The effects of nafazatrom on arrhythmias and prostanoid release during coronary artery occlusion and reperfusion in anaesthetized greyhounds.
The effects of the antithrombotic drug nafazatrom (BAY g 6575) were investigated in chloralose-anaesthetized greyhounds subject to coronary artery occlusion and reperfusion. Pretreatment with nafazatrom 10 mg/kg p.o. did not significantly reduce the number of extrasystoles or the incidence of ventricular fibrillation (VF) during the first 30 min occlusion of the left anterior descending coronary artery. However, the incidence of VF resulting from release of a 40-min coronary artery occlusion was markedly reduced (from 88% in the controls to 14% in the nafazatrom group). Both thromboxane B2 (TxB2) and 6-keto PGF1 alpha (breakdown products of TxA2 and prostacyclin respectively) were released from the acutely ischaemic myocardium in control dogs. Nafazatrom did not alter the release of TxB2 but the concentrations of 6-keto PGF1 alpha were elevated in blood draining from both the ischaemic and normal regions of the myocardium. The pronounced anti-fibrillatory effect of nafazatrom during reperfusion of the ischaemic myocardium may be related to the ability of this drug to elevate prostacyclin concentrations in the coronary circulation.


[Patients with metal-on-metal hip arthroplasty: evaluation and management of complications].
The potentially severe complications related to metal-on-metal (MoM) hip replacements have led to a dramatic decrease of their use. Large diameter heads are more likely to fail than smaller diameters, but complications have been described even with « small » diameters. Therefore, monitoring of MoM arthroplasties is mandatory. This includes physical examination, X-Rays, metal ion levels, and potentially cross-sectional imaging. Despite pathophysiology of adverse reactions to metal debris (ARMD) is better understood, their evolution and the potential systemic complications remain unclear. Symptomatic hip arthroplasties, elevated ions levels, and ARMD may lead to revision of the components. In such a situation, an adaquate stategy must be achieved given the high potential for complications.


The application of the Comet assay in fish cell lines.
The use of fish models has been proven to be an effective and sensitive tool for the evaluation of genotoxicity of pure compounds and complex mixtures of chemicals in the context of environmental screening of pollutants and hazard assessment in aquatic toxicology. In particular, fish cell lines have been successfully introduced for detection of genotoxic effects and can serve as an alternative to animal testing in preliminary eco-/genotoxicological studies. For this purpose comet assay has been extensively used in fish cell lines for the evaluation of genotoxic potential of chemicals and complex environmental matrices. The most often used fish cell lines in the comet assay are RTG-2, RTgill-W1 and RTL-W1 derived from rainbow trout (Onchorhynchus mykiss) gonads, gills and liver, respectively, and ZFL and ZF4 cells established from zebrafish (Danio rerio) liver and embryos, respectively. The present review gives an overview of the most often-used permanent fish cell lines in genotoxicology and discusses their application in the comet assay.


Decreased expression of interleukin-2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus.
Using radiolabeled interleukin-2 (IL-2), affinity cross-linking and binding assays revealed that the expression of intermediate-affinity IL-2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL-2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporesponsiveness to IL-2 of T cells in patients with SLE.


[Diffusion-weighted MR imaging of meningeal involvement in Wegener's granulomatosis].
We report a 65-year-old female with meningeal involvement in Wegener's granulomatosis (WG). At 52 years of age, she was diagnosed as having WG by lung biopsy and elevated proteinase3 anti-neutrophil cytoplasmic antibody titer. She had been maintained on prednisolone. Three weeks before admission, she developed deterioration of mental status. On examination, neurological abnormalities included right hemiparesis, confusion, memory loss, psychomotor slowing and agraphia. CSF was normal. Diffusion-weighted images (DWI) showed high intensity lesions in the subarachnoid space over the left hemisphere. Fluid attenuated inversion recovery (FLAIR) images showed high intensity signal in the subarachnoid space with mild swelling of the cortex and abnormal meningeal enhancement corresponding to the high intensity area on DWI. She was treated with intravenous administration of methylprednisolone (1,000 mg/day for 3 days) and cyclophosphamide, and gradually improved in symptoms and abnormal hyperintensity on DWI. Involvement of the meninges in WG is rare. The dura mater is involved more frequently than the pia mater. Pathological findings of the meninges in WG has been reported to be granulomatous inflammation. Restricted diffusion in the subarachnoid space has been described to occur in a viscous mixture of proteins and inflammatory cells, similarly to the DWI hyperintensity in pyogenic abscesses. In our case, abnormal hyperintensity on DWI was interpreted as a dense inflammatory infiltrate in the leptomeninges. Therefore, DWI and FLAIR image have been shown to be useful for demonstration of leptomeningeal lesions in WG.


Multistrain probiotic and lactulose in the treatment of minimal hepatic encephalopathy.
Some evidence has shown benefits of probiotics in the management of minimal hepatic encephalopathy (MHE). We evaluated the efficacy of a multistrain probiotic compound, alone and in combination with lactulose, in the treatment of MHE. This study has two parts. First, consecutive adult patients with MHE were randomized to receive lactulose (30-60 mL/day) + probiotic (200 million colony forming units of seven bacteria species/day) (Gp-LPr) or lactulose + placebo (Gp-L). In second part, a non-randomized group of patients received probiotic alone (Gp-Pr). Medication duration was for 2 weeks and patients were followed-up for another 8 weeks. Improvement in MHE status was assessed by psychometric hepatic encephalopathy score (PHES). Development of overt encephalopathy, hospitalization, and death were considered as secondary outcomes. Sixty patients (80% male, mean age 38.4 ± 9.6 years) completed the intervention. PHES significantly improved after medication in all the three groups (Gp-LPr: -3.8 ± 3.9 to -1.6 ± 3.0; Gp-L: -4.8 ± 4.1 to -1.6 ± 2.9; and Gp-Pr: -4.9 ± 3.7 to -2.1 ± 2.5, P < 0.001). After 8 weeks follow-up, improvement was maintained in Gp-LPr and Gp-Pr, but there was deterioration in those who did not receive probiotics (Gp-L: PHES score reversed to -4.8 ± 4.2). Two patients (one each in Gp-L and Gp-Pr) experienced overt encephalopathy. One patient was hospitalized due to worsening of ascites (Gp-LPr) and one due to spontaneous bacterial peritonitis (Gp-L). Side effects were mild and not significantly different among the groups. Lactulose and probiotics are effective for the treatment of MHE; however, probiotics, but not lactulose, have long-term effects. More studies are required before suggesting probiotics for the standard treatment of MHE.


Development and validation of a system for the growth of cells and tissues under intermittent hydrostatic pressure.
Various cell populations have been shown to respond to hydrostatic pressure; however, many of the culture systems suffer from shortcomings in design or methodology. Of particular interest to us is the potential role of pressure and other environmental factors in modulating stem cell behavior in intervertebral disk repair. A system was developed for the growth of cells and tissues under intermittent hydrostatic pressure. The system was validated with NIH 3T3 fibroblasts for sterilizability and cytotoxicity. Further experiments were conducted with canine mesenchymal stem cells under various levels of pressure, oxygen, glucose, and conditioned medium. The culture system showed no cytotoxicity and was able to demonstrate that the proliferation and metabolism of mesenchymal stem cells are sensitive to medium glucose and oxygen concentration and hydrostatic pressure. The cells exposed to hydrostatic pressure differed in their morphology from nonexposed cells. The system is capable of supporting long-term cell culture and examining the role of mechanical and environmental stimulation in vivo.


[Early relaparotomy in the surgical treatment of abdominal viscera].
Analysis of 88 repeated surgical interventions after 4,017 operations on the abdominal organs showed the obvious advantages of early relaparotomy with the performance of laparostomy, according to indications, in patients with postoperative pyoinflammatory complications in the abdominal cavity. The mortality rate was 19.3% in early and 80.7% in delayed relaparotomy. A complex of symptoms was determined providing evidence of the development of postoperative pyoinlammatory complications and allowing substantiated indications for a repeated operation to be set.


A Technique of Carotid Endarterectomy and Carotid Shunting.
With the advent of carotid arterial operations, concerns of interruption of cerebral perfusion and ischemic injury loomed as the major deterrent. The physiologic basis for cerebral protection is to diminish its oxygen requirement by chemical or hypothermic means or to continue its adequate arterial perfusion. The first successful carotid reconstruction resecting an internal carotid stenosis with anastomosis of the patent external carotid to the distal internal carotid artery was performed by Carrea of Argentina in 1951. Preoperatively, ascorbic acid and phenobarbital was given but its rationale was not explained.


Primary leiomyosarcoma of the inferior vena cava presenting as a renal mass.
Leiomyosarcoma of the inferior vena cava (IVC) is an extremely rare entity. We present the case of a 62-year-old woman who was found to have a large right upper quadrant mass upon examination by her primary care physician in evaluation for diffuse abdominal pain accompanied by anorexia and weight loss. A computed tomographic scan and magnetic resonance imaging demonstrated a 13-cm retroperitoneal lesion that appeared to stem from the right kidney and yielded a tumor thrombus up to the level of the hepatic venous confluence. The patient underwent a right radical nephrectomy and IVC thrombectomy for treatment of a presumed renal cell carcinoma. Instead, pathology revealed the tumor to be a leiomyosarcoma of the IVC. We document this unusual presentation of an extremely rare tumor entity.


Direct-to-consumer genomic testing: Are nurses prepared?
Genomic testing is increasingly common in the consumer marketplace. The role of nurses in educating and counseling patients requires them to be prepared to respond to questions about the results of direct-to-consumer genomic testing. This article describes one individual's reflections upon undergoing this testing, the challenges of interpreting the results, and nursing considerations for integrating these results into clinical practice.


Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival.
The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants.


