Vaccinia virus E3 protein prevents the antiviral action of ISG15.
The ubiquitin-like modifier ISG15 is one of the most predominant proteins induced by type I interferons (IFN). In this study, murine embryo fibroblast (MEFs) and mice lacking the gene were used to demonstrate a novel role of ISG15 as a host defense molecule against vaccinia virus (VACV) infection. In MEFs, the growth of replication competent Western Reserve (WR) VACV strain was affected by the absence of ISG15, but in addition, virus lacking E3 protein (VVDeltaE3L) that is unable to grow in ISG15+/+ cells replicated in ISG15-deficient cells. Inhibiting ISG15 with siRNA or promoting its expression in ISG15-/- cells with a lentivirus vector showed that VACV replication was controlled by ISG15. Immunoprecipitation analysis revealed that E3 binds ISG15 through its C-terminal domain. The VACV antiviral action of ISG15 and its interaction with E3 are events independent of PKR (double-stranded RNA-dependent protein kinase). In mice lacking ISG15, infection with VVDeltaE3L caused significant disease and mortality, an effect not observed in VVDeltaE3L-infected ISG15+/+ mice. Pathogenesis in ISG15-deficient mice infected with VVDeltaE3L or with an E3L deletion mutant virus lacking the C-terminal domain triggered an enhanced inflammatory response in the lungs compared with ISG15+/+-infected mice. These findings showed an anti-VACV function of ISG15, with the virus E3 protein suppressing the action of the ISG15 antiviral factor.


Suicide attempts among the elderly in East Asia.
Among the one million suicide deaths worldwide each year, as many as 60% occur in Asia. The World Health Organization (WHO) found higher suicide rates among the elderly in rapidly industrialized Asian countries such as China, Hong Kong, Japan, South Korea, Malaysia, and Singapore, compared to the corresponding rates of recently industrializing Asian countries like Vietnam and Sri Lanka (WHO, 2014). As a case in point, suicide rates in South Korea have been the highest in the world since 2003 and are rising especially among older people (Hong and Knapp, 2014). Suicide attempts and older age are strong predictors of completed suicide (Szanto et al., 2002; Simon et al., 2013) and, as such, are important in guiding our efforts for suicide prevention; however, most epidemiological studies focus on completed suicides across all ages rather than understanding the reasons behind suicide attempts in older populations.


[Complex Trauma-related Disorders in Research and Practice].
Complex Trauma-related Disorders in Research and Practice Frequent traumata in childhood and adolescence are long-term or repeated interpersonal traumata caused by perpetrators in the close environment of the minors. For the description of the extensive symptoms after interpersonal Type II traumata, the complex trauma-related disorders Complex Posttraumatic Stress Disorder (CPTSD) or Disorder of Extreme Stress Not Otherwise Specified (DESNOS) and the Developmental Trauma Disorder (DTD) are being discussed for inclusion in the classification systems for mental disorders. Scientific knowledge and practical experiences regarding CPTSD, DESNOS and DTD in children and adolescents up to 18 years were examined by 1) a Systematic Review of 1,070 publications identified by database research and additional search strategies, and 2) a nationwide online survey of 374 psychotherapists and psychiatrists for children and adolescents in Germany. Of 13 included empirical studies (8 CPTSD or DESNOS, 5 DTD), 9 were conducted in the USA, 4 based on file coding and 3 on secondary data analysis and only 7 reported diagnosis rates (range: 0-78 %). Of the interviewed therapists, 100 % considered the CPTSD as being met with at least one patient with interpersonal traumata up to 18 years of age in 2014 and 99 % gave this estimate for the DTD. Two thirds of therapists rated the diagnostic option CPTSD and DTD as "very often" or "often" helpful for their therapeutic work with children and adolescents. While empirical data available is to be considered insufficient and characterized by methodological limitations, the relevance of complex trauma-related disorders is perceived as high by practitioners.


Importance of reversed-phase chromatographic parameters in predicting biopharmaceutical and pharmacokinetic descriptors on the group of androgen derivatives.
Nowadays the standard measure of lipophilicity, the logarithm of n-octanol-water partition coefficient, logP, is proposed to be replaced with chromatographic techniques. Chromatography techniques (reversed phase thin layer chromatography RPTLC and reversed phase thin layer chromatography RPHPLC) are the most widely used alternatives to the shake flask method. However, it is shown that, by changing the temperature or concentration of organic modifier in the chromatography experiment, it is possible to derive data matrix of retention parameters from which, by principle component analysis, structural characteristics of the examined molecules can be gained. The question may be asked which of the chromatography experimentally obtained and calculated parameters: capacity factor k, ΔGx (the change in Gibbs energy of binding of molecule for stationary phase), ΔHx (the change in enthalpy of binding of molecule for stationary phase) or ΔSx (the change in the entropy of binding of molecule for stationary phase) is the most suitable in describing hydrophobicity. The canonical correlation analysis (CCA) method is used to evaluate the importance of the n functions in explaining the variance of molecular descriptors connected to pharmaceutical processes and wherein molecule's hydrophobicity is expressed and possible differences between molecular descriptors with realistic conformations of the analyzed molecules steroid skeleton are discussed. Conformational analysis showed that structure of steroid skeleton in hydrophobicity is most completely described with k or ΔGx, and connection between conformation of the steroid skeleton and hydrophobicity to a lesser extent is projected on temperature dependence on ΔHx and similarly on ΔSx, so in describing molecules hydrophobicity it is necessary to observe entropic as well as enthalpic contribution together, expressed with ΔGx function. Canonical conformation analysis (CCA) showed that hydrophobicity contained in ΔGx and k explains 61% of variance represented in in silico descriptors. Analyzed molecular descriptors, derived from different molecules fragments don't map conformational specifics of those molecules in small groups so recommendation is to use them complementary with chromatographic data in describing hydrophobicity.


Cultural Adaptation, Content Validation, and Reliability of the SACS 2.0 Instrument for Colombian Spanish.
To realize the cultural adaptation and content validation and evaluate the reliability of the SACS 2.0 instrument in Colombian Spanish. The researchers conducted a methodological study with a quantitative approach. The adaptation process was carried out in five stages: translation, synthesis, reverse translation, evaluation by a committee of experts, and testing of the adapted version. In addition, the interobserver reliability was evaluated by four nurses who examined 210 stomas. All of the proposed stages were carried out successfully, and an adapted version of the instrument in Colombian Spanish was obtained. During the content validation stage, the instrument obtained a content validity index of 1. The adapted version of the test showed substantial agreement for the aspect of clarity, adequacy, and understandability. In the interobserver reliability, there was agreement in 95.7% of the evaluations for the classification of the lesions according to the quadrants (κ = 0.97-0.99). Authors achieved a culturally adapted, valid, and reliable instrument for the evaluation and classification of peristomal skin alterations in Colombian Spanish.


