The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus.
Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.


Medical students' and postgraduate residents' observations of professionalism.
There is increasing interest in teaching professionalism to medical learners. The purpose of this study was to explore professionalism observed among medical learners and faculty in a Canadian academic institution. A total of 253 medical learners (30% response rate) completed an online survey measuring medical professionalism. The survey used a validated professionalism scale "Climate of Professionalism", which queries subjects' observations of professional and unprofessional behavior in clinical teaching environments. Overall, 73.3% of medical learners felt prepared in the area of medical professionalism. Differences existed in observed professionalism by level of training. By respondents' reports, both medical students and residents viewed their peer groups as more professional than the other. Both groups also rated faculty as the poorest in terms of observed professional behaviors but the best in observed unprofessional behavior. Most learners in this Canadian medical school felt well prepared in the area of professionalism, and each training level viewed their peer group as the most professional. Peer groups may rate themselves more favorably due to increased interaction with their group, and active recall of professional communications. This study found differences in observations of professionalism by training level, therefore provides support for specialized professionalism education tailored to the learners level of medical training.


Transition state stabilization by the N-terminal anticodon-binding domain of lysyl-tRNA synthetase.
Lysyl-tRNA synthetase from Bacillus stearothermophilus (B.s. LysRS) (EC ) catalyzes aminoacylation of tRNA(Lys) with l-lysine, in which l-lysine was first activated with ATP to yield an enzyme (lysyladenylate complex), and then the lysine molecule was transferred from the complex to tRNA(Lys). B.s. LysRS is a homodimeric enzyme with a subunit that consists of two domains, an N-terminal tRNA anticodon-binding domain (TAB-ND: Ser(1)-Pro(144)) and a C-terminal Class II-specific catalytic domain (CAT-CD: Lys(151)-Lys(493)). CAT-CD alone retained catalytic activity, although at a low level; TAB-ND alone showed no activity. Size exclusion chromatography revealed that CAT-CD exists as a dimer, whereas TAB-ND was a monomer. The formation of a complex consisting of these domains was detected with the guidance of surface plasmon resonance. In accordance with this, the addition of TAB-ND to CAT-CD significantly enhanced both the l-lysine activation and the tRNA aminoacylation reactions. Kinetic analysis showed that deletion of TAB-ND resulted in a significant destabilization of the transition state of CAT-CD in the l-lysine activation reaction but had little effect on the ground state of substrate binding. A significant role of a cross-subunit interaction in the enzyme between TAB-ND and CAT-CD was proposed for the stabilization of the transition state in the l-lysine activation reaction.


Attenuation of Th1 response in decoy receptor 3 transgenic mice.
The soluble decoy receptor 3 (DcR3) is a member of the TNFR superfamily. Because DcR3 is up-regulated in tumor tissues and is detectable in the sera of cancer patients, it is regarded as an immunosuppressor to down-regulate immune responses. To understand the function of DcR3 in vivo, we generated transgenic mice overexpressing DcR3 systemically. In comparison with HNT-TCR (HNT) transgenic mice, up-regulation of IL-4 and IL-10 and down-regulation of IFN-gamma, IL-12, and TNF-alpha were observed in the influenza hemagglutinin(126-138) peptide-stimulated splenocytes of HNT-DcR3 double-transgenic mice. When infected with Listeria monocytogenes, DcR3 transgenic mice show attenuated expression of IFN-gamma as well as increased susceptibility to infection. The Th2 cell-biased phenotype in DcR3 transgenic mice is attributed to decreased IL-2 secretion by T cells, resulting in the suppression of IL-2 dependent CD4(+) T cell proliferation. This suggests that DcR3 might help tumor growth by attenuating the Th1 response and suppressing cell-mediated immunity.


Oxcarbazepine for the treatment of trichotillomania.
There is no pharmacological treatment of trichotillomania that has consistently demonstrated efficacy, although good results have been obtained with antidepressants and other drugs such as atypical antipsychotics, bupropion, lithium, and topiramate. The anticonvulsant oxcarbazepine has also been used as mood stabilizer and has been tested for treating binge eating, but there is no report on oxcarbazepine in trichotillomania. We report the case of an obese 43-year-old woman with a diagnosis of trichotillomania in comorbidity with binge eating disorder who was treated with a flexible dose of the anticonvulsant oxcarbazepine. We administered oxcarbazepine at a dosage of 1200 mg/d, and this subject improved both in hair pulling and in eating behaviors with no relapse after 9 months. Further studies with a wide sample of patients are needed to prove the efficacy of oxcarbazepine and the long-term maintenance of these benefits. Relationships of trichotillomania with bipolar spectrum should also be investigated.


Satisfaction and difficulties of French professional home caregivers in supporting older people with Alzheimer's disease or alcohol misuse.
In France, few studies have examined home care when it comes to ageing support and even fewer have considered alcohol misuse in this context. The studies also show that being old and having alcohol use disorders are two unfavourable conditions for receiving help, whereas for the Alzheimer's disease, there is a clear need for optimal care. In this article, we study professional home caregiver's perceptions of their job along with their difficulties and satisfactions in supporting older people with Alzheimer's disease or alcohol misuse. Out of the 23 professionals approached, 17 took part in a research interview from October 2013 to January 2014. All interviews were recorded, fully transcribed and lexically analysed with Alceste® software. Among the five classes that were identified from 63% of the initial data, the main themes that emerged illustrate the nature of the associated pathologies, the perceptions and satisfactions related to the profession, their adaptive skills, the difficulties related to the life context of the older person, and the wine consumption of the latter. The lexical discourse analysis shows that the professional home caregivers are involved in looking after not only people with Alzheimer's disease but also those with alcohol misuse. However, despite the difficulties and satisfactions encountered, adaptation to the older people seems to be their priority and one of the many skills that they have acquired during their professionalisation. Most of the older people who are helped are women and the difficulties mentioned by their caregivers usually arise at the time of their death. Lastly, when caring for alcohol misusers, they describe negative attitudes in their support. Although research in this area is rare while home care for the older person, whatever the pathology, is increasing, professionals need to be supported by the associations or companies that employ them and should be trained to help them provide the appropriate care.


Long term studies of pancreas transplantation in experimental diabetes mellitus.
Alloxan diabetes was induced in inbred rats that then were divided into four groups consisting of unoperated diabetic controls, sham-operated diabetic controls, rats given pancreaticoduodenal isografts, and rats given duct-ligated pancreas isografts. The animals were studied for from 18 months (controls) to two years (transplants) and the following important results were obtained: 1) In striking contrast to the diabetic controls, pancreas transplants of both types produced immediate and permanent relief of hyperglycemia, immediate and lasting elevation of serum insulin levels, a normal weight and growth curve, and good health for two years. Removal of the graft was followed by recurrence of severe diabetes. 2) Pancreas transplants of both types prevented the widespread and severe renal, ophthalmic and neural lesions of diabetes that were found in the diabetic controls. 3) The duct-ligated pancreas graft and pancreaticoduodenal transplant were equally effective in controlling diabetes. Ligation of the pancreatic duct was not followed by significant morphologic or clinical evidence of pancreatitis or by loss of endocrine function. 4) Portal venous drainage of the pancreas transplant was unnecessary for good endocrine function.


AT1 receptor signaling pathways in the cardiovascular system.
The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins. In addition, there is functional cross-talk between the AT1 receptor signaling pathway and other signaling pathways. In this review, we will summarize an up to date overview of essential AT1 receptor signaling events and their functional significances in the cardiovascular system.


Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.
Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.


A Multi-Attribute Pheromone Ant Secure Routing Algorithm Based on Reputation Value for Sensor Networks.
With the development of wireless sensor networks, certain network problems have become more prominent, such as limited node resources, low data transmission security, and short network life cycles. To solve these problems effectively, it is important to design an efficient and trusted secure routing algorithm for wireless sensor networks. Traditional ant-colony optimization algorithms exhibit only local convergence, without considering the residual energy of the nodes and many other problems. This paper introduces a multi-attribute pheromone ant secure routing algorithm based on reputation value (MPASR). This algorithm can reduce the energy consumption of a network and improve the reliability of the nodes' reputations by filtering nodes with higher coincidence rates and improving the method used to update the nodes' communication behaviors. At the same time, the node reputation value, the residual node energy and the transmission delay are combined to formulate a synthetic pheromone that is used in the formula for calculating the random proportion rule in traditional ant-colony optimization to select the optimal data transmission path. Simulation results show that the improved algorithm can increase both the security of data transmission and the quality of routing service.


Behavioural and psychiatric disorders in paediatric Wilson's disease.
An 11-year-old boy was treated since 6-years-old with methylphenidate for combined attention deficit and hyperactivity disorder. At age nine his behaviour had worsened and he started to have phobias. One year later persistent hypertransaminasemia was found. Physical examination showed a dysdiadocokinesia. Laboratory investigation revealed a low caeruloplasmin and augmented basal urinary copper with a positive postpenicillamine test. Liver biopsy showed high liver copper (853 µg/g) and brain MRI was normal. D-penicillamine and zinc acetate were started without side effects. ATP7B gene mutation was confirmed after treatment initiation.


[Effects of allelochemical EMA isolated from Phragmites communis on algal cell membrane lipid and ultrastructure].
In order to reveal the antialgal mechanisms of allelochemicals, effects of the allelochemical eathyl-2-methyl acetoacetate (EMA) on cell membrane lipid and ultrastructure of Chlorella pyrenoidosa, Microcystis aeruginosa and Chlorella vulagaris were studied in this paper. The lipid fatty acids of the algal membrane were isolated following the Bligh and Dye method and quantified by gas chromatograph/mass spectrometry. The ultrastructure of algal cells was observed with TEM. The results showed that EMA increased the contents of linolenic acid and linolic acid with increment of 14%, while decreased the content of myristic acid and cetylic acid in C. pyrenoidosa, membrane. The content of unsaturated fatty acids C18:1 and C18:2 increased 12% and 10% in M. aeruginosa with the addition of EMA, while the content of saturated fatty acids C18:0 and C16:0 decreased. EMA showed no significant change in the fatty acid composition in C. vulagaris under the experiment condition. EMA broke off cell wall of C. pyrenoidosa and M. aeruginosa. EMA damaged the cell membrane and the inclusion of algal cell leaked out. Nuclear and mitochondrial structure was damaged with the addition of EMA. EMA showed no significant change in the ultrastructure of C. vulgaris.