Evaluation of Model-Based Biomimetic Control of Prosthetic Finger Force for Grasp.
Restoring neuromuscular reflex properties in the control of a prosthetic hand may potentially approach human-level grasp functions in the prosthetic hand. Previous studies have confirmed the feasibility of real-time emulation of a monosynaptic spinal reflex loop for prosthetic control. This study continues to explore how well the biomimetic controller could enable the amputee to perform force-control tasks that required both strength and error-tolerance. The biomimetic controller was programmed on a neuromorphic chip for real-time emulation of reflex. The model-calculated force of finger flexor was used to drive a torque motor, which pulled a tendon that flexed prosthetic fingers. Force control ability was evaluated in a "press-without-break" task, which required participants to press a force transducer toward a target level, but never exceeding a breakage threshold. The same task was tested either with the index finger or the full hand; the performance of the biomimetic controller was compared to a proportional linear feedback (PLF) controller, and the contralateral normal hand. Data from finger pressing task in 5 amputees showed that the biomimetic controller and the PLF controller achieved 95.8% and 66.9% the performance of contralateral finger in success rate; 50.0% and 25.1% in stability of force control; 59.9% and 42.8% in information throughput; and 51.5% and 38.4% in completion time. The biomimetic controller outperformed the PLF controller in all performance indices. Similar trends were observed with full-hand grasp task. The biomimetic controller exhibited capacity and behavior closer to contralateral normal hand. Results suggest that incorporating neuromuscular reflex properties in the biomimetic controller may provide human-like capacity of force regulation, which may enhance motor performance of amputees operating a tendon-driven prosthetic hand.


A probabilistic framework based on SLIC-superpixel and Gaussian processes for segmenting nerves in ultrasound images.
We deal with an important problem in the field of anesthesiology known as automatic segmentation of nerve structures depicted in ultrasound images. This is important to aid the experts in anesthesiology, in order to carry out Peripheral Nerve Blocking (PNB). Ultrasound imaging has gained recent interest for performing PNB procedures since it offers a non-invasive visualization of the nerve and the anatomical structures around it. However, the location of these nerves in ultrasound images is a difficult task for the specialist due to the artifacts (i.e. speckle noise) that affect the intelligibility of a given image. In this paper, we present a probabilistic approach based on Simple Linear Iterative Clustering (SLIC-superpixels) and Gaussian processes for automatic segmentation of peripheral nerves. First, we use Graph cuts segmentation to define a region of interest (ROI). Such a ROI is divided into several correlated regions using SLIC-superpixels, then, a nonlinear Wavelet transform is applied as feature extraction stage. Finally, we use a classification scheme based on Gaussian Processes in order to predict the label of each parametrized superpixel (the label can be "nerve" or "background"). The accuracy of the proposed method is measured in terms of the Dice coefficient. Results obtained show performances with a Dice coefficient of 0.6524±0.0085 which brings accurate performances in nerve segmentation processes.


Minireview: Estrogen receptor-beta: mechanistic insights from recent studies.
The discovery of estrogen receptor-beta (ERbeta) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERbeta action. We now know that ERbeta plays a major role in mediating estrogen action in several tissues and organ systems, including the ovary, cardiovascular system, brain, and the immune system, and that ERbeta and ERalpha generally play distinct physiological roles in the body. Although significant progress has been made toward understanding the molecular mechanisms of ERbeta action, particularly in vitro, there remains a large gap in our understanding of the mechanisms by which ERbeta elicits its biological functions in a true physiological context.


TaggerOne: joint named entity recognition and normalization with semi-Markov Models.
Text mining is increasingly used to manage the accelerating pace of the biomedical literature. Many text mining applications depend on accurate named entity recognition (NER) and normalization (grounding). While high performing machine learning methods trainable for many entity types exist for NER, normalization methods are usually specialized to a single entity type. NER and normalization systems are also typically used in a serial pipeline, causing cascading errors and limiting the ability of the NER system to directly exploit the lexical information provided by the normalization. We propose the first machine learning model for joint NER and normalization during both training and prediction. The model is trainable for arbitrary entity types and consists of a semi-Markov structured linear classifier, with a rich feature approach for NER and supervised semantic indexing for normalization. We also introduce TaggerOne, a Java implementation of our model as a general toolkit for joint NER and normalization. TaggerOne is not specific to any entity type, requiring only annotated training data and a corresponding lexicon, and has been optimized for high throughput. We validated TaggerOne with multiple gold-standard corpora containing both mention- and concept-level annotations. Benchmarking results show that TaggerOne achieves high performance on diseases (NCBI Disease corpus, NER f-score: 0.829, normalization f-score: 0.807) and chemicals (BioCreative 5 CDR corpus, NER f-score: 0.914, normalization f-score 0.895). These results compare favorably to the previous state of the art, notwithstanding the greater flexibility of the model. We conclude that jointly modeling NER and normalization greatly improves performance. The TaggerOne source code and an online demonstration are available at: http://www.ncbi.nlm.nih.gov/bionlp/taggerone email@example.com Supplementary data are available at Bioinformatics online.


De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives.
Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the binding of small-molecule effectors. To date, such effectors are derived from thalidomide and confer a broad substrate spectrum that is far from being fully characterized. Here, we employed a rational and modular approach to design novel and minimalistic CRBN effectors. In this approach, we took advantage of the binding modes of hydrolyzed metabolites of several thalidomide-derived effectors, which we elucidated via crystallography. These yielded key insights for the optimization of the minimal core binding moiety and its linkage to a chemical moiety that imparts substrate specificity. Based on this scaffold, we present a first active de-novo CRBN effector that is able to degrade the neo-substrate IKZF3 in the cell culture.


Heart rate variability: response following a single bout of interval training.
We investigated the effect of exercise on heart rate variability by analysing the heart rate power spectrum prior to, and 1 and 72 h following, an interval training session. Subjects initially performed a graded test to exhaustion to determine maximal oxygen uptake (VO(2) max) and the running speed at which VO(2) max was first attained (vVO(2) max). The training session was completed on a separate day and comprised six 800 m runs at 1 km x h (-1) below vVO(2) max. Prior to the training session (pre), 1 h following the training session (+ 1h), and 72 h following the training session (+ 72 h), subjects sat quietly in the laboratory for 20 min whilst breathing frequency was maintained at 12 breath x min (-1). Cardiac cycle R-R interval data were collected over the final 5 min of each 20 min period and analysed by means of autoregressive power spectral analysis to determine the high frequency (HF) and low frequency (LF) components of heart rate variability. Heart rate was higher, and the standard deviation of the R-R intervals was lower, at + 1 h than for pre or + 72 h (p < 0.05). The HF and the LF components of heart rate variability were also lower (p < 0.05) for + 1 h than for pre or + 72 h when the data were expressed in ms(2). However, no changes in the LF:HF ratio were observed, and the changes in the HF and LF components disappeared when the data were expressed as a fraction of the total power. Whilst these findings illustrate the importance of controlling the timing of exercise prior to the determination of heart rate variability, the time course of the post-exercise heart rate variability response remains to be quantified.


Peripheral T-cell lymphoma: frequency and distribution in a tertiary referral center in South India.
Peripheral T/NK-cell lymphomas are uncommon types of non-Hodgkin's lymphoma (NHL) with a higher frequency in Far East countries as compared to the West. This study was undertaken to ascertain the frequency and distribution pattern of peripheral T-cell lymphomas (PTCLs) diagnosed in a tertiary care center in South India. This retrospective study was carried out in Department of General Pathology, Christian Medical College, Vellore. The time period was for 2 years from 1 st January 2008 till 31st December 2009. All PTCLs were reviewed and classified according to the World Health Organization (WHO) 2008 classification. Of a total of 1032 cases of NHL, 180 cases were PTCL, which accounted for 17.4% cases of all the NHLs. Of these, PTCL, not otherwise specified (PTCL, NOS) was the most common subtype (48 cases, 26.1%), followed by anaplastic large cell lymphoma (41 cases, 22.8%), mycosis fungoides (21 cases, 11.7%), angioimmunoblastic T-cell lymphoma (16 cases, 8.9%), subcutaneous panniculitis like T-cell lymphoma (15 cases, 8.4%), extranodal NK/T-cell lymphoma, nasal type (12 cases, 6.7%), and hepatosplenic T-cell lymphoma (10 cases, 5.6%). The most common primary site of presentation was nodal accounting for 42% followed by cutaneous (34%), upper aerodigestive sites (8.9%), spleen (6.7%), and gastrointestinal tract (GIT; 3.3%). This is the largest single study on PTCLs in India and we document that its frequency is higher than that reported in Western literature and previous Indian studies and almost similar to that reported in some Far East studies. The frequency of mycosis fungoides, subcutaneous panniculitis like T-cell lymphoma, and hepatosplenic T-cell lymphoma was higher than that reported in the World literature and previous Indian studies. The frequency of extranodal NK/T-cell lymphoma and angioimmunoblastic T-cell lymphoma was much lower than that reported in the Far East literature.


[CHANGING OF PHYSICO-CHEMICAL PARAMETERS OF NON-CONTACT (ELECTROCHEMICAL) ACTIVATED DRINKING WATER IS ASSOCIATED WITH INDUCTION OF GENOMIC INSTABILITY OF CULTIVATED HUMAN BLOOD LYMPHOCYTES].
In the article there are presented data which are the fragment of large multidisciplinary study of genetic safety of non-contact electrochemically activated water (NAW). The aim of this study was the analysis of the relation of impacts of genomic instability (micronucleus test with cytochalasin B) detected in human blood cells, cultured in medias prepared on the base of these NAWs, with physical and chemical properties of these NaWs. In experiments there were used catholytes and anolytes obtained by activation of osmotic, tap and dining bottled water As a result of such activation, all waters were shown to acquire the ability to induce genomic instability in cellular cultures. Notably in cell cultures on catholytes and anolytes these effects differed between themselves and have been associated with different physical and chemical properties of the NAWs.


