23% and 4% yield gain in the respective temperature/time combinations 150 °C/10 min, 150 °C/20 min, 180 °C/10 min and 180 °C/20 min. Conversely, the eight pre-treatments with H2SO4 catalyst incurred a methanogenic inhibition in association with high SO4(2-) concentration in the hydrolysate, known to enhance sulphate reducing bacteria. Furfurals were also detected in the hydrolysate of five strong pre-treatments with H2SO4 catalyst.


Improving childhood immunizations in a family practice office.
In the fall of 1993, the Family Medicine Center (FMC) of the Medical Center of Delaware instituted an office-based program designed to improve preventive care for children. This study examined whether the "Pediatric Prevention Program" (PPP) resulted in an improvement in childhood immunization rates for FMC patients. Using chart review, we compared the percentage of two-year-old FMC patients who had completed appropriate immunizations before and after the PPP. We examined completion rates for the primary series of each immunization, for booster immunizations and for the combined total immunization series (four DPTs, three OPVs, one MMR, four HIBs). We also determined whether immunization rates were affected by patient demographics, pattern of office visits, and physician level of experience. After implementation of the program, the percentage of 2-year-old children who had completed the appropriate immunizations increased for all types of immunizations. The increase was greatest for HIBs (6 percent for the primary HIB series and 7 percent increase for the HIB booster) and for the combined total series (10 percent increase). Children who made few office visits were the least likely to have completed immunizations, but also saw the greatest benefit from the PPP. This study shows the positive impact of an office-based intervention for improving childhood immunizations. However, the improvements are relatively small and not sufficient to achieve optimal immunization rates throughout the community. In order to achieve these goals, additional interventions are needed which target high risk children, especially those who change physicians or who visit their physician infrequently. Targeting such children will likely require better data systems to track immunizations both in the office and across the community. These efforts should be given a high priority in Delaware.


TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheumatoid arthritis patients after 10 years.
To investigate the effect of TNF inhibitors (TNFis) on incidental and progressive hand OA in recent-onset RA patients after a 10 year follow-up. Radiographs of 262 RA patients (mean age 52 years, 66% women) from the BeSt study were scored for osteophytes in DIP/PIP joints using the Osteoarthritis Research Society International atlas (0-3; summed score 0-54) and according to the Kellgren-Lawrence (KL) score (0-4; summed score 0-72) at baseline and 10 year follow-up. TNFi treatment was assessed on visits every 3 months. Associations between TNFi treatment and hand OA were analysed on the patient and joint level using generalized linear models and generalized estimating equations, respectively. Fifty-eight percent of the patients were treated with TNFi, with a median duration of 42 months. A total of 143 patients (55%) had hand OA in any IP joint at baseline based on the Osteoarthritis Research Society International osteophyte score. On the patient level, TNFi treatment duration did not affect incidental hand OA. However, every month of TNFi treatment resulted in a reduced relative risk (RR) of hand OA progression in DIP joints [relative risk (RR) 0.987 (95% CI 0.978, 0.996)] but not in PIP joints. On the joint level, the effect on hand OA progression was observed in DIP joints [RR 0.996 (95% CI 0.991, 1.000)] but not in PIP joints. The results from the KL score analyses were comparable to the osteophyte score. TNFi treatment was associated with a reduced risk on radiographic hand OA progression in DIP joints but not in PIP joints after 10 years. Although the effect sizes are small, these results provide evidence for influence of TNF-α in hand OA pathogenesis.


[Influence of cyclophosphamide on the production of experimentale autoimmune encephalomyelitis (author's transl)].
The aim of the so carried out experiments is to establish whether the created disbalance between T- and B-lymphocyte populations influences the final stages of a cell-mediated reaction in vivo. The chosen model was one of experimental autoimmune encephalomyelitis (EAE). Guinea pigs were given a single challenge (intradermally in the hind foot-pads) of 70 microgram myelin basic protein (MBP)--isolated from bovine spinal cord--in complete Freund's adjuvant (CFA). Another group of animals was treated intraperitoneally with 200 mg/kg cyclophosphamide (CY) 3 days before the MBP-CFA challenge. The control group received only CY. At different times after the administration of MBP, CY or CY-MBP, the popliteal lymph nodes have been examined and the morphological changes together with the number of anti-MBP antibody synthesizing cells (ASC) were recorded. In the guinea-pigs treated with the CY 3 days before the antigen challenge the disease develops earlier and shows a degree of severity with a threefold greater mean score. The number of ASC is increasing up till the 10th day and slightly decreases toward the 20th day when there are clinical and histological signs of EAE. If MBP is administered after a 3-day action of CY, the number of these cells till the 7th day after the antigen challenge is strongly reduced, then surpasses the normal value about the 10th day and comes back to it towards the 20th day. The results so obtained confirm the concept of the T-lymphocyte mediation of EAE and give us grounds for discussing the CY action on the lymphocyte subpopulation.