[CLINICAL AND DIAGNOSTIC SIGNIFICANCE OF IMMUNOGLOBULIN G SUBCLASSES IN IMMUNODEFICIENCY VERIFICATION].
In general practice of clinical immunologists must be use the detection of immunoglobulin G subclasses in cases with symptoms of recurrent and chronic infectious diseases with normal serum IgG. Thus, these patients are not examined and they are under treatment. Over the years, these patients has a sharp decrease in IgG subclasses, which is accompanied by a long course of various infectious processes and complications. Therefore; early diagnosis, early treatment and prevention of complications immunodeficiency knowledge-based clinical immunologists and general practitioners of modern diagnostic methods.


Gene and protein expression analysis of mesenchymal stem cells derived from rat adipose tissue and bone marrow.
Mesenchymal stem cells (MSC) are multipotent and reside in bone marrow (BM), adipose tissue and many other tissues. However, the molecular foundations underlying the differences in proliferation, differentiation potential and paracrine effects between adipose tissue-derived MSC (ASC) and BM-derived MSC (BM-MSC) are not well-known. Therefore, we investigated differences in the gene and secretory protein expressions of the 2 types of MSC. ASC and BM-MSC were obtained from subcutaneous adipose tissue and BM of adult Lewis rats. ASC proliferated as rapidly as BM-MSC, and had expanded 200-fold in approximately 2 weeks. On microarray analysis of 31,099 genes, 571 (1.8%) were more highly (>3-fold) expressed in ASC, and a number of these genes were associated with mitosis and immune response. On the other hand, 571 genes (1.8%) were more highly expressed in BM-MSC, and some of these genes were associated with organ development and morphogenesis. In secretory protein analysis, ASC secreted significantly larger amounts of growth factor and inflammatory cytokines, such as vascular endothelial growth factor, hepatocyte growth factor and interleukin 6, whereas BM-MSC secreted significantly larger amounts of stromal-derived factor-1α. There are significant differences between ASC and BM-MSC in the cytokine secretome, which may provide clues to the molecule mechanisms associated with tissue regeneration and alternative cell sources.


Diagnosis and treatment of viral STDs in women.
Viral sexually transmitted diseases (STDs) are a major health problem for women. Over many years the incidence of these infections has increased steadily to epidemic proportions. These infections not only cause short-term morbidity but also have been associated with significant long-term morbidity and mortality. This paper focuses on two of the most common viral STDs-Genital Herpes Simplex Virus (HSV) infection and Human Immunodeficiency Virus (HIV) infection of the female. The steady increase in the incidence of HIV infection and subsequent adult immunodeficiency disease (AIDS) among women requires health care providers to assume an active role in detection and treatment in order to avoid transmission, to protect the health of women with HIV/AIDS, and to reduce the risk of maternal-fetal (vertical) transmission. Because treatment with zidovudine has been shown to reduce vertical transmission, routine offering of HIV testing is currently recommended for all pregnant women. The approach to testing nonpregnant patients, i.e., the choice between selective screening or routine testing, rests with the individual clinician. Testing large numbers of patients within a practice may be facilitated by the availability of an oral antibody testing system. The sensitivity and specificity of the oral test is equivalent to blood testing. Serum and oral specimens are tested by enzyme-linked immunosorbent assays (ELISA) and confirmatory Western blot assays specifically designed for use with oral samples. Controversies in diagnosis as well as the most updated treatments for these infections are discussed.


A loop suture for dynamic tendon transfer in the repair of chronic or acute extensor pollicis longus ruptures.
Ruptures of extensor pollicis longus (EPL) tendon may need a tendon transfer for repair, especially in chronic ruptures. We describe a novel transfer technique using a loop-tendon suture for dynamic transfer of extensor pollicis brevis to EPL. We performed an end-to-side transfixing-loop self-locking suture preserving the extensor pollicis brevis, which acts as a motor unit for the distal end of the repaired tendon. Contraindications would mainly be simultaneous rupture of EPL and brevis tendons. No complications were observed, except for mild metacarpal-phalangeal stiffness in chronic ruptures. An early rehabilitation program may be started when no other associated injuries exist.


CT visualization of the major pulmonary fissures: value of 25 degrees cranially tilted axial scans.
CT visualization of the major (oblique) pulmonary fissures is often hampered by partial volume effects of adjacent lung parenchyma. We attempted to improve visualization of the fissures by using 25 degrees cranially tilted axial scans. An initial in vitro study also was performed. Both conventional and 25 degrees tilted axial CT scans were obtained in 40 adult patients. After scans with 2-mm collimation were obtained at 1 cm and 6 cm below the carina, the gantry was tilted 25 degrees cranially to be perpendicular to the plane of the major fissures, and scans with 2-, 5-, and 10-mm collimation were obtained at the same two levels. The appearance of the fissures was classified as linear opacity, band-like opacity, or avascular area for each lung at each level. On 2-mm conventional axial scans, the major fissures were seen as linear opacities in three to 23 patients (8-58%), as band-like opacities in 13-31 (32-78%), and as avascular areas in one to seven (2-18%). (Ranges indicate lowest and highest values when data for the two levels in the two lungs are grouped separately.) On 2-mm tilted scans, the ranges were 32-38 patients (80-95%), one to eight (2-20%), and zero to one (0-2%), respectively. The 2-mm tilted scans were significantly superior to the 2-mm conventional axial scans for showing the fissures (p < .01). Direct visualization as linear or band-like opacities was possible even on 10-mm tilted scans in 15-32 cases (38-80%). Our results show that visualization of the major fissure is improved when tilted CT scans rather than conventional axial scans are used.


pKa at Quartz/Electrolyte Interfaces.
Acidity of silanol sites at the crystalline quartz/aqueous electrolyte (NaCl, NaI, KCl) interfaces are calculated from ab initio molecular dynamics simulations. pKa's are found to follow a combination of the cationic and anionic Hofmeister series in the order pKa(neat solution) < pKa(NaCl) < pKa(NaI) < pKa(KCl), in agreement with experimental measurements. Rationalization of this ranking is achieved in terms of the microscopic local solvation of the protonated silanols and their conjugated bases, the silanolates SiO(-). The change in the pKa is the result of both water destructuring by alkali halides, as well as of the specific cation/SiO(-) interaction, depending on the electrolyte. Molecular modeling at the atomistic level is required to achieve such comprehension, with ab initio molecular dynamics being able to model complex inhomogeneous charged interfaces and the associated interfacial chemical reactivity.


Up-to-Date Imaging and Diagnostic Techniques for Prostate Cancer: A Literature Review.
Prostate cancer (PCa) faces great challenges in early diagnosis, which often leads not only to unnecessary, invasive procedures, but to over-diagnosis and treatment as well, thus highlighting the need for modern PCa diagnostic techniques. The review aims to provide an up-to-date summary of chronologically existing diagnostic approaches for PCa, as well as their potential to improve clinically significant PCa (csPCa) diagnosis and to reduce the proliferation and monitoring of PCa. Our review demonstrates the primary outcomes of the most significant studies and makes comparisons across the diagnostic efficacies of different PCa tests. Since prostate biopsy, the current mainstream PCa diagnosis, is an invasive procedure with a high risk of post-biopsy complications, it is vital we dig out specific, sensitive, and accurate diagnostic approaches in PCa and conduct more studies with milestone findings and comparable sample sizes to validate and corroborate the findings.


Traumatic brain injury and employment outcomes: integration of the working alliance model.
Individuals who have suffered polytrauma injuries must often contend with a complex constellation of physical, psychological, and psychosocial factors. These variables must be understood and addressed by rehabilitation specialists in order to optimize employment outcomes and overall quality of life for persons who have incurred these injuries. This article provides an abridged review of the current empirical data concerning the relationship between polytrauma and employment outcomes, with a focus on traumatic brain injury (TBI). In addition, Bordin's [4] working alliance model is recommended as a framework for strengthening the relationship between rehabilitation professionals and persons with TBI, thereby optimizing their employment outcomes.


Effect of sulpiride in endogenous depression.
Clinical practice and pharmacological data suggest a possible antidepressive action of sulpiride given in low dosages. To further explore the therapeutic efficacy of sulpiride 11 patients with an endogenous type of depression were studied during treatment with an oral daily dose of 150 mg sulpiride. The present data allows the conclusion that (A) low dosed sulpiride seems to act as an antidepressant in severe and milder forms of depression, (B) a clinical progress is seen earlier than is common during treatment with tricyclics and (C) a significant increase of drive is observable. However, sulpiride maintenance therapy did not prevent early relapse into depression. The preliminary nature of these clinical observations does not allow conclusions about the ultimate utility of this drug. Moreover, it remains unclear for which patients sulpiride is appropriate or perhaps superior to conventional treatment modalities of depression.