6-Allyl-5,6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species: specified 1H and 13C NMR assignments, mutagenic and immunomodulating testings.
A lactone (6-allyl-5,6-dihydro-5-hydroxypyran-2-one) was isolated from a new Drechslera sp. 1H and 13C NMR assignments, not previously specified, are published. No mutagenic activity on Ames/Salmonella test (strains TA98 and TA100 has been observed. Results on the respiratory metabolism of J774.1 murine macrophage indicate that the lactone might exhibit immunomodulating activity as a function of time of cellular contact and of concentration.


A histological comparison of the tissue interface of bioglass and silica glass.
The objectives of the present article are to confirm the bone bonding phenomenon of Bioglass (BG) developed by Hench et al., and to observe the singularity of tissue reaction to it. BG and nonreactive silica glass (SG) were implanted in the femurs of rabbits and rats. Histological examination revealed that a relatively acellular zone with little inflammation was formed on BG surface at 1 day after implantation. Neither fibrous tissue nor a distinct boundary was observed between BG and bone after 7 days. On the contrary, a moderate postoperative inflammatory reaction was observed on SG at 1 day, and fibrous tissue was observed between SG and bone after 7 days. From these findings, it was confirmed that BG bonded directly with bone. As the relatively acellular zone observed on BG surface at 1 day was replaced by bone after 7 days, the formation of this zone might play an important role in bone-bonding process. Further research should be focused on the mechanism and biological meaning of bone bonding, for this phenomenon can not be explained by the conventional pathological theory of foreign body encapsulation.


Effects of the metal center and substituting groups on the linear and nonlinear optical properties of substituted styryl-bipyridine metal(II) dichloride complexes: DFT and TDDFT computational investigations and harmonic light scattering measurements.
UV-visible absorption spectroscopy and harmonic light scattering measurements coupled with density functional theory (DFT) calculations have been carried out for a series of 4,4'-bis(X-styryl)-2,2'-bipyridine M(II) dichloride complexes (M = Co, Ni, Cu, Zn; X = H, OMe, SMe, NMe(2), NEt(2), CN, NO(2)). The roles of the metal and the substituent X on their coordination geometries, absorption, and quadratic nonlinear optical properties have been investigated. We show that these complexes all exhibit a high-spin configuration and display a distorted tetrahedral metallic environment except the copper ones, which are distorted square-planar complexes. When X is a strong electron-donating group (X = NMe(2), NEt(2)), TDDFT calculations clearly demonstrate that, whereas the Zn complexes show an ILCT transition in the visible range, the Co, Ni, and Cu complexes exhibit additional MLCT and LLCT transitions. These latter transitions are vectorially opposed to the ILCT and could contribute to the decrease of the experimental quadratic hyperpolarizability beta values, in the order Zn > Ni approximately Cu > Co. The computation of the beta values using TDDFT for the whole series of the closed-shell Zn(II) complexes featuring different X substituents established that the NLO activity increases with the donating strength of X and more generally with the decrease of the HOMO-LUMO energy gap. When X is a strong withdrawing group, the drastic decrease of the NLO response is explained by the negligible participation of the HOMO-LUMO transitions.


The Multifarious Effects of Various Glaucoma Pharmacotherapy on Corneal Endothelium: A Narrative Review.
Corneal endothelium is a single cell layer that is mainly responsible for maintaining corneal clarity. Endothelial damage secondary to toxicity, stress, or genetic predisposition are common and in conjunction with the low regenerative ability of the cells, making their preservation critical for maintaining visual acuity. Patients with glaucoma, who are estimated to be close to 80 million worldwide, have a plethora of reasons for developing endothelial damage, being exposed to a spectrum that extends from various medical and surgical interventions to the disease itself. The wide spectrum of glaucoma pharmacotherapy that has been recently extended by addition of newer classes of medications has been the focus of extensive research on its effects on corneal endothelium. Both basic and clinical research have attempted to shine a light on the complex mechanisms associated with the effects of glaucoma medication on corneal endothelium and to answer the important question as to whether these findings are clinically significant. The aim of this review is to summarize and present current literature of the various findings, both from in vivo and in vitro studies that have focused on the complex relationship between different classes of glaucoma medication and their effect on corneal endothelium.


Studying transcription initiation by RNA polymerase with diffusion-based single-molecule fluorescence.
Over the past decade, fluorescence-based single-molecule studies significantly contributed to characterizing the mechanism of RNA polymerase at different steps in transcription, especially in transcription initiation. Transcription by bacterial DNA-dependent RNA polymerase is a multistep process that uses genomic DNA to synthesize complementary RNA molecules. Transcription initiation is a highly regulated step in E. coli, but it has been challenging to study its mechanism because of its stochasticity and complexity. In this review, we describe how single-molecule approaches have contributed to our understanding of transcription and have uncovered mechanistic details that were not observed in conventional assays because of ensemble averaging.


Adult Onset Sacrococcygeal Teratoma.
Sacrococcygeal teratoma (SCT), one of the most common neoplastic tumors in newborns, is found very rarely in adults. These teratomas are germ cell tumours. Most of these tumors are benign and cystic in nature, with only 1-2% of them having a malignant transformation. Most of these tumors are benign and cystic in nature, with only 1-2% of them having malignant transformation. A higher incidence was seen in females. Typically, cystic teratomas are asymptomatic, and so the diagnosis was often made inadvertently during radiographic studies. The majority of treatment is complete surgical excision, and both open and laparoscopic procedures have been proven to be efficient. Histopathologic examination can confirm the diagnosis. We present this unusual instance of a 56-year-old female patient with a sacrococcygeal teratoma.


[Action of central depressants on the nitrous oxide anesthesia (author's transl)].
The synergistic action of seven central depressants three benzodiazepines, two neuroleptics on barbiturate and morphine on the anesthetic activity of nitrous oxide was studied in mice. The benzodiazipines and among them nitrazepam and flunitrazepam were found to be the most potent drugs in this respect; morphine on the other hand was innefective even in toxic doses. There was a significant difference in the slope of log dose-response curves; these curves were much steeper for pentobarbitone, droperidol and chlorpromazine than for nitrazepam, flunitrazepam, and diazepam. The theoretical and practical implications of this difference are discussed.