Quantitative analysis of depolarization-induced ATP release from mouse brain synaptosomes: external calcium dependent and independent processes.
We and others have shown previously that ATP is secreted from mouse brain synaptosomes following depolarization of the membrane by high [K+]o and the time course can be monitored accurately by measuring the light emitted from luciferin-luciferase included in the reaction medium. In the present work we have evaluated the relative importance of [Ca2+]o and membrane potential on the ATP secretion process by modelling the time course of ATP release under different conditions. After correction of the records for destruction of released ATP by synaptosomal ecto-ATPase activity, we found that ATP secretion occurs by an apparent first order process. We also established that, in addition to the classical [Ca2+]o-dependent mode, ATP secretion also occurred in the absence of extracellular calcium ([Ca2+]o less than 1 microM). Upon lowering the extracellular Ca2+ concentration, both the rate and the extent of ATP secretion decreased. To assess the contribution of membrane potential to the release rate we measured ATP secretion at membrane potentials determined by extracellular [K+]o (or [Rb+]o) as defined by the distribution of the carbocyanine dye, diSC3(5). Rate constants computed from measured secretion curves revealed that this parameter was essentially independent of membrane potential in the absence of [Ca2+]o. Noise analysis of the light signal showed that the variance increased upon stimulation by high [K+]o, suggesting that both modes of secretion are quantal. Thus, we conclude that the rate of ATP secretion from nerve terminals depends upon Ca2+ entry but not on membrane potential, per se.


Weakly localized waves on the corrugated surface of a medium of arbitrary anisotropy
The existence of weakly localized surface and pseudosurface waves on the corrugated surface of a medium of arbitrary symmetry is studied. The localized solution originates from an exceptional bulk wave associated with a transonic state of positive or negative curvature. It is shown that the period of corrugation or the frequency of the wave can universally be chosen such that the solution will exist. The range of permissible periods (frequencies) is different for positive and negative curvature transonic states, it being wider near transonic states of positive curvature. The imaginary component of the pseudosurface wave velocity is found to vary as the height of grooves to period of corrugation ratio raised in fourth or sixth power, depending on the transonic state with which the exceptional wave is associated. A simple analytical expression is derived allowing estimations to be made of the penetration depth and the velocity of the localized wave.


A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome.
The aim of this study was to derive dietary patterns associated with cardio-metabolic traits and to examine whether these predict prospective changes in these traits and incidence of the metabolic syndrome (iMetS). Subjects from the Malmö Diet and Cancer Study cardiovascular cohort without cardio-metabolic disease and related drug treatments at baseline (n 4071; aged 45-67 years, 40 % men) were included. We applied reduced rank regression on thirty-eight foods to derive patterns that explain variation in response variables measured at baseline (waist circumference, TAG, HDL- and LDL-cholesterol, systolic and diastolic blood pressure, fasting glucose and insulin). Patterns were examined in relation to change in cardio-metabolic traits and iMetS in subjects who were re-examined after 16·7 years (n 2704). Two dietary patterns ('Western' and 'Drinker') were retained and explained 3·2 % of the variation in response variables. The 'Western' dietary pattern was inversely associated with HDL-cholesterol and positively with all other response variables (both at baseline and follow-up), but there was no association with LDL at follow-up. After adjustment for potential confounders, the 'Western' dietary pattern was associated with higher risk of iMetS (hazard ratio Q4 v. Q1: 1·47; 95 % CI 1·23, 1·77; P trend=1·5×10-5). The 'Drinker' dietary pattern primarily explained variation in HDL and was not associated with iMetS. In conclusion, this study supports current food-based dietary guidelines suggesting that a 'Western' dietary pattern with high intakes of sugar-sweetened beverages and red and processed meats and low intakes of wine, cheese, vegetables and high-fibre foods is associated with detrimental effects on cardio-metabolic health.