MetaTox: Web Application for Predicting Structure and Toxicity of Xenobiotics' Metabolites.
A new freely available web-application MetaTox ( http://www.way2drug.com/mg ) for prediction of xenobiotic's metabolism and calculation toxicity of metabolites based on the structural formula of chemicals has been developed. MetaTox predicts metabolites, which are formed by nine classes of reactions (aliphatic and aromatic hydroxylation, N- and O-glucuronidation, N-, S- and C-oxidation, and N- and O-dealkylation). The calculation of probability for generated metabolites is based on analyses of "structure-biotransformation reactions" and "structure-modified atoms" relationships using a Bayesian approach. Prediction of LD50 values is performed by GUSAR software for the parent compound and each of the generated metabolites using quantitative structure-activity relationahip (QSAR) models created for acute rat toxicity with the intravenous type of administration.


3-Hydroxymethyl coenzyme A reductase inhibition attenuates spontaneous smooth muscle tone via RhoA/ROCK pathway regulated by RhoA prenylation.
RhoA prenylation may play an important step in the translocation of RhoA in the basal internal anal sphincter (IAS) smooth muscle tone. Statins inhibit downstream posttranslational RhoA prenylation by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition (HMGCRI). The role of statins in relation to RhoA prenylation in the pathophysiology of the spontaneously tonic smooth muscle has not been investigated. In the present studies, we determined the effect of classical HMGCRI simvastatin on the basal IAS tone and RhoA prenylation and in the levels of RhoA/Rho kinase (ROCK) in the cytosolic vs. membrane fractions of the smooth muscle. Simvastatin produced concentration-dependent decrease in the IAS tone (via direct actions at the smooth muscle cells). The decrease in the IAS tone by simvastatin was associated with the decrease in the prenylation of RhoA, as well as RhoA/ROCK in the membrane fractions of the IAS, in the basal state. The inhibitory effects of the HMGCRI were completely reversible by geranylgeranyltransferase substrate geranylgeranyl pyrophosphate. Relaxation of the IAS smooth muscle via HMGCRI simvastatin is mediated via the downstream decrease in the levels of RhoA prenylation and ROCK activity. Studies support the concept that RhoA prenylation leading to RhoA/ROCK translocation followed by activation is important for the basal tone in the IAS. Data suggest that the role of HMG-CoA reductase may go beyond cholesterol biosynthesis, such as the regulation of the smooth muscle tone. The studies have important implications in the pathophysiological mechanisms and in the novel therapeutic approaches for anorectal motility disorders.


Factors associated with admission to a day school treatment program.
In this study the authors examine the individual and family characteristics of youth (N = 105) admitted over a five year period to a day school treatment program in a western New York community. All had exhausted alternative school placements within their home school districts and had a history of severe emotional or behavioral problems. Consistent with national patterns, more males (78%) than females were admitted, but in contrast to national trends, more Caucasians (63.8%) than students of color (36.2%) were admitted. Most lived in female headed single-parent households (51.4%). A few were foster children living with relatives or in non-relative foster homes (14.3%). Poverty was common with 45.7% of these youth eligible for free lunches. Most were on psychotropic medications (57.1%) and had histories of outpatient (62.9%) and inpatient hospitalizations (23.6%) at admission. Involvement in the juvenile justice system was common with nearly a quarter involved in the juvenile justice system (n = 25; 23.8%).


Robotic-assisted transmaxillary approach for removal of juvenile nasopharyngeal angiofibroma of the pterygopalatine and infratemporal fossa.
Endoscopic transmaxillary approaches to remove juvenile nasopharyngeal angiofibromas (JNAs) have been described previously and are used for tumors that extend laterally in the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). There is no previous description of robotic-assisted JNA removal in the literature. The video will demonstrate the success of this technique. Robotic transmaxillary approaches to the lateral PPF and ITF are easily achieved through an extended Caldwell-Luc antrostomy. Total operative time was 519 minutes. Total robotic operative time was 283 minutes. The endoscopic approach provided no assistance in tumor dissection or removal. Robotic-assisted transmaxillary JNA removal allows the operating surgeon to control the endoscope and to operate free of collisions from the robotic console while having an active assistant surgeon at the patient bedside. A video demonstrating the technique is found on Head & Neck's web site.


Application of capillary electrophoresis to the simultaneous determination of betaines in plants.
The simultaneous determination of betaines, the key compounds for osmotic regulation in plants, was established by capillary electrophoresis (CE). After four betaines, glycine betaine (GB), beta-alanine betaine (AB), proline betaine (PB), and 2-hydroxyproline betaine (HPB), were esterified with p-bromophenacyl bromide, the esters were electrophoresed in 100 mM sodium phosphate at pH 3.0. A low-pH condition in CE and esterification gave an advantage of resolving each of the ester peaks as well as those of the unreacted reagent and other components. Furthermore, the addition of 4% polyethylene glycol (PEG) gave a better resolution of 4 peaks, resulting in the separation of the overlapped peaks of PB and AB. It was found from the standard addition method being applied to barley leaves that the GB content in plants could be evaluated by using a calibration curve of the GB standard solution. The extraction of GB from plant leaves was also improved by adopting water as the extraction solvent instead of a mixture of organic solvents. The present method was suitably applied to actual plant specimens collected from a saline area of China.


Laser micro-etching of metal prostheses for personal identification.
Denture marking techniques play a vital role in establishing personal identification in suitable clinical and forensic situations. The denture marking techniques are categorized broadly into additive and ablative methods. Additive methods involve embedding or impregnation of markers for establishing personal identity. Ablative methods involve partial removal of the denture surface thereby providing a marking for identification. Engraving and etching methods are the commonly used ablative methods. Ablative methods can be of contact and noncontact subtypes. Laser micro-etching is a precise noncontact ablative denture marking technique that could be used for prostheses-guided personal identification.


Blockade of PD-1 and LAG-3 expression on CD8+ T cells promotes the tumoricidal effects of CD8+ T cells.
The diffuse large B-cell lymphoma (DLBCL) has the highest incidence of all lymphomas worldwide. To investigate the functions of lymphocyte activation gene 3 (LAG-3) and programmed cell death 1 (PD-1) in tissues and peripheral blood of patients with DLBCL, the expression of LAG-3 and PD-1 genes in DLBCL-TCGA were analyzed. LAG-3 and PD-1 mRNA levels in DLBCL were analyzed using data from The Cancer Genome Atlas (TCGA) database. Utilize the Genotype-Tissue Expression (GTEx) database for assessing the variance in the expression of LAG-3, PD-1, and other associated factors between the tissues of DLBCL patients and healthy individuals. Immunohistochemistry was applied to detect the expression of LAG-3 and PD-1 levels in 137 cases of DLBCL tissues and 20 cases of reactive lymphoid hyperplasia. The prognostic value of LAG-3 and PD-1 were assessed using the Kaplan-Meier curve. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) and ssGSEA algorithm were used to explore the immune microenvironment of DLBCL. Additionally, the expression and co-expression of LAG-3 and PD-1 were detected on CD4 and CD8 T cells in peripheral blood samples from 100 cases of DLBCL tissues and 30 cases of healthy individuals using flow cytometry. According to TCGA database, LAG-3 and PD-1 gene expression levels were significantly up-regulated in DLBCL tissues. LAG-3 and PD-1 levels were also strongly positively correlated with those of most infiltrating immune cells. Overall survival of patients with high LAG-3 and PD-1 co-expression was significantly shorter than that of patients with low co-expression. In DLBCL patients, LAG-3 and PD-1 were highly expressed in peripheral blood CD8+ T cells. In addition, LAG-3 was highly expressed in CD4+ T cells, while the expression of PD-1 in CD4+ T cells of DLBCL patients showed no significant difference compared to healthy individuals. Additionally, CD8+ T cells and SU-DHL6/OCI-LY3 from patients with DLBCL were co-cultured in vitro; after addition of LAG-3 and/or PD-1 inhibitors alone, an increased perforin and granzyme B secretion levels by CD8+ T cells were detected, as well as an increase in the overall proportion of tumor cells undergoing apoptosis. High LAG-3 and PD-1 levels significantly inhibit CD8+ T cell function, resulting in weakened ability to kill tumor cells. Combined LAG-3 and PD-1 blockade can restore CD8+ T cell function and provides a potential avenue for development of personalized cellular immunotherapy for DLBCL.


Blood serum levels of soluble forms of adhesion molecules ICAM-1 (sICAM-1) and selectin E (s-selectin E) in patients with various phases of non-Hodgkin's lymphomas.
Monitoring of disease activity and effectiveness of treatment plays an important role in curative management of patients with non-Hodgkin's lymphomas (n-HL). In the search for markers useful for biochemical monitoring of n-HL patients, a group of proteins called adhesion molecules attracted attention. Particular attention has been devoted to sICAM-1 (intercellular adhesion molecule-1). A correlation between sICAM-1 levels and histological malignancy grades and clinical staging of n-HL, activity of the disease and tumor mass has been observed. The aim of the study was to assess the utility of determining serum levels of selected adhesion molecules in n-HL monitoring. The study was carried out in 60 patients with intermediate and high malignancy grade n-HL according to Working Formulation (anaplastic, lymphoblastic, immunoblastic, centroblastic and centroblastic-centrocytic). Soluble ICAM-1 adhesion molecule (sICAM-1) and selectin E levels were determined in the sera of 31 newly diagnosed patients, 18 with complete remission, and 11 with relapse of the disease. The control group consisted of 15 healthy subjects. The results were expressed in ng/ml. sICAM1 levels were similar in healthy controls and patients in the remission phase and significantly lower in patients with diagnosed active disease and relapses. Relapses were associated with slightly lower levels (on borderline of statistical significance) than of diagnosis Serum selectin E levels, however, demonstrated no differences among patient groups or as compared with controls. The presented results indicate the utility of serum sICAM-1 level determination in assessment of activity of intermediate and high malignancy grade non-Hodgkin's lymphomas.