Value of myocardial defect size measured by thallium-201 SPECT: results of a multicenter trial comparing heparin and a new fibrinolytic agent.
In a multicenter randomized double-blind trial comparing heparin and a new fibrinolytic agent, anisoylated plasminogen streptokinase activator complex (APSAC), 231 patients presenting with a less than 5 hr acute myocardial infarction underwent a contrast angiography (CA) before the end of the first week of admission, and radionuclide cardiac blood-pool imaging and a 201Tl single photon emission computed tomography (SPECT) study before the end of the third week. Left ventricular ejection fraction (LVEF) and a wall motion score (WM) were calculated from CA. LVEF was also obtained from cardiac blood-pool imaging, and defect size (DS) from 201Tl SPECT. Results demonstrated that all parameters were significantly improved in patients treated with APSAC versus heparin (contrast LVEF 53 +/- 13 vs. 47 +/- 14 p less than 0.01, WM 9.8 +/- 6.5 vs. 13.3 +/- 7.9 p less than 0.001, radionuclide LVEF 43 +/- 12 vs. 40 +/- 13 p less than 0.05, DS 14 +/- 12 vs. 18 +/- 14 p less than 0.05). When the patients were divided according to infarct site and infarct-related coronary artery patency, it was demonstrated with all four parameters that the beneficial effect of APSAC can be largely explained by the lower incidence of vessel obstruction in this group (37% vs. 77% in the heparin group, p less than 0.001). It is concluded that (a) when compared with heparin and in the conditions of the trial, APSAC significantly improves the cardiac function and decreases the DS and (b) DS measured by 201Tl SPECT is as valuable a quantitative parameter of therapeutic evaluation as are LVEF and WM.


Studies of association between LPIN1 variants and common metabolic phenotypes among 17,538 Danes.
Lipin-1, encoded by LPIN1, is expressed in the major metabolically active tissues. Decreased expression of lipin-1 in adipose tissue correlates with increased insulin resistance, and tagging of the LPIN1 locus has shown that rs33997857, rs6744682, and rs6708316 associate with metabolic phenotypes, specifically body mass index (BMI) and fasting serum lipid levels, both on the individual single-nucleotide polymorphism level and with a three-marker haplotype. Our aim was to validate the reported findings in the Danish population. In the present study, variants were analyzed in LPIN1 using case-control studies, haplotype analyses, and quantitative trait analyses in a population of 17,538 Danes. The three LPIN1 variants were genotyped in 17,538 Danes from four study populations of middle-aged people. This provided us with a statistical power >99% to replicate previous findings. Variants were analyzed individually and in haplotype combinations in studies of quantitative metabolic traits and in case-control studies. None of the three variants were associated with the examined quantitative traits including BMI, waist circumference, blood pressure, fasting serum lipid concentrations, or plasma glucose or serum insulin concentrations in the fasting state and following an oral glucose tolerance test. Haplotypes were tested for association with quantitative traits; however, only nominal association with blood pressure (P=0.04) and waist circumference (P=0.04) was observed. In case-control studies, no association was found for individual variants or the three-marker haplotype. LPIN1 rs33997857, rs6744682, and rs6708316 did not associate with type 2 diabetes, obesity, or related quantitative metabolic phenotypes in the Danish population examined.


Direct attachment of fibronectin to tresyl chloride-activated titanium.
The aim of this study was to bind fibronectin directly to a titanium surface treated with tresyl chloride (2,2,2-trifluoroethanesulfonyl chloride) for the development of a strong connection of a dental implant to subepithelial connective tissues and/or peri-implant epithelia. Basic terminal OH groups of mirror polished titanium were allowed to react with tresyl chloride at 37 degrees C for 2 days. The tresylated titanium disk was then immersed into a fibronectin/phosphate-buffered saline solution for 24 h at 37 degrees C. The activation reaction of the basic OH of titanium with tresyl chloride was confirmed by S2p, F1s, and O1s spectra using X-ray photoelectron spectroscopy and -O-S-O2- bonds using Fourier transform infrared reflection-absorption spectroscopy. After the reaction of fibronectin with titanium, the X-ray photoelectron spectroscopy revealed the remarkable effect of the activation of terminal OH groups with the tresyl chloride treatment. The N1s peak derived from the attached fibronectin still remained after 60 s of argon-ion sputtering after tresyl chloride treatment. In contrast, the N1s peak of the specimen not treated with tresyl chloride almost disappeared after only 10 s of argon-ion etching. Fibronectin, a well-known cell-adhesive protein, could easily be attached to the titanium surface by use of the tresyl chloride activation technique.


Adenocarcinoma esophagus with choroid metastasis.
Metastases to the eye are rare and those from carcinoma esophagus are very rare, with only one report in the English literature. We report a 46-year-old man with adenocarcinoma of esophagus who developed isolated choroid metastasis after definitive treatment of the primary tumor.


A randomized trial of the topical effect of antifibrinolytic epsilon aminocaproic Acid on coronary artery bypass surgery without cardiopulmonary bypass.
We assessed the effect of the topical application of epsilon-aminocaproic antifibrinolytic acid (EACA) on the pericardium of patients submitted to coronary artery bypass graft (CABG) without the use of cardiopulmonary bypass (CPB). This is a prospective, randomized, and double-blind study. We evaluated 26 patients with chronic coronary heart disease indicated for CABG without CPB (EACA and placebo groups). The analysis of the postoperative hematological results showed no difference between groups in hemoglobin and hematocrit. There was no difference between the groups regarding the postoperative bleeding through the drains in the first 24 hours, 48 hours, and accumulated loss until removal of drains. The use of EACA in patients undergoing CABG without CPB presented no difference in the reduction of the amount of bleeding and the need for blood transfusions.


Laparoscopic myomectomy.
Laparoscopic myomectomy was performed on 154 women, with minimal perioperative complications resulting. Small and single leiomyomata were managed more easily than multiple and larger tumors. Although suturing the excisional sites improved healing, it increased the incidence of adhesion formation. We conclude that laparoscopic myomectomy can be a safe and cost-effective alternative to laparotomy when performed by a skilled operative laparoscopist, but only in selected cases.


Shared Decision-Making for Drug-Drug Interactions: Formative Evaluation of an Anticoagulant Drug Interaction.
Warnings about drug-drug interactions (DDIs) between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) within electronic health records indicate potential harm but fail to account for contextual factors and preferences. We developed a tool called DDInteract to enhance and support shared decision-making (SDM) between patients and physicians when both warfarin and NSAIDs are used concurrently. DDInteract was designed to be integrated into electronic health records using interoperability standards. The purpose of this study was to conduct a formative evaluation of a DDInteract that incorporates patient and product contextual factors to estimate the risk of bleeding. A randomized formative evaluation was conducted to compare DDInteract to usual care (UC) using physician-patient dyads. Using case vignettes, physicians and patients on warfarin participated in simulated virtual clinical encounters where they discussed the use of taking ibuprofen and warfarin concurrently and determined an appropriate therapeutic plan based on the patient's individualized risk. Dyads were randomized to either DDInteract or UC. Participants completed a postsession interview and survey of the SDM process. This included the 9-item Shared Decision-Making Questionnaire (SDM-Q-9), tool usability and workload National Aeronautics and Space Administration (NASA) Task Load Index, Unified Theory of Acceptance and Use of Technology (UTAUT), Perceived Behavioral Control (PBC) scale, System Usability Scale (SUS), and Decision Conflict Scale (DCS). They also were interviewed after the session to obtain perceptions on DDInteract and UC resources for DDIs. Twelve dyad encounters were performed using virtual software. Most (n=11, 91.7%) patients were over 50 years of age, and 9 (75%) had been taking warfarin for more than 2 years (75%). Regarding scores on the SDM-Q-9, participants rated DDInteract higher than UC for questions pertaining to helping patients clarify the decision (P=.03), involving patients in the decision (P=.01), displaying treatment options (P<.001), identifying advantages and disadvantages (P=.01), and facilitating patient understanding (P=.01) and discussion of preferences (P=.01). Five of the 8 UTAUT constructs showed differences between the 2 groups, favoring DDInteract (P<.05). Usability ratings from the SUS were significantly higher (P<.05) for physicians using DDInteract compared to those in the UC group but showed no differences from the patient's perspective. No differences in patient responses were observed between groups using the DCS. During the session debrief, physicians indicated little concern for the additional time or workload entailed by DDInteract use. Both clinicians and patients indicated that the tool was beneficial in simulated encounters to understand and mitigate the risk of harm from this DDI. Overall, DDInteract may improve encounters where there is a risk of bleeding due to a potential drug-drug interaction involving anticoagulants. Participants rated DDInteract as logical and useful for enhancing SDM. They reported that they would be willing to use the tool for an interaction involving warfarin and NSAIDs.


Efficacy of sodium hypochlorite in the degradation antineoplastic drugs by NMR spectroscopy.
Antineoplastic drugs are used to treat cancer, having their therapeutic effect by inhibiting the cell division process. Although cancer cells, due to their rapid growth, are more sensitive to the toxic effects of chemotherapeutic agents, healthy cells and tissues may also be damaged. Many studies show acute and chronic toxicity both in patients treated with chemotherapy and in exposed workers. In fact, exposure to these substances can also be linked to the formation of different types of secondary tumors. The International Agency on Research on Cancer (IARC) included some antineplastic drugs in Group 1 (carcinogenic to humans), in Group 2A (probable carcinogens for In recent years, many studies have evidenced the presence of antineoplastic drug contamination on work surfaces, materials and floors and based on these observations, international and national guidelines have been published to limit occupational exposure, with particular attention to procedures post-preparation of chemotherapy to limit as much as possible the accumulation of contaminated residues. The aim of the following study is to determine the effectiveness of the degradation of four antineoplastic drugs: 5-fluorouracil, azacitidine, cytarabine and irinotecan using a low concentration of sodium hypochlorite solution (0.115%). The analytical platform used to monitor the degradation course of the substances under examination was hydrogen nuclear magnetic spectroscopy (1H NMR). In the same experimental conditions the effectiveness of the degradation of the same antineoplastic drugs with a 99.9% ethanol solution was also evaluated. The study showed that the best degradation efficiency (> 90% ) is obtained with the hypochlorite solution after 15 minutes.