Infected echinococcal cyst. A common cause of pyogenic hepatic abscess.
Twenty-one cases of hepatic abscesses treated during a period of four years (from 1981 to 1985) at the University of Patras, Greece, are presented. This material includes 10 cases with abscesses caused by suppurated echinococcal cysts, corresponding to 21% of the total number of 47 cases of echinococcal cysts of the liver treated at our department during the same period. A preoperative diagnosis of the suppurated echinococcal cysts by conventional laboratory methods was not reliable. Because of the high frequency of echinococcal disease in our region and the risk of contamination of the peritoneal cavity from echinococcal parasites if the cyst is punctured, the new therapeutic techniques of treating hepatic abscesses by percutaneous drainage have not been applied. The exclusive method of treatment used was surgical drainage which had a satisfactory outcome and a mortality rate as low as 9%.


Validation analysis of probabilistic models of dietary exposure to food additives.
The validity of a range of simple conceptual models designed specifically for the estimation of food additive intakes using probabilistic analysis was assessed. Modelled intake estimates that fell below traditional conservative point estimates of intake and above 'true' additive intakes (calculated from a reference database at brand level) were considered to be in a valid region. Models were developed for 10 food additives by combining food intake data, the probability of an additive being present in a food group and additive concentration data. Food intake and additive concentration data were entered as raw data or as a lognormal distribution, and the probability of an additive being present was entered based on the per cent brands or the per cent eating occasions within a food group that contained an additive. Since the three model components assumed two possible modes of input, the validity of eight (2(3)) model combinations was assessed. All model inputs were derived from the reference database. An iterative approach was employed in which the validity of individual model components was assessed first, followed by validation of full conceptual models. While the distribution of intake estimates from models fell below conservative intakes, which assume that the additive is present at maximum permitted levels (MPLs) in all foods in which it is permitted, intake estimates were not consistently above 'true' intakes. These analyses indicate the need for more complex models for the estimation of food additive intakes using probabilistic analysis. Such models should incorporate information on market share and/or brand loyalty.


Defeat-induced activation of the ventral medial prefrontal cortex is necessary for resistance to conditioned defeat.
The ventral medial prefrontal cortex (vmPFC) controls vulnerability to the negative effects of chronic or uncontrollable stress. Dominance status alters responses to social defeat in the conditioned defeat model, which is a model characterized by loss of territorial aggression and increased submissive and defensive behavior following an acute social defeat. We have previously shown that dominant individuals show a reduced conditioned defeat response and increased defeat-induced neural activation in the vmPFC compared to subordinates. Here, we tested the hypothesis that defeat-induced activation of the vmPFC is necessary to confer resistance to conditioned defeat in dominants. We paired weight-matched male Syrian hamsters (Mesocricetus auratus) in daily 5-min aggressive encounters for 2 weeks and identified dominants and subordinates. Twenty-four hours after the final pairing, animals were bilaterally injected with 200 nl of the GABAA receptor agonist muscimol (1.1 nmol) or 200 nl of saline vehicle 5 min prior to social defeat. Defeat consisted of 3, 5-min encounters with resident aggressor hamsters at 10-min intervals. Twenty-four hours following social defeat, animals received conditioned defeat testing which involved a 5-min social interaction test with a non-aggressive intruder. Muscimol injection prior to social defeat prevented the reduced conditioned defeat response observed in vehicle-treated dominants. Further, there was no effect of muscimol injection on the conditioned defeat response in subordinates or controls. These data support the conclusion that activation of the vmPFC during social defeat is necessary for the protective effects of dominant social status on the acquisition of conditioned defeat.


Cellular schwannoma of the paranasal sinuses: initial report of a case.
Cellular schwannomas are a benign variant of classic schwannomas. Their histologic appearance closely mimics that of malignant peripheral nerve-sheath tumors, which are high-grade sarcomas. In this article, we describe what to our knowledge is the first reported case of a cellular schwannoma of the paranasal sinuses and only the 33rd reported case of any schwannoma at this site. We also discuss the histology and management of cellular schwannomas and review the pertinent literature.


Corneal Wound Repair After Rose Bengal and Green Light Crosslinking: Clinical and Histologic Study.
To evaluate corneal wound healing after treatment with a new collagen crosslinking protocol using rose bengal dye and green light (RGX). One cornea of 20 New Zealand rabbits was de-epithelialized (DE) in an 8-mm diameter circle and, in another group (n = 25), the DE corneas were then stained with 0.1% rose bengal for 2 minutes and exposed to green light (532 nm) for 7 minutes (RGX). The contralateral eyes without treatment acted as controls. The animals were clinically followed including fluorescein staining and pachymetry. Healing events were analyzed after euthanasia at 2, 30, and 60 days. Cell death (TUNEL assay), cell proliferation (5-bromo-2'-deoxyuridine incorporation), and cell differentiation to myofibroblasts (α-SMA labeling) were carried out. In addition, loss of keratocytes and subsequent repopulation of the corneal stroma were quantified on hematoxylin-eosin-stained sections. Wound closure was slower after RGX (4.4 days) then after DE (3.3 days). Cell death was restricted to the anterior central stroma, and the cellular decrease did not differ significantly between RGX and DE corneas. Cell proliferation in the epithelium and stroma appeared at 2 days. In both DE and RGX corneas, recovery of the epithelium was complete at day 30, although cell repopulation of the stroma was not complete at 60 days. The healing response in corneas after RGX is very similar to that observed after DE alone, suggesting that, along with its short treatment time and limited effect on keratocytes, RGX displays good potential for clinical cornea stiffening.


Continuous transanal decompression for infants with long- and total-type Hirschsprung's diseases as a bridge to curative surgery: a single-center experience.
The purpose of this study is to assess the usefulness of continuous bowel decompression using an indwelling transanal tube (ITT) for preoperative management in infants with long-segment (L)- or total (T)-type Hirschsprung's disease (HD). Between 2012 and 2015, seven patients with L- or T-type HD underwent preoperative bowel management by continuous bowel decompression using an ITT during waiting period for curative surgery. Continuous bowel decompression was done using an ITT, a 10-12F flexible dual lumen tube placed through the rectum up to the dilated colon under fluoroscopic guidance and secured to the bilateral buttocks. The ITT tips were located at least in a dilated colon or the cecum if there was no radiographic transitional zone. The ITT was left open for continuous drainage, and its patency was checked by regular suction until the curative operation. The patient status and complications of this preoperative management were reviewed retrospectively. The median duration of decompression management was 65 (17-137) days. During decompression period, neither abdominal distention, enterocolitis, nor other complications occurred and six patients could stay at home until the curative operation. The weight-for-age Z-score at curative surgery was the same as or higher than that at birth in five patients. ITT replacement was needed three times per patient on an average for accidental ITT removal, ITT stenosis, or ITT hardening. Bowel management by continuous bowel decompression using an ITT is easy, safe, and effective for preoperative management in patients with L- or T-type HD and may permit single-stage surgery rendering colostomy or enterostomy unnecessary.