Clinicopathologic features of superficial esophageal cancer: results of consecutive 100 patients.
The depth of tumor penetration is a crucial factor in determining the prognosis of patients with esophageal carcinoma. Patients with superficial esophageal carcinoma (SEC) have a far more favorable clinical course compared with those with advanced cancers. The outcome for patients with mucosal cancer is excellent with a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often metastasizes to regional and/or distant lymph nodes or other organs, and the prognosis of these patients are far from satisfactory. Among 334 patients with esophageal cancer who underwent surgery between December 1980 and December 2006, 100 patients (30%) had SEC confined to the epithelium, lamina propria mucosa, or submucosa. Patient and tumor characteristics of those 100 patients were studied. The prevalence of SEC has increased from 13% (8 of 61) in the initial 5-year period (1985-1989) to 44% (41 of 93) in the recent 7-year period (2000-2006). Subjective symptoms were present in 7 (14%) of 51 mucosal cancers and in 13 (27%) of 49 submucosal cancers. The remaining 80 patients (80%) had no subjective symptoms. Ninety-one patients (91%) were diagnosed to have the lesions by endoscopy at the time of screening for gastric problems, and only nine were detected by gastrointestinal series. Four of 51 patients with mucosal cancer had venous or lymph vessel invasion, and among those, only one (2%) had a solitary perigastric lymph node metastasis. In 49 patients with submucosal cancer, 35 (71%) had lymph vessel invasion, 28 (57%) had venous invasion, and 16 (33%) had lymph node metastases. In particular, 15 of 35 patients with positive lymph vessel invasion had lymph node metastasis, whereas only 1 of 14 with negative lymph vessel invasion had lymph node metastasis (P < .05). Among 17 patients with nodal involvement, 4 patients with upper thoracic SEC had upper mediastinum and/or cervical nodal metastases, 11 patients with middle thoracic SEC had widespread upper and lower mediastinal and abdominal metastases, and 2 patients with lower thoracic SEC had lower and abdominal lymph node metastases. Seventy-nine patients were alive without recurrence at last follow-up. Five of 49 patients with submucosal cancer died of recurrent disease, and 4 of these developed regional nodal recurrence around the bilateral laryngeal recurrent nerves. Forty-two patients (42%) developed double cancers during the follow-up period, and 5 died of a second cancer. The 3- and 5-year survival rates of all 100 patients were 85% and 73%, and those disease-specific survival rates were 96% and 93%, respectively. The 3- and 5-year survival rates for patients with mucosal cancer were 89% and 83%, and those for submucosal cancer were 80%, and 64%, respectively. Esophagectomy with extensive lymphadenectomy should be carried out particularly for upper thoracic submucosal cancer, whereas esophagectomy with moderate lymphadenectomy may be preferred for mucosal cancer. Patients with SEC should be examined for another primary cancer preoperatively and periodically during follow-up.


Experience of an Anatomic Femoral Stem in a United Kingdom Center - Excellent Survivorship and Negligible Periprosthetic Fracture Rates at Mean 12 Years Following Primary Total Hip Arthroplasty.
As the clinical burden of periprosthetic fractures (PPFs) continues to increase, it has been suggested that the use of anatomical femoral stems may help reduce PPF risk. The primary aim of this study was to determine the survivorship and PPF rate of an anatomical femoral stem in a single center at minimum 10-year follow-up. A total of 1,000 consecutive total hip arthroplasties (THAs) performed using an anatomical femoral stem were identified from a prospectively collected arthroplasty database. Patient radiographs were reviewed finally at a mean of 12 years (range, 10 to 16 years) following surgery to identify any revision surgery, dislocations or PPFs. Mean patient age at surgery was 69 years (range, 24 to 93). There were 634 women (63%). Osteoarthritis was the operative indication in 946 patients (95%). All-cause THA survivorship was 99.1% (95% confidence interval (CI), 99.0-99.3%) at 10 years and 97.9% (CI, 97.8 - 98.0%) at 15 years. Stem survivorship at 10 years was 99.6% (CI, 99.5-99.7%) and at 15 years was 98.2% (CI, 98.1-98.3%). The 15-year stem survival for aseptic loosening was 100% with no cases of significant lysis found (lucent line >2mm). Implant survivorship was not significantly impacted by patient sex (P = .65), body mass index (P = .49), deprivation level (P = .284), operative indication (P = .33), or American Society of Anesthesiologists class (P = .374). There were 3 PPFs identified (0.3%) at mean 12-year follow-up and 15 dislocations (1.5%). This anatomical femoral stem demonstrated excellent survivorship and negligible PPF rates at mean 12-year follow-up following primary THA.


Sonographic whirlpool sign in ovarian torsion.
To describe an additional maneuver during sonography for ovarian torsion and to assess its diagnostic value. During a period of about 2 years 6 months, 21 patients with acute or intermittent lower abdominal pain who had an ovarian mass and an extraovarian mass suggestive of a twisted vascular pedicle on sonography were studied. The gray scale features of the ovarian mass were recorded. The presence of a twisted vascular pedicle was evaluated. Its location and gray scale features were noted. The probe was moved to and fro along the axis of the pedicle, and the presence of a whirlpool sign was evaluated. The same procedure was repeated on a color Doppler study. A twisted pedicle with a whirlpool sign was seen in all 21 patients. Ovarian torsion was confirmed in all 20 patients who underwent surgery. The last patient was pregnant and did well with conservative treatment. Hemorrhagic infarction or early hemorrhage of the ovary or ovarian mass was seen in all 8 patients who did not show flow in the twisted pedicle on the color Doppler study and in 2 patients who showed flow in the artery in the proximal part of the pedicle. Of the 6 patients who showed flow in the artery alone, the ovary was removed in 4, and all had hemorrhagic infarction or early hemorrhage. The ovary was viable in all 5 patients in whom flow was seen in both the artery and vein. A positive whirlpool sign in the twisted vascular pedicle of the ovary is the most definitive sign of ovarian torsion. Absence of blood flow in the twisted pedicle and visualization of the flow in the artery alone are predictive of nonviability of the ovary.


An ultra-high vacuum chamber for scattering experiments featuring in-vacuum continuous in-plane variation of the angle between entrance and exit vacuum ports.
A concept that enables in-vacuum continuous variation of the angle between two ports in one plane has been developed and implemented. The vacuum chamber allows for measuring scattering cross sections as a function of scattering angle and is intended for resonant inelastic X-ray scattering experiments. The angle between the ports can be varied in the range of 30°-150°, while the pressure change is less than 2 × 10(-10) mbars.


Subcutaneous phaeohyphomycosis caused by Exophiala equina, with susceptibility to eight antifungal drugs.
A case of subcutaneous phaeohyphomycosis caused by Exophiala equina is reported in a 75-year-old female, who showed subcutaneous abscesses on both forearms for 8 months. A lesion was initiated by inoculation with a spine from a tree. Histopathologically, suppurative granulomatous inflammation was present and short hyphal elements were observed. Upon culture greyish-black, velvety colonies of a black yeast were obtained after 3 weeks. The strain grew well at 25 °C, but poorly at 37 °C. After sequencing the internal transcribed spacer domain and the partial β-tubulin gene, the fungus was identified as E. equina. The patient was successfully treated with fluconazole for 3 months.


Non-equilibrium solid-phase microextraction coupled directly to ion-trap mass spectrometry for rapid analysis of biological samples.
To determine sub-ppb levels of drugs in biological samples, selective, sensitive and rapid analytical techniques are required. This work shows the possibilities for high-throughput analysis of solid-phase microextraction (SPME) directly coupled to an ion-trap mass spectrometer equipped with an atmospheric pressure chemical ionisation source. As no chromatographic separation is performed, the SPME procedure is the time-limiting step. Direct immersion SPME under non-equilibrium conditions permits the determination of lidocaine in urine within 10 min. After a 5 min sorption time with a 100 microm polydimethylsiloxane-coated fibre, the extraction yield of lidocaine from urine is about 7%. When applying 4 min desorption, using a mixture of ammonium acetate buffer (pH 4.5) and acetonitrile (85 + 15 v/v), about 10% of the analyte is retained on the fibre. An extra cleaning step of the fibre is therefore used to prevent carry-over. By use of tandem MS, no matrix interference is observed. The detection limit for lidocaine is about 0.4 ng ml(-1) and the intraday and interday reproducibility are within 14% over a concentration range of 2-45 ng ml(1).


Checkpoint Blockade - a New Treatment Paradigm in Renal Cell Carcinoma.
Nivolumab is the first checkpoint inhibitor for the treatment of renal cell carcinoma (RCC), which is in line for approval in Europe. Despite its novelty in the treatment algorithm of RCC, it offers a whole new strategy of therapy management with safe applicability. The aim of this work was to review current data on checkpoint inhibitors in RCC and discuss future perspectives for this novel approach in RCC. A selective literature search was performed in the Pubmed database: Nivolumab is a first-in-class agent for the treatment of RCC, and its European label is anticipated for 2016. Contrary to many other agents, nivolumab was able to show a benefit in overall survival and health-related quality of life when compared to everolimus. Current trials focus on optimizing and expanding its use to metastatic RCC. In conclusion, nivolumab has already acquired a role in the treatment algorithm of RCC. However, which patient population derives the most benefit as well its optimal use in the treatment algorithm remain to be determined. A number of ongoing trials will provide novel insights and might help to untangle this novel network of therapy management for immunotherapies.


Analgesic, antiinflammatory, and ulcerogenic studies of meloxicam solid dispersion prepared with polyethylene glycol 6000.
Meloxicam is a nonsteroidal antiinflammatory drug, used in the treatment of rheumatoid arthritis and oestoarthritis. It is practically insoluble in water, leading to poor dissolution, variations in bioavailability, and gastric irritation on oral administration. In the attempt to reduce its gastric side effect and to increase aqueous solubility, physical mixture and solid dispersion of the drug were prepared with polyethylene glycol 6000. The analgesic, antiinflammatory, and ulcerogenic effects were assessed for physical mixture and solid dispersion in comparison with meloxicam alone. The results indicate that both physical mixture and solid dispersion possess better analgesic and antiinflammatory properties with less ulcerogenic potential when compared with pure meloxicam.