Inosine analogs. Their metabolism in mouse L cells and in Leishmania donovani.
The growth of Leishmania donovani promastigotes and mouse L cells is differentially inhibited by several inosine analogs with modifications in the imidazole ring. The protozoal and mammalian cells also demonstrate differential metabolism of these analogs. 7-Deazainosine, 7-thia-7,9-dideazainosine, and formycin B were converted to their respective ATP analogs by both cell types. 8-Azainosine was converted to a GTP analog by mouse L cells; L. donovani did not metabolize this nucleoside. 9-Deazainosine and allopurinol riboside were metabolized only to their respective IMP analogs by L cells. L. donovani metabolized 9-deazainosine and allopurinol riboside to their ATP analogs and also metabolized 9-deazainosine to its GTP analog. All nucleosides studied were resistant to cleavage by either organism. From metabolism studies in the presence of a specific enzyme inhibitor, it was deduced that allopurinol riboside, formycin B, and 9-deazainosine were phosphorylated by at least two different routes in the mouse L cells. The metabolism of formycin B was inhibited 65% by the adenosine kinase inhibitor, 5-iodotubercidin, whereas the metabolism of allopurinol riboside (14% inhibition) and 9-deazainosine (0% inhibition) was only slightly affected by this inhibitor. The metabolism of allopurinol riboside and 9-deazainosine by L. donovani was not affected by 5-iodotubercidin. In contrast to the results of L cells, the metabolism of formycin B by L. donovani was also not affected by 5-iodotubercidin. The abilities of mouse L cells and L. donovani to metabolize these inosine analogs to the corresponding nucleotide analogs of ATP or GTP may be considered to be an activating step and correlates well with the respective cytotoxic effects of these compounds.


Real-time detection of nitric oxide isotopes in lung function tests.
In lung function tests, the determination of the pulmonary diffusing capacity (D) using the single-breath method is a commonly applied technique. The calculation of D is performed on the basis of accurate measurements of indicator gas concentrations. In this chapter, we demonstrate the appropriateness of the stable nitric oxide (NO) isotopes 14NO and 15NO in revealing reliable data of D. We performed studies on animals (14NO) by using respiratory mass spectrometry (M3) and on humans (15NO) by applying laser magnetic resonance spectroscopy (LMRS). The equipment was characterized by sufficient detection limits of 70 parts/billion at [14NO] = 0.001% (M3) and 40 parts/billion at [15NO] = 0.002 % (LMRS), respectively. Lastly, we were able to show that D-values for 14NO indeed reveal the entire diffusive properties of the alveolar-capillary membrane and that 15NO is a useful indicator gas for reflecting disturbances of pulmonary gas exchange.


Spatial dependence of the nonlinear BOLD response at short stimulus duration.
Most functional magnetic resonance imaging studies use linear models to predict the measured response by convolution of an impulse response with the stimulus profile. Using very short visual presentation times (<2 s), deviation from the linear model in the measured BOLD data from the human brain was found for the response integral, amplitude, and width. In this study, high temporal and spatial resolution were used to quantify nonlinear effects and investigate the spatial dependence. Data at 4 Tesla showed at short stimulus duration a nonlinearity, i.e., deviation from a linear model, with an index up to 400%, whereas data at 7 Tesla exhibited a nonlinearity index up to 40%. The effect was more pronounced for response amplitude than for response area. A reduced width and sharpening of responses at shorter stimulus duration was also found. A voxel-based analysis of 7 Tesla data with 1.2 x 1.2 x 2 mm(3) resolution revealed a correlation between response onset and nonlinearity index. This suggests that the nonlinearity effects are a tissue-specific phenomenon and are likely to be more localized to the site of neuronal activity. The observed magnetic field dependence and the demonstrated nonlinearity in the response width support the hypothesis that the source of the nonlinearity at short stimulus duration has a considerable hemodynamic contribution. The nonlinearity was modeled as a "switch"-type initial hemodynamic response onset. Understanding these nonlinearities in the BOLD response is important for design and the analysis of rapid event-related fMRI experiments with brief stimulus presentations.


Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate.
Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx). The left kidney was retrieved from 300-g Lewis rats after in situ cold perfusion and transplanted after 2 hr of HPP. A 30-min period of preretrieval warm ischemia was induced. Kidneys were divided into four groups: nonischemic controls (n=9), ischemic (isch) kidneys not receiving ET-R blockade during HPP (n=7), isch kidneys receiving the ETA receptor antagonist (n=7), and isch kidneys receiving the ETA/B receptor antagonist (n=8). ET-R blockade was induced by adding the ETA, A-147627, or the ETA/B, A-182086, receptor antagonist (Abbott Laboratories, Abbott Park, IL) directly to the preservation solution (5x10-6M). The kidneys were then isografted into genetically identical Lewis rats and GFR, determined by measurement of urinary iohexol clearance, measured 2 weeks after Tx. Two-week GFRs (mL/min) for each of the study cohorts are as follows: nonischemic controls, 1.18+/-0.11; ischemic (isch) only, 0.57+/-0.08 (P< or =0.05 vs. nonischemic controls); isch + ETA blockade, 0.95+/-0.15 (P< or =0.05 vs. isch only); isch + ETA/B blockade, 0.90+/-0.08 (P< or =0.05 vs. isch only). Addition of an ETA, A-147627, or an ETA/B, A-182086, receptor antagonist to preservation solution used during HPP of kidneys subjected to preretrieval warm ischemia resulted in a normalization of GFR measured 2 weeks after Tx. The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx.


Effect of ectopic epithelial tissue within the stroma on keratocyte apoptosis, mitosis, and myofibroblast transformation.
The purpose of this study was to examine the effects of the epithelium on processes involved in stromal wound healing. Lamellar epithelial-stromal flaps were produced in rabbit corneas with a microkeratome. Peripheral corneal epithelial tissue, central corneal epithelial tissue, or no epithelial tissue (control) was introduced beneath the flap. Corneas were removed at time points from 4 hr to 1 month after surgery. Tissue sections were analyzed with immunocytochemistry for Keratin 3 (K3) to detect epithelial antigen, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis, immunocytochemistry for Ki67 to detect cell proliferation, and immunocytochemistry for alpha-smooth muscle actin (SMA) to detect myofibroblasts. K3 was detected at the level of the interface from 4 hr to 1 month after surgery in corneas in which epithelial tissue was introduced, but not control corneas, with the exception of one that developed epithelial in growth. Keratocyte apoptosis was significantly higher at 4 hr after flap formation in both groups in which corneal epithelial tissue was introduced beneath the flap compared with controls. Keratocyte proliferation was significantly greater at 72 hr in corneas in which epithelial tissue was introduced beneath the flap compared to the controls. Corneas in which epithelial tissue was introduced into the interface, but not control corneas, had stromal cells expressing alpha-SMA in the stroma anterior and posterior to the interface at 1 week and 1 month after surgery. This was also noted in the control cornea in which there was epithelial ingrowth. Signals derived from the corneal epithelium promote keratocyte apoptosis. Keratocyte proliferation is higher in corneas that have lamellar surgery when epithelial tissue is introduced into the interface. Epithelium-derived signals also participate in the generation and/or maintenance of myofibroblasts in the corneal stroma.


Echocardiographic guidance for neonatal right ventricular outflow tract stent implantation.
The use of combined fluoroscopic and echocardiographic imaging in congenital intervention is a well-established and developing concept. We report the case of a 1.2 kg, hemodynamically unstable neonate with tetralogy of Fallot, in whom we implanted a right ventricular outflow tract stent under primarily echocardiographic guidance. This represents the smallest reported patient in whom a right ventricular outflow tract stent has been placed and the latest application of integrated echocardiography and fluoroscopy in the catheterization laboratory.


[Diseases of the vitreo-macular interface].
A pathological vitreomacular adhesion is a common pathogenetic mechanism of various clinical entities such as idiopathic epimacular membrane, vitreomacular traction syndrome, and macular hole. Vitrectomy is recommended for these disorders. Anatomical and functional results in 207 operated eyes are discussed. The results of a vitrectomy in 3 groups of patients were compared: idiopathic epimacular membrane (group 1, n = 52), vitreomacular traction syndrome (group 2, n = 48); macular hole (group 3, n = 107; 33 eyes without and 74 eyes with retinal detachment). After excision of the vitreous gel, a thin layer of epimacular vitreous cortex was identified and excised by gentle aspiration under continuous air infusion. In 50 of the 107 eyes of group 3, the vitrectomy was combined with the application of a drop of autologous blood to the macular hole. A vitreomacular adhesion existed in 56% of group 1, 74% of group 2, and 84% of group 3. The visual acuity improved in 54%, 62% and 50% of eyes of the 3 groups, respectively. More eyes with an initial visual acuity of at least 40/200 achieved final vision of 80/200 or better (57%, 65% and 48% of group 1 to 3, respectively) than eyes with acuities of less than 80/200. A postoperative cataract was the main reason for reduced visual results in all cases. In group 3-eyes with retinal detachment and/or myopia, a significant postoperative visual improvement was achieved only after application of autologous blood to the macular hole. A pathological vitreomacular adhesion was identified in the majority of patients with idiopathic epimacular membranes, vitreomacular traction syndrome, and macular hole, respectively. Vitreoretinal surgery for syndromes with vitreomacular traction is indicated as it warrants a significant improvement of visual function and relief of metamorphopsia.