Electrocardiographical case. Acute severe chest tightness.
The early diagnosis of acute myocardial infarction is crucial for the institution of appropriate reperfusion therapy. We describe a 56-year-old man who developed sudden onset of severe chest tightness. Inferior, posterior and right ventricular ST elevation myocardial infarction was diagnosed on electrocardiography (ECG). The ECG interpretation, differential diagnosis and management are discussed.


Heart beat characterization from ballistocardiogram signals using extended functions of multiple instances.
A multiple instance learning (MIL) method, extended Function of Multiple Instances (eFUMI), is applied to ballistocardiogram (BCG) signals produced by a hydraulic bed sensor. The goal of this approach is to learn a personalized heartbeat "concept" for an individual. This heartbeat concept is a prototype (or "signature") that characterizes the heartbeat pattern for an individual in ballistocardiogram data. The eFUMI method models the problem of learning a heartbeat concept from a BCG signal as a MIL problem. This approach elegantly addresses the uncertainty inherent in a BCG signal (e. g., misalignment between training data and ground truth, mis-collection of heartbeat by some transducers, etc.). Given a BCG training signal coupled with a ground truth signal (e.g., a pulse finger sensor), training "bags" labeled with only binary labels denoting if a training bag contains a heartbeat signal or not can be generated. Then, using these bags, eFUMI learns a personalized concept of heartbeat for a subject as well as several non-heartbeat background concepts. After learning the heartbeat concept, heartbeat detection and heart rate estimation can be applied to test data. Experimental results show that the estimated heartbeat concept found by eFUMI is more representative and a more discriminative prototype of the heartbeat signals than those found by comparison MIL methods in the literature.


Potential Role of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs (RECK) in Regulation of Matrix Metalloproteinases (MMPs) Expression in Periodontal Diseases.
Periodontal diseases are characterized by pathological destruction of extracellular matrix (ECM) of periodontal tissues. Matrix metalloproteinases (MMPs) are a significant part of the degradation of ECM. However, the regulation of MMPs expression level in periodontal diseases is as yet undetermined. RECK (reversion-inducing cysteine-rich protein with Kazal motifs), a novel membrane-anchored inhibitor of MMPs, could regulate the expressions of MMP-2, 9 and MT1-MMP as a cell surface-signaling molecule. Thus, we propose that RECK may play an important role in regulating MMPs in the ECM degradation of periodontal diseases. The RECK/MMPs signaling pathway could provide a new approach for prevention and treatment of RECK in periodontal diseases by blocking MMPs.


Clinical manifestations of cutaneous leishmaniasis in Sri Lanka - possible evidence for genetic susceptibility among the Sinhalese.
Human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a pathogen more usually associated with visceral leishmaniasis, is now endemic in Sri Lanka. This report details the characteristics of 200 patients with locally acquired CL, who were recruited prospectively for an ongoing study into the genetic susceptibility to CL in Sri Lanka. In each case, the CL was confirmed by the demonstration of amastigotes in a direct smear and/or promastigotes in a culture. Although only 82% of the Sri Lankan population is Sinhalese, all 200 patients belonged to this ethnic group. The patients had a median age of 32 years (range=4-80 years). Most of them each had a single, non-tender, non-itching and dry lesion which had started as a papule and then gradually enlarged and ulcerated, with changes in the surrounding skin. None of the patients had any signs of systemic disease. Eleven (5.5%) each had at least one other affected family member. Patients with multiple lesions were most likely to be found in families with more than one affected member (P=0.002) but multiple lesions were not associated with diabetes mellitus (P>0.05). Although the results of passive detection under-estimate the true occurrence of a disease, the present data point towards enhanced susceptibility to CL among the Sinhalese and/or certain individuals, possibly determined by genetic factors.


Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study.
Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to (1) identify patient-prioritized symptoms for the development of symptom relief therapies and (2) elicit preferences for treatments among individuals receiving hemodialysis. We conducted a mixed methods study that included focus groups in Carrboro, North Carolina; Tucson, Arizona; and Seattle, Washington and a nationally distributed online survey. Focus group transcripts were analyzed for patterns, and the highest priority symptoms were determined on the basis of frequency and report severity. We used focus group findings to inform survey items. Focus group and survey results were crossvalidated and synthesized for final symptom prioritization. There were 32 participants across three focus groups and 87 survey respondents from 27 states in the United States. The physical symptoms of insomnia, fatigue, muscle cramping, and nausea/vomiting and the mood symptoms of anxiety and depressed mood were reported by participants in all focus groups. Among survey respondents, fatigue (94%), cramping (79%), and body aches (76%) were the most common physical symptoms, and feeling depressed (66%), worried (64%), and frustrated (63%) were the most common mood symptoms. The top-prioritized symptoms were consistent across focus group and survey participants and included the physical symptoms insomnia, fatigue, and cramping and the mood symptoms anxiety, depression, and frustration. Participants indicated that symptom frequency, duration, unpredictability, and social and financial effects factored most heavily into symptom prioritization. Patients prioritized the physical symptoms of insomnia, fatigue, and cramping and the mood symptoms of anxiety, depression, and frustration as the top symptoms for which to find new therapies.


Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis.
Small interfering RNA (siRNA) has been proposed as a novel treatment for atopic dermatitis (AD) because it suppresses sequence-specific mRNA expression. Indeed siRNA-based therapy achieves an almost complete cure with fewer side effects than currently available treatments. However, the tight junctions in the granular layer of the epidermis in the atopic skin are barriers to siRNA delivery. We previously reported the potential clinical utility of AT1002, a peptide that opens tight junctions. In the present study, we evaluated a topical siRNA-based therapy for AD using AT1002 in combination with a flexible liposome. The 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS) liposome was chosen as a carrier for siRNA because of its highly flexible structure and permeability. We prepared siRNA-encapsulated DOPE/CHEMS liposomes and examined their physical properties, safety, uptake into RAW264.7 cells, and topical application in healthy and AD-affected skin. We then assessed the efficacy of anti-nuclear factor-kappa B (NF-κB) (RelA) siRNA (siRelA)-encapsulated DOPE/CHEMS liposomes with AT1002 in AD model mice. The siRNA-DOPE/CHEMS liposomes were absorbed significantly better than siRNA alone and they enhanced siRNA skin penetration without toxicity. Moreover, siRelA-DOPE/CHEMS liposomes with AT1002 alleviated AD symptoms and reduced the levels of inflammatory cytokines in AD model mice. Therefore, the combination of AT1002 and DOPE/CHEMS liposomes could be a dermally applied RNA interference therapeutic system for effective RNA delivery and AD treatment.


[Xanthogranulomatous pyelonephritis presenting a subcutaneous mass in the lower abdomen: a case report].
A 72-year-old female presented with the complaint of left lower abdominal swelling in May, 2005. Laboratory analysis revealed elevated white blood cell counts and C-reactive protein. Abdominal computed tomography showed left ureteral calculi, left hydronephrosis and a mass extending through the perinephric space, psoas major muscle into the left flank and lower abdomen. Echo-guided needle mass biopsy was performed. Histopathological findings revealed xanthogranulomatous changes. Under the diagnosis of diffuse xanthogranulomatous pyelonephritis extended into psoas muscle and subcutaneous tissue, antibiotic therapy was given for 5 months. After reduction of subcutaneous mass, left nephroureterectomy was performed. Histopathological findings revealed xanthogranulomatous pyelonephritis and ureteritis. Postoperative course was uneventful without any relapse of inflammation.


Streptomyces xanthii sp. nov. and Streptomyces roseirectus sp. nov. isolated from a Chinese medicinal plant.
Two strains of Actinobacteria, designated CRXT-Y-14T and CRXT-G-22T, were isolated from the healthy leaves and seeds, respectively, of a medicinal plant Xanthium sibiricum. Their taxonomic positions were determined using a polyphasic approach. Strain CRXT-Y-14T produced flexuous chains of smooth-surfaced spores. Strain CRXT-G-22T produced straight chains of smooth-surfaced spores. Their morphological features were consistent with the diagnostic characteristics of members of the genus Streptomyces. The results of 16S rRNA gene sequence analyses indicated two strains represented members of the genus Streptomyces. CRXT-Y-14T shared 99.3, 98.9, 98.8 % sequence similarities to Streptomyces atriruber NRRL B-24165T, Streptomyces avermitilis MA-4680T and Streptomyces davaonensis JCM 4913T, respectively. Whilst CRXT-G-22T exhibited highest similarity to Streptomyces acidiscabies ATCC 49003T (98.9 %). The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the closest phylogenetic neighbours of strains CRXT-Y-14T and CRXT-G-22T were S. atriruber NRRL B-24165T and S. acidiscabies ATCC 49003T, respectively. The phylogenomic analyses further confirmed the relative relationship between strain CRXT-G-22T and S. acidiscabies ATCC 49003T, but indicated that CRXT-Y-14T could represent a novel species of the genus Streptomyce. However, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CRXT-Y-14T and strain CRXT-G-22T, between CRXT-Y-14T and S. atriruber NRRL B-24165T, and between CRXT-G-22T and S. acidiscabies ATCC 49003T were 85.4 and 23.2 %, 85.8 and 23.9 % and 89.1 and 34.1 %, respectively, far below the 95~96 and 70 % cut-off points recommended for delineating species. Furthermore, these two novel isolates were distinctly differentiated from their relatives in the genus Streptomyces with respect to phenotypic and chemotaxonomic characteristics. On the basis of these data, CRXT-Y-14T and CRXT-G-22T clearly represent two novel species within the genus Streptomyces, for which the names Streptomyces xanthii sp. nov. (type strain CRXT-Y-14T = MCCC 1K04966T= JCM 34527T) and Streptomyces roseirectus sp. nov. (type CRXT-G-22T = MCCC 1K04979T= JCM 34565T) are proposed.


Laboratory surveillance for wild poliovirus and vaccine-derived poliovirus, 2000-2001.
After the 1988 World Health Assembly resolution to eradicate poliomyelitis, the Global Laboratory Network for Poliomyelitis Eradication (the laboratory network) was established by the World Health Organization (WHO). The laboratory network is one component of the international surveillance system for detecting polio through notification of cases of acute flaccid paralysis (AFP). As progress is made in eradicating polio worldwide, the laboratory network provides critical virologic evidence about where poliovirus is circulating as a guide to supplementary vaccination activities aimed at interrupting transmission. This report summarizes the laboratory data for documenting the decline in wild poliovirus transmission and the occurrence of vaccine-derived polioviruses and highlights the expanding role of the laboratory network in global polio eradication.