HOXA4 induces expansion of hematopoietic stem cells in vitro and confers enhancement of pro-B-cells in vivo.
Members of the homeobox (Hox) gene family are known to mediate expansion of hematopoietic stem cells (HSCs) and progenitors. The absence of oncogenic properties promoted HOXB4 as prime candidate in the quest to expand HSCs for clinical purposes. Despite its potential to expand HSCs, studies with mutant mice showed that Hoxb4 is not essential for HSC generation and function under physiological conditions. Expression studies and the existence of functional redundancy in particular between paralog Hox genes suggest that HOXA4 might have potent properties to expand HSCs. Here we measured the ability of HOXA4 to promote ex vivo expansion of HSCs and progenitors using retrovirus-mediated overexpression. Our results provide evidence that HOXA4-transduced HSCs and primitive progenitors expand in culture conditions and demonstrate that the potential of expanded HOXA4 HSCs to give rise to mature myeloid and lymphoid progeny in normal proportions remained intact. Interestingly, constitutive overexpression of HOXA4 resulted in an unbalanced expansion of lymphoid/myeloid progenitors in bone marrow chimeras favorable to B-cell progenitors responsive to interleukin-7. This expansion was specific for these progenitors and not for the more primitive Whitlock-Witte-initiating cells. These data indicate that early stages of B-cell development associated with proliferation are in particular sensitive to HOXA4. Thus, this study supports the potential use of HOXA4 to expand both HSCs and B-cell progenitor populations for therapeutic strategies.


Sources and build up of Zn, Cd, Cr and Pb in the sludge of Gaza.
A comprehensive monitoring program was conducted for the sludge of Gaza between 2001 and 2006. All 32 tested parameters except zinc and adsorbable organic halogens were within the allowable values for sludge to be applied in agriculture. Average concentrations of zinc (Zn) in the sludge from the Gaza Strip for the 4 years 2002-2005 reached 2,000 mg/kg which represents a major limiting factor for sludge application in agriculture. This study aimed to measure levels of Zn in the wastewater and sludge in December 2006 and to identify the sources and the build up of Zn in the sludge in Gaza. Cd, Cr and Pb were also assessed for their relationship to sources and buildup of Zn. The results showed that there is no significant fluctuation in the concentration of Cd, Cr and Pb in the different stages of wastewater treatment. Zn, however, is concentrated inside the treatment plant by processes of precipitation and/or absorption, particularly in the aerobic facilities. Although the plant receives wastewater with Zn concentrations of only 9 microg/l, this concentration increased 18-fold inside the aerobic lagoon of the treatment plant, before dropping to an average of 14 microg/l in the effluent wastewater. The sludge from the first sedimentation pond showed a Zn concentration of 567 mg/kg and increased in the effluent polishing pond to 1,643 mg/kg. The Zn concentration in 3-month-old sludge averaged 592 mg/kg. There was no correlation between the Zn concentrations in the sludge and the wastewater at the same location. However, there was a strong correlation between Zn and Pb in the sludge. The electroplating and galvanization industries are the major Zn producing industries in Gaza, with an average Zn of 2,995 and 1,557 microg/l, respectively in their effluent wastewater. These values do not represent a significant Zn pollution load to the treatment plant because these industries are limited in size and number, and their effluents are diluted before entering the treatment plant. Industrial activity decreased in 2006 to less than 70% of that in the previous four years. Consequently, the average concentrations of Zn in selected industrial effluents decreased from 1,500 for 2002-2005 to 400 microg/l in December 2006. Sludge from these industries showed 1,300 mg/kg Zn for 2002-2005 and only 400 mg/kg in 2006. Moreover, the Zn in the influent wastewater discharged to the treatment plant decreased from 65 to 9 microg/l for the same period. Exposure of sludge to the sun for few months reduces the Zn concentration. One reason is probably leaching. This simple procedure may solve the problem of sludge application in agriculture. This will be especially important if industrial production returns to its former level.


Examining the relationship between obesity and prostate cancer.
Affecting over 30% of the population, obesity is an epidemic in the United States and is associated with multiple chronic medical problems. Obesity is also associated with numerous hormonal changes, many of which have been implicated in prostate cancer development and progression. Although, on the whole, controversy exists over whether obesity increases the risk of prostate cancer, data strongly suggest that obesity is a significant risk factor for prostate cancer death. In this review, we discuss the epidemiologic data surrounding obesity and prostate cancer. We also discuss some of the sequelae of obesity and their relationships with prostate cancer, including alterations in insulin, the insulin-like growth factor axis, and leptin levels; insulin resistance; and diabetes. Although a complete overview of all the various dietary and lifestyle factors that are associated with obesity and prostate cancer risk is beyond the scope of this review, we discuss data concerning the relationship between a high-fat diet and prostate cancer.


Differential diagnosis of palpitations. Preliminary development of a screening instrument.
To develop a self-report screening instrument to assist in the differential diagnosis of medical outpatients complaining of palpitations. Patients completed self-report questionnaires assessing somatization, cardiac symptoms, and hypochondriacal concerns about health. Principal components analysis was performed to identify a subset of questions that could be used to distinguish patients with palpitations who have panic disorder from those with palpitations who do not have panic disorder. Sixty-seven medical outpatients referred for Holter monitoring because of a complaint of palpitations. Patients with palpitations were classified into 2 groups, those with and those without current panic disorder (established with a structured, diagnostic interview). The sensitivity, specificity, and posttest probability of the screening instrument were determined. A reliable, stable, 10-item instrument was derived. It seems to tap diffuse, vague, or generalized somatic complaints and worry about physical illness. With the use of a criterion cutoff score of 21, this instrument had a sensitivity of 0.81, a specificity of 0.80, and a post-test probability of.57 in detecting current panic disorder in patients with palpitations. A psychometrically sound and brief self-report instrument was developed to assist in the differential diagnosis of palpitations. It can be used to identify patients whose symptoms are more likely to result from panic disorder and in whom ambulatory monitoring might be deferred.


Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones.
Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.


Tissue and species differences in the application of quantum dots as probes for biomolecular targets in the inner ear and kidney.
Quantum dots (QDs) are useful biological probes because of the increased photostability and quantum efficiency they offer over organic fluorophores. However, toxicity concerns arise because the QD core is composed of cadmium and selenium, metals known to be unsafe for humans and animals. We investigated the feasibility of quantum dots as biological labels for imaging studies of inner ear and kidney, tissues that share a polarized epithelial arrangement and drug susceptibility. We found that methods for labeling the actin cytoskeleton of monolayers of cultured amphibian kidney cells (Xenopus A6) with 565 nm QD conjugates were not feasible with large Xenopus inner ear organs. We then compared the uptake of 565 nm cationic peptide-targeted and nontargeted QDs in live kidney cell lines (amphibian, A6 and XLK-WG; human, HEK-293). Results showed that targeted QDs are internalized by all three kidney cell lines, and that nontargeted CdSe nanocrystals are sequestered only by human kidney cells. CellTracker Red CMTPX confirmed the membrane integrity and viability of HEK-293 cells that internalized QDs. Our results demonstrate species and tissue differences in QD uptake and labeling, and underscore the need for long-term studies of QD toxicity and fate in cells.


Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.
Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.


Achieving convenient CO2 electroreduction and photovoltage in tandem using potential-insensitive disordered Ag nanoparticles.
Photovoltaic-electrochemical (PV-EC) systems can not only make full use of solar energy, but also transform CO2 into organic molecules. However, it is difficult to achieve PV-EC systems since most CO2 reduction catalysts are potential-dependent. This paper describes the rational design of potential-insensitive disordered Ag, which can achieve more than 90% faradaic efficiency (FE) for CO within a wide voltage range of 1.1 V in an electroreduction CO2 system. The system shows attractive activity under different photovoltage conditions in a PV-EC system. By employing in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), we address the origin of the volcano peak of FE on Ag nanoclusters to understand the mechanism of the carbon dioxide reduction reaction (CO2RR). In addition, we find that the CO2RR on disordered Ag nanoparticles is a proton-electron coupling transfer (PECT) reaction mechanism, which may result in high activity in a wide potential range.


Factors Compromising Glucuronidase Performance in Urine Drug Testing Potentially Resulting in False Negatives.
Next generation β-glucuronidases can effectively cleave glucuronides in urine at room temperature. However, during the discovery studies, additional challenges were identified for urine drug testing across biologically relevant pH extremes and patient urine specimens. Different enzymes were evaluated across clinical urine specimens and commercially available urine control matrices. Each enzyme shows distinct substrate preferences, pH optima, and variability across clinical specimens. These results demonstrate how reliance on a single glucuronidated substrate as the internal hydrolysis control cannot ensure performance across a broader panel of analytes. Moreover, sample specific urine properties compromise β-glucuronidases to varying levels, more pronounced for some enzymes, and thereby lower the recovery of some drug analytes in an enzyme-specific manner. A minimum of 3-fold dilution of urine with buffer yields measurable improvements in achieving target pH and reducing the impact of endogenous compounds on enzyme performance. After subjecting the enzymes to pH extremes and compromising chemicals, one particular β-glucuronidase was identified that addressed many of these challenges and greatly lower the risk of failed hydrolyses. In summary, we present strategies to evaluate glucuronidases that aid in higher accuracy urine drug tests with lower potential for false negatives.