An integrated and multi-purpose microscope for the characterization of atomically thin optoelectronic devices.
Optoelectronic devices based on graphene and other two-dimensional (2D) materials, such as transition metal dichalcogenides (TMDs), are the focus of wide research interest. They can be the key to improving bandwidths in telecommunications, capacity in data storage, and new features in consumer electronics, safety devices, and medical equipment. The characterization of these emerging atomically thin materials and devices strongly relies on a set of measurements involving both optical and electronic instrumentation ranging from scanning photocurrent mapping to Raman and photoluminescence (PL) spectroscopy. Furthermore, proof-of-concept devices are usually fabricated from micro-meter size flakes, requiring microscopy techniques to characterize them. Current state-of-the-art commercial instruments offer the ability to characterize individual properties of these materials with no option for the in situ characterization of a wide enough range of complementary optical and electrical properties. Presently, the requirement to switch atomically thin materials from one system to another often radically affects the properties of these uniquely sensitive materials through atmospheric contamination. Here, we present an integrated, multi-purpose instrument dedicated to the optical and electrical characterization of devices based on 2D materials which is able to perform low frequency electrical measurements, scanning photocurrent mapping, and Raman, absorption, and PL spectroscopy in one single setup with full control over the polarization and wavelength of light. We characterize this apparatus by performing multiple measurements on graphene, transition metal dichalcogenides (TMDs), and Si. The performance and resolution of each individual measurement technique is found to be equivalent to that of commercially available instruments. Contrary to nowadays' commercial systems, a significant advantage of the developed instrument is that for the first time the integration of a wide range of complementary optoelectronic and spectroscopy characterization techniques is demonstrated in a single compact unit. Our design offers a versatile solution to face the challenges imposed by the advent of atomically thin materials in optoelectronic devices.


[The effect of melaxen administration on the tissue oxidative status in rats with brain ischemia/reperfusion].
Melaxen administration to rats with brain ischemia/reperfusion was accompanied by a decrease of the lactate level (an organ ischemia marker), biochemiluminescence parameters characterizing the intensity of free radical processes and total antioxidant activity, the content of lipid peroxidation products, activity of superoxide dismutase and catalase, as compared with the values determined in rats with induced brain ischemia/reperfusion. Activity of aconitate hydratase, a sensitive target of free radicals action, and the citrate level in the brain and blood serum of melaxen-treated animals changed towards control values of intact animals. It is assumed that the effect of melaxen is associated with implementation of the antioxidant and protective properties of melatonin, the melaxen constituent, under conditions of post-ischemic reperfusion injury, accompanied by oxidative stress development.


Assessing the distribution and human health risk of organochlorine pesticide residues in sediments from selected rivers.
Sediment samples from major agricultural producing areas in Edo state Nigeria were analysed for α-HCH, γ-HCH, β-HCH and ∑DDT with the aim of elucidating contamination profiles, distribution characteristics, carcinogenic and non-carcinogenic risk of these compounds in these regions. Analysis was done using a gas chromatography (GC) equipped with electron capture detector (ECD), while health risk assessment was carried out using the Incremental Lifetime Cancer Risk (ILCR) and the chronic daily intake (CDI). Results showed varying concentrations of α-HCH, γ-HCH, β-HCH and ∑DDT pesticides in sediment samples with hexachlorocyclohexane (∑HCHs) (4.6 µg/g/dw) being the dominant contaminants as it was widely detected in all samples and stations. Source identification revealed that the current levels of HCHs and DDT in sediments were attributed to both historical use and fresh usage of these pesticides. Risk estimates using ILCR and CDI showed that the risk of cancer and non-cancer effects was highest when exposure route was through ingestion. Furthermore, model projections highlights children as high risk population groups for non-dietary exposure to OCPs. These findings suggests the need for increased monitoring programmes, with a wider scope for both currently used pesticides and legacy/banned pesticides.


