The Role of HSP70 in the Protective Effects of NVP-AUY922 on Multiple Organ Dysfunction Syndrome in Endotoxemic Rats.
Sepsis is defined as a life-threatening organ dysfunction syndrome with high morbidity and mortality caused by bacterial infection. The major characteristics of sepsis are systemic inflammatory responses accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). As a molecular chaperon to repair unfolded proteins, heat shock protein 70 (HSP70) maintains cellular homeostasis and shows protective effects on inflammatory damage. HSP 90 inhibitors were reported to exert anti-inflammatory effects via activation of the heat shock factor-1 (HSF-1), leading to induction of HSP70. We evaluated the beneficial effect of HSP 90 inhibitor NVP-AUY 922 (NVP) on multiple organ dysfunction syndrome induced by lipopolysaccharide (LPS) and further explored the underlying mechanism. NVP (5 mg/kg, i.p.) was administered 20 h prior to LPS initiation (LPS 30 mg/kg, i.v. infusion for 4 h) in male Wistar rats. Results demonstrated that pretreatment with NVP significantly increased survival rate and prevented hypotension at 6 h after LPS injection. Plasma levels of ALT, CRE and LDH as well as IL-1β and TNF-α were significantly reduced by NVP at 6 h after LPS challenge. The induction of inducible NO synthase in the liver, lung and heart and NF-κB p-p65 and caspase 3 protein expression in the heart were also attenuated by NVP. In addition, NVP markedly induced HSP70 and HO-1 proteins in the liver, lung and heart after LPS injection. These results indicated that NVP possessed the anti-inflammatory and antioxidant effects on LPS-induced acute inflammation, which might be associated with HSP70 and HO-1, leading to prevent MODS in sepsis. NVP might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS.


Use of an inactivated vaccine for prevention of parvovirus-induced reproductive failure in gilts.
Gilts from dams that had been inoculated with inactivated porcine parvovirus (PPV) vaccine before breeding became seronegative to PPV by 26 weeks of age. Vaccination of these gilts with inactivated PPV vaccine at 32 weeks of age resulted in an antibody response that peaked at about 2 weeks after vaccination, with -log10 mean hemagglutination inhibiting (HI) antibody titers of less than 2. In the first-year group (82 gilts), HI titers gradually decreased, 20% of the gilts being seronegative by 6 to 7 weeks after vaccination and 75% being seronegative by 16 weeks after vaccination. In the second-year group, 93 gilts were infected naturally by a field strain of PPV at about 11 weeks after single vaccination with inactivated PPV. Additionally, in the second year, 20 vaccinated and 6 nonvaccinated gilts were immune-challenged with virulent PPV at 10 to 12 weeks after vaccination. Neither field nor challenge PPV infection of vaccinated pregnant gilts caused reproductive failure, even though some of the gilts became seronegative for PPV before challenge. Our findings suggest that single vaccination of gilts with inactivated PPV vaccine should give adequate protection from PPV-induced reproductive failure, even though serum HI titers decrease to an undetectable level shortly before PPV infection.


Frontier Expansion Sampling: A Method to Accelerate Conformational Search by Identifying Novel Seed Structures for Restart.
Traditional molecular dynamics (MD) simulations have difficulties in tracking the slow molecular motions, at least partially due to the waste of sampling in already sampled regions. Here, we proposed a new enhanced sampling method, frontier expansion sampling (FEXS), to improve the sampling efficiency of molecular simulations by iteratively selecting seed structures diversely distributed at the "frontier" of an already sampled region to initiate new simulations. Different from other enhanced sampling methods, FEXS identifies the "frontier" seeds by integrating the Gaussian mixture model and the convex hull algorithm, which effectively improves the structural variation among the selected seeds and thus the descendant simulations. Validation in three protein systems, including the folding of chignolin, open-to-closed transition of maltodextrin binding protein, and internal conformational change of bovine pancreatic trypsin inhibitor, confirmed the effectiveness of this novel method in enhancing the sampling of conventional MD simulations to observe the large-scale protein conformational changes. When compared with other enhanced sampling methods like the structural dissimilarity sampling (SDS), FEXS reached at least the same level of sampling efficiency but was capable of providing complementary information in the three tested protein systems.


Exploring complementary and alternative medicine in pediatrics: parents and professionals working together for new understanding.
In the United States, consumer interest in and use of complementary and alternative medicine (CAM), including in pediatrics, is growing. Despite the reservations of many conventional practitioners, the multi-billion dollar industry is here to stay. To maintain positive relationships with pediatric patients and their families, health care professionals must acknowledge the reality of CAM, be informed themselves about its various therapies, and encourage open dialogue with patients and families. This article offers background about the current status of CAM, in general as well as specific information about CAM in pediatrics. The parent/family perspective, a list of suggested questions to help initiate parent/professional discussion about exploration and use of CAM, and a resource list for use by both parents and professionals are provided.


Persistent recruitment of somatosensory cortex during active maintenance of hand images in working memory.
Working memory (WM) supports temporary maintenance of task-relevant information. This process is associated with persistent activity in the sensory cortex processing the information (e.g., visual stimuli activate visual cortex). However, we argue here that more multifaceted stimuli moderate this sensory-locked activity and recruit distinctive cortices. Specifically, perception of bodies recruits somatosensory cortex (SCx) beyond early visual areas (suggesting embodiment processes). Here we explore persistent activation in processing areas beyond the sensory cortex initially relevant to the modality of the stimuli. Using visual and somatosensory evoked-potentials in a visual WM task, we isolated different levels of visual and somatosensory involvement during encoding of body and non-body-related images. Persistent activity increased in SCx only when maintaining body images in WM, whereas visual/posterior regions' activity increased significantly when maintaining non-body images. Our results bridge WM and embodiment frameworks, supporting a dynamic WM process where the nature of the information summons specific processing resources.


The cholinergic agonist RS 86: a pharmacopsychological study.
The cholinergic-adrenergic balance hypothesis of affective disorders postulates noradrenergic over-activity and cholinergic hypoactivity in mania and the converse in depression. Some evidence for cholinergic contributions to mood regulation derives from the antimanic and depressiogenic activity of physostigmine and arecoline. However, both drugs have pharmacodynamic and pharmacokinetic disadvantages. Therefore, the orally active muscarinic agonist RS 86 was tested in a double-blind dose-response study for its psychotropic effects in one healthy volunteer. A dose-dependent anergic-anhedonic syndrome was identified in comparison to placebo. The study confirms the physostigmine syndrome to be mediated by muscarinic, possibly M1 receptors, and gives further support to the hypothesis of a cholinergic modulation of mood and behavior in man.


Embedded Ultrasonic Inspection on the Mechanical Properties of Cold Region Ice under Varying Temperatures.
The mechanical properties of ice in cold regions are significantly affected by the variation in temperature. The existing methods to determine ice properties commonly rely on one-off and destructive compression and strength experiments, which are unable to acquire the varying properties of ice due to temperature variations. To this end, an embedded ultrasonic system is proposed to inspect the mechanical properties of ice in an online and real-time mode. With this system, ultrasonic experiments are conducted to testify to the validity of the system in continuously inspecting the mechanical properties of ice and, in particular, to verify its capabilities to obtain ice properties for various temperature conditions. As an extension of the experiment, an associated refined numerical model is elaborated by mimicking the number, size, and agglomeration of bubbles using a stochastic distribution. This system can continuously record the wave propagation velocity in the ice, giving rise to ice properties through the intrinsic mechanics relationship. In addition, this model facilitates having insights into the effect of properties, e.g., porosity, on ice properties. The proposed embedded ultrasonic system largely outperforms the existing methods to obtain ice properties, holding promise for developing online and real-time monitoring techniques to assess the ice condition closely related to structures in cold regions.


Long-term injection sclerotherapy for the primary and secondary management of variceal haemorrhage.
The beneficial effects of long-term sclerotherapy upon rebleeding from esophageal varices have been well established by several controlled trials, although the high frequency of early recurrent hemorrhage remains an important limitation. The beneficial effect of sclerotherapy on survival in such patients is less clear, but may also be concluded when the comparison is with control groups managed by conservative methods alone. The future probably lies with concepts of less intensive regimes of sclerotherapy. The evidence available with respect to prophylactic sclerotherapy is clearly conflicting. However, there is little to support the further use of this therapy in unselected groups of patients. Subsequent studies should be aimed specifically towards the selection of patients at high risk of first variceal hemorrhage, which might then be candidates more likely to benefit from prophylactic treatment.


Vaping: What Every Emergency Nurse Practitioner Should Know!
As of December 10, 2019, according to the Centers for Disease Control and Prevention (CDC), more than 2,668 hospitalized cases of lung injury and 60 deaths associated with use of electronic nicotine delivery systems, or "vaping." In many cases, patients required multiple health care visits prior to diagnosis. Recognition of the risk factors, symptoms, and examination findings that have been consistently reported is critical to making the diagnosis and initiating treatment early in the progression of disease. The precise mechanism and causative agent have yet to be elucidated, but the association with vaping has been established. Multidisciplinary collaboration among health care providers, poison centers, health departments, reference laboratories, and the CDC will be necessary to identify the cause and prevent further harm.