Voice quality after treatment for T1a glottic carcinoma--radiotherapy versus laser cordectomy.
The purpose of this study was to assess the anatomic and functional outcomes and compare the voice quality in patients affected by T1a glottic carcinoma treated with curative intent with radiotherapy or laser cordectomy. Fifty-seven cases were analysed: 27 after curative radiotherapy and 30 after laser cordectomy. All patients were studied with videolaryngostroboscopy, voice analysis by narrow spectrogram, and vocal parameters (Jitter, Shimmer, noise/harmonic ratio, and diplophonia). Videolaryngostroboscopy showed severe glottic inadequacy in 25% of cases treated with radiation and insufficient compensation 'ventricular band' or 'with arytenoid hyperadduction' in 65% of cases after surgery. Severe dysphonia on the electro-acoustic analysis of voice was observed in 25% of cases after radiation and 70% after laser (p < 0.001). Fundamental frequency and vocal parameters showed more favourable results in the radiation group (p < 0.001). Voice assessment showed better results after radiotherapy compared with laser cordectomy. Voice outcome should be carefully considered in the treatment decision for T1 glottic carcinoma.


Within-Person Relationship between Attenuated Positive Symptoms and Suicidal Ideation among Individuals at Clinical High Risk for Psychosis.
Individuals at clinical high-risk for psychosis (CHR-P) are at increased risk for suicide. However, the relationship between attenuated positive symptoms and suicidal ideation are not well understood, particularly as they interact over time. The current study addressed this gap in the literature. We hypothesized that greater attenuated symptoms would be concurrently and prospectively associated with suicidal ideation. Further, we hypothesized that suspiciousness and perceptual abnormalities would have the strongest relationship with suicidal ideation. Within-person variation in symptoms and suicidal ideation were examined across 24 treatment sessions for individuals at CHR-P. Attenuated positive symptoms (unusual thought content, suspiciousness, grandiose ideas, perceptual abnormalities, and disorganized communication) and suicidal ideation were assessed at each session. Logistic mixed effect models examined concurrent and time-lagged relationships between symptoms and suicidal ideation among 36 individuals at CHR-P. Results indicated that suicidal ideation was more likely during weeks when participants reported more severe total attenuated positive symptoms. Further, suspiciousness was uniquely associated with suicidal ideation, both concurrently and at the following session. Post hoc models examined the reverse direction of this relationship, demonstrating that suicidal ideation also prospectively predicted suspiciousness at the following session. These results suggest that within-person attenuated symptoms, particularly suspiciousness, are associated with suicidal ideation among individuals at CHR-P. However, the bidirectional relationship between suspiciousness and suicidal ideation raises questions about causal nature of this relationship. Further research is needed to examine the dynamic interplay of suspiciousness and suicidal ideation.


Identification of viral polypeptides involved in pseudorabies virus ribonucleotide reductase activity.
We studied pseudorabies virus-induced ribonucleotide reductase and found that it exhibited biochemical properties very similar to those of herpes simplex virus reductase. A polyclonal rabbit antiserum (P9) directed against the carboxy terminus of subunit H2 polypeptide (38,000 daltons) of herpes simplex virus reductase neutralized the pseudorabies virus reductase, as well as the herpes simplex virus isozyme. This serum recognized two pseudorabies virus-specified polypeptides of 34,000 and 110,000 daltons, which may represent the two subunits of the enzyme. Furthermore, as already shown for herpes simplex virus reductase (E. A. Cohen, P. Gaudreau, P. Brazeau, and Y. Langelier, Nature [London] 321:441-443, 1986), we show that the nonapeptide itself specifically inhibited pseudorabies reductase activity.


Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target.
Aspartic acid semialdehyde dehydrogenase (ASADH) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB) target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80%) in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.


Dental caries in a group of 20-year-olds after previous participation in public child dental health services in Copenhagen, Denmark.
The present study was undertaken to investigate the prevalence of dental caries in a group of 20-year-olds who had previously participated in Public Child Dental Health Services. Dental caries was related to social status and preventive vists to the private dentist after termination of school. The study population comprised 389 persons aged 20, out of which 313 (80.5%) were examined clinically and radiographically by one dentist according to standardized criteria. Mean DMFT was 10.4 and mean DMFS 16.7. Differences in relation to sex were not significant. The distribution of subjects according to DMFS was uneven. The 20% with the highest DMFS accounted for about 45% of the total amounts of DS. A consistent pattern with higher mean DMFS in the low social groups was found. Attendance to Regular Youth Dental Service was higher the longer the subjects had been students and higher mean DMFS was found in nonregular attenders. The presence of a high caries risk group is discussed in relation to the dental care system received by the study population.


Immunonutrition in patients with cyctic fibrosis leads to drop of serum amyloid A and increase of oxidative stress.
The aim of the present study is to evaluate of the impact of immunonutrition on parameters of oxidative stress and inflammation in patients with cystic fibrosis and malnutrition. In the 30 patients with cystic fibrosis and long-term enteral nutrition support for malnutrition the effect of standard and immunonutrion sipping on oxidative stress and inflammatory activity parameters was compared. Malonyldialdehyde (MDA) as parameter of oxidative stress and serum amyloid A (SAA), interleukin 1 and 6, hsCRP, IgM, IgA, IgG as parameters of inflammatory activity were examined. Immunonutrition decreased SAA to 17.6 mg/L comparing to 25.6 mg/L when standard nutrition was given (p = 0.014). MDA was 0.66 µM on standard and 0.96 µM on immunonutrition support (p<0.01). The significant negative correlation was recorded between MDA and SAA, hs-CRP, interleukin 6, IgA and IgG. In conclusion, the application of immunonutrition in patients with cystic fibrosis and malnutrition is associated with drop of SAA but with the rise of MDA.


The effect of illumination of the malic acid content and anion/cation balance of mustard leaves (Sinapis alba).
1. Mustard plants have been grown under conditions in which the length of artificial day could be controlled. 2. Leaf samples were analysed for malic acid and citric acid, and for a number of inorganic anions and cations. A simple method is described by which sap was obtained from 0.5g. samples of leaves. 3. In days of 16hr. or more, malic acid was accumulated; the chief cation accumulated was calcium. 4. When the day-length was reduced the malic acid content decreased considerably but the calcium content remained the same. There was little change in the pH value of the sap, the balance of anions and cations having been maintained mainly by increases in citrate and nitrate contents. Analyses of the whole leaf still showed some deficiency in anion after sodium, potassium, calcium, magnesium, nitrate, sulphate, inorganic phosphate, chloride, malate and citrate had been accounted for. 5. Analyses at shorter intervals revealed a large diurnal variation in malic acid content, which increased during the first 5-6hr. of the light period, and fell during darkness. 6. The significance of these findings is discussed, and it is suggested that malic acid accumulation is a by-product of photosynthesis, calcium being taken up irreversibly to maintain anion/cation balance, and hence creating a continuing need for anions to balance it.


Functional Status Scale: Cross-Cultural Adaptation and Validation in Brazil.
The goal of the present study was to perform a cross-cultural adaptation and clinical validation of the Functional Status Scale for use in the Brazilian population. Cross-cultural adaptation study followed by a cross-sectional validation study. Single-center PICU at a hospital in Porto Alegre, Brazil. Children and adolescents of both sexes, 1 month and under 18 years old, who had been treated at the PICU. The cross-cultural adaptation consisted of the following stages: translation, synthesis of the translated versions, back translations, synthesis of the back translations, committee review, and pretesting. For the clinical validation stage, the Brazilian Functional Status Scale was applied within 48 hours after discharge from the PICU. The Brazilian Functional Status Scale's reliability and validity properties were tested. A total of 314 patients were evaluated. Median age was 24 months (7.0-105.0 mo), 54.1% were males, and their overall functional score was 9 ± 2.8. The Brazilian Functional Status Scale demonstrated excellent interobserver reliability, with an intraclass correlation coefficient of 0.98, and κ coefficients between 0.716 and 1.000 for the functional domains, which indicated good to excellent agreement. Using the Bland-Altman method, we confirmed low variability among the evaluator's responses (0.93 to -1.06 points). Regarding the Brazilian Functional Status Scale's content validity, there was a correlation between length of PICU stay (r = 0.378; p < 0.001) and time on invasive mechanical ventilation (r = 0.261; p < 0.05), and the test could discriminate between groups with different comorbidity levels (p < 0.001). The Functional Status Scale has been culturally adapted and validated for use in Brazil and is now available for use in the assessment of functionality in Brazilian children and adolescents.


Regional therapy in the management of intrahepatic recurrence after surgery for hepatoma.
The significance of regional therapy against the intrahepatic recurrence for hepatocellular carcinoma (HCC) was evaluated. During the past 6 years, 101 patients who had radical operations for HCC (liver cirrhosis, 75%; chronic hepatitis, 22%) were followed. Forty-seven patients (47%) had recurrences; the liver was the site of first recurrence in 43 patients and distant site recurrence in four patients. In the patients where the liver was the recurrent site, 33 patients (77%) received regional therapies for an aggregate total of 60 times. Transcatheter arterial chemoembolization was chosen as the first preferred therapy against recurrence in the liver in 30 of 33 patients (91%). Postrecurrence survival of the patients treated with regional therapy was significantly better than disease-free survival (p less than 0.001). Disease-free survival after surgery, postrecurrence survival, and postsurgery survival were compared in the patients treated with regional therapy and untreated patients. Fifty per cent survival after recurrence of the treated patients was 27 months, and that of the untreated patients was 3 months. Postrecurrence survival (p less than 0.001) and postsurgery survival (p less than 0.01) of the treated patients were significantly better than those of the untreated patients. To obtain successful long-term survival after surgery for the cirrhotic patients with HCC, it is necessary to repeat active regional therapies against the recurrent liver.