The third crus of the anthelix and another minor anomaly of the external ear.
One minor anomaly of the external ear is a "third crus", which is an addition to the normal upper and lower crura at the anterior end of the anthelix. Another minor deformity is an extension of the crus of the helix, wherein it runs as a crest across the concha. An operation to correct the latter deformity is described.


RECALMIN: The association between management of Spanish National Health Service Internal Medical Units and health outcomes.
To investigate the association between management of Internal Medical Units (IMUs) with outcomes (mortality and length of stay) within the Spanish National Health Service. Data on management were obtained from a descriptive transversal study performed among IMUs of the acute hospitals. Outcome indicators were taken from an administrative database of all hospital discharges from the IMUs. Spanish National Health Service. One hundred and twenty-four acute general hospitals with available data of management and outcomes (401 424 discharges). IMU risk standardized mortality rates were calculated using a multilevel model adjusted by Charlson Index. Risk standardized myocardial infarction and heart failure mortality rates were calculated using specific multilevel models. Length of stay was adjusted by complexity. Greater hospital complexity was associated with longer average length of stays (r: 0.42; P < 0.001). Crude in-hospital mortality rates were higher at larger hospitals, but no significant differences were found when mortality was risk adjusted. There was an association between nurse workload with mortality rate for selected conditions (r: 0.25; P = 0.009). Safety committee and multidisciplinary ward rounds were also associated with outcomes. We have not found any association between complexity and intra-hospital mortality. There is an association between some management indicators with intra-hospital mortality and the length of stay. Better disease-specific outcomes adjustments and a larger number of IMUs in the sample may provide more insights about the association between management of IMUs with healthcare outcomes.


Morphometric and molecular analysis of the Encarsia inaron species-group (Hymenoptera: Aphelinidae), parasitoids of whiteflies (Hemiptera: Aleyrodidae).
Several series of host-reared specimens of an Encarsia species, initially thought to be the cosmopolitan Encarsia inaron (Walker), were collected in the Azores Islands (Portugal). Subsequent morphometric analysis supported the presence of two species: E. inaron and a new species, described herein as Encarsia estrellae Manzari & Polaszek sp. n. Encarsia estrellae was reared from Aleyrodes singularis Danzig, A. ?singularis, and Bemisia sp. afer-group on several host plants. In addition, the D2 region of the 28S rDNA gene was sequenced in eight individuals belonging to these species, as well as single representatives of two closely related and one distantly related species. Phylogenetic analysis of these DNA sequences, together with 23 additional Encarsia sequences retrieved from the European Molecular Biology Laboratory (EMBL) and GenBank databases, further supported the specific status of E. estrellae, and the placement of E. dichroa (Mercet) in the E. inaron species-group. Additionally, E. inaron is redescribed and some taxonomic problems in the E. inaron species-group are discussed.


Origin and outcome of pregnancies affected by androgenetic/biparental chimerism.
Androgenetic diploid cells confined to the placenta have recently been reported in several cases of normally developed fetuses in association with placental mesenchymal dysplasia (PMD). We investigated two singleton, mildly growth-restricted, female pregnancies ascertained on the basis of PMD. One case had liver hemangiomas and both infants had multiple skin hemangiomas. Post-natal development was normal. Molecular marker analysis confirmed the diagnosis of androgenetic and normal mixed cell populations in the placenta. Both cases derived from a single maternal genome (M1) and two distinct paternal genomes (P1 and P2). In one case, the androgenetic cell population contained both paternal genomes (P1P2), with one shared in common with the biparental (M1P1) population. In the second case, the androgenetic lineage showed complete homozygosity (P2P2) for a paternal genome not common to the biparental cell population. These new PMD cases help to define the range of possible clinical presentations of androgenetic/biparental mosaicism or chimerism. Placentas with androgenetic/biparental chimeric cell populations may derive from a single tri-pronuclear (3PN) zygote in which one or more parental genomes are not equally apportioned to the daughter cells in the first cell division.


The modulation of extracellular superoxide dismutase in the specifically enhanced cellular immune response against secondary challenge of Vibrio splendidus in Pacific oyster (Crassostrea gigas).
Extracellular superoxide dismutase (EcSOD) is a copper-containing glycoprotein playing an important role in antioxidant defense of living cells exposed to oxidative stress, and also participating in microorganism internalization and cell adhesion in invertebrates. EcSOD from oyster (designated CgEcSOD) had been previously reported to bind lipopolysaccharides (LPS) and act as a bridge molecule in Vibrio splendidus internalization. Its mRNA expression pattern, PAMP binding spectrum and microorganism binding capability were examined in the present study. The mRNA expression of CgEcSOD in hemocytes was significantly up-regulated at the initial phase and decreased sharply at 48 h post V. splendidus stimulation. The recombinant CgEcSOD protein (rCgEcSOD) could bind LPS, PGN and poly (I:C), as well as various microorganisms including Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Vibrio anguillarum, V. splendidus, Pastoris pastoris and Yarrowia lipolytica at the presence of divalent metal ions Cu(2+). After the secondary V. splendidus stimulation, the mRNA and protein of CgEcSOD were both down-regulated significantly. The results collectively indicated that CgEcSOD could not only function in the immune recognition, but also might contribute to the immune priming of oyster by inhibiting the foreign microbe invasion through a specific down-regulation.


The content and turnover of norepinephrine in the rabbit brain regions and cardiovascular tissues.
The content and turnover of norepinephrine (NE) in the hypothalamus, midbrain, pons-medulla, mesenteric artery, aorta and left ventricle were studied in the normal rabbit. Turnover rate of NE was determined by measuring the rate of decline in NE content of the tissue after blockade of synthesis with alpha-methyl-p-tyrosine. The NE content of the hypothalamus (1.44+/-0.03 microgram/g) was significantly higher than those of the midbrain (0.25+/-0.01 microgram/g) and the pons-medulla (0.36+/-0.01 microgram/g) (p less than 0.001), whereas the rate constant of NE turnover for the pons-medulla (0.213+/-0.009 hr-1) was significantly greater than those for the hypothalamus (0.164+/-0.008 hr-1, p less than 0.001) and the midbrain (0.180+/-0.008 hr-1, p less than 0.01). In the cardiovascular tissues examined, the NE content was highest in the mesenteric artery (6.33+/-0.19 microgram/g), moderate in the left ventricle (2.08+/-0.10 microgram/g) and lowest in the aorta (0.70+/-0.06 microgram/g). The differences among them were significant (p less than 0.001). However, the rate constant of NE turnover for the aorta (0.119+/-0.014 hr-1) was significantly greater than those for the mesenteric artery (0.059+/-0.008 hr-1, p less than 0.001) and the left ventricle (0.069+/-0.006 hr-1, p less than 0.005). The turnover rate of NE in the mesenteric artery was high, 0.372 microgram/g-hr, which suggests the very active NE synthesis. These results indicate that there are regional differences in content and turnover of NE of the cardiovascular tissues as well as of the brain.


Circulating Variants of SARS-CoV-2 Among Macedonian COVID - 19 Patients in the First Year of Pandemic.
Genomic epidemiology has proven to be a useful tool for investigating pandemic outbreaks and tracking pathogen spread and evolution. This study describes the circulation of SARS-CoV-2 strains in N. Macedonia during a period of one year, encompassing three waves of the COVID-19 pandemic. A certain percentage (2-3%) of positive cases were continuously selected and analyzed by whole genome sequencing (WGS) technology. Using this approach, a total of 337 SARS-CoV-2 genomes were sequenced and 26 different lineages belonging to 7 clades were detected. During the first wave of the pandemic, the most dominant lineage was B.1.1, followed by B.1.1.70, which became the most dominant in the second wave. The B.1.1.7 lineage completely overpassed all other variants in the third wave. Our study strengthens the notion that the progression of COVID-19 pandemic is associated with emergence of new SARS-CoV-2 variants with increased virulence. The measure of the impact of this viral dynamic on the spread of the pandemic should be evaluated in association with other factors that might influence the transmission.


[The tunneled supraclavicular island flap--a fasciocutaneous flap for head and neck reconstructions].
Reconstructive procedures in the head and neck region use a wide range of flaps for defect closure. The methods range from local, mostly myocutaneous flaps and skin grafts to free microsurgical flaps. To ensure a satisfactory functional and aesthetic result, good texture and color of the flap are always essential. Moreover, the donor-site defect needs to be reduced, with no resulting functional or aesthetic impairment. We have found that the shoulder is a region providing an optimum skin texture match to the neck and face. Fasciocutaneous island flap, nourished by the supraclavicular artery is used purely as a subcutaneously tunneled island flap. The tunneling maneuver significantly improves the donor site by reducing scarring. The flap is characterized by a long subcutaneous pedicle of up to 20 cm. The pivot point is in the supraclavicular region and allows the flap to be used in the upper chest, neck, chin, and cheek. In this article we present clinical cases in reconstructive procedures with supraclavicular flap and its expanded indications.


Development of TUA-WELLNESS screening tool for screening risk of mild cognitive impairment among community-dwelling older adults.
Focus on screening for cognitive impairment has to be given particular importance because of the rising older adult population. Thus, this study aimed to develop and assess a brief screening tool consisting of ten items that can be self-administered by community dwelling older adults (TUA-WELLNESS). A total of 1,993 noninstitutionalized respondents aged 60 years and above were selected for this study. The dependent variable was mild cognitive impairment (MCI) assessed using neuropsychological test batteries. The items for the screening tool comprised a wide range of factors that were chosen mainly from the analysis of ordinal logistic regression (OLR) and based on past literature. A suitable cut-off point was developed using receiver operating characteristic analysis. A total of ten items were included in the screening tool. From the ten items, eight were found to be significant by ordinal logistic regression and the remaining two items were part of the tool because they showed strong association with cognitive impairment in previous studies. The area under curve (AUC), sensitivity, and specificity for cut-off 11 were 0.84%, 83.3%, and 73.4%, respectively. TUA-WELLNESS screening tool has been used to screen for major risk factors of MCI among Malaysian older adults. This tool is only suitable for basic MCI risk screening purpose and should not be used for diagnostic purpose.