Isolation of the yeast phosphoglyceromutase gene and construction of deletion mutants.
The PGM1 gene (also called GPM; Fraenkel 1982) coding for phosphoglyceromutase was isolated by functional complementation. When present on a multicopy vector and introduced into yeast cells it led to an about eightfold increase in specific enzymatic activity. This apparent overproduction was confirmed by SDS-polyacrylamide gel electrophoresis of crude extracts and at the transcriptional level by Northern analysis. By subcloning of the yeast DNA insertions of the plasmids originally isolated the PGM1 coding region was located within a 1.3 kb SalI-HindIII fragment. Integration at the chromosomal locus confirmed that the PGM1 gene had indeed been isolated. Southern analysis of genomic digests showed the same restriction patterns as the cloned sequences. However, a BamHI restriction polymorphism was observed. Furthermore, a repetitive element was found in the PGM1 flanking region. Finally, the chromosomal copy of the gene was deleted by replacement with a URA3 marker. The deletion mutants showed that the gene is not essential for yeast growing in the presence of a combination of glycerol and ethanol. However, growth was inhibited by glucose and neither glycerol nor ethanol alone were sufficient to support growth.


The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r.
The H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded in H19's first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extra-embryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth-promoting insulin-like growth factor 1 receptor (Igf1r) gene. Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress-response RNA-binding protein HuR. These results suggest that H19's main physiological role is in limiting growth of the placenta before birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.


HDAC2-dependent miRNA signature in acute myeloid leukemia.
Acute myeloid leukemia (AML) arises from a complex sequence of biological and finely orchestrated events that are still poorly understood. Increasingly, epigenetic studies are providing exciting findings that may be exploited in promising and personalized cutting-edge therapies. A more appropriate and broader screening of possible players in cancer could identify a master molecular mechanism in AML. Here, we build on our previously published study by evaluating a histone deacetylase (HDAC)2-mediated miRNA regulatory network in U937 leukemic cells. Following a comparative miRNA profiling analysis in genetically and enzymatically HDAC2-downregulated AML cells, we identified miR-96-5p and miR-92a-3p as potential regulators in AML etiopathology by targeting defined genes. Our findings support the potentially beneficial role of alternative physiopathological interventions.


Antihemolytic activity and mineral contents of Juglans regia L. flowers.
Juglans (J.) regia L. is known to possess many biological properties. In this study, antihemolytic activity of methanol extract of Juglans regia L. flower were investigated. Antihemolytic activities of Juglans regia L. flowers were evaluated by various in vitro assays. In addition, scavenging of hydrogen peroxide and mineral contents of flowers were determined using atomic absorption spectroscopy. Extract showed good antihemolytic activity against H2O2 and CuOOH induced hemolysis in comparison with control. Extract was capable of scavenging H2O2 in a concentration dependent manner. IC50 for H2O2 scavenging activity was 311±12.8 µg ml-1. The amount of eight elements was determined and was in the order: Mn > Cu > Fe > Zn. Our study indicate that J. regia flower has remarkable antihemolytic activity, which maybe result of its high phenol and flavonoid contents, especially quercetin.


Carbamazepine extended-release capsules: a new treatment option for bipolar I disorder.
Carbamazepine has a long history in psychiatry and neurology. More recently, carbamazepine extended-release capsules have been approved by the US Food and Drug Administration for the treatment of manic and mixed episodes associated with bipolar I disorder. This decision represents a significant step forward for the agent, which was first described to have efficacy in the disorder in the early 1970s. Approval of carbamazepine extended-release capsules was aided by two large placebo-controlled, 3-week trials. Using nearly identical protocols, these trials demonstrated that monotherapy with carbamazepine extended-release capsules was effective for the treatment of acute mania in patients with bipolar I disorder. Recent data collected based on this new formulation of carbamazepine illustrate the need for education about the utility of this compound in bipolar disorder.


William Glenn lecture. The cavopulmonary shunt. Evolution of a concept.
A bold and imaginative development, the cavopulmonary anastomosis, appeared to originate in several centers almost simultaneously. After extensive research on right heart bypass, Glenn was the first in North America to perform a successful experimental cavopulmonary shunt, and it became known by his name. In properly selected patients, palliation success was excellent, and mortality rates were low. From 1961 through 1988, we used a cavopulmonary anastomosis for palliation in 139 infants and children. There were eight hospital deaths, and most occurred early in the series. Palliation generally lasted 6-8 years-until the child outgrew the blood supply to the contralateral lung. Palliation could be restored by increased flow to that lung with another shunt. Six otherwise inoperable patients received benefit from the addition of an axillary arteriovenous fistula. Late pulmonary arteriovenous fistulas were identified in 11% of our patients by angiography, but with more sensitive testing, the incidence rate may be as high as 21%. The occurrence of pulmonary arteriovenous fistulas caused general concern and less frequent use of the shunt. Recent application of an end-to-side anastomosis, creating a bidirectional shunt, has restored interest. A major legacy of the cavopulmonary anastomosis was demonstration of the feasibility of partial right heart bypass, which paved the way for the Fontan operation, and it is frequently constructed as part of that operation. Currently, the Glenn shunt is most often used as a temporary or permanent alternative to a Fontan repair if there appears to be significant risk. The risk factors usually encountered include small pulmonary arteries, young age, poor ventricular function, atrioventricular valve incompetence, and myocardial hypertrophy-sometimes alone but often in combination.(ABSTRACT TRUNCATED AT 250 WORDS)


Miltefosine in children with visceral leishmaniasis.
Sixty four children (38 boys and 26 girls), aged 1 yr to 14 yr, presenting with fever, splenomegaly and positive LD body in splenic smear examination, admitted to pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 04 were taken for study. Patients were categorized into two groups: 44 were in Group I (Patients who had not received prior antileishmanial drug) and 20 in Group II (Patients who had received 30 days course of SAG; 20 mg per kg per day). All patients were given Miltefosine in dose of 2.5 per kg per day od or bid per orally to a maximum of 100 mg and were followed at completion of therapy, 1 month and 6 months for clinical response, splenic size and parasite density. 63 patients had parasitological cure with relapse in one patient of Group I during follow up. One patient in Group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In Group I, one patient had persistent splenomegaly and found to have associated portal hypertension. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients respectively. Majority of patients had pancytopenia. Elevated ALT (> 3 times of normal) were seen in 28 and 11 patients of Group I and Group II respectively which returned to normal in subsequent follow up. The final cure rates were 93.2 percent and 95 percent in Groups I and II respectively.