[Influence of subthalamic nucleus deep brain stimulation on cognition and acetylcholine in a rat model of Parkinson's disease].
Objective: To illustrate the effect of subthalamic nucleus deep brain stimulation (STN-DBS)on cognitionand its underlying mechanisms in a rat model of Parkinson's disease (PD). Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (healthy rats, n=10), model group (PD rats, n=10), and stimulation group (PD rats receiving high frequency stimulation, n=10). The cognitive functionof rats was tested through Morris water maze and acetylcholine levels in cortex, hippocampus and striatum have been examined through ELISA. Results: During Morris water mazetest, spatial learning and memory of PD ratsdeteriorated compared with healthy ones, withlonger escape latency[on day 4, (38±14) s vs (20±4) s, P=0.047; on day 5, (32±13) s vs (16±8) s, P=0.032]and shorter time in the platform region[(10±6) s vs (19±5) s, P=0.023], which could be restored by STN-DBS. Similar results demonstrated that the expression of Ach in hippocampus[(1 473±233) s vs (1 950±344) s, P=0.039]and striatum[(1 661±271) s vs (2 240±290) s, P=0.007]was significantly lower in PD rats than those in healthy rats, and STN-DBS treatment reversed this decline to insignificant. Conclusion: The rat model of PD suffer from a decline in cognition, and STN-DBS contributes to cognitive recovery, possibly due to regulating Ach levels in cognition-associated regions of the brain, includinghippocampus and striatum.


Surface antigenic profile of uveal melanoma lesions analysed with a panel of monoclonal antibodies directed against cutaneous melanoma.
The surface antigenic profile of 10 surgically removed uveal melanoma lesions and 5 conjunctival melanomas was analyzed with a panel of 22 monoclonal antibodies (mAbs) raised against membrane bound cutaneous melanoma-associated antigens (MAA). In addition these lesions were tested for their reactivity with mAbs against MHC class I and II molecules, CD7 (Pan-T) and CD10 (CALLA). The anti-MAA mAbs can be divided into two major groups: first those mAbs detecting markers expressed by the majority of uveal melanomas such as NKI-Beteb, NKI/C3, G7E2, M-2-2-4, Mel-14, G7A5, AMF6, AMF7, Pal M1, Pal M2, Me14/D12. The staining intensity for these mAbs was rather high, ranging in intensity between 70 and 100%. The second group of antibodies includes mAbs detecting markers not or very poorly expressed on ocular melanomas. The anti-ICAM-1 mAb P358 did not react with any of the lesions tested and mAb Muc18 and Muc54 only with one and two out of 15 lesions, respectively. The majority of spindle lesions and mixed type lesions and half of the epitheloid type lesions expressed HLA class I molecules, while HLA class II molecules were found on half of the spindle and epitheloid type lesions and on a small number of mixed cell type lesions. All spindle lesions were found to express the CD10 (CALLA) molecule and less than half of the other type of lesions were stained with an anti CD10 mAb. The melanoma associated ganglioside GD3 was mainly expressed on epitheloid type lesions while GD2 was predominantly expressed on mixed type lesions. In essence, the overall surface phenotype of the uveal melanoma lesions tested, as defined by the panel of mAbs used, differs markedly from the surface phenotype of cutaneous melanoma lesions defined by a very similar antibody panel.


[A case of toxocariasis with eosinophilic pleural effusion].
A 76-year-old man admitted for general malaise with fever was found in clinical examination on admission to have eosinophilic pleural effusion, peripheral eosinophilia, and a slightly elevated inflammatory reaction. Immunological examination, including microplate ELISA, showed a high titer of specific antibody against Toxocara canis in both the serum and pleural effusion. We started treatment using albendazole, and found inflammatory findings and serum IgE were ameliorated. Parasitic disease is an important consideration in the differential diagnosis of eosinophilic pleural effusion, and serology is useful in screening for this.


Aortic root replacement using composite valve graft in patients with aortic valve disease and aneurysm of the ascending aorta: twenty years' experience of late results.
The purpose of this study was to evaluate the clinical outcome of composite valve graft replacement in 193 patients with aortic valve disease and aneurysm of the ascending aorta from January 1980 to June 1999. The clinical outcome was compared between the patients diagnosed with Marfan syndrome (M group) and those without Marfan syndrome (non-M group), between those with aortic dissection (AD group) and without dissection (non-AD group), between 2 different techniques for coronary artery reattachment (modified Bentall [mB] and modified Piehler [mP]), and between the time of operation (1980-1989 and 1990-1999). Long-term outcome of this procedure was almost satisfactory with actuarial survival of 71.5 +/- 4.4% at 10 years and freedom from reoperation of 76.5 +/- 4.4% at 10 years. Freedom from cardiovascular events and freedom from reoperation were significantly lower in the M group and AD group than in the non-M and non-AD groups. Also, actuarial survival was significantly higher in the latter 10 years compared with the former 10 years. It was concluded that the improvement of perioperative management and proper selection of the technique for coronary artery reattachment could have improved the clinical outcome. In patients with Marfan syndrome or aortic dissection, there still remains a higher risk of cardiovascular event and future reoperation. Extensive aortic reconstruction or staged operation should be performed in such patients.


Effects of 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) Exposure on Reproduction and Endocrine System of Zebrafish.
The compound 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP), a derivative of bisphenol S (BPS), has been detected in thermal paper and human urine samples; however, its potential effects on the endocrine system are largely unknown. The present study was conducted to determine the adverse effects of BPSIP on egg production, relative organ weights, plasma levels of sex hormones, and transcription of genes related to the hypothalamus-pituitary-gonad (HPG) axis in zebrafish (Danio rerio). In male fish, the gonadosomatic index was significantly decreased at concentrations of 5 and 50 μg/L BPSIP. The estrogenic (increase in the 17β-estradiol/testosterone [E2/T] ratio) and antiandrogenic (decrease in T) effects were observed in fish exposed to BPSIP and males were more sensitive to the adverse effects than females. The changes in sex hormones were supported by the regulation of genes along the HPG axis, such as cyp19, 17βhsd, and cyp17 transcripts. Although the effective concentration for endocrine disruption was greater than that of BPS, the actions of BPSIP on the steroidogenic pathway were similar to the effects of BPS exposure.


Comparing Reading Speeds for Reading Standardized Single Sentences and Paragraphs in Patients with Maculopathy.
The purpose of this study was to compare reading speeds (RS) of either paragraphs of text or single sentences in patients with maculopathy by investigating the repeatability of RS to decide which text type to use in studies on patients with maculopathy. RS was measured for standardized texts in 25 participants with a central scotoma due to maculopathy (mean age 77.8 years ± 9.9 SD, mean binocular visual acuity 0.65 logMAR (±0.85 SD), median magnification requirement 3-fold). Reading 3 single sentences taken from the Radner reading charts (sample #1, #2, and #3) of 14 words and reading 3 paragraphs of International Reading Speed Texts (IReST, sample # 3, #6, and #10) with a mean of 132 (±3.2 SD) words, each in German, were compared. The 6 texts were read aloud in random order from a closed-circuit TV system, with size adjusted according to the individual magnification requirement. Reading time was measured by stopwatch, and speed was calculated in correctly read words per minute (wpm). Differences in RS depending on text length (single sentence vs. paragraph) and text sample were calculated by the Bland-Altman analysis. The mean RS showed no significant difference between 2 charts of the same kind (sentences: 93 wpm ± 37 SD; paragraphs: 95 wpm ± 38 SD). RS differences between 2 charts were lower in paragraphs than in single sentences. Highest correlations of RS between all 6 texts existed between the 3 IReST text samples (r = 0.98, 0.98, and 0.98) compared with the 3 Radner sentences (r = 0.89, 0.81, and 0.90). The inter-chart reliability (coefficient of repeatability) was smaller for the paragraphs (12.9 wpm) than for the single sentences (36.4 wpm). In patients with maculopathy, single sentences are well suited for single measurement of RS. For repeated measurements (e.g., monitoring the course of a reading disorder or assessing effects of interventions), paragraphs are preferable because of their lower variability of RS between the paragraphs.


A Bivariate Mixed Model Approach in Characterizing the Evolution of Longitudinal Body Mass Index and Quality of Life Processes in Adolescents with Severe Obesity Following Bariatric Surgery: A 5-year follow-up of the TeenLABS cohort.
Obesity is identified as a major global health problem. Along with measuring body mass index (BMI), the most common metric for defining weight status, health related quality of life (HRQol) has been accepted as a routine method to evaluate how body weight may be impacted by psychosocial factors. The objective of the current study is to characterize the joint association of change in longitudinal BMI and HRQol following metabolic and bariatric surgery and to examine the correlation between these two outcomes measured concurrently over time. We identified the optimal modeling strategy by comparing four models, all of which involved the covariance structures appropriate for correlated outcomes, BMI and HRQol in a repeated measures analysis. The bivariate random effects models performed better than the univariate random effects models. Moreover, bivariate models with composite covariate structures had better model fit compared to the bivariate random slope models. The bivariate models with composite covariate structures reflected that changes in HRQol (and BMI) were most significant during the first 6 months, a clinically useful window to monitor changes in post-operative HRQol and BMI, and if there might need to be additional interventions or at least, closer monitoring.


Saturated salt solution method: a useful cadaver embalming for surgical skills training.
This article evaluates the suitability of cadavers embalmed by the saturated salt solution (SSS) method for surgical skills training (SST). SST courses using cadavers have been performed to advance a surgeon's techniques without any risk to patients. One important factor for improving SST is the suitability of specimens, which depends on the embalming method. In addition, the infectious risk and cost involved in using cadavers are problems that need to be solved. Six cadavers were embalmed by 3 methods: formalin solution, Thiel solution (TS), and SSS methods. Bacterial and fungal culture tests and measurement of ranges of motion were conducted for each cadaver. Fourteen surgeons evaluated the 3 embalming methods and 9 SST instructors (7 trauma surgeons and 2 orthopedists) operated the cadavers by 21 procedures. In addition, ultrasonography, central venous catheterization, and incision with cauterization followed by autosuture stapling were performed in some cadavers. The SSS method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for SST. The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal to those embalmed by the TS method. Ultrasound images were clear in the cadavers embalmed by both the methods. Central venous catheterization could be performed in a cadaver embalmed by the SSS method and then be affirmed by x-ray. Lungs and intestines could be incised with cauterization and autosuture stapling in the cadavers embalmed by TS and SSS methods. Cadavers embalmed by the SSS method are sufficiently useful for SST. This method is simple, carries a low infectious risk, and is relatively of low cost, enabling a wider use of cadavers for SST.