The Healthcare Cost of Mandibular Nonunions.
The aim of this retrospective cohort study was to compare the costs and characteristics between isolated mandible fractures and mandibular nonunions. From October 2015 to December 2016, the National Inpatient Sample (NIS) was searched for patients admitted with a primary diagnosis of a mandible fracture. The sample was divided between those admitted for an initial evaluation of an isolated fracture and a fracture nonunion. Demographic descriptors, injury characteristics, and inpatient factors were recorded. A total of 1432 patients were included in the final sample, of whom 51 (3.6%) were admitted for a nonunion. Nonunion patients were significantly older (P < 0.01), and nonunions were more often localized to the body (24 vs 11%; P = 0.02). Compared to that of isolated fractures, a greater proportion of nonunions required open reduction and internal fixation (86 vs 59%; P < 0.01) and bone grafting (37 vs 1.4%; P < 0.01), and nonunions imparted +32.6% greater hospitals costs (median: $10,680 vs 14,162; P < 0.01). In conclusion, compared to isolated mandible fractures, mandibular nonunions occurred in older patients, had a higher frequency in body of the mandible, and utilized significantly more hospital resources per admission.


Multivariate association analysis with somatic mutation data.
Somatic mutations are the driving forces for tumor development, and recent advances in cancer genome sequencing have made it feasible to evaluate the association between somatic mutations and cancer-related traits in large sample sizes. However, despite increasingly large sample sizes, it remains challenging to conduct statistical analysis for somatic mutations, because the vast majority of somatic mutations occur at very low frequencies. Furthermore, cancer is a complex disease and it is often accompanied by multiple traits that reflect various aspects of cancer; how to combine the information of these traits to identify important somatic mutations poses additional challenges. In this article, we introduce a statistical approach, named as SOMAT, for detecting somatic mutations associated with multiple cancer-related traits. Our approach provides a flexible framework for analyzing continuous, binary, or a mixture of both types of traits, and is statistically powerful and computationally efficient. In addition, we propose a data-adaptive procedure, which is grid-search free, for effectively combining test statistics to enhance statistical power. We conduct an extensive study and show that the proposed approach maintains correct type I error and is more powerful than existing approaches under the scenarios considered. We also apply our approach to an exome-sequencing study of liver tumor for illustration.


Adductor avulsive injuries near the symphisis pubis.
Avulsion injuries occurring near the symphisis pubis are related to the sites of origin of the adductor longus, adductor brevis, and gracilis muscles. Young athletes complain of pain near the symphisis which is increased by active adduction of the limb against resistance. Radiographic findings, similar to those found in infection and neoplasms, are mixed bone destruction and sclerosis on one side of the symphisis, frequently extending inferior pubic ramus.


Differential sensitivity of climate conditions on birth weight genetic values in mice divergently selected for birth weight residual variance.
After 32 generations of a divergent selection experiment for residual variance of birth weight in mice, two divergent lines were thus obtained: the heterogeneous line (H-line) and the homogeneous line (L-line). Throughout the generations, differences were observed between the two lines in traits such as litter size, survival at weaning, and birth weight variability caused by unidentified environmental conditions. The L-line exhibited advantages in terms of higher survival rates, larger litter sizes, and less sensitivity to changes in food intake. The study is an examination of the effects of climate as an environmental factor on the performance of these animals. Climate factors including maximum, minimum, and mean temperature (T), humidity (H), and TH index; at three stages (the fecundation, a week before the parturition and the parturition), were linked to a birth weight dataset consisting of 22,614 records distributed as follows: 8,853 corresponding to the H-line, 12,649 to the L-line, and 1,112 to the initial population. Out of the 27 analyzed climatic variables, the maximum temperature 1 wk before parturition (MXTW) was identified as the most influential when comparing heteroscedastic models with the deviance information criterion. The order of Legendre polynomial to apply in the following random regression model was tested by a cross-validation using homoscedastic models. Finally, MXTW was compared on how it affected the two divergent lines by analyzing predicted breeding values (PBV) obtained from a random regression heteroscedastic model. The mean PBV of the H-line in the first generation showed a range of 0.070 g with a negative slope, which was 35 times higher than the range obtained for the L-line, which varied within 0.002 g. In the last generation of selection, the H-line exhibited greater instability of PBV across temperatures, with a difference of 0.101 g between the maximum and minimum mean PBV, compared to 0.017 g for the L-line. The standard deviations of the slopes in the H-line were more dispersed than in the L-line. Unlike the H-line, the L-line had slopes that were not significantly different from 0 throughout the generations of selection, indicating greater stability in response to MXTW variations. The H-line exhibited a higher sensitivity to changes in MXTW, particularly in birth weight, with the L-line being more stable. The selection for uniformity of birth weight could lead to less sensitive animals under environmental changes.


Triple probe signal detection electronics for systems lacking a well defined ground.
Triple probes have been used to measure plasma parameters of low temperature and edge plasmas, yielding simultaneous measurements of electron temperature, ion density, and floating potential. Unlike standard Langmuir and double probe techniques, there is no requirement to sweep the probe potential relative to the plasma, thus allowing fast time resolution. However, in some plasma systems "ground" is not well defined with respect to a known ground, may vary strongly in time, or may be at an inconveniently high voltage. The resulting high plasma (or floating) potential requires common mode rejection before the signals can be digitized. A signal detection circuit constructed from inexpensive operational amplifiers and that makes use of a novel floating bias generation configuration is described.


Expression of Cytokines in Porcine Iris, Retina and Choroidal Tissues Stimulated by Microbe-associated Molecular Patterns.
The innate immune system is strongly implicated in the pathogenesis of uveitis. This study was designed to clarify the responses of the innate immune system in uveal tissues. We utilized quantitative, real-time RT-PCR to measure mRNA of innate immune system receptors from porcine iris, choroid, and retina tissues. We used RT-PCR for cytokines to evaluate the responses of these tissues to specific ligands or extracts of whole bacteria that activate the innate immune system. We used ELISA for IL-6 on selected choroidal supernatants to confirm that the mRNA measurement correlated with protein levels. In each of the studied tissues, we detected the expression of important receptors belonging to the innate immune system including dectin-1, TLR4, TLR8, and NOD2. Relative mRNA expression was generally lower in the retina compared to iris or choroid. All three tissues demonstrated upregulation of cytokine mRNA in response to a range of ligands that activate the innate immune system. The measurement of IL-6 protein was consistent with results based on mRNA. Notably, the expression of mRNA for IL-23 was more pronounced than IL-12 in all three tissues after stimulation with various innate immune system ligands. These data provide evidence of a potent innate immune response intrinsic to uveal tissues. Specific innate immune system ligands as well as bacterial extracts enhanced the production of several inflammatory cytokines. Furthermore, the observation of higher upregulation of IL-23 mRNA, compared to IL-12 in response to innate immune stimuli, suggested that a local TH17 response might be more robust than a local TH1 response in uveal tissues. Our results expand the understanding as to how the innate immune system may contribute to uveitis.


Dipeptidyl peptidase-4 inhibitors as preferable oral hypoglycemic agents in terms of treatment satisfaction: Results from a multicenter, 12-week, open label, randomized controlled study in Japan (PREFERENCE 4 study).
To compare the treatment satisfaction of four classes of oral hypoglycemic agents (OHAs): dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase inhibitors (αGI), biguanides (BG) and sulfonylureas (SU), which are common initial treatments for type 2 diabetes mellitus patients in Japan, and to identify the best oral hypoglycemic agent in terms of treatment satisfaction. In this 12-week, randomized, controlled, open-label study, Japanese outpatients with type 2 diabetes mellitus who were naïve to pharmacological treatment were randomly assigned a DPP-4 inhibitor, a BG., an αGI or a SU. The primary end-point was the Oral Hypoglycemic Agent Questionnaire (OHA-Q) total and subscale scores (treatment convenience, somatic symptoms and satisfaction) at week 4. Adherence, glycated hemoglobin (HbA1c) level and safety were also evaluated. The DPP-4 inhibitor group scored highest in the OHA-Q total and all subscale scores at week 4. The total score was significantly higher in the DPP-4 inhibitor group than in the BG or αGI groups (P = 0.0084 and 0.0147, respectively). The mean total score at week 12 was also highest in the DPP-4 inhibitor group, with a significant difference compared with the αGI group (P = 0.0293). The mean HbA1c decreased from baseline to week 12 in all groups. The DPP-4 inhibitor group had the highest adherence at weeks 4 and 12. A total of 11 patients reported adverse events, including one hypoglycemic event in the SU group. The DPP-4 inhibitor was the most preferable option in terms of treatment satisfaction.


5 V Compatible Two-Axis PZT Driven MEMS Scanning Mirror with Mechanical Leverage Structure for Miniature LiDAR Application.
The MEMS (Micro-Electronical Mechanical System) scanning mirror is an optical MEMS device that can scan laser beams across one or two dimensions. MEMS scanning mirrors can be applied in a variety of applications, such as laser display, bio-medical imaging and Light Detection and Ranging (LiDAR). These commercial applications have recently created a great demand for low-driving-voltage and low-power MEMS mirrors. However, no reported two-axis MEMS scanning mirror is available for usage in a universal supplying voltage such as 5 V. In this paper, we present an ultra-low voltage driven two-axis MEMS scanning mirror which is 5 V compatible. In order to realize low voltage and low power, a two-axis MEMS scanning mirror with mechanical leverage driven by PZT (Lead zirconate titanate) ceramic is designed, modeled, fabricated and characterized. To further decrease the power of the MEMS scanning mirror, a new method of impedance matching for PZT ceramic driven by a two-frequency mixed signal is established. As experimental results show, this MEMS scanning mirror reaches a two-axis scanning angle of 41.9° × 40.3° at a total driving voltage of 4.2 Vpp and total power of 16 mW. The effective diameter of reflection of the mirror is 2 mm and the operating frequencies of two-axis scanning are 947.51 Hz and 1464.66 Hz, respectively.