Light production by green plants.
1. Green plants have been found to emit light of approximately the same color as their fluorescent light for several minutes following illumination. This light is about 10(-3) the intensity of the fluorescent light, about one-tenth second after illumination below saturation or 10(-6) of the intensity of the absorbed light. 2. The decay curve follows bimolecular kinetics at 6.5 degrees C. and reaction order 1.6 at 28 degrees C. 3. This light saturates as does photosynthesis at higher light intensities and in about the same intensity range as does photosynthesis. 4. An action spectrum for light emitted as a function of the wave length of exciting light has been determined. It parallels closely the photosynthetic action spectrum. 5. The intensity of light emission was studied as a function of temperature and found to be optimal at about 37 degrees C. with an activation energy of approximately 19,500 calories. Two-temperature studies indicated that the energy may be trapped in the cold, but that temperatures characteristic for enzymatic reactions are necessary for light production. 6. Illumination after varying dark periods showed initial peaks of varying height depending on the preceding dark period. 7. 5 per cent CO(2) reversibly depresses the amount of light emitted by about 30 per cent. About 3 minutes are required for this effect to reach completion at room temperatures. 8. Various inhibitors of photosynthesis were tested for their effect on luminescence and were all inhibitory at appropriate concentrations. 9. Irradiation with ultraviolet light (2537A) inhibits light production at about the same rate as it inhibits photosynthesis. 10. This evidence suggests that early and perhaps later chemical reactions in photosynthesis may be partially reversible.


Protective effect of Liuwei Dihuang decoction on early diabetic nephropathy induced by streptozotocin via modulating ET-ROS axis and matrix metalloproteinase activity in rats.
We aimed to investigate the effects of Liuwei Dihuang decoction (LW) on the endothelin-1-reactive oxidative species (ET-ROS) system and matrix metalloproteinases (MMPs) in the early diabetic nephropathy induced by streptozotocin (STZ) in rats. Rats were divided into six groups as follows: the control group, the untreated model group, the treated groups with the LW (5, 10 and 15 g kg(-1), p.o.) and the aminoguanidine-treated group (100 mg kg(-1), orally). The treatment was performed for 4 weeks, beginning on the fifth week after one intraperitoneal injection of STZ (65 mg kg(-1)). In the untreated model group, increased blood glucose, decreased plasma insulin level and an impaired renal function were observed. There was an altered redox system shown by an increased malondialdehyde and decreased activity of glutathione peroxidase and superoxide dismutase in the renal cortex. An enhanced inducible nitric oxide synthetase, total nitric oxide synthase and constitutive nitric oxide synthase and a declined nitric oxide were found. An increased extracellular matrix was indicated by an abnormality of MMP-2 and MMP-9 activities and an increase in hydroxyproline. An up-regulated ET-1 level and increased mRNA expression of endothelin-converting enzyme, preproET-1 and ET( A) receptor were presented in the affected renal cortex, but no change in ET(B) receptor mRNA. The LW was most effective in reversing these changes in diabetic rats and was as effective as aminoguanidine. The benefits of the extracts in relieving the abnormalities in early diabetic nephropathy are likely to be mediated by suppression of the renal ET-ROS system and escalating the activity of MMPs.


Factors influencing the choice of antihypertensive agents.
Personal, social, and medical factors unique to individual patients have a bearing on the efficacy of specific antihypertensive agents and on the frequency and severity of side effects. The factors relate to age, sex, occupation, potential for adherence to a prescribed program of therapy, and associated health problems. The importance of a simple, inexpensive program is emphasized.


Whispering gallery resonators for studying orbital angular momentum of a photon.
We propose a simple method for generation and detection of photons with nonzero angular momentum. The method utilizes high-quality factor ring resonators that transform a plane electromagnetic wave into a wave with nonzero angular momentum, and vice versa. We show that the method is especially promising for studying high-order Bessel beams, unreachable by other techniques.


[Uremic media affects hemostatic properties of human endothelial cells in culture and increases the production of von Willebrand factor].
We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effect of the uremic media on the morphology of ECs, and their resistance to flow was analyzed. The reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic media resulted in abnormal morphology and signs of accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (22% vs 13%). Platelet deposition and formation of aggregates were significantly elevated on ECMs generated in the presence of uremic media (40.23 +/- 6.43% vs 25.42 +/- 2.69%, p < 0.05, n = 5). Immunocytochemical methods detected an enhanced expression of von Willebrand factor antigen on uremic ECMs (uremic 17.1 +/- 4.2% vs control 13.57 +/- 3.98%, p < 0.05) and its mRNA expression in endothelial cells (uremic 213.24 +/- 6.13 vs control 200.77 +/- 7.52, p < 0.05). These results suggest that uremic medium alters endothelial function and impairs the antithrombotic functions of cultured endothelial cells. This effect may contribute to the increased cardiovascular and thrombotic risk reported in ESRD patients.


Theory-of-Mind Development and Early Sibling Relationships after the Birth of a Sibling: Parental Discipline Matters.
This study investigated relations among children's Theory-of-Mind (ToM) development, early sibling interactions, and parental discipline strategies during the transition to siblinghood. Using a sample of firstborn children and their parents (N = 208), we assessed children's ToM before the birth of a sibling and 12 months after the birth, and sibling interactions (i.e., positive engagement and antagonism) and parental discipline strategies (i.e., child-centred and parent-centred discipline) at 4 and 8 months in the first year of siblinghood. Structural equation modelling analyses revealed that children's ToM before the birth of the sibling predicted children's positive engagement with the infant sibling, whereas children's antagonistic behaviours towards the infant sibling negatively predicted children's ToM at 12 months, but only when mothers used low levels of child-centred discipline. These findings emphasize the role of parents in the development of young children's social- cognitive understanding in the context of sibling interactions even as early as the first year after the sibling's birth.


Subcellular localization of hepatitis C virus structural proteins in the liver of transgenic mice.
Hepatitis C virus (HCV) core and envelope proteins are suggested to be responsible for the pathogenesis of hepatic and extrahepatic manifestations in chronic hepatitis C. Moreover, the core protein is implicated in the regulation of the transcription of cellular genes including c-myc, RB and p53. Determining the subcellular localization of the core and envelope proteins is therefore necessary to elucidate their behaviors, particularly in vivo ones, regarding the interaction with transcriptional regulatory proteins or gene elements. We defined the subcellular localization of HCV envelope and core proteins which were expressed in substantial levels in the liver of transgenic mice. Subcellular fractionation by ultra-centrifugation revealed that the envelope proteins were present principally in the microsomes of the liver, while a small amount of the protein was detected also in the nuclei. Immunohistochemistry confirmed the localization of envelope proteins in the nuclei. In contrast, the core protein was detected principally in the cytoplasmic fraction, where it was closely associated with lipids. A low level of the core protein was detected also in the nuclei and microsomal fraction. These results suggest possible interaction of the HCV structural proteins with some factors in hepatocytes thereby perturbing intracellular circumstances.


Occupational Diesel Exposure, Duration of Employment, and Lung Cancer: An Application of the Parametric G-Formula.
If less healthy workers terminate employment earlier, thus accumulating less exposure, yet remain at greater risk of the health outcome, estimated health effects of cumulative exposure will be biased downward. If exposure also affects termination of employment, then the bias cannot be addressed using conventional methods. We examined these conditions as a prelude to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study. We applied an accelerated failure time model to assess the effect of exposures to respirable elemental carbon (a surrogate for diesel) on time to termination of employment among nonmetal miners who ever worked underground (n = 8,307). We then applied the parametric g-formula to assess how possible interventions setting respirable elemental carbon exposure limits would have changed lifetime risk of lung cancer, adjusting for time-varying employment status. Median time to termination was 36% shorter (95% confidence interval = 33%, 39%), per interquartile range width increase in respirable elemental carbon exposure. Lung cancer risk decreased with more stringent interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1) comparing a limit of ≤25 µg/m respirable elemental carbon to no intervention. The fraction of cases attributable to diesel exposure was 27% in this population. The g-formula controlled for time-varying confounding by employment status, the signature of healthy worker survivor bias, which was also affected by diesel exposure. It also offers an alternative approach to risk assessment for estimating excess cumulative risk, and the impact of interventions based entirely on an observed population.


Phylogenetic placement of the lichenicolous, anamorphic genus Lichenodiplis and its connection to Muellerella-like teleomorphs.
Lichenicolous fungi are a specialized group of taxa which inhabit lichens and develop diverse degrees of specificity and parasitic behaviour towards their hosts. They are recognized only by their phenotypic symptoms and sexual or asexual spore-producing structures on the lichen thalli. Only recently, molecular data and culture dependent approaches have helped in uncovering the species diversity and in verifying the phylogenetic position and anamorph-teleomorph relationships of some taxa. Here, we studied the phylogenetic placement of representative taxa of two lichenicolous genera, the coelomycete Lichenodiplis and the ascomycete Muellerella. We obtained molecular data for three nuclear and mitochondrial loci (28S, 18S, and 16S), both from fresh collected specimens and culture isolates. Our multilocus phylogeny places Lichenodiplis and Muellerella samples in one monophyletic, fully supported clade, sister to Epibryon (Epibryaceae) in Chaetothyriales (Eurotiomycetes). Morphological analyses of axenically cultured fungi show the formation of conidiomata and conidiospores in both Lichenodiplis and Muellerella isolates. We suggest that the species Lichenodiplis lecanorae and Muellerella atricola represent, respectively, the anamorphic and teleomorphic stages of the same fungus and discuss their relationships with the other fungal families in Chaetothyriomycetidae.


Quiescent-interval single-shot unenhanced magnetic resonance angiography of peripheral vascular disease: Technical considerations and clinical feasibility.
We performed technical optimization followed by a pilot clinical study of quiescent-interval single-shot MR angiography for peripheral vascular disease. Quiescent-interval single-shot MR angiography acquires data using a modified electrocardiographic (ECG)-triggered, fat suppressed, two-dimensional, balanced steady-state, free precession pulse sequence incorporating slice-selective saturation and a quiescent interval for maximal enhancement of inflowing blood. Following optimization at 1.5 T, a pilot study was performed in patients with peripheral vascular disease, using contrast-enhanced MR angiography as the reference standard. The optimized sequence used a quiescent interval of 228 ms, alpha/2 catalyzation of the steady-state magnetization, and center-to-out partial Fourier acquisition with parallel acceleration factor of 2. Spatial resolution was 2-3mm along the slice direction and 0.7-1mm in-plane before interpolation. Excluding stented arterial segments, the sensitivity, specificity, and positive and negative predictive values of quiescent-interval single-shot MR angiography for arterial narrowing greater than 50% or occlusion were 92.2%, 94.9%, 83.9%, and 97.7%, respectively. Quiescent-interval single-shot MR angiography provided robust depiction of normal peripheral arterial anatomy and peripheral vascular disease in less than 10 min, without the need to tailor the technique for individual patients. Moreover, the technique provides consistent image quality in the pelvic region despite the presence of respiratory and bowel motion.