Enteric fever: a retrospective 6-year analysis of 82 paediatric cases in a teaching hospital.
To evaluate the clinical and laboratory properties, to see the response to therapy, incidence of antimicrobial resistance and complications of Enteric Fever in children. This is a retrospective study of 82 cases of enteric fever admitted in department of pediatrics, Manipal Teaching hospital, Pokhara, Nepal. Study period was six years from (Jan 2000 to Dec 2005). Total of 82 cases of Salmonella infections were admitted .There were 50 (60%) males and 32 (40%) females. Most of the patients were above the age of five. The leading clinical feature were Fever (100%) , GI symptoms (73%), followed by splenomegaly (60%), hepatomegaly (58%), chills & rigor (41%), headache(33%),coated tongue(17%), lymphadenopathy (13%), Respiratory signs (13%), toxic look (7%). The laboratory reports revealed leucopenia in 26% and leukocytosis in 16%. Widal test was positive in 83%, Blood culture was positive in 37 %.Bone marrow was done in 8 cases, out of which 5(62.5%) were culture positive. Out of 35 culture positive cases 32 were Salmonella typhi and 3 were Salmonella paratyphi A. Regarding the treatment 55% were treated with ciprofloxacin, 29 % with ceftriaxone, 7% with ampicillin, 6% with cefotaxime and 2.4 % with chloramphenicol. Response to therapy was assessed by day of defervescence after antibiotics. Best response was observed with ciprofloxacin (4.7 days) followed by ceftriaxone (5 days), ampicillin (5.5 days), cefotaximee (6.4 days), chloramphenicol (10 days) respectively. In the antibiogram resistance was 43% with chloramphenicol, 37% with ampicillin, 31% with trimethoprim- sulfamethoxazole, 5.7%with ciprofloxacin and 4% with cefotaxime. Resistance was 0% with ceftriaxone, cefuroxime, and ofloxacin. Gentamycin was found to show high sensitivity (91%). The complications observed were anemia in 10%, 5% had neurologic signs like clouding of consciousness and 3.7% had CNS irritability. It is important to include Enteric fever in the differential diagnosis of febrile patients with abdominal symptoms. Though blood culture is the definite test, Widal test plays supportive role in diagnosis of enteric fever, especially when patients come after a course of antibiotics. Sometimes when both blood culture and Widal tests are negative Bone marrow can be the diagnostic tool for the diagnosis. Based on this analysis ciprofloxacin is still a good drug for the treatment of Enteric Fever. Ceftriaxone, Cefuroxime and Ofloxacin can be considered as first line treatment for Enteric fever since resistance was nil with these drugs on culture reports.


Ternary choline chloride/caffeic acid/ethylene glycol deep eutectic solvent as both a monomer and template in a molecularly imprinted polymer.
A molecularly imprinted polymer based on a ternary deep eutectic solvent comprised of choline chloride/caffeic acid/ethylene glycol was prepared. The caffeic acid in the ternary deep eutectic solvent was used as both a monomer and template. The molecularly imprinted polymer based on the ternary deep eutectic solvent was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, field-emission scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, atomic force microscopy, and elemental analysis. A series of molecularly imprinted polymers based on choline chloride/caffeic acid/ethylene glycol with different molar ratios was prepared and applied to the molecular recognition of polyphenols. A comparison of the recognition ability of molecularly imprinted polymers to polyphenols revealed that the choline chloride/caffeic acid/ethylene glycol (1:0.4:1, molar ratio) molecularly imprinted polymer had the best molecular recognition effect with 132 μg/g of protocatechuic acid, 104 μg/g of catechins, 80 μg/g of epicatechin, and 123 μg/g of caffeic acid in 6 h, as well as good molecular recognition ability for polyphenols from a Radix Asteris sample. These results show that the ternary deep eutectic solvent based molecularly imprinted polymer is a potential medium that can be applied to drug purification, drug delivery, and drug analysis.


Yeast sphingolipids do not need to contain very long chain fatty acids.
Synthesis of VLCFAs (very long chain fatty acids) and biosynthesis of DHS (dihydrosphingosine) both are of vital importance for Saccharomyces cerevisiae. The bulk of VLCFAs and DHS are used for ceramide synthesis by the Lag1p (longevity-assurance gene 1)/Lac1p (longevity-assurance gene cognate 1)/Lip1p (Lag1p/Lac1p interacting protein) ceramide synthase. LAG1 and LAC1 are redundant but LIP1 is essential. Here we show that 4Delta (lag1Deltalac1Deltaypc1Deltaydc1Delta) cells devoid of all known endogenous ceramide synthesis pathways are unviable but can be rescued by the expression of Lass5, a mouse LAG1 homologue. Ceramide synthase activity of 4Delta.Lass5 cells only utilizes C16 and C18 fatty acids and does not require the help of Lip1p, an essential cofactor of Lag1p/Lac1p. HPLC-electrospray ionization-MS/MS analysis demonstrated that in IPCs (inositolphosphorylceramides) of 4Delta.Lass5, the very long chain fatty acids (C26 and C24) account for <1% instead of the normal >97%. Notwithstanding, IPCs incorporated into glycosylphosphatidylinositol anchors of 4Delta.Lass5 show normal mobility on TLC and the ceramide- and raft-dependent traffic of Gas1p (glycophospholipid-anchored surface protein) from endoplasmic reticulum to Golgi remains almost normal. Moreover, the biosynthesis of C24:0 fatty acids remains essential. Thus, C(24:0) and dihydrosphingosine are both necessary for survival of yeast cells even if they utilize C16 and C18 fatty acids for sphingolipid biosynthesis.


Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic - China, October 2016-February 2017.
During March 2013-February 24, 2017, annual epidemics of avian influenza A(H7N9) in China resulted in 1,258 avian influenza A(H7N9) virus infections in humans being reported to the World Health Organization (WHO) by the National Health and Family Planning Commission of China and other regional sources (1). During the first four epidemics, 88% of patients developed pneumonia, 68% were admitted to an intensive care unit, and 41% died (2). Candidate vaccine viruses (CVVs) were developed, and vaccine was manufactured based on representative viruses detected after the emergence of A(H7N9) virus in humans in 2013. During the ongoing fifth epidemic (beginning October 1, 2016),* 460 human infections with A(H7N9) virus have been reported, including 453 in mainland China, six associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one in an asymptomatic poultry worker in Macao (1). Although the clinical characteristics and risk factors for human infections do not appear to have changed (2,3), the reported human infections during the fifth epidemic represent a significant increase compared with the first four epidemics, which resulted in 135 (first epidemic), 320 (second), 226 (third), and 119 (fourth epidemic) human infections (2). Most human infections continue to result in severe respiratory illness and have been associated with poultry exposure. Although some limited human-to-human spread continues to be identified, no sustained human-to-human A(H7N9) transmission has been observed (2,3).


The introduction of generic workers into the ward team: an exploratory study.
This study arose from a quantitative study that defined the role and resources required for the introduction of generic workers into the ward team. A month's trial was conducted to explore the staff attitudes and perceptions associated with such an introduction, thereby identifying potential problems and benefits that may influence successful introduction into the ward team. A small convenient sample that included trained, untrained and domestic staff was used. The methodological strategies in the study were semi-structured interviews, pre- and post-trial, and non-participant observations during the trial. The data obtained were transcribed and analysed using 'thematic content analysis' and 'within method triangulation'. The findings indicated positive support for the introduction of such workers and the transfer of responsibility from a central domestic team to the ward manager. The ward environment improved and nursing staff were freed from non-nursing activity, leaving more time for patient care. Recommendations to facilitate the smooth introduction of these workers are stated within the study and are now in place within the Trust. The introduction of these workers has been agreed and a staggered roll out of the project is underway in all wards across the Trust.


Effect of oral mucosal transplantation on the expression of EGF and VEGF-C during skin wound repair.
This study evaluated the effects of oral mucosal transplantation on epidermal growth factor (EGF) and vascular endothelial growth factor C (VEGF-C) in skin wound repair. Sixty-four rats were randomly separated into group A, B, C and D (16 rats in each group). The right abdomen skin was excised 1, 3, 5 and 7 days after injury, respectively. Oral mucosa of the rat tongue was transplanted to the right abdomen skin. Fourteen days after the healing of the oral mucosa graft, the rat skin full-thickness model was prepared at the transplant site (the study group) and the contralateral site (the control group). Rats in each group were anesthetized and sacrificed at 1, 3, 5 and 7 days after injury. Expression of EGF and VEGF-C in skin tissue was detected by RT-qPCR and ELISA. At 3 days, expression levels of EGF and VEGF-C mRNA and protein in skin tissue were significantly higher than those at 1 day (P<0.05). At 5 days, expression levels of EGF and VEGF-C mRNA and protein in skin tissue were significantly higher than those at 3 days (P<0.05). At 7 days, expression levels of EGF mRNA and protein in skin tissue were significantly lower than those at 5 days (P<0.05), while VEGF-C levels were significantly increased (P<0.05). Expression levels of EGF and VEGF-C mRNA and protein in the skin tissue of the study group were significantly lower than those in the control group at all days (P<0.05). EGF and VEGF-C may be involved in scar formation, and play an important role in the process of skin wound repair.