Complete nucleotide and deduced protein sequence of CMP-NeuAc: poly-alpha-2,8 sialosyl sialyltransferase of Escherichia coli K1.
Poly-alpha-2,8 N-acetylneuraminic acid (polySia) is an important virulence factor in infections caused by Escherichia coli K1 and Neisseria meningitidis B. In E. coli K1 a membranous CMP-NeuAc: poly-alpha-2,8 sialosyl sialyltransferase (polysialyltransferase) complex catalyses the synthesis of linear polySia chains. The complex also elongates sialyl oligomers that serve as exogenous acceptors. The gene encoding a polysialyltransferase of E. coli has been identified by subcloning and DNA sequence analysis. The subcloned DNA fragment codes for a polypeptide with a molecular mass of 47 kDa catalysing the in vitro synthesis of polySia by elongation of exogenous acceptors.


Bioabsorbable fixation for Mitchell's bunionectomy osteotomy.
Although bioabsorbable pins have been used to successfully stabilize a wide range of osteotomies, to date there have been not published studies describing the results of their use for fixation of first metatarsal osteotomies in Mitchell's bunionectomy. The purpose of this retrospective investigation of 78 first metatarsal osteotomies was to evaluate the effectiveness of polydioxanone bioabsorbable pin fixation of the first metatarsal osteotomy in Mitchell's bunionectomy. The mean length of the first metatarsal preoperatively was 6.65 +/- 0.42 cm, and postoperatively it was 6.31 +/- 0.57 cm (P < .0001). The mean first IMA preoperatively was 17.59 degrees +/- 3.51 degrees , and postoperatively it was 9.91 degrees +/- 2.58 degrees (P < .0001). The mean HVA preoperatively was 29.74 degrees +/- 4.70 degrees , and postoperatively it was 12.89 degrees +/- 4.26 degrees (P < .0001). The average time to bony union was 6.01 +/- 0.61 weeks. There were 5 (6.41%) superficial wound infections that resolved with oral antibiotics, 1 (1.28%) deep-seated infection requiring surgical debridement, and 2 (2.56%) patients complained of transfer metatarsalgia. Five (6.41%) patients displayed persistent localized translucency at some portion of the osteotomy site on postoperative radiographs, and there were no cases of progressive osteolysis. In this series there were no complications related to pin fracture or failure of osteotomy fixation. Based on the results observed in this study, it appears that the use of polydioxanone bioabsorbable pins provides satisfactory stabilization of the first metatarsal osteotomy in Mitchell's bunionectomy, and was not associated with any serious complications. 2.


Centrosome duplication: three kinases come up a winner!
Despite over one hundred years of research, the duplication of the centrosome is a poorly understood process. Three recent papers--exploring three different kinases--may have provided the answer.


FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis(x) hapten.
FC-2.15 is a murine IgM monoclonal antibody that recognizes breast and colon human carcinomas, chronic myeloid leukemias, Sternberg cells of Hodgkin's lymphoma and some normal cells, such as peripheral polymorphonuclear granulocytes. It has been previously demonstrated that FC-2.15 recognizes the carbohydrate moiety of different glycoproteins. FC-2.15 is able to mediate the in vitro lysis of Ag-2.15+ cells by human complement. In a phase I clinical trial, FC-2.15 induced antitumor responses and reversible neutropenia was its main toxicity. In this work, analysis of epitope specificity has demonstrated that FC-2.15 specifically recognizes terminally exposed Lewis(x) trisaccharide but not sialyl-Lewis(x), Lewis(a), trifucosylated Lewis(y), blood-group antigens A and B, globo H and gangliosides. In polymorphonuclear granulocytes (PMN), myeloid leukemic cells and colon carcinoma T84 cells, Lewis(x) was found to be almost exclusively N-linked to the protein core, whereas in breast carcinoma MCF-7 cells, Lewis(x) appeared to be mostly O-linked. Treatment with neuraminidase increased detection by FC-2.15 in normal PMN, myeloid leukemia cells and T84 cells but not in MCF-7 cells.


Religious perspectives on withdrawal of treatment from patients with multiple organ failure.
Religious or spiritual values often influence health care decision-making by patients and their families, particularly in times of crisis. Though religious values might seem to be irrelevant where continuing treatment is judged to be "futile", such clinical assessments should instead serve to open a dialogue about values and beliefs. The six major religious traditions in Australia have some similar values and principles about death and provision of care for the dying, but differ in their processes of ethical reasoning, cosmologies, and key moral concepts. Engaging with religious traditions on the common ground of basic values (such as human dignity, care, the sacredness of human life, non-violence, compassion, and selflessness) promotes negotiation of the manner in which care is provided, even where conflicts exist.