[Detection of the communication site by dye injection method at the surgery for pleuroperitoneal communication].
A 65-year-old male with end stage renal failure due to IgA nephritis commenced continuous ambulatory peritoneal dialysis (CAPD). Three weeks after initiation of CAPD, right hydrothorax developed. Then, we strongly assumed pleuroperitoneal communication( PPC) although the pleural effusion did not show high concentration of glucose. He underwent thoracoscopic surgery for PPC. On the inner, central tendons part of the diaphragm, there were a few blebs. One hour after 3 l of peritoneal dialysis solution containing 15 ml indigocarmine was instilled into the abdomen through a CAPD catheter, the blebs were tense and colored blue by the dye solution. The blebs were directly sutured and diaphragm was covered by polyglycolic acid sheet and fibrin glue all over. Since then, he resumed CAPD, without recurrence of hydrothorax. Then we investigated the treatment outcome of video-assisted thoracic surgery (VATS) for PPC in Japan. The outcome was poorer in cases in which communication was not detected intraoperatively. These patients should be given sufficient consideration for surgical procedure.


CASC2: An emerging tumour-suppressing long noncoding RNA in human cancers and melanoma.
Deregulation of long noncoding RNAs (lncRNAs) has been implicated in tumourigenesis. Cancer Susceptibility Candidate 2 (CASC2) is a lncRNA downregulated in multiple cancer types, including endometrial, lung, gastric and colorectal cancers. CASC2 functions as a tumour-suppressive lncRNA though multiple mechanisms, such as sequestration of oncogenic microRNAs and repression of Wnt/β-catenin signalling. Pertinent to clinical practice, the use of CASC2 as a prognostic marker has been demonstrated in sporadic studies. These findings suggested that CASC2 might play an important role in human cancers and melanoma. More efforts are warranted to examine the function role of CASC2 in other cancer types. Further validation is also needed to promote its development to be a clinically utilizable prognostic biomarker.


Women's perception of intrapartal care in relation to WHO recommendations.
The aims of this study were to elucidate women's perception of intrapartal care and women's perceptions of normal birth. A questionnaire developed from the WHO's recommendations for care in normal birth was answered by 138 (response rate 66.0% Swedish women. The women were asked to evaluate items in two ways: their perceived reality of care received and the subjective importance of each item. Most women reported receiving care in the category (A) practices that are good and should be encouraged. However, women to a minor degree reported assessment for physical health, enquiring about support needs and pain assessment on admission. Many women received electronic foetal monitoring, repeated vaginal examinations, oxytocin augmentation and suturing after birth which fall under the category (B) practices that are harmful, (C) insufficient evidence exists and (D) practices frequently used inappropriately. The women who reported 'Yes' for perceived reality also reported high subjective importance for those items regardless of category A-D. Eighty-four per cent of the women perceived that they had a normal delivery. The result suggests that women have great trust that the care midwives give them is the best care. Midwives, therefore, have an ethical responsibility to keep themselves informed about the best evidence-based care and to implement critical reviewing of their practice as part of continuing professional development. The women's perceptions of a normal birth allows for a wide range of interventions. The result emphasises the importance of midwives' knowledge of evidence-based care and how to implement this into practice. Further research should include elucidation of the meaning of normal childbirth to childbearing women.


Fluid-fluid level on magnetic resonance images may predict the occurrence of pituitary adenomas in cystic sellar-suprasellar masses.
The aim of the present study was to evaluate the value of identifying fluid-fluid level via preoperative magnetic resonance (MR) images in differentiating pituitary adenomas from craniopharyngioma, Rathke's cleft cyst (RCC), and other cystic sellar-suprasellar lesions. The data of 293 consecutive patients who underwent surgery for sellar-suprasellar lesions between July 2010 and December 2012 was retrospectively reviewed, and a total of 133 cystic cases were included in the present study. MR images and pathological features of all subjects were examined. Among the 133 cystic sellar-suprasellar masses, there were 78 cases of pituitary adenomas, 31 cases of craniopharyngioma, 21 cases of RCC, one case of epidermoid cyst and two cases of abscess. Fluid-fluid levels were identified n 43 cases (55.13%) of cystic pituitary adenomas, with a single fluid level in 23 cases, two fluid levels in 8 cases, and three levels or more in 12 cases. Two cases (6.45%) of craniopharyngioma, and one case (4.76%) of RCC presented single fluid level. No instances of fluid-fluid levels were observed in epidermoid cyst or abscess. Fluid-fluid levels were typically exhibited on axial T2-weighted images. The identification of fluid-fluid level in cysts provides useful diagnostic value in distinguishing pituitary adenoma from other sellar-suprasellar lesions. The findings of the present study suggest that a sellar-suprasellar mass with a fluid-fluid level inside the tumor is most likely a pituitary adenoma, particularly if multiple fluid levels are observed in the same tumor. The fluid-fluid level is typically clearly depicted on axial or sagittal MR images, suggesting subacute or chronic hemorrhage in pituitary adenomas.


Early growth response transcription factor EGR-1 regulates Galphaq gene in megakaryocytic cells.
Galphaq (Gene GNAQ) plays a major role in platelet signal transduction but little is known regarding its transcriptional regulation. We studied Galphaq promoter activity using luciferase reporter gene assays in human erythroleukemia (HEL) cells treated with phorbol 12-myristate 13-acetate (PMA) for 24 h to induce megakaryocytic transformation. PMA-treated HEL cells showed enhanced Galphaq expression. Reporter (luciferase) gene studies on 5' upstream construct (up to -116 bp from ATG) revealed a negative regulatory site at -238/-202 and two positive sites at -203/-138 and -1116/-731. The positive regulatory region -203/-138 contained overlapping Sp1/AP-2/EGR-1 consensus sites. Gel shift studies on Galphaq oligonucleotides 1 (-203/-175) and 2 (-174/-152) using HEL cell extracts demonstrated protein binding that was due to early growth response factor EGR-1 at two sites. Mutations in either EGR-1 site markedly decreased the gene activity, indicating functional relevance. Mutation of consensus E-Box motif (-185/-180) had no effect. Reduction in the expression of endogenous EGR-1 with antisense oligonucleotide to EGR-1 inhibited PMA-induced Galphaq transcription. Correspondingly, Egr-1 deficient mouse platelets also showed approximately 50% reduction in the Galphaq expression relative to wild-type platelets. These studies suggest that Galphaq gene is regulated during PMA-induced megakaryocytic differentiation by EGR-1, an early growth response transcription factor that regulates a wide array of genes and plays a major role in diverse activities, including cell proliferation, differentiation and apoptosis, and in vascular response to injury and atherosclerosis.


Immunological mechanisms of epidermal damage in toxic epidermal necrolysis.
The purpose of the present review is to introduce recent findings on the pathomechanisms of toxic epidermal necrolysis (TEN), which is characterized by widespread epidermal detachment due to keratinocyte apoptosis. In the mechanism of epidermal damage, the roles of drug metabolites, cytotoxic lymphocytes, and apoptosis-inducing factors have been noted. In addition, recent studies have focused on monocytes/macrophages, which may participate in epidermal damage through the production of apoptosis-inducing factors and the expression of costimulatory factors with the ability to activate CD8 T cells. Epidermal keratinocyte death is a hallmark of TEN. In a very high proportion of cases, drugs are responsible for TEN. It has been suggested that toxic drug metabolites produced by keratinocytes act like electrophilic agents to induce apoptosis and inflammation. Next, cytotoxic lymphocytes and monocytes function in the development of widespread epidermal damage through direct or indirect cytotoxic pathways. In addition, T-cell activation may be strengthened by the impairment of regulatory T-cell function and activated monocytes. The development of epidermal damage in TEN may require the coordinated action of these factors.


Association of atherosclerotic plaque features with collateral circulation status in elderly patients with chronic carotid stenosis.
To determine the association of carotid plaque features with collateral circulation status in elderly patients with moderate to severe carotid stenosis. Elderly patients (> 60 years) with moderate to severe carotid stenosis were recruited and categorized into good and poor collateral circulation groups, and underwent magnetic resonance imaging and computed tomography imaging. The carotid plaque features including lipid-rich necrotic core, intraplaque hemorrhage, calcification, and fibrous cap rupture (FCR) were evaluated, and maximum wall thickness, normalized wall index (NWI), and luminal stenosis were measured. The association between these variables and collateral circulation status was analyzed. Of the 97 patients (78 males, mean age: 69.0 ± 6.1 years), 19 (19.6%) had poor collaterals. The poor collateral group had a significantly higher NWI (93.7% ± 5.0% vs. 89.0% ± 7.9%, P = 0.011), a greater extent of stenosis (80.0% ± 11.4% vs. 75.3% ± 9.4%, P = 0.036) and FCR (84.2% vs. 55.1%, P = 0.020) compared with good collateral group. Carotid NWI (OR = 3.83, 95% CI: 1.36-10.82, P = 0.011) and more FCR (OR = 6.77, 95% CI: 1.35-33.85, P = 0.020) were associated with poor collateral circulation after adjustment for the confounding factors. The combination of NWI, FCR, systolic blood pressure, and triglycerides had the highest area-under-the-curve (AUC = 0.85) for detection of poor collaterals. Carotid plaque features, specifically NWI and FCR, are independently associated with poor collateral circulation, and the combination of carotid plaque features and traditional risk factors has a stronger predictive value for poor collateral circulation than plaque features alone.