[Management of ovarian metastasis from a lobular breast carcinoma].
Ovarian metastatic breast cancer is infrequent and usually is originating from lobular carcinomas. It was found that the risk of developing an ovarian neoplasm is approximately doubled in women with a history of breast cancer. The finding of an adnexal mass in these patients involves a particular concern and requires a study. We report a case of a 67-year-old female diagnosed of an infiltrating lobular breast carcinoma. It is done lumpectomy and an axillary dissection of lymph nodes resulting 2 of 13 lymph nodes positives. She was treated with chemotherapy and hormone treatment staying the disease in remission for years. After she was admitted with malignant pleural effusion and pathological costal fracture. The ultrasound shows an increase of size of annexes and a CA125 and CA15.3 increased in the analysis. Bilateral oophorectomy was performed. The pathology was consistent with lobular breast carcinoma. Subsequently another income was required because of disease progression. Currently after almost two years since the adnexectomy, is in close monitoring by medical oncologists. Although the diagnosis of an adnexal mass in a woman who has had breast cancer is usually a benign finding, the risk in these women to develop a malignant ovarian pathology is increased compared to the general population. Therefore, although the patient remains asymptomatic, it is important an abdominopelvic exploration from time to time. If the ultrasound image of the adnexal mass is suspect, the CA125 is increased, or estrogen receptors are negatives in the original breast tumor, should be performed surgical evaluation.


[Assessment of optic nerve decompression efficiency in resection of sellar region meningiomas via intradural subfrontal approach].
In this article we analyze results of the different variants of the optic nerve transcranial decompression in cases with different chiasmal region tumors. We operate 70 patient with different type meningioma (tuberculum sella, shenoid wings, anterior clinoid, optic canal), pituitary adenoma and one case with tuberculoma (we operate it thinking on meningioma, but histology was unexpected). Groups of the patients. Group1. 20 patients with pituitary adenoma with cavernous sinus invasion. It was our "pre-endoscopic" period when we frequently operated adenomas by transcranial approach. In this 20 patients we used intra-extradural Dolenc approach to cavernous sinus. In that cases we removed anterior clinoid process and decompressed optic canal. Here we use the results of surgery in this group for showing the possibility of using high speed drill for the optic canal decompression - for showing it safety. On our opinion this type of optic canal decompression is radical and safe but superfluous for the optic canal invasion by the meningioma. Group 2. 19 patients with meningioma. In that cases we partially unroofed optic canal by Kerrison and additionally we cut the falciform ligament. Group 3. 31 patients with meningioma. It's our "main" group. Here we made intradural wide unroofing the optic canal by high speed drill. Additionaly we cut the falciform ligament and open the dural sheet of the optic nerve. We propose this methodic like sufficient, safe and useful. In this cases we frequently saw the tumor spread inside the dural sheet of the optic nerve, without seeing it on the MRI. A lot of cases in this group was a recurrent after previous meningioma removal. Like a control groups we use two. Group 4. 11 cases with meningioma. In that cases we removed tumor from optic canal without any decompression. It was our archive group - we made this type of surgery before starting optic canal decompression. This group shows the risks of any manipulation with fixed optic nerves without optic canal decompression. Group 5. 31 case with meningioma. In this cases we saw the optic canal invasion by the tumor but we didn't try to decompress it. It was our archive group - we made this type of surgery before starting optic canal decompression. We use this group for found out the risks of canal decompression. This group shows the poor perspectives for the vision in optic canal invasion by the tumor without it decompression. We analyze the results of surgery on the day of discharge and on catamnesis - we decide that the optic nerves need time to recovery. We analyzed the results of surgery in patients with 3 types of the visual dysfunction: moderate (1.0-0.5), hard (0.5-0.1), decompensating (0.1-0). For showing the real risks and effectivety of any type of decompression and surgery without decompression we look for results in patients with decompensating of visual functions. For statistical analyses we use Fisher criteria which used in small series. We statistically showed that any attempts of tumor removal form the optic canal is more risky than decompression. Also we found a tendency that wide intradural decompresstion made by high speed drill with additional falciform ligament cutting and the dural sheet opening is more effective and safe than opening the optic canal by Kerrisson. This technique also could be used during the transcranial surgery for the other type of pathology particularly in cases with short optic nerves and prefixed chiasm - it gives the mobility for the nervesand decreased the nerve damaging.


Gas-flushed packaging contributes to calcium lactate crystals in Cheddar cheese.
Gas-flushed packaging is commonly used for cheese shreds and cubes to prevent aggregation and loss of individual identity. Appearance of a white haze on cubed cheese is unappealing to consumers, who may refrain from buying, resulting in lost revenue to manufacturers. The objective of this study was to determine whether gas flushing of Cheddar cheese contributes to the occurrence of calcium lactate crystals (CLC). Cheddar cheese was manufactured using standard methods, with addition of starter culture, annatto, and chymosin. Two different cheese milk compositions were used: standard (lactose:protein = 1.47, protein:fat = 0.90, lactose = 4.8%) and ultrafiltered (UF; lactose:protein = 1.23, protein:fat = 0.84, lactose = 4.8%), with or without adjunct Lactobacillus curvatus. Curds were milled when whey reached 0.45% titratable acidity, and pressed for 16 h. After aging at 7.2 degrees C for 6 mo, cheeses were cubed (1 x 1 x 4 cm) and either vacuum-packaged or gas-flushed with carbon dioxide, nitrogen, or a 50:50 mixture of carbon dioxide and nitrogen, then aged for an additional 3 mo. Heavy crystals were observed on surfaces of all cubed cheeses that were gas-flushed, but not on cheeses that were vacuum-packaged. Cheeses without Lb. curvatus exhibited L(+)-CLC on surfaces, whereas cheeses with Lb. curvatus exhibited racemic mixtures of L(+)/D(-)-CLC throughout the cheese matrices. The results show that gas flushing (regardless of gas composition), milk composition, and presence of nonstarter lactic acid bacteria, can contribute to the development of CLC on cheese surfaces. These findings stress the importance of packaging to cheese quality.