Reductive methylation of membrane proteins in human erythrocyte ghosts.
The first demonstration of a method to incorporate radiolabeled methyl groups from [14C]formaldehyde into membrane proteins in human erythrocytes by reductive methylation in the presence of NaCNBH3 is described. This method is based on the work of Jentoft and Dearborn [(1979) J. Biol. Chem. 254, 4359-4365], who demonstrated the feasibility of this procedure in soluble proteins. The results of the present study suggest that cytoskeletal protein components of erythrocyte membranes are primarily labeled and that this procedure provides a useful method to investigate the structure of membrane proteins.


Studies on liver toxicants: influence of bromobenzene on hepatic microsomal enzymes in mice.
The effect of acute bromobenzene intoxication on drug-metabolizing liver enzymes was studied. After an oral dose of 3000 mg/kg body weight of bromobenzene, the glucuronyltransferases I and II were increased, indicating an enzyme activation by this organic solvent via membrane irritation. The mixed-function oxidases were inhibited with the exception of the ketamine N-demethylase. Microsomal lipoperoxidation was reduced whilst H2O2 formation was unchanged.


Impact of effort reward imbalance at work on suicidal ideation in ten European countries: The role of depressive symptoms.
Evidence of the association between effort reward imbalance (ERI) and suicidal ideation is sparse. This study examined the influence of ERI at work on suicidal ideation and the mediating effect of depressive symptoms. There were 4963 workers aged 50+ without suicidal ideation at baseline in the Survey of Health, Aging and Retirement in Europe, these workers were followed-up for 8-years to detect incident suicidal ideation. ERI was measured by a short ERI questionnaire. Suicidal ideation was evaluated by one item derived from the 12-item Europe-depression scale, and depressive symptoms were assessed by the remaining 11 items in the scale. Cox models were employed to explore the relationship adjusting for potential confounders. Mediation analysis was used to test the mediating effect of depressive symptoms. A significantly higher incidence of suicidal ideation was related with high effort (HR = 1.51) and low reward (HR = 1.42), respectively. A high effort-low reward imbalance was associated with even higher risk of suicidal ideation (HR = 1.96) as compared to low effort-high reward combination. The association was varied by gender, region, education and household income. Depressive symptoms mediated a modest proportion (natural indirect effect 14.4%) of the total association between ERI and suicidal ideation. Suicidal ideation definition based on self-administered questionnaires which could lead to false negatives. And some unmeasured confounders might have biased the results. Efforts in promoting balanced effort-reward at work may reduce suicidal ideation among working population aged 50+. Avoiding depressive symptoms may further enhance such efforts.


Organochlorine chemicals in skin lipids as an index of their accumulation in the human body.
Application of a noninvasive method of analyzing skin lipids was considered as a means of monitoring human exposure to organochlorine pesticides. Skin lipids were collected by wiping the face with cotton and purified by gel permeation chromatography and treatment with H2SO4. Organochlorine chemicals were determined by electron capture gas chromatography with a fused silica capillary column. p,p'-DDE, beta-HCH and chemicals related to chlordane were detected in the skin lipids. Residue levels of p,p'-DDE, beta-HCH and oxychlordane in the skin lipids correlated with those in the adipose tissue; correlation coefficients for p,p'-DDE, beta-HCH and oxychlordane were 0.93, 0.92, and 0.68, respectively. The correlation between skin lipids and adipose tissue for trans-nonachlor was poor (gamma = 0.46). The component pattern of chlordanes in skin lipids was similar to that of technical chlordane. The results suggested that chemicals in the skin lipids reflected both their accumulation in the body burden and dermal exposure. Skin lipids collected during 1986 to 1988 in Japan were determined for p,p'-DDE, beta-HCH and the chlordanes. Residue levels of p,p'-DDE and beta-HCH in the aged were high compared with those in the young (gamma = 0.31-0.45). Chlordanes were detected from inhabitants in the southern area of Japan where chlordane had been used for termite control.


A novel postoperative immobilization model for murine Achilles tendon sutures.
The body's motion and function are all in part effected by a vital tissue, the tendon. Tendon injury often results in limited functioning after postoperative procedures and even for a long time after rehabilitation. Although numerous studies have reported surgical procedures using animal models which have contributed to both basic and clinical research, modeling of tendon sutures or postoperative immobilizations has not been performed on small experimental animals, such as mice. In this study we have developed an easy Achilles tendon suture and postoperative ankle fixation model in a mouse. Right Achilles tendons were incised and 10-0 nylons were passed through the proximal and distal ends using a modified Kessler method. Subsequently, the right ankle was immobilized in a plantarflexed position with novel splints, which were made from readily available extension tubes. Restriction of the tendon using handmade splints reduced swelling, as opposed to fixating with the usual plaster of Paris. Using this method, the usage of the right Achilles tendons began on postoperative days 13.5 ± 4.6, which indicated healing within two weeks. Therefore our simple short-term murine Achilles tendon suture procedure is useful for studying immediate tendon repair mechanisms in various models, including genetically-modified mice.