Surface catalysis of water oxidation by the blue ruthenium dimer.
Single-electron activation of multielectron catalysis has been shown to be viable in catalytic water oxidation with stepwise proton-coupled electron transfer, leading to high-energy catalytic precursors. For the blue dimer, cis,cis-[(bpy)(2)(H(2)O)Ru(III)ORu(III)(H(2)O)(bpy)(2)](4+), the first well-defined molecular catalyst for water oxidation, stepwise 4e(-)/4H(+) oxidation occurs to give the reactive precursor [(O)Ru(V)ORu(V)(O)](4+). This key intermediate is kinetically inaccessible at an unmodified metal oxide surface, where the only available redox pathway is electron transfer. We report here a remarkable surface activation of indium-tin oxide (In(2)O(3):Sn) electrodes toward catalytic water oxidation by the blue dimer at electrodes derivatized by surface phosphonate binding of [Ru(4,4'-((HO)(2)P(O)CH(2))(2)bpy)(2)(bpy)](2+). Surface binding dramatically improves the rate of surface oxidation of the blue dimer and induces water oxidation catalysis.


Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options.
Autosomal dominant polycystic kidney disease (ADPKD) is the reported etiology in 10% of end-stage kidney disease (ESKD) patients and has an estimated prevalence of 12.5 million cases worldwide across all ethnicities. There have been major advancements over the last two decades in understanding the pathogenesis and development of disease-modifying treatment options for ADPKD, culminating in regulatory approval of tolvaptan for ADPKD patients at risk of rapid progression to kidney failure. This review highlights the genetic mutations associated with ADPKD, defines patients at risk of rapid progression to ESKD, and focuses on the management of ADPKD in the era of disease-modifying agents.


Independently living seniors and vitamin therapy. What nurses should know.
1. Over-the-counter vitamin/mineral supplement consumption has become customary among many older adults in the United States. Inappropriately used, these dietary supplements possess the capacity for producing toxic reactions. 2. Vitamins/minerals can be harmful when taken incorrectly or in lavish proportions. Even though the Food and Drug Administration does not classify dietary supplements as drugs, a vitamin must be viewed as a medication when consumed in excess. Excessive intakes of vitamins A, C, and D are known to have adverse effects. 3. It is imperative that nurses incorporate vitamin therapy assessment into their practice, whether it be administration, education, or research. Unless ordered by a physician for a medically based pathology, nutrient supplementation should not exceed the RDA levels for older adults, if supplementation is used at all.


Endoscopic ultrasound features of gastric schwannomas with radiological correlation: a case series report.
Gastric schwannomas are rare mesenchymal tumors of the gastrointestinal tract. They are usually misdiagnosed as other submucosal tumors preoperatively. Experience of the imaging features of gastric schwannomas is extremely limited. In this report, we summarize the features of a series of endoscopic ultrasound (EUS) images of gastric schwannomas in an effort to improve the diagnosis and differential diagnosis rate. We retrospectively reviewed the endosonographic features of four patients with gastric schwannomas and their computed tomography imaging results. Gastric schwannomas had heterogeneous hypoechogenicity or isoechogenicity, and a well-demarcated margin. The tumors originated from the fourth layer. Cystic changes and calcification were uncommon. Marginal hypoechoic haloes were observed in two patients. The results described here were different from those of previous studies. In the EUS evaluation, the internal echogenicity of gastric schwannomas was heterogeneous and low, but slightly higher than that of muscularis propria. These features might help us differentiate gastric schwannomas from other submucosal tumors. Further investigation is needed to differentiate these mesenchymal tumors.


Regulation of smooth muscle cells in development and vascular disease: current therapeutic strategies.
Vascular smooth muscle cells (SMCs) exhibit extensive phenotypic diversity and rapid growth during embryonic development, but maintain a quiescent, differentiated state in adult. The pathogenesis of vascular proliferative diseases involves the proliferation and migration of medial vascular SMCs into the vessel intima, possibly reinstating their embryonic gene expression programs. Multiple mitogenic stimuli induce vascular SMC proliferation through cell cycle progression. Therapeutic strategies targeting cell cycle progression and mitogenic stimuli have been developed and evaluated in animal models of atherosclerosis and vascular injury, and several clinical studies. Recent discoveries on the recruitment of vascular progenitor cells to the sites of vascular injury suggest new therapeutic potentials of progenitor cell-based therapies to accelerate re-endothelialization and prevent engraftment of SMC-lineage progenitor cells. Owing to the complex and multifactorial nature of SMC regulation, combinatorial antiproliferative approaches are likely to be used in the future in order to achieve maximal efficacy and reduce toxicity.


Successful delayed bilateral renal revascularization during active phase of Takayasu's arteritis.
Successful bilateral renal revascularization was performed 24 days after the development of angiotensin converting enzyme-inhibitor-induced bilateral renal artery thrombosis and anuric acute renal failure in a patient with Takayasu's arteritis. Excellent results were obtained after an unusually long ischemic time for a patient with active-phase disease. The outcome suggests that aggressive surgical revascularization can benefit patients with renal failure caused by renal arterial occlusion during the active phase of Takayasu's arteritis.


A multidisciplinary approach to short bowel syndrome.
Short bowel syndrome is a complex clinical picture, characterized by signs and symptoms of malabsorption and subsequent malnutrition, which often occurs after extensive bowel resections. Short bowel syndrome's treatment must begin together with the planning of the first surgery, especially for disease that may need multiple interventions. Patients with short bowel should be individually managed because they all are different in diagnosis, length of the remaining bowel and in psychosocial characteristics. For all these reasons, a multidisciplinary approach between the various specialists is therefore needed.


Source of Chronic Inflammation in Aging.
Aging is a complex process that results from a combination of environmental, genetic, and epigenetic factors. A chronic pro-inflammatory status is a pervasive feature of aging. This chronic low-grade inflammation occurring in the absence of overt infection has been defined as "inflammaging" and represents a significant risk factor for morbidity and mortality in the elderly. The low-grade inflammation persists even after reversing pro-inflammatory stimuli such as LDL cholesterol and the renin-angiotensin system (RAS). Recently, several possible sources of chronic low-grade inflammation observed during aging and age-related diseases have been proposed. Cell senescence and dysregulation of innate immunity is one such mechanism by which persistent prolonged inflammation occurs even after the initial stimulus has been removed. Additionally, the coagulation factor that activates inflammatory signaling beyond its role in the coagulation system has been identified. This signal could be a new source of chronic inflammation and cell senescence. Here, we summarized the factors and cellular pathways/processes that are known to regulate low-grade persistent inflammation in aging and age-related disease.


Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells.
We identified a novel gene HJURP (Holliday junction-recognizing protein) whose activation seemed to play a pivotal role in the immortality of cancer cells. HJURP was considered a possible downstream target for ataxia telangiectasia mutated signaling, and its expression was increased by DNA double-strand breaks (DSB). HJURP was involved in the homologous recombination pathway in the DSB repair process through interaction with hMSH5 and NBS1, which is a part of the MRN protein complex. HJURP formed nuclear foci in cells at S phase and those subjected to DNA damage. In vitro assays implied that HJURP bound directly to the Holliday junction and rDNA arrays. Treatment of cancer cells with small interfering RNA (siRNA) against HJURP caused abnormal chromosomal fusions and led to genomic instability and senescence. In addition, HJURP overexpression was observed in a majority of lung cancers and was associated with poor prognosis as well. We suggest that HJURP is an indispensable factor for chromosomal stability in immortalized cancer cells and is a potential novel therapeutic target for the development of anticancer drugs.


Using Generalized Anxiety Disorder-2 (GAD-2) and GAD-7 in a Primary Care Setting.
Anxiety disorders are highly prevalent in the primary care setting and are responsible for significant morbidity as well as a loss of productivity. Evaluation by mental health specialists and behavioral specialists can sometimes be confounded with problems of availability, accessibility, and the patient's hesitancy to talk to new providers due to lack of prior relationship and trust. Primary care providers already have the advantage of being available for their patients, and have built years of trust behind them to strengthen this relationship. The biggest problems which confront primary care are the time constraints as well as the presence of multiple medical demands. This leads to a constant need for tools that facilitate early recognition and diagnosis of mental health disorders while also providing judicious utilization of clinic time. This article attempts to review the use of two of these popular tools: Generalized Anxiety Disorder scale-2 (GAD-2) and GAD-7 in the primary care setting.


Black Phosphorus Quantum Dots as the Ratiometric Fluorescence Probe for Trace Mercury Ion Detection Based on Inner Filter Effect.
In this work, a novel ratiometric fluorescence sensor has been constructed for the selective and sensitive detection of Hg2+, which is based on the inner filter effect (IFE) of tetraphenylporphyrin tetrasulfonic acid (TPPS) toward black phosphorus quantum dots (BP QDs). Highly fluorescent BP QDs were successfully synthesized from bulk BP by sonication-assisted solvothermal method via a top-down route. In the presence of Hg2+, the IFE originating from spectral overlap between the excitation of BP QDs and the absorption of TPPS is inhibited and the fluorescence of BP QDs is restored. At the same time, the red fluorescence of TPPS is quenched due to its coordination with Mn2+. These phenomena result from the rapid coordination between Mn2+ and TPPS in the presence of Hg2+, which leads to the dramatic decrease of the absorption of TPPS. On the basis of these findings, we design a ratiometric fluorescence sensor for the detection of Hg2+. The as-constructed sensor reveals a good linear response to Hg2+ ranging from 1 to 60 nM with a detection limit of 0.39 nM. Furthermore, the sensing assay is applicable to detecting Hg2+ in real samples.