Advancing alcohol biomarkers research.
Biomarkers to detect past alcohol use and identify alcohol-related diseases have long been pursued as important tools for research into alcohol use disorders as well as for clinical and treatment applications and other settings. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a workshop titled "Workshop on Biomarkers for Alcohol-Induced Disorders" in June 2008. The intent of this workshop was to review and discuss recent progress in the development and implementation of biomarkers for alcohol use and alcohol-related disorders with a goal to formulate a set of recommendations to use to stimulate and advance research progress in this critical area of alcoholism research. Presentations at this workshop reviewed the current status of alcohol biomarkers, providing a summary of the history of biomarkers and the major goals of alcohol biomarker research. Moreover, presentations provided a comprehensive overview of the current status of several well-recognized biomarkers of alcohol use, a summary of recent studies to characterize novel biomarkers and their validation, along with perspectives and experiences from other NIH institutes and from other federal agencies and industry, related to regulatory issues. Following these presentations, a panel discussion focused on a set of issues presented by the organizers of this workshop. These discussion points addressed: (i) issues related to strategies to be adopted to stimulate biomarker discovery and application, (ii) the relevance of animal studies in biomarker development and the status of biomarkers in basic science studies, and (iii) issues related to the opportunities for clinical and commercial applications. This article summarizes these perspectives and highlights topics that constituted the basis for recommendations to enhance alcohol biomarker research.


Modulation by melatonin of glutamatergic synaptic transmission in the carp retina.
Melatonin is involved in a variety of physiological functions through activating specific receptors coupled to GTP-binding protein. Melatonin and its receptors are abundant in the retina. Here we show for the first time that melatonin modulates glutamatergic synaptic transmission from cones to horizontal cells (HCs) in carp retina. Immunocytochemical data revealed the expression of the MT1 receptor on carp HCs. Whole-cell recordings further showed that melatonin of physiological concentrations potentiated glutamate-induced currents from isolated cone-driven HCs (H1 cells) in a dose-dependent manner, by increasing the efficacy and apparent affinity of the glutamate receptor. The effects of melatonin were reversed by luzindole, but not by K 185, indicating the involvement of the MT1 receptor. Like melatonin, methylene blue (MB), a guanylate cyclase inhibitor, also potentiated the glutamate currents, but internal infusion of cGMP suppressed them. The effects of melatonin were not observed in cGMP-filled and MB-incubated HCs. These results suggest that the melatonin effects may be mediated by decreasing the intracellular concentration of cGMP. Consistent with these observations, melatonin depolarized the membrane potential of H1 cells and reduced their light responses, which could also be blocked by luzindole. These effects of melatonin persisted in the presence of the antagonists of receptors for dopamine, GABA and glycine, indicating a direct action of melatonin on H1 cells. Such modulation by melatonin of glutamatergic transmission from cones to HCs is thought to be in part responsible for circadian changes in light responsiveness of cone HCs in teleost retina.


Regulation of expression of symbiotic genes in Rhizobium sp. NGR234.
Research in the field of Rhizobium-legume symbiosis faces a new challenge: integrate the wealth of information generated by genomic projects. The goal: apprehend the complexity of the molecular mechanisms involved in symbiotic associations. At the time of writing, the genomes of three micro-symbionts (Bradyrhizobium japonicum, Mesorhizobium loti and Sinorhizobium meliloti) have been sequenced, and two more (those of Rhizobium leguminosarum and Rhizobium etli) will be completed in the near future. Together, completed rhizobial genomes represent already 23,393,822 bp of DNA sequence and 21,797 predicted open reading frames (ORFs). To identify candidate-symbiotic genes in such a broad database, predict their function and dissect the regulatory networks that govern their expression are no simple tasks. One way to confront this problem is to combine different datasets, in particular genetic and transcriptional maps as well as predicted promoters from bioinformatics analyses. Here, we would like to illustrate this type of approach with the analysis of the symbiotic plasmid (pNGR234a) of the broad host-range Rhizobium sp. NGR234.


Building resilient organisations: Proactive risk management in organisations and their supply chains.
Resilient organisations proactively identify and manage anticipated risks, as well as build capacity to cope with adversity, whether anticipated or unanticipated. Resilience is the outcome of fully integrating a proactive, enterprise-wide, multidisciplinary and holistic risk management approach into the organisation's business management processes. Resilience is an aspirational objective - there is no endpoint, nor is there a one-size-fits-all solution. Resilient organisations promote an inclusive culture of risk thinking throughout the organisation and its supply chain. By integrating a proactive approach to managing risk, organisations can become more agile, adaptable and responsive to changes in their operating environment.


Effect of reduced atmospheric pressure on patients with fluctuating hearing loss due to Ménière's disease.
Subjective symptomatic and objective audiologic effects of reduced atmospheric pressure on patients with confirmed fluctuating hearing loss due to Ménière's disease were statistically assessed on a prospective basis. The effect of hypobaric environments on absolute hearing thresholds was investigated in 10 normal subjects at 6,500 ft. Absolute hearing threshold levels obtained at altitude, after one hour altitude exposure, and on descent to normobaric conditions were compared with levels obtained prior to the hypobaric exposure. The results indicated slightly increasing sensitivity of the audiometer headphones with altitude and an insignificant difference in hearing threshold when comparing the differing experimental conditions. The Ménière's disease study group of 16 patients was followed symptomatically and audiologically for one year prehypobaric exposure and for one month post-treatment. The results in this group utilizing the same experimental protocol as with normal subjects indicated a mild deterioration of hearing in the lower frequencies (1,000, 2,000 Hz and calculating the Ménière's pure tone average) despite significant improvements in the vertigo and disability components of their disease.


Parenting education for employees.
Effective parenting is a skill that can be learned and developed through company supported programs for employees. The occupational health nurse is an appropriate professional within the corporation to facilitate parental support programs. The family unit is changing. Industry and community resources working together to provide support and education can make a positive impact on family life in America. The children of today will be the work force of tomorrow. An investment in the family is an investment in the future.


KCTD12 modulation of GABA(B) receptor function.
The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain-containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model. Human KCTD12 co-expression altered the kinetics of GABABR-mediated GIRK channels, speeding rates of both activation and desensitization. Analysis of concentration-response curves showed that KCTD12 coexpression did not alter effects of the agonists GABA or baclofen on GABABR. KCTD12 coexpression enhanced the potentiating effects of the positive allosteric modulator CGP7930, and its effects on GABABR activation and desensitization. The function of KCTD12 in vivo was examined, using the KCTD12 knockout mouse model. The knockout mice were more resistant to a pentylenetetrazole proconvulsant challenge suggesting reduced seizure susceptibility. In the two bottle preference test, KCTD12 knockout mice demonstrated a reduced consumption at high ethanol concentrations. In summary, human KCTD12 accelerated the kinetics of GABABR in vitro, in a manner possibly sensitive to allosteric pharmacological modulation. This study also provides novel in vivo evidence that the interaction between KCTD12 and GABABR is of physiological significance, and may be a mechanism to more selectively modulate GABABR.


[Chemoembolization with degradable starch microspheres in malignant hepatic tumors].
A new method of chemoembolization with degradable starch microspheres (DSM) was used for patients with malignant hepatic tumors. DSM, 40-45 micron in diameter, which are degraded by serum amylase, temporarily obstruct arterial blood flow at the arteriolar capillary bed. Experimental studies have demonstrated that such occlusion enhances the regional uptake and reduces systemic exposure to simultaneously administered arterial anticancer drugs. Transcatheter chemoembolization with DSM was performed in 14 cases of hepatocellular carcinoma and 8 cases of metastatic liver cancer. Adriamycin or Mitomycin C mixed with DSM was injected into the patients with hepatocellular carcinoma or metastatic liver cancer, respectively, through the proper hepatic artery. The therapeutic effect of this chemoembolization was evaluated by the change in tumor size measured by angiography or computed tomography. In hepatocellular carcinoma, tumor regression of over 50% was observed in 5 of 14 patients. Elevated serum AFP level of more than 200 ng/ml was decreased in all 6 cases. In metastatic liver cancer, tumor regression of over 50% was observed in 4 of 8 cases. Although half of the patients had transient pain within 2 hours, no major side effects such as bone marrow suppression and hepatotoxicity were observed. Our results suggest that chemoembolization with DSM can be effectively used in the treatment of malignant hepatic tumors.


Pandemic Challenges: Keeping Nursing Research Alive.
Nursing has been pandemic-slammed. Although 2020 will be forever entangled with the COVID-19 pandemic, we, as nurse leaders, must continue to move forward and beyond this endemic challenge. We cannot lose focus on generating new knowledge to continue nursing excellence and move our profession forward.


The platelet microparticle proteome.
Platelet-derived microparticles are the most abundant type of microparticle in human blood and contribute to many biologically significant processes. Here, we report the first proteomic analysis of microparticles generated from activated platelets. Using 1D SDS-PAGE and liquid chromatography coupled to a linear ion trap mass spectrometer, the identification of 578 proteins was accomplished using a minimum of 5 MS/MS detections of at least two different peptides for each protein. These microparticles displayed many proteins intrinsic to and well-characterized on platelets. For example, microparticles in these experiments were found to contain membrane surface proteins including GPIIIa, GPIIb, and P-selectin, as well other platelet proteins such as the chemokines CXCL4, CXCL7, and CCL5. In addition, approximately 380 of the proteins identified were not found in two previous studies of the platelet proteome. Since several of the proteins detected here have been previously implicated in microparticle formation and/or pathological function, it is hoped that this study will help fuel future work concerning the possible role of microparticles in various disease states.