Sildenafil citrate use in Addis Ababa: characteristics of users and pharmacists' dispensing practices.
Background Studies have reported misuse of sildenafil citrate for recreational purpose, not least by healthy young men. This is becoming a major concern, for medical and other reasons. Objective The aim of this study was to document the characteristics of sildenafil citrate users and to explore the dispensing practices of the medicine in selected community pharmacies in Addis Ababa, Ethiopia. Setting Data was collected in community pharmacies in Addis Ababa, Ethiopia. Method A survey, using a self-administrated questionnaire, was conducted among customers who purchased sildenafil citrate from community pharmacies. Simple descriptive statistics were used to analyse data. Also, semi-structured interviews were conducted with community pharmacists. These were analysed thematically. Main outcome measures Socio-demographic characteristics (survey), themes (interviews). Results All survey respondents (n = 197) were men, 57.9% were below 40 years old, 53.8% had never been married and 58.4% had used sildenafil citrate before. A minority (16.2%) were diagnosed with erectile dysfunction. The main reason for buying sildenafil citrate was experimentation (45.7%). Pharmacists reported that sildenafil citrate was often dispensed without a prescription. The reason for this was, according to the interviewees, competition in the market. Also, the medicine was often dispensed without adequate information or counselling. Conclusions Selling and buying sildenafil citrate without a prescription seems to be common practice in pharmacies in Addis Ababa. It is crucial to strengthen the regulatory activity to protect customers from health risks. In addition pharmacy professionals should be supported to work in accordance with professional and legal standards.


Intramolecular Pd-Catalyzed Reductive Amination of Enolizable sp3-C-H Bonds.
A palladium-catalyzed reductive cyclization of nitroarenes has been designed to construct sp3-C-NHAr bonds from sp3-C-H bonds by using an enolizable nucleophile to intercept a nitrosoarene intermediate. Exposure of ortho-substituted nitroarenes to 5 mol % of Pd(OAc)2 and 10 mol % of phenanthroline under 2 atm of CO constructs partially saturated 5-, 6-, or 7-membered N-heterocycles using α-pyridyl carboxylates, malonates, 1,3-dimethylbarbituric acid, 1,3-diones, or difurans as the nucleophile.


An incentive program designed to develop and reward clinical competence.
A conceptual model is presented for establishing a salary and classification plan which structures a separate career pathway for staff nurses and provides an economic incentive for incrementally achieving higher excellence as a staff practitioner. The plan establishes standard or behavioral norms for four discrete practice levels and systematically measures the content of both line and staff positions to determine their relative difficulty. Consequently equitable salary relationships are made available for all nursing activity, while simultaneously assuring a congruent and competitive posture in the health care community.


An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.
Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease. Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic for an anti-ovalbumin T-cell receptor or an anti-hen egg lysozyme B-cell receptor were studied. Adoptive transfers were performed of T or B cells or both from nuclear factor of activated T cells c2-deficient mice into nuclear factor of activated T cells c2-deficient recombinase activating gene-deficient animals, in the presence or absence of antibodies that neutralize interleukin-10 activity. Nuclear factor of activated T cells c2-deficient, recombinase activating gene-deficient animals spontaneously developed a severe inflammatory bowel syndrome that resembled ulcerative colitis but was composed entirely of nonlymphocytes. The disease was suppressed by the adoptive transfer of polyclonal B-cell populations, even on neutralization of interleukin-10, but not by the presence of monoclonal T or B cells. Nuclear factor of activated T cells plays a critical role in the regulation of bowel inflammation by nonlymphoid immune cells, and B cells suppress bowel inflammation by innate immune cells. Such findings indicate a novel, interleukin-10-independent role for nuclear factor of activated T cells in the regulation of innate immunity and in intestinal immune tolerance.


Rethinking work with "multicultural populations".
This article examines the importance of ethnic and cultural factors in mental health and mental illness, through consideration of race and culture in the diagnosis and treatment of mental illness, by examining patterns of service utilization by multicultural populations, and by advocating for policies which support multicultural initiatives in public mental health.