Additive Value of Preprocedural Computed Tomography Planning Versus Stand-Alone Transesophageal Echocardiogram Guidance to Left Atrial Appendage Occlusion: Comparison of Real-World Practice.
Background Transesophageal echocardiogram is currently the standard preprocedural imaging for left atrial appendage occlusion. This study aimed to assess the additive value of preprocedural computed tomography (CT) planning versus stand-alone transesophageal echocardiogram imaging guidance to left atrial appendage occlusion. Methods and Results We retrospectively reviewed 485 Watchman implantations at a single center to compare the outcomes of using additional CT preprocedural planning (n=328, 67.6%) versus stand-alone transesophageal echocardiogram guidance (n=157, 32.4%) for left atrial appendage occlusion. The primary end point was the rate of successful device implantation without major peri-device leak (>5 mm). Secondary end points included major adverse events, total procedural time, delivery sheath and devices used, risk of major peri-device leak and device-related thrombus at follow-up imaging. A single/anterior-curve delivery sheath was used more commonly in those who underwent CT imaging (35.9% versus 18.8%; P<0.001). Additional preprocedural CT planning was associated with a significantly higher successful device implantation rate (98.5% versus 94.9%; P=0.02), a shorter procedural time (median, 45.5 minutes versus 51.0 minutes; P=0.03) and a less frequent change of device size (5.6% versus 12.1%; P=0.01), particularly device upsize (4% versus 9.4%; P=0.02). However, there was no significant difference in the risk of major adverse events (2.1% versus 1.9%; P=0.87). Only 1 significant peri-device leak (0.2%) and 5 device-related thrombi were detected in follow-up (1.2%) with no intergroup difference. Conclusions Additional preprocedural planning using CT in Watchman implantation was associated with a higher successful device implantation rate, a shorter total procedural time, and a less frequent change of device sizes.


Self-assembly of halogenated cobaltacarborane compounds: boron-assisted C--H...X--B hydrogen bonds?
Full structural characterisation and complete synthetic procedures for three monohalogenated cobaltacarborane compounds closo-[3-Co(eta5-C5H5)-8-X-1,2-C2B9H10] (X=Cl (1), Br (2), I (3)) and the dibromo derivative closo-[3-Co(eta5-C5H5)-8,9-Br2-1,2-C2B9H9] (4) are reported. The supramolecular structures of 1, 3, and 4 reveal the existence of intermolecular C--HX--B interactions. The role of these interactions has been investigated through a CSD search and subsequent analysis of the reported crystalline compounds. The results show that halogens become reasonably good hydrogen-bond acceptors when bonded to boron and, in this respect, are comparable in strength to metal-bound halogens.


Cationic starch (Q-TAC) pre-treatment of cotton fabric: influence on dyeing with reactive dye.
Reactive dyes require high concentrations of an electrolyte to improve dye-fiber interaction, leading to the discharge of harmful effluent. One approach to reduce this unsafe release is treatment of the cotton fabric with cationic chemical reagents. This paper reports on the treatment of cotton fabric with cationic starch (Q-TAC), a commercial product, by batchwise method and pad batch method for the first time prior to reactive dyeing process. Furthermore,three commercial reactive dyes, based on monochloro triazine, vinyl sulfone and monochlorotriazine + vinyl sulfonechemistry, was applied on the cotton fabrics by continuous (pad-dry-cure) method. The treated cotton fabric by batchwise method produced 70% higher color yield (K/S) and 20% enhanced dye fixation (%F) than the untreated cotton fabric. X-ray photoelectron spectrometer (XPS) analysis revealed the presence of N1s peaks in the treated cotton fabrics. The crystallinity of treated cotton fabrics was reduced in comparison to untreated cotton fabric as revealed by wide angle X-ray diffraction (WAXD) measurements. Field Emission Scanning Electron Microscopy (FE-SEM) showed that the surface of treated cotton fabrics was rougher than untreated cotton fabric due to the deposition of cationic starch. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrum confirmed the existence of quaternary ammonium groups, N(+)(CH3)3, in the treated cotton fabrics. The analysis of color fastness tests demonstrated good to excellent ratings for treated cotton fabrics. In this way, cationic starch treatment of cotton fabric before reactive dyeing process has been proven potentially a more environmentally sustainable method than conventional dyeing method.


Multilocus sequence types of invasive pneumococcal isolates from Danish infants (0-90 days) 2003-2013.
A pneumococcal conjugate vaccine (PCV) has been part of the Danish childhood immunization programme since October 2007. It is administered at the ages of 3, 5 and 12 months and healthy infants younger than 90 days are consequently not vaccinated. Initially the PCV-7 vaccine was used but this was replaced by the PCV-13 in April 2010. Vaccination coverage in Denmark is approximately 90%.The aim of this study was to present multilocus sequence typing (MLST) profiles of Streptococcus pneumoniae isolates from Danish infants (0-90 days) with invasive pneumococcal disease (IPD) in the period 2003-2013. 32 IPD isolates were investigated for their MLST profiles. The identified sequence types (STs) had previously been observed in other European countries. Among the clones were ST 306 (serotype 1), ST 180 (serotype 3) and ST 191 (serotype 7F). The ST profile distribution in this study is similar to that observed in other European studies and show a variety of STs. Our data show that the majority of STs found in Denmark is also observed in other European countries, indicating that the IPD isolates were from clones generally circulating in Europe.


Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment.
To evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance. We recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4. In total, 158 participants were included in this study with a mean age of 60.5 (56.0-66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively. Serum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.


Improving transition outcomes in adolescents with permanent hearing loss.
Young people with permanent hearing loss need to transition into adult services and engagement with the transition process is required to achieve this. Although there are clear national recommendations about the transition process and transfer to the adult services limited evidence has been published about the implementation and efficacy of transition programmes in young adults with permanent hearing loss. The primary aim of this quality improvement project was to significantly increase the number of teenagers with a clear transition protocol documented in their notes. The secondary aims were to ensure good medical and audiological outcomes based on all completing their medical investigations prior to transfer to the adult services and also based on a survey regarding attitudes to hearing aids use. A multiphase intervention programme was developed; (1) staff update with national transition protocols, (2) development of a clear transition protocol, (3) allocated key worker (4) access and (5) engagement. Through these interventions we increased the number of teenagers who had a clear transition protocol documented in their notes from 11% to 91%. 84% of our teenagers had completed their medical investigations, although documented discussion about the investigations had been done with 100% of the cohort. 9.2 % of adolescents felt pressurised to use hearing aids compared to 35% prior to the interventions. This project resulted in clear, measurable conclusions and we have shown that we better understand the needs of our patients and the improvement is sustainable.


Acute lymphoblastic leukemia: long-term psychological outcome.
Children diagnosed with acute lymphoblastic leukemia (ALL) now have an excellent chance for a medical cure. Nearly 90% can expect to attain an initial remission and the majority of those will remain disease-free. There is increasing concern about the long-term consequences of ALL and its treatment on the psychological adjustment of the survivor. This article selectively reviews the available literature on the neuropsychological and psychosocial adjustment of long-term survivors of ALL. The risk of neuropsychologic deficiencies among children who have remained in continuous remission has been the focus of conflicting findings, while the risk among those who have survived CNS relapse is clearly elevated. Generally, long-term survivors of childhood cancer have a 30-40% risk of school-related problems. Moreover, children treated for ALL with cranial irradiation have 3-4 times the risk of school problems relative to those who are not irradiated. Early identification of problems would facilitate referrals for appropriate intervention and hopefully minimize future difficulties.


Subfield and layer-specific depletion in calbindin-D28K, calretinin and parvalbumin immunoreactivity in the dentate gyrus of amyloid precursor protein/presenilin 1 transgenic mice.
The depletion of neuronal calcium binding proteins deprives neurons of the capacity to buffer high levels of intracellular Ca(2+) and this leaves them vulnerable to pathological processes, such as those present in Alzheimer's disease (AD). The aim of the present study was to investigate the expression of the calcium binding proteins, calbindin-D28K, calretinin and parvalbumin in the dentate gyrus (DG) of amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (Tg) mice and their non-Tg littermates, as well as the relation with the deposition of human amyloid beta (Abeta). We measured the expression of these three proteins at seven different rostro-caudal levels, and in the molecular, granular and polymorphic layers of the DG. We found that, except in the most caudal part of the DG, there is a substantial loss of calbindin-D28K immunoreactivity in all three layers of the DG in APP/PS1 mice compared with the non-Tg mice. Significant loss of calretinin immunoreactivity is present in most of the polymorphic layer of the DG of APP/PS1 mice compared with the non-Tg mice, as well as in the rostral and intermediate part of the inner molecular layer. Compared with the non-Tg mice parvalbumin immunoreactivity is significantly reduced throughout the whole polymorphic layer as well as in the rostral and intermediate part of the granular layer of DG in APP/PS1 mice. The relatively preservation of calbindin immunoreactivity in the caudal part of molecular and granular layers as well as calretinin immunoreactivity in the caudal part of polymorphic layer of the DG is likely related to the lower Abeta expression in those parts of DG. The present data suggest an involvement of calcium-dependent pathways in the pathogenesis of AD and indicate that there exists a subfield and layer-specific decrease in immunoreactivity which is related to the type of calcium-binding protein in APP/PS1 mice. Moreover, it seems that APP expression affects more the calbindin expression then parvalbumin and calretinin expression in the DG of APP/PS1 Tg mice.


Crystal structure of oxygenated Scapharca dimeric hemoglobin at 1.7-A resolution.
The crystal structure of the cooperative dimeric hemoglobin from the blood clam Scapharca inaequivalvis has been determined in the oxygenated state and refined to an R-factor of 0.157 at 1.7-A resolution. The structure is very similar to the carbon monoxide-liganded form with subtle differences in ligand binding geometry. Oxygen binds to the heme iron in a bent conformation with Fe-O-O angles of 135 degrees and 150 degrees for the two subunits. These observed angles are lower than the equivalent angles in the carbon monoxide-liganded form and intermediate between the angles observed in structures of oxygenated sperm whale myoglobin and oxygenated human hemoglobin. This third high resolution structure of Scapharca dimeric hemoglobin permits a detailed analysis of the water structure in the highly hydrated interface between subunits.