Pax8, Napsin A, and CD10 as Immunohistochemical Markers of Canine Renal Cell Carcinoma.
Pax8, napsin A, and CD10 are useful immunohistochemical markers of human renal cell carcinoma (RCC); however, their diagnostic utility in canine RCC is unclear. Forty formalin-fixed paraffin-embedded renal cell carcinomas from dogs (15 papillary, 12 solid, and 13 tubular) and 10 metastases were evaluated for expression of Pax8, napsin A, and CD10. Thirty-nine (98%), 24 (60%), and 19 (50%) tumors expressed Pax8 (nuclear labeling), napsin A (cytoplasmic labeling), and CD10 (cytoplasmic and membranous labeling), respectively. Pax8 was expressed in 92% of solid, 100% of papillary, and 100% of tubular tumors. Napsin A was expressed in 58% of solid, 60% of papillary, and 62% of tubular RCC. CD10 was expressed in 33% of solid, 47% of papillary, and 62% of tubular RCC. Pax8 was expressed in 80% of the metastatic tumors, napsin A in 60%, and CD10 in 50%. Additionally, Pax8 immunoreactivity was stronger overall than that of napsin A or CD10. In summary, Pax8 is a more sensitive marker than napsin A or CD10 for primary and metastatic canine RCC; its nuclear and more intense reactivity also makes it easier to interpret. Tubular and papillary RCCs were more likely than solid RCC to express all 3 markers. These findings highlight the utility of Pax8 as an immunohistochemical marker in diagnosing all major subtypes of canine primary and metastatic renal cell carcinoma.


Potential for the anaerobic oxidation of benzene and naphthalene in thermophilic microorganisms from the Guaymas Basin.
Unsubstituted aromatic hydrocarbons (UAHs) are recalcitrant molecules abundant in crude oil, which is accumulated in subsurface reservoirs and occasionally enters the marine environment through natural seepage or human-caused spillage. The challenging anaerobic degradation of UAHs by microorganisms, in particular under thermophilic conditions, is poorly understood. Here, we established benzene- and naphthalene-degrading cultures under sulfate-reducing conditions at 50°C and 70°C from Guaymas Basin sediments. We investigated the microorganisms in the enrichment cultures and their potential for UAH oxidation through short-read metagenome sequencing and analysis. Dependent on the combination of UAH and temperature, different microorganisms became enriched. A Thermoplasmatota archaeon was abundant in the benzene-degrading culture at 50°C, but catabolic pathways remained elusive, because the archaeon lacked most known genes for benzene degradation. Two novel species of Desulfatiglandales bacteria were strongly enriched in the benzene-degrading culture at 70°C and in the naphthalene-degrading culture at 50°C. Both bacteria encode almost complete pathways for UAH degradation and for downstream degradation. They likely activate benzene via methylation, and naphthalene via direct carboxylation, respectively. The two species constitute the first thermophilic UAH degraders of the Desulfatiglandales. In the naphthalene-degrading culture incubated at 70°C, a Dehalococcoidia bacterium became enriched, which encoded a partial pathway for UAH degradation. Comparison of enriched bacteria with related genomes from environmental samples indicated that pathways for benzene degradation are widely distributed, while thermophily and capacity for naphthalene activation are rare. Our study highlights the capacities of uncultured thermophilic microbes for UAH degradation in petroleum reservoirs and in contaminated environments.


Tropisetron ameliorates cyclophosphamide-induced hemorrhagic cystitis in rats.
Hemorrhagic cystitis is one of the most important complications of cyclophosphamide, a drug widely used in cancer chemotherapy and bone marrow transplantation. 5-HT3 antagonists are anti-emetic agents and have been shown to have notable anti-inflammatory and antioxidant properties. This study was designed to investigate the possible protective effects of tropisetron against cyclophosphamide-induced hemorrhagic cystitis in rats. Hemorrhagic cystitis was induced in female rats by cyclophosphamide (270 mg/kg). Tropisetron (2.5, 5 and 7.5 mg/kg), granisetron (2.5 and 5 mg/kg), and ondansetron (5 mg/kg) were injected 15 min before, 4 and 8 h after cyclophosphamide. To evaluate the role of alpha7 nicotinic acetylcholine receptor (α7nAChR), its antagonist, methyllycaconitine (5 mg/kg) was administered 30 min before tropisetron. After 24 h, animals were killed under anesthesia. Macroscopic and histological changes were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Evans blue were measured spectrophotometrically. Furthermore, the protein levels of p38 mitogen-activated protein kinases (P38 MAPK), p-P38, signal transducer and activator of transcription 3 (STAT3), p-STAT3 and Poly (ADP-ribose) polymerase (PARP) were determined using Western blot. Cyclophosphamide administration significantly induced histopathological damages and increased MDA, p-p38/p38, p-STAT3/STAT3, and PARP levels compared with the saline group. Tropisetron treatment diminished histopathological injuries as well as MDA level, and STAT3 activity compared to cyclophosphamide treated rats. Co-administration of methyllycaconitine with tropisetron, partially or completely reversed the protective effects of tropisetron. Our results showed that prophylactic administration of tropisetron markedly ameliorated the cyclophosphamide-induced bladder hemorrhage and inflammation in rats. These effects of tropisetron were α7nAChR dependent.


Retroviral recombination during reverse transcription.
After mixed infection, up to half of related retroviruses are recombinants. During infection, retroviral RNA genomes are first converted to complementary DNA (cDNA) and then to double-stranded DNA. Thus recombination could occur during reverse transcription, by RNA template switching, or after reverse transcription, by breakage and reunion of DNA. It has not been possible to distinguish between these two potential mechanisms of recombination because both single-stranded cDNA and double-stranded proviral DNA exist in infected cells during the eclipse period. Therefore we have analyzed for recombinant molecules among cDNA products transcribed in vitro from RNA of disrupted virions. Since recombinants from allelic parents can only be distinguished from parental genomes by point mutations, we have examined the cDNAs from virions with distinct genetic structures for recombinant-specific size and sequence markers. The parents share a common internal allele that allows homology-directed recombination, but each contains specific flanking sequences. One parent is a synthetically altered Harvey murine sarcoma virus RNA that lacks a retroviral 3' terminus but carries a Moloney murine retrovirus-derived envelope gene (env) fragment 3' of its transforming ras gene. The other parent is intact Moloney virus. Using a Harvey-specific 5' primer and a Moloney-specific 3' primer, we have found recombinant cDNAs with the polymerase chain reaction, proving directly that retroviruses can recombine during reverse transcription unassisted by cellular enzymes, probably by template switching during cDNA synthesis. The recombinants that were obtained in vitro were identical with those obtained in parallel experiments in vivo.