Suppression of somatostatin release by duodenogastric reflux in dogs.
The effect of duodenogastric reflux on systemic and portal venous blood concentrations of somatostatin has been studied in the dog. Duodenogastric reflux suppressed somatostatin concentrations in both systemic and portal venous blood, but this did not occur when bile alone was diverted into the stomach. The suppression was also much less marked when truncal vagotomy accompanied the reflux. These findings suggest that altered somatostatin activity may play a part in the production of the pathophysiological changes occurring in clinical conditions such as peptic ulceration, in which there is an increase in duodenogastric reflux.


Improving interviewing techniques through the bug-in-the-ear.
The author describes a simple, efficient and inexpensive tool to improve and accelerate the teaching of interviewing techniques. There are major advantages and some shortcomings to this method. Both are reviewed along with a survey carried out to gauge the experiences of psychiatric residency training programs across the continent with the "bug-in-the-ear". The author discusses the implications for residents, supervisors and patients and offers suggestions how to make this approach more available to non-using centers.


Stereotactic body radiation therapy for prostate cancer patients with old age or medical comorbidity: a 5-year follow-up of an investigational study.
We evaluated 5-year follow-up of stereotactic body radiation therapy (SBRT) with Cyberknife for prostate cancer patients. Forty-five men with prostate adenocarcinoma who received SBRT using Cyberknife from May 2006 to November 2012 were enrolled in this study. They were prostate cancer patients with old age and medical comorbidities who received a total of 36 Gy to the prostate in 5 fractions with either everyday or every other day schedule. Prostate-specific antigen (PSA) levels at initial diagnosis and after radiation were traced. Primary endpoints were biochemical relapse-free survival (bRFS), progression-free survival (PFS), and overall survival (OS). The definition of biochemical relapse was a PSA level of nadir+2 ng/mL. Progression was defined as biochemically or clinically detected disease and the start of salvage therapy. After median follow-up of 63 months, the 5-year bRFS for all patients was estimated at 89.7%. The 5-year PFS was estimated at 71%. Four cases of biochemical relapse were observed, including two patients who experienced locoregional failure and one patient who had distant metastasis with biochemical relapse. The 5-year OS was estimated at 94.3%. There were five deaths, all of which were unrelated to prostate cancer. There was no grade 3 or higher acute complication. Grade 3 or higher late urinary toxicity was reported in 2 (4.4%) of 45 patients. The 5-year survival and toxicity outcome of SBRT using Cyberknife on prostate cancer patients with old age or comorbidities were favorable and safe in an investigational study.


Different erythrocyte and platelet surface electric charge in various types of glomerulonephritis.
Some preliminary observations suggest that predisposition to a particular type of glomerulonephritis (GN) may be connected with the genetically determined charge of the glomerular capillary wall. A correlation between erythrocyte surface and the glomerular capillary wall charges has also been observed. The purpose of this study was to verify and extend previous investigations. Therefore we measured erythrocyte and platelet surface charge from patients with idiopathic membranous and mesangial GN as well as idiopathic membranoproliferative GN and lupus nephritis. The erythrocyte and platelet surface charge was determined by the binding of the cationic dye, alcian blue (AB). A fresh alcoholic AB solution was made for each experiment, which were run in batches of four, each including cells from a healthy person and from patients each with a different type of GN. In patients with idiopathic membranous and membranoproliferative GN, a significant decrease in the erythrocyte and platelet charges was observed irrespective of their clinical state (remission or nephrotic syndrome). Erythrocyte charge was decreased despite the normal amount of membranous sialic acid. In contrast, patients with idiopathic mesangial GN, in complete or partial remission, exhibited normal erythrocyte and platelet surface charges. Exclusively in this type of GN, the appearance of nephrotic proteinuria was associated with a slight decrease, the erythrocyte charge, which was not statistically significant (P > 0.1). A reduction in the negative erythrocyte charge in lupus nephritis was less in magnitude than in idiopathic membranous or membranoproliferative GN, and occurred independently of the level of daily proteinuria, whereas the platelet charge was normal. The decrease of the erythrocyte and platelet charge in idiopathic membranous and mebranoproliferative GN seems to be a pre-morbid feature.


Effect of GEN1 interference on the chemosensitivity of the breast cancer MCF-7 and SKBR3 cell lines.
Chemotherapy is a notable method for the treatment of breast cancer. Numerous genes associated with the sensitivity of cancer to chemotherapy have been found. In recent years, evidence has suggested that a particular structure termed Holliday junction (HJ) plays a crucial role in cancer chemosensitivity. Targeting HJ resolvases, such as structure-specific endonuclease subunit SLX4 (Slx4) and MUS81 structure-specific endonuclease subunit (Mus81), significantly increases the chemosensitivity of tumor cells. Flap endonuclease GEN homolog 1 (GEN1) is a HJ resolvase that belongs to the Rad2/xeroderma pigmentosum complementation group G nuclease family. Whether GEN1 affects the chemosensitivity of tumor cells in a similar manner to Slx4 and Mus81 remains unknown. The aim of the present study was to determine the effect of GEN1 interference on the chemosensitivity of breast cancer cell lines. The investigation of the function of GEN1 was performed using MCF-7 and SKBR3 cells. Short hairpin RNA was used to suppress the expression of GEN1, and western blot analysis and reverse transcription-quantitative polymerase chain reaction were used to detect gene expression. In addition, a cell counting kit-8 assay was performed to detect the viability of cells and flow cytometry was performed to test apoptosis levels. Suppression of GEN1 in SKBR3 cells effectively increased the sensitivity to the chemotherapeutic drug 5-fluorouracil (5-FU), while MCF-7 cells showed no significant change in sensitivity following GEN1 suppression. However, when GEN1 was targeted in addition to Mus81, the MCF-7 cells also demonstrated a significantly increased sensitivity to 5-FU. In addition, when the level of Mus81 was low, GEN1 expression was increased under a low concentration of 5-FU. The present results suggest that GEN1 may play different roles in different breast cancer cell lines. The function of GEN1 may be affected by the level of Mus81 in the cell line. In addition, GEN1 interference may improve the sensitivity to chemotherapy induced by targeting Mus81 alone.


Chemical mixtures in untreated water from public-supply wells in the U.S.--occurrence, composition, and potential toxicity.
Chemical mixtures are prevalent in groundwater used for public water supply, but little is known about their potential health effects. As part of a large-scale ambient groundwater study, we evaluated chemical mixtures across multiple chemical classes, and included more chemical contaminants than in previous studies of mixtures in public-supply wells. We (1) assessed the occurrence of chemical mixtures in untreated source-water samples from public-supply wells, (2) determined the composition of the most frequently occurring mixtures, and (3) characterized the potential toxicity of mixtures using a new screening approach. The U.S. Geological Survey collected one untreated water sample from each of 383 public wells distributed across 35 states, and analyzed the samples for as many as 91 chemical contaminants. Concentrations of mixture components were compared to individual human-health benchmarks; the potential toxicity of mixtures was characterized by addition of benchmark-normalized component concentrations. Most samples (84%) contained mixtures of two or more contaminants, each at concentrations greater than one-tenth of individual benchmarks. The chemical mixtures that most frequently occurred and had the greatest potential toxicity primarily were composed of trace elements (including arsenic, strontium, or uranium), radon, or nitrate. Herbicides, disinfection by-products, and solvents were the most common organic contaminants in mixtures. The sum of benchmark-normalized concentrations was greater than 1 for 58% of samples, suggesting that there could be potential for mixtures toxicity in more than half of the public-well samples. Our findings can be used to help set priorities for groundwater monitoring and suggest future research directions for drinking-water treatment studies and for toxicity assessments of chemical mixtures in water resources.


A follow-up study of the use of DIAGNOdent for monitoring fissure caries in children.
The aim of this study was to evaluate the utility of the laser fluorescence device DIAGNOdent for monitoring occlusal caries longitudinally as part of a routine dental check-up in a public dental clinic. Children aged 7-8 and 13-14 years at baseline participated in the study. As part of two consecutive dental check-ups with a mean interval of 1,19, years, 423 permanent molars and 315 primary molars in 81 children were examined visually and using DIAGNOdent by one dentist. In teeth where, as judged by visual examination, caries had emerged or progressed during the follow-up, the DIAGNOdent values had increased significantly from the baseline. In permanent teeth with a change in visual score from sound to enamel or dentin caries, the mean DIAGNOdent value increased from 24 to 37 and in primary teeth from 8 to 40. The increase in DIANGOdent values correlated positively with the increase in visual score. The mean DIAGNOdent value at baseline was significantly higher in teeth that became carious than in those that remained sound during the follow-up. For permanent teeth with a visual reversal from inactive or active enamel caries to a sound surface, the mean DIAGNOdent value decreased from 36 to 24. These results suggest that DIAGNOdent is useful in monitoring occlusal caries in both permanent and primary molars.


Iron Catalyzed Cascade Construction of Molybdenum Carbide Heterointerfaces for Understanding Hydrogen Evolution.
The intercrystalline interfaces have been proven vital in heterostructure catalysts. However, it is still challenging to generate specified heterointerfaces and to make clear the mechanism of a reaction on the interface. Herein, this work proposes a strategy of Fe-catalyzed cascade formation of heterointerfaces for comprehending the hydrogen evolution reaction (HER). In the pure solid-phase reaction system, Fe catalyzes the in situ conversion of MoO2 to MoC and then Mo2 C, and the consecutive formation leaves lavish intercrystalline interfaces of MoO2 -MoC (in Fe-MoO2 /MoC@NC) or MoC-Mo2 C (in Fe-MoC/β-Mo2 C@NC), which contribute to HER activity. The improved HER activity on the interface leads to further checking of the mechanism with density functional theory calculation. The computation results reveal that the electroreduction (Volmer step) produced H* prefers to be adsorbed on Mo2 C; then two pathways are proposed for the HER on the interface of MoC-Mo2 C, including the single-molecular adsorption pathway (Rideal mechanism) and the bimolecular adsorption pathway (Langmuir-Hinshelwood mechanism). The calculation results further show that the former is favorable, and the reaction on the MoC-Mo2 C heterointerface significantly lowers the energy barriers of the rate-determining steps.