Immunocytochemical localization of amylase in the parotid gland of developing and adult rats.
An antiserum against purified rat parotid amylase was used to localize the protein in parotid glands of developing and adult rats. The unlabeled antibody peroxidase-antiperoxidase method and the protein A-gold colloid technique were used at the light and electron microscope levels, respectively. Immunoreactive amylase was detected in a few scattered cells in the glands of 2-day-old rats. During the following days the number of cells stained immunocytochemically for amylase increased rapidly; at 15 days of age all acinar cells revealed amylase, but the intensity of immunostaining varied from cell to cell. Electron microscopically, amylase was localized in the secretory granules, and by using a more concentrated antiserum, in the rough endoplasmic reticulum and Golgi complex. At early stages of development the acinar cells contained fewer and smaller secretory granules than in adult animals; the gold particles indicative of amylase were randomly distributed over the secretory granules. In the glands of adult rats, amylase was distributed inhomogeneously within the secretory granules. In the majority of secretory granules gold colloid particles were located over the electron-dense portions of the granules. However, secretory granules in which an amylase-rich shell surrounded an amylase-poor or amylase-negative "core" were not infrequent.


A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells.
With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells.


[Practical application of digital therapy verification].
The following describes the technical details which are of importance preparing portal radiographs using digital luminescence radiography. There are some advantages to this method: In comparison with the conventional portal radiographs using a low speed film, the new doses is ten to thirty times less than generally required. Double exposure techniques can be more easily applied than with conventional portal films. The contrast may be subsequently manipulated. In addition the dynamic range of the radiation detector is automatically adjusted to the exposure range. These facts may improve the verification quality. However, there are also some disadvantages: You need more apparatus, and the whole procedure is more time-consuming. Using typical examples we shall compare the procedure of digital portal radiographs and its results to traditional techniques.


Forecasting the milk yield of cows on farms equipped with automatic milking system with the use of decision trees.
The purpose of this paper was to utilize the decision trees technique to determine the factors responsible for high monthly milk yield in Polish Holstein-Friesian cows from 27 herds equipped with milking robots. The applied statistical method-the decision tree technique-showed that the most important factors responsible for monthly milk yield of dairy cows using robots were, in descending order of importance: milking frequency, lactation number, month of milking, and type of lying stall. At the same time, it has been ascertained that the highest monthly milk yield (47.24 kg) can be expected from multiparous cows kept in barns with a deep bedding that were milked more frequently than three times per day. On the other hand, the lowest milk production (13.56 kg) was observed among dairy cows milked less frequently than two times a day, with an average number of milked quarters lower than 3.97. The application of the decision trees technique allows a breeder to select appropriate levels of environmental factors and parameters that will help to ensure maximized milk production.


Infarct tissue characterization in implantable cardioverter-defibrillator recipients for primary versus secondary prevention following myocardial infarction: a study with contrast-enhancement cardiovascular magnetic resonance imaging.
Knowledge about potential differences in infarct tissue characteristics between patients with prior life-threatening ventricular arrhythmia versus patients receiving prophylactic implantable cardioverter-defibrillator (ICD) might help to improve the current risk stratification in myocardial infarction (MI) patients who are considered for ICD implantation. In a consecutive series of (ICD) recipients for primary and secondary prevention following MI, we used contrast-enhanced (CE) cardiovascular magnetic resonance (CMR) imaging to evaluate differences in infarct tissue characteristics. Cine-CMR measurements included left ventricular end-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and mass. CE-CMR images were analyzed for core, peri, and total infarct size, infarct localization (according to coronary artery territory), and transmural extent. In this study, 95 ICD recipients were included. In the primary prevention group (n = 66), LVEF was lower (23 ± 9% vs. 31 ± 14%; P < 0.01), ESV and WMSI were higher (223 ± 75 ml vs. 184 ± 97 ml, P = 0.04, and 1.89 ± 0.52 vs. 1.47 ± 0.68; P < 0.01), and anterior infarct localization was more frequent (P = 0.02) than in the secondary prevention group (n = 29). There were no differences in infarct tissue characteristics between patients treated for primary versus secondary prevention (P > 0.6 for all). During 21 ± 9 months of follow-up, 3 (5%) patients in the primary prevention group and 9 (31%) in the secondary prevention group experienced appropriate ICD therapy for treatment of ventricular arrhythmia (P < 0.01). There was no difference in infarct tissue characteristics between recipients of ICD for primary versus secondary prevention, while the secondary prevention group showed a higher frequency of applied ICD therapy for ventricular arrhythmia.


The painful knee.
The painful knee is discussed in the context of being the presenting symptom and a structured approach to diagnosis is offered. Mechanism of the pain is defined and related to the common clinical conditions. Diagnosis is essential to management and is possible in most instances with the aid of arthrography and arthroscopy.


Isolation and characterization of the genomic human CD7 gene: structural similarity with the murine Thy-1 gene.
The human CD7 molecule is a 40-kDa member of the immunoglobulin gene superfamily that is expressed on T-lymphoid and myeloid precursors in fetal liver and bone marrow. CD7 is also expressed on T lymphocytes in multiple stages of T-cell development, including a major subset of mature peripheral T cells. In this paper we report the isolation and characterization of the human CD7 gene and 5' flanking region. Sequence analysis revealed that the CD7 gene comprises four exons that span 3.5 kilobases. The 5' flanking region (506 base pairs) has a high G + C content and no "TATA" or "CCAAT" elements. DNase I sensitivity analysis of chromatin from the CD7+ progenitor cell leukemia line, DU528, and the CD7-, CD4+, CD8+, TCR alpha beta + T-cell line, DU980 (where TCR is the T-cell receptor), revealed two distinct hypersensitive sites 5' of the CD7 gene. Hypersensitive site 1, present in the DU980 T-cell line, was located 4.5 kilobases upstream of the presumed CD7 transcription initiation site. Only DNase I hypersensitive site 2, which mapped to the promoter region, was found in the DU528 line. Comparison of the organization of the CD7 gene with that of other members of the immunoglobulin gene superfamily revealed that the human CD7 gene most closely resembles the murine Thy-1 gene. Both CD7 and Thy-1 are encoded by small genes with four exons, contain TATA-less promoters, and have a similar functional organization. These structural similarities suggest that human CD7 and murine Thy-1 may be functional homologues.


Perceptions and functions of play and real fighting in early adolescence.
The hypothesis is tested that adolescent boys' (mean age of 12.8 years) intrasexual rough-and-tumble play (R&T) is used for dominance and intersexual R&T is used to establish heterosexual relationships. In Study 1, boys' observed R&T was related to both dominance and aggression. In the first half of the school year, R&T occurred primarily between males, possibly to establish dominance. In the second half of the year, both boys and girls engaged in R&T, possibly to establish heterosexual relationships. Counter to the hypothesis, observed aggression increased across the year. In Study 2, youngsters viewed taped R&T bouts in which they were participants or nonparticipants. Participant, more than nonparticipant, males saw R&T as related to dominance whereas participant, more than nonparticipant, females saw it as playful.


Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice.
Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Aβ aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders.


Cytotoxicity of quercetin is related to mitochondrial respiration impairment in Saccharomyces cerevisiae.
Quercetin is a flavonol ubiquitously present in fruits and vegetables that shows a potential therapeutic use in non-transmissible chronic diseases, such as cancer and diabetes. Although this phytochemical has shown promising health benefits, the molecular mechanism behind this compound is still unclear. Interestingly, quercetin displays toxic properties against phylogenetically distant organisms such as bacteria and eukaryotic cells, suggesting that its molecular target resides on a highly conserved pathway. The cytotoxicity of quercetin could be explained by energy depletion occasioned by mitochondrial respiration impairment and its concomitant pleiotropic effect. Thereby, the molecular basis of quercetin cytotoxicity could shed light on potential molecular mechanisms associated with its health benefits. Nonetheless, the evidence supporting this hypothesis is still lacking. Thus, this study aimed to evaluate whether quercetin supplementation affects mitochondrial respiration and whether this is related to quercetin cytotoxicity. Saccharomyces cerevisiae was used as a study model to assess the effect of quercetin on energetic metabolism. Herein, we provide evidence that quercetin supplementation: (1) decreased the exponential growth of S. cerevisiae in a glucose-dependent manner; (2) affected diauxic growth in a similar way to antimycin A (complex III inhibitor of electron transport chain); (3) suppressed the growth of S. cerevisiae cultures supplemented with non-fermentable carbon sources (glycerol and lactate); (4) promoted a glucose-dependent inhibition of the basal, maximal, and ATP-linked respiration; (5) diminished complex II and IV activities. Altogether, these data indicate that quercetin disturbs mitochondrial respiration between the ubiquinone pool and cytochrome c, and this phenotype is associated with its cytotoxic properties.


Generation of ribbons, helicoids, and complex Scherk surfaces in laser-matter interactions.
Motivated by a diversity of the shape instability phenomena in condensed-matter physics, we study the formation of elastic ribbon structures and transformation into helicoidal structures. Using the multipulse laser-matter interaction with the Co-coated surface, a one-dimensional high-density vortex-filament array has been created. Increasing the number of pulses, the oscillatory strain field causes the cascade of the shape transformations into structures of increasing topological complexity: vortex filaments into ribbons, into ribbon helicoids and tubular-ribbon helicoids, and then into short ribbon structures with the complex Scherk surface being identified. The cascade of transformations follows the scenario in which the topological complexity of the new structure increases with the number of pulses, thus, realizing configurations with more efficient energy relaxation. Above a critical number of pulses, the system is catastrophically disintegrated into small-scale wrinkled and crumpled surfaces. We show that the critical parameter for the ribbon transformations is the number of laser pulses which is equivalent to some critical oscillatory frequency.