Role transformation of special care unit nurses: a comparative study.
To investigate whether special care unit nurses have characteristics different from nurses who work in nonintensive care settings and whether SCU nurses make more effective role transformations than non-SCU nurses, this posthoc descriptive study utilized data from 213 new graduate nurses in their first jobs in eight medical centers across the United States. The 213 nurses were a subsample of 307 new graduate nurses in a parent study that tested effect of a bicultural orientation program in role transformation. The nurses in the subsample worked in one of four nursing areas: medical--surgical, medical--surgical specialty, parent--child, and SCU. They were pretested at six weeks of employment regarding their: professional, bureaucratic, and service role conceptions; total role deprivation; professional, bureaucratic, and bicultural role behavior; self-esteem; and degree of self-actualization. SCU nurses had significantly higher self-actualization scores initially than medical--surgical nurses. Posttesting at nine months of employment included all of the above variables plus measures of empathy and change-agent activity. Performance ratings and resignations were examined at one year of employment. Analyses of variance of the difference scores and posttest-only scores showed no significant differences by type of unit except for self-actualization. To examine the relationship between the degree of specialization and the variables under study, units were rank ordered according to degree of specialization. Nurses working on units which required the most specialization had significantly higher increases in bicultural scores and self-esteem and trends toward higher increases in bureaucratic role conception and higher performance ratings. However, SCU nurses also had the most decrease in professional role conception scores, least increase in self-actualization scores, least amount of empathy with co-workers, and least amount of effective change-agent activity--all undesirable occurrences.


Establishment of Over-The-Scope-Clips (OTSC®) in daily endoscopic routine.
Alongside the evolution of interventional endoscopy, the need for a more sophisticated closure tool tailored to the treatment of new challenging indications has been increasing rapidly. We here present our collected data on 262 Over-The-Scope-Clip (OTSC®) placements in a total of 233 interventions at our institution. Follow-up was focused on clinically lasting success with regards to different indications. Immediate success of OTSC® treatment was observed in 87.1% of all sessions (203/233). The success rates per indication were as follows: spontaneous bleeding 84.8% (28/33); iatrogenic bleeding 100% (20/20); acute perforation 90.3% (65/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 61.1% (11/18); fistulae 80.7% (46/57); diameter reduction of the gastrojejunal anastomosis 100% (6/6); and stent fixation 100% (3/3). At 30-day follow-up, the overall success rate was 67.4% (157/233). The success rates per indication were as follows: spontaneous bleeding 69.7% (23/33); iatrogenic bleeding 90% (18/20); acute perforation 86.1% (62/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 33.3% (6/18); fistulae 29.8% (17/57), diameter reduction of the gastrojejunal anastomosis 83.3% (5/6); and stent fixation 66% (2/3). Our cohort confirms previous data on the clinical usefulness of the OTSC® in daily routine practice.


A novel therapeutic with two SNAP-25 inactivating proteases shows long-lasting anti-hyperalgesic activity in a rat model of neuropathic pain.
A pressing need exists for long-acting, non-addictive medicines to treat chronic pain, a major societal burden. Botulinum neurotoxin type A (BoNT/A) complex - a potent, specific and prolonged inhibitor of neuro-exocytosis - gives some relief in several pain disorders, but not for all patients. Our study objective was to modify BoNT/A to overcome its inability to block transmitter release elicited by high [Ca2+]i and increase its limited analgesic effects. This was achieved by fusing a BoNT/A gene to that for the light chain (LC) of type/E. The resultant purified protein, LC/E-BoNT/A, entered cultured sensory neurons and, unlike BoNT/A, inhibited release of calcitonin gene-related peptide evoked by capsaicin. Western blotting revealed that this improvement could be due to a more extensive truncation by LC/E of synaptosomal-associated protein of Mr = 25 k, essential for neuro-exocytosis. When tested in a rat spared nerve injury (SNI) model, a single intra-plantar (IPL) injection of LC/E-BoNT/A alleviated for ∼2 weeks mechanical and cold hyper-sensitivities, in a dose-dependent manner. The highest non-paralytic dose (75 U/Kg, IPL) proved significantly more efficacious than BoNT/A (15 U/Kg, IPL) or repeated systemic pregabalin (10 mg/Kg, intraperitoneal), a clinically-used pain modulator. Effects of repeated or delayed injections of this fusion protein highlighted its analgesic potential. Attenuation of mechanical hyperalgesia was extended by a second administration when the effect of the first had diminished. When injected 5 weeks after injury, LC/E-BoNT/A also reversed fully-established mechanical and cold hyper-sensitivity. Thus, combining advantageous features of BoNT/E and/A yields an efficacious, locally-applied and long-acting anti-hyperalgesic.


Metabolic syndrome and health-related quality of life in patients with schizophrenia.
The association of metabolic syndrome (MetS) with health-related quality of life (HRQol) in schizophrenia is poorly documented. The relationship between MetS, HRQol and global functioning were examined. For this goal, 76 individuals with schizophrenia and schizoaffective disorder (DSM-IV criteria) were interviewed to obtain sociodemographic data, lifestyle habits, psychopathology (PANSS scale), global functioning (GAF scale), sef-reported quality of life (EQ-5D scale) and the anthropometric measures and blood test results. MetS was defined by the NCEP (2005) criteria. The prevalence of MetS was 36.8%. MetS was directly associated with personal background of dyslipidaemia and diabetes mellitus. Subjects with MetS had greater weight, BMI, waist, blood pressure, triglycerides, fasting glucose and a lower HDL-cholesterol. The MetS is also associated with age, inactive employment status and better self-care. The EQ VAS (visual analogue scale) of EQ-5D shows that subjects with MetS who practice physical activity indicates a better subjctive perception of health, which remarks the necessity of improving healthy lifestyle and an interdisciplinary treatment of the MetS. There is no association between global functioning and HRQol. This is the first study which investigates the relationship between MetS, HRQol and GAF in individuals with schizophrenia in the European context.


Ellipse fitting for interferometry. Part 2: experimental realization.
Extracting phase and amplitude information from the quadrature signals of an optical interferometer is an essential first step in any measurement. Where these signals are displayed as a Lissajous figure, the primary limitation to accuracy is determined by the goodness-of-fit to the ellipse, which is especially problematic for ellipses with high ellipticity. In a companion paper by Collett and Tee [J. Opt. Soc. Am. A31, 2573 (2014)10.1364/JOSAA.31.002573], we described a novel, linear ellipse fitting method that outperforms all previously published algorithms. Here, we demonstrate the experimental application of this algorithm to several measurement problems of practical interest.