The National Echocardiography Database Australia (NEDA): Rationale and methodology.
The National Echocardiography Database Australia (NEDA) is a new echocardiography database collecting digital measurements on both a retrospective and prospective basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 ± 17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months follow-up have been collected. These data will inform a number of initial analyses focusing on pulmonary hypertension, aortic stenosis and the role of artificial intelligence to facilitate accurate diagnoses of cardiac abnormalities.


Biomechanical Analysis of Functionally Graded Root Analog Implants on Alveolar Bone: A 3D Finite Element Study.
This study aimed to investigate whether axial or radial functionally graded root analog implants can optimize the stress and strain distribution near the implant-bone interface in alveolar bone models under static loads using finite element analysis (FEA). The 3D profile of the root analog implant was captured from a natural tooth in CBCT data. The implant was separated into different layers (3, 5, and 10 layers) to vary the Young modulus axially or radially. The variation in Young modulus was designed to be linear, exponential, or parabolic. Different occlusal loads were applied. The von Mises stress and strain were used to evaluate the system risk of failure. The difference in the numbers of layers had no significant effect on the alveolar bone. In the radial functionally graded implant models, the maximum von Mises stress of the alveolar bone decreased as the outer layer's elastic modulus increased; however, in the vertical functionally graded implants, this stress varied little. The maximum von Mises stress of the cancellous bone changed only slightly, from 2 to 5 MPa in all models. The maximum strain of the alveolar bone varied from 0.001478 mm to 0.003999 mm. Those FEA results were in line with previous findings. The functionally graded root analog implants show no significant biomechanical advantages over dense zirconia implants. Radial functionally graded root analog implants should optimize the peri-implant stresses and are biomechanically favorable for design.


[Cognitive Abilities Screening Instrument, Chinese Version 2.0 (CASI C-2.0): administration and clinical application].
Abstract- The Cognitive Abilities Screening Instrument (CASI) has been commonly used in dementia research and clinical practice to evaluate a subject's cognitive abilities and to follow-up possible progression of dementia. It has a detailed manual for test administration and scoring in order to minimize testing errors. The Chinese version of CASI (CASI C-2.0) has been used in many clinical and epidemiological studies in Taiwan. Since cognitive abilities are influenced by education, and there are high rates of illiterate or low education individuals among the elderly in Taiwan, the normative data of CASI, including its total score and its cognitive domain scores, should be divided into different education ranges. In clinical practice, the cut-off scores in differentiating between dementia and normal are suggested to be: 49/50 for Education year = 0; 67/68 for Education years = 1-5; and 79/80 for Education years more than 6.


Identification of an adipose tissue-like lipoprotein lipase in perfusates of chicken liver.
The nature of the lipolytic activity released from chicken livers perfused with Krebs-Ringer buffer (pH 7.0) containing heparin (50 or 10 U/ml), fraction V albumin (3%), and glycerol (20%) was investigated. The nonrecirculating perfusates contained both previously described NaCl-resistant "liver lipase" as well as an apoLp-Gluactivated lipoprotein lipase (LPL). Crude perfusate lipolytic activity was separated on heparin-Sepharose columns into two enzymatic peaks which were eluted at mean NaCl molarities of 0.75 M (liver lipase) and 1.2 M (LPL). The liver LPL activity was stimulated 7-fold by human apoLp-Glu (half maximal activity at 1.5 microgram/ml) and inhibited by apoLp-Ala, apoLp-Ser, apoLp-GlnI, and apoLP-GlnII. Liver LPL was fully inhibited by anti-adipose LPL immunoglobulins. The "liver lipase" was not affected by apoLp-Glu (3-34 microgram/ml) or anti-adipose LPL immunoglobulins. The data demonstrate the presence in liver perfusates of a LPL with properties similar to adipose tissue lipoprotein lipase.


[Testicular scanning in intrascrotal lesions].
Testicular scanning with technetium-99m sodium pertechnetate was performed on 152 patients with a variety of intrascrotal lesions. Scrotal images were obtained serially in the perfusion, tissue phase, illustrating the features of each phase in various clinical conditions. The relationship of scrotal imaging to the overall clinical presentation and evaluation of these patients is emphasized in testicular torsion of the testicular appendix, epididymitis, abscess, trauma, tumor, spermatocele, and varicocele. Technical problems of the scanning are also discussed.


Validity of the self-reported number of natural teeth in Japanese adults.
The aims of this research were to assess the validity of self-reporting of the number of teeth by comparing the number with that obtained through clinical dental examinations, and to investigate factors affecting the discordance between the two measures. Self-administered questionnaires and dental examinations were conducted among 1152 dentate community residents in Japan. The validity of the patients' reports of the number of teeth was assessed by comparing the self-reported number with that determined at the clinical examination. Factors affecting the absolute value of the difference between the self-reported number of teeth and the number at clinical examination were investigated using a multivariate analysis. Overall, 47.5% of participants had perfect agreement in their self-report with the clinical examination. There was a slight tendency toward underestimation of the number of natural teeth by self-reporting. Pearson's correlation coefficient was 0.80, and the intraclass correlation coefficient was 0.78 for all patients. Decayed, filled, sound teeth, and fixed prosthetic pontics were significantly associated with the absolute value of the difference between self-reports and clinical examinations. Patients' reported number of remaining teeth, the data for which were collected via the questionnaire, provided reasonably valid data on the actual number of teeth within a population group.


[Evaluation of prescription practices and of the rational use of medicines in Niger].
With the aim of evaluating an essential drugs and costs recovery program in Niger, rational drug use and prescribing patterns were studied in 19 health centers in Tahoua region. Drug use indicators were measured by retrospective and prospective surveys, achieved before and after a training intervention for nurses in using national standard treatments guideline. In the first study period, 627 retrospective randomized prescriptions and 295 prospective prescriptions in successive consultations were collected, and in the second period, ten months later, 665 and 274 prescriptions, respectively. Findings were compared between the two periods, and discussed in regard to referentials and data from other studies. The average number of drugs per prescription increased from 2.96 to 3.14 (p < 0.01) between the two periods, and the percentage of prescriptions with injections from 29.9 to 36.6% (p < 0.02), whereas the percentage of prescriptions containing antibiotics decreased from 75.2 to 68% (p < 0.01). These values were higher than regional or international standards, which were 2 for the average of drugs 17% for the injections and 50% for the antibiotics. Prescribing in essential and generic names of the national drug list was very close to 100% for the two periods. The average cost of prescriptions increased from 437 to 553 francs CFA (p < 0.001), which was higher than the calculated reference cost of 400 francs, but lower than data in literature. Correct prescriptions according to standard treatment guideline were only around 50%, in the two retrospective surveys. The averages of consultation time were 5.4 and 6.1 minutes for the two prospective surveys respectively, and dispensing times were 3.1 and 3.4 minutes, longer than those noticed in most of other studies in developing countries. Prescribed drugs were actually dispensed in almost 100% of the cases during the two periods. Drugs were properly labeled in 92.8% of the cases in the first period survey, and in 89.7% of the cases in the second (p < 0.03), whereas the percentage of patients who knew the correct dosage for drugs delivered increased from 64.4% to 75.5% (p < 0.01). Drug formularies and treatment guidelines were available in all facilities except in one case. Key drug availability ratio at the time of visit were good, in spite of a regression from 97.6 to 85.6% between the two periods. Improving drug purchasing and communal management in the health centers, this program contributed to the availability of essentials generic drugs delivered in a satisfactory way to the patients, and to set up a favorable professional environment for the nurses. On the other hand, the training courses seemed to have a limited impact on prescribing patterns for the nurses. However, better availability of drugs, as well as dispatching courses on the two retrospective surveys periods, could have underestimated this impact. Increasing prescription cost, although remaining compatible with costs recovery of drugs, was probably caused by the negative evolution of some indicators: abusive use of injections, higher number of drugs prescribed, few prescriptions according to standard treatment. These bad habits, often the most dangerous, justify undertaking actions of adapted formation, but also of communication with the patients, which should be regularly evaluated. For that, it will be necessary to have more qualitative indicators, helpful for the assessment of most efficient therapeutic attitude, tempting to value the global impact of these actions on health populations in developing countries.


The effects of brain death and ischemia on tolerance induction are organ-specific.
We have previously shown that 12 days of high-dose calcineurin inhibition induced tolerance in MHC inbred miniature swine receiving MHC-mismatched lung, kidney, or co-transplanted heart/kidney allografts. However, if lung grafts were procured from donation after brain death (DBD), and transplanted alone, they were rejected within 19-45 days. Here, we investigated whether donor brain death with or without allograft ischemia would also prevent tolerance induction in kidney or heart/kidney recipients. Four kidney recipients treated with 12 days of calcineurin inhibition received organs from donors rendered brain dead for 4 hours. Six heart/kidney recipients also treated with calcineurin inhibition received organs from donors rendered brain dead for 4 hours, 8 hours, or 4 hours with 4 additional hours of cold storage. In contrast to lung allograft recipients, all isolated kidney or heart/kidney recipients that received organs from DBD donors achieved long-term survival (>100 days) without histologic evidence of rejection. Proinflammatory cytokine gene expression was upregulated in lungs and hearts, but not kidney allografts, after brain death. These data suggest that the deleterious effects of brain death and ischemia on tolerance induction are organ-specific, which has implications for the application of tolerance to clinical transplantation.


Automated preconcentration of Fe, Zn, Cu, Ni, Cd, Pb, Co, and Mn in seawater with analysis using high-resolution sector field inductively-coupled plasma mass spectrometry.
A rapid, automated, high-throughput analytical method capable of simultaneous analysis of multiple elements at trace and ultratrace levels is required to investigate the biogeochemical cycle of trace metals in the ocean. Here we present an analytical approach which uses a commercially available automated preconcentration device (SeaFAST) with accurate volume loading and in-line pH buffering of the sample prior to loading onto a chelating resin (WAKO) and subsequent simultaneous analysis of iron (Fe), zinc (Zn), copper (Cu), nickel (Ni), cadmium (Cd), lead (Pb), cobalt (Co) and manganese (Mn) by high-resolution inductively-coupled plasma mass spectrometry (HR-ICP-MS). Quantification of sample concentration was undertaken using isotope dilution for Fe, Zn, Cu, Ni, Cd and Pb, and standard addition for Co and Mn. The chelating resin is shown to have a high affinity for all analyzed elements, with recoveries between 83 and 100% for all elements, except Mn (60%) and Ni (48%), and showed higher recoveries for Ni, Cd, Pb, Co and Mn in direct comparison to an alternative resin (NOBIAS Chelate-PA1). The reduced recoveries for Ni and Mn using the WAKO resin did not affect the quantification accuracy. A relatively constant retention efficiency on the resin over a broad pH range (pH 5-8) was observed for the trace metals, except for Mn. Mn quantification using standard addition required accurate sample pH adjustment with optimal recoveries at pH 7.5 ± 0.3. UV digestion was necessary to increase recovery of Co and Cu in seawater by 15.6% and 11.4%, respectively, and achieved full break-down of spiked Co-containing vitamin B12 complexes. Low blank levels and detection limits could be achieved (e.g., 0.029 nmol L-1 for Fe and 0.028 nmol L-1 for Zn) with the use of high purity reagents. Precision and accuracy were assessed using SAFe S, D1, and D2 reference seawaters, and results were in good agreement with available consensus values. The presented method is ideal for high throughput simultaneous analysis of trace elements in coastal and oceanic seawaters. We present a successful application of the analytical method to samples collected in June 2014 in the Northeast Atlantic Ocean.


Blood damage, platelet and clotting activation during application of radiofrequency or cryoablation catheters: a comparative in vitro study.
During catheter ablation of cardiac tissue, the insulting stimulus may damage and activate the blood. Specifically activation of platelets and the clotting system is a potential risk by their formation of thrombi. In this study the effect of two different techniques, a radiofrequency and a cryo-application procedure, on the activation of platelets and clotting in an in vitro blood circulation model was investigated. The radio-frequency procedure induced significantly more blood cell damage, platelet activation and clotting than did the cryo-application procedure. Macroparticles were circulating in blood after the radiofrequency procedure. In the cryo procedure, blood damage was limited to the frozen blood spherule around the tip of the catheter. It is concluded that at least in those circumstances where blood is directly contacting the tip of the radiofrequency or cryo-application catheter, the latter is more safe with regard to thrombus formation.


Pulmonary resection for non-small-cell lung cancer in patients on hemodialysis: clinical outcome and long-term results.
Patients on hemodialysis (HD) who undergo surgery represent a high risk group requiring careful perioperative management to avoid electrolyte imbalance and hemodynamic instability. The aim of the study was to analyze the postoperative outcome in terms of complications and survival of a group of patients on HD who had undergone pulmonary resection for non-small cell lung cancer (NSCLC). Six patients on HD underwent seven pulmonary resections at our institution from 1998 to 2003. The underlying kidney disease was nephrosclerosis in two patients and glomerulonephritis in four. The mean levels of blood urea nitrogen and serum creatinine were 107 +/- 11.5 mg/dl and 7.9 +/- 0.64 mg/dl, respectively. The mean preoperative PO2 and FEV1 were 77.6 +/- 2.4 mmHg and 2.4 +/- 0.16 liters, respectively. The histologic diagnosis was squamous cell carcinoma in four cases and adenocarcinoma in three. One patient underwent two lung resections in 4 years for two primary lung cancers. Five patients underwent lobectomy, one underwent a wedge resection, and in one case pneumonectomy was performed after neoadjuvant chemotherapy. There was no operative mortality. Postoperatively, atrial fibrillation occurred in two patients associated with sputum retention in both, and two other patients had hyperkalemia (complication rate 57%). One patient died of cardiac complications 27 months after surgery. The remaining five patients are currently alive with no evidence of disease. Patients on HD who undergo lung resection have a high rate of postoperative complications. Although the underlying disease influences long-term survival, radical lung resection in NSCLC patients is recommended in selected cases. Careful metabolic, hematologic, and pharmaceutical management is mandatory during the perioperative period.


Rapidithrix thailandica gen. nov., sp. nov., a marine gliding bacterium isolated from samples collected from the Andaman sea, along the southern coastline of Thailand.
The taxonomic positions of three strains of marine gliding bacteria, TISTR 1736, TISTR 1741 and TISTR 1750(T), isolated from the southern coastline of Thailand were evaluated by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the three isolates formed a distinct lineage within the family 'Flammeovirgaceae', phylum Bacteroidetes, and were related to the genus Flexithrix. The DNA G+C contents of the isolates were in the range 40-43 mol%. The major respiratory quinone was MK-7. The major cellular fatty acids were 16 : 1omega5c (cis-5-hexadecenoic acid) and 15 : 0 (pentadecanoic acid). The major hydroxyl fatty acids were 3-OH 17 : 0 (3-hydroxyheptadecanoic acid), 3-OH 15 : 0 (3-hydroxypentadecanoic acid) and 3-OH 16 : 0 (3-hydroxyhexadecanoic acid). On the basis of phenotypic, chemotaxonomic, genotypic and phylogenetic data, these marine bacteria are considered to represent a novel species of a new genus, for which the name Rapidithrix thailandica gen. nov., sp. nov. is proposed. The type strain of Rapidithrix thailandica is TISTR 1750(T) (=IAM 15448(T)).


[Acute fungal endocarditis due to Trichosporon beigelli].
We report a 59-year-old woman with acute fungal endocarditis of a prosthetic valve caused by the endogenic organism, Trichosporon beigelli. This slowly developing disease mainly effects drug addicts who use intravenous narcotics. In nonaddicts it is rare, with mortality as high as 50%. There are only sporadic reports of T. beigelli as a complication long after open heart surgery. The ongoing infection is undetected for even years after the primary infection, due to its prolonged latent phase. We present the difficulties of diagnosis, and of treating the disease with a combination of surgery and of long-term chemotherapy.


Biochemical differences in tumorigenic and nontumorigenic cells measured by Raman and infrared spectroscopy.
Both infrared and Raman spectroscopies have the potential to noninvasively estimate the biochemical composition of mammalian cells, although this cannot be unambiguously determined from analysis approaches such as peak assignment or multivariate classification methods. We have developed a fitting routine that determines biochemical composition using basis spectra for the major types of biochemicals found in mammalian cells (protein, DNA, RNA, lipid and glycogen), which is shown to be robust and reproducible. We measured both infrared and Raman spectra of viable suspensions of pairs of nontumorigenic and tumorigenic rat fibroblast cell lines. To model in vivo conditions, we compared nonproliferating, nontumorigenic cells to proliferating, tumorigenic cells. Reproducible differences in biochemical composition were found for both nontumorigenic/tumorigenic cell models, using both spectroscopic techniques. These included an increased fraction of protein and nucleic acids in the tumorigenic cells, with a corresponding decrease in lipid and glycogen fractions. Measurements of each cell type in both the proliferating and nonproliferating states showed that proliferative status was the major determinant of differences in vibrational spectra, rather than tumorigenicity per se. The smallness of the spectral changes associated with tumorgenicity may be due to the subtle nature of the oncogenic change in this system (a single mutant oncogene).


Variation in breast cancer risk of heterozygotes for ataxia-telangiectasia according to environmental factors.
Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder, characterized by progressive neuronal degeneration, immunological deficiency, radio-sensitivity and an increased risk of cancer. Although several studies have confirmed that AT heterozygosis increases the risk of breast cancer (BC), we do not know how exogenous factors affect this risk. We performed an epidemiological study on the cancer risks associated with AT heterozygosis in France and explored the variation in BC risk according to environmental factors, such as reproductive factors and exposure to ionizing radiation. Information on the amount of ionizing radiation received by an individual in their lifetime and on their reproductive life was collected from the living relatives of 34 AT children (175 female relatives). Consistent with previous reports and with our previous estimate on the entire retrospective cohort, we found that the risk of developing BC is 3.6-fold higher among ATM heterozygous women. An increased risk was associated with an early age at menarche, a late age at first childbirth, nulliparity, premenopausal status and increasing periods of breast cell mitotic activity (BCMA) prior to the first childbirth. Age at menarche, age at 1st childbirth and BCMA seemed to have a stronger effect in ATM heterozygotes than in non-ATM heterozygotes. However, the tests were not all statistically significant (only age at 1st childbirth). Surprisingly, the risk of BC decreased when the chest or breasts were irradiated. It is difficult to interpret the data because of the small sample size, but further investigations should provide a biological explanation for the variation in BC risk associated with exogenous factors according to ATM heterozygosis status.


Silver nanoparticle enhanced Raman scattering-based lateral flow immunoassays for ultra-sensitive detection of the heavy metal chromium.
We report a simple and ultra-sensitive surface enhanced Raman scattering (SERS) strip sensor based on silver nanoparticles (AgNPs) and lateral flow immunoassays (LFIAs). LFIAs are inexpensive, simple, portable and robust, thus making them commonplace in medicine, agriculture and food safety. However, their applications are limited due to the low signal intensity of the color-formation reaction based on the label accumulation. SERS is a powerful molecular spectroscopy technique for ultra-detection, which is based on the enhancement of the inelastic scattering from molecules located near nanostructured metallic surfaces when the molecules are illuminated and the surface plasmons are excited. Because of the rapidity and robustness of LFIAs and the high sensitivity of SERS, we introduce SERS into LFIAs (SERS-LFIA). Our SERS-LFIA demonstrates fast, excellent performance and is suitable for the semiquantitative examination of ultratrace analytes (Cr(3+)), with the limit of the detection (LOD) as low as 10(-5) ng mL(-1), which is 10(5)-fold more highly sensitive than those previously used to detect Cr(3+) within 15 min.