Pneumatosis intestinalis with a benign clinical course: a report of two cases.
Pneumatosis intestinalis (PI) is a rare condition characterized by the presence of gas within the gastrointestinal tract wall. Most cases of PI have a benign clinical course, although some have serious outcomes. Mechanical stress on or bacterial infection of the gastrointestinal tract wall may be responsible for the onset of PI, but the detailed mechanism of PI pathogenesis is still unclear. Here, we describe two Japanese patients presenting with benign PI. Case 1, a 37-year-old previously healthy male patient, had a 1-week history of abdominal pain, and case 2, a 78-year-old female diabetic patient, had a 2-week history of voglibose treatment and abdominal pain. Intramural gas was mainly distributed in the colon in case 1 and in the small intestine in case 2. Interestingly, neither patient showed obvious inflammatory signs upon admission and recovered spontaneously with conservative treatment, including fasting and fluid infusion without antibiotics. Voglibose treatment was terminated in case 2. Recent studies have shown the presence of nonpathogenic bacteria, such as Clostridium spp., in PI lesions, which usually play an important role in modulating the tolerance of the gastrointestinal immune responses. The benign clinical course and spontaneous resolution of PI in these patients, without specific treatment, suggests that nonpathogenic indigenous bacteria in the gastrointestinal tract participate in the pathogenesis of PI. In patients with benign PI, the absence of an inflammatory response and the spontaneous resolution of the disease without specific treatment suggest the participation of nonpathogenic indigenous bacteria of the gastrointestinal tract.


Is bariatric surgery necessary after intragastric balloon treatment?
The use of the Bio-Enterics intra-gastric balloon (BIB) has been shown to be a safe and effective procedure for the temporary treatment of morbid obesity. We conducted a retrospective comparative analysis of the weight loss in patients that after BIB removal underwent bariatric surgery and those who did not wish surgery. From January 2000 to March 2004, 182 BIBs were positioned in 175 patients (104 F / 71 M; mean age 37.1+/-11.6 years, range 16-67; mean BMI 54.4 +/- 8.1 kg/m(2), range 39.8-79.5; mean %EW 160.8+/-32.9% range 89-264). Patients were excluded from this study who had emergency BIB removal for balloon rupture (n=2, 1.1%) and for psychological intolerance (n=7, 7.8%). All patients were scheduled for a bariatric operation, before BIB positioning. After BIB removal, a number of patients now declined surgery. Consequently, patients were allocated into 2 groups: Group A in whom BIB removal was followed by bariatric surgery (Lap-Band, laparoscopic gastric bypass, duodenal switch) (n=86); Group B patients who after BIB removal refused any surgical procedure (n=82). Both groups were followed for a minimum of 12 months. Results were reported as mean BMI and %EWL +/- SD. Statistical analysis was done by Student t-test or Fisher's exact test, with P<0.05 considered significant. Mean BMI and mean %EWL in the 166 patients at time of removal were 47.3 +/- 8.1 kg/m(2) and 32.1+/-16.6%, respectively. At the same time, mean BMI was 47.6+/-6.9 and 48.1+/-6.5 kg/m(2) in group A and B (P=NS). At 12 months follow-up (100%), mean BMI was 35.1 kg/m(2) in Group A (BIB + surgery) and 51.7 kg/m(2) in Group B (BIB alone) (P<0.001). After BIB removal, half (49.4%) of the patients scheduled for surgery refused a bariatric operation. These patients returned to their mean initial weight at 12 months follow-up. Therefore, bariatric surgery after BIB removal is highly recommended.


Effect of Climate and Competition on Radial Growth of Pinus sylvestris var. mongolica Forest in Hulunbuir Sandy Land of Inner Mongolia, China.
(1) Background: The forest of Pinus sylvestris var. mongolica is an important semi-arid ecosystem in Hulunbuir sandy land that plays a key role in the carbon cycle and wind erosion control. It is crucial to explore the main factors affecting the radial growth of trees of P. sylvestris var. mongolica. (2) Methods: The study established the tree-ring chronology of P. sylvestris var. mongolica and analyzed the relationships among the radial growth, competition index, and climate variables using correlation analysis and a linear mixed effect model to explore the influence of competition and climate on radial growth of P. sylvestris var. mongolica. (3) Results: The results indicated that tree growth is mainly affected by the maximum average temperature (Tmax) and precipitation in June and July of the current year and that tree growth significantly decreased with increasing competition pressure. Analysis of the linear mixed effect model showed that tree age, competition intensity, self-calibrating Palmer drought severity index (scPDSI) from May to July, and vapor pressure deficit (VPD) have a significant impact on radial growth. (4) Conclusions: The competition plays a dominant role in radial growth of P. sylvestris var. mongolica compared to climate factors. This study helps to understand the growth mechanism of P. sylvestris var. mongolica forests under climate change and provides a scientific basis for effective management of semi-arid forests.


Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment.
Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.


Momentum imaging spectrometer for molecular fragmentation dynamics induced by pulsed electron beam.
A momentum imaging spectrometer has been built for studying the electron impact molecular fragmentation dynamics. The setup consists of a pulsed electron gun and a time of flight system as well as a two-dimensional time and position sensitive multi-hit detector. The charged fragments with kinetic energy up to 10 eV can be detected in 4π solid angles and their three-dimensional momentum vectors can be reconstructed. The apparatus is tested by electron impact ionization of Ar and dissociative ionization of CO2. By analyzing the ion-ion coincidence spectra, the complete and incomplete Coulomb fragmentation channels for CO2(2+) and CO2(3+) are identified. The kinetic energy release (KER) and angular correlation for the two-body breakup channel CO2(2+*) → O(+) + CO(+) are reported. The peak value of total KER is found to be 6.8 eV which is consistent with the previous photoion-photoion coincidence studies, and the correlation angle of O(+) and CO(+) is also explicitly determined to be 172.5°.


Comparison of patient questionnaires and plasma assays in intentional drug overdoses.
Our aim was to explore the agreement between clinically collected information on purported drug intake and plasma data in intentional drug overdose. We included all subjects with intentional drug overdose above 15 years of age consecutively admitted to the Emergency Department of the University Hospital during 4 months. Information about drugs used and sources of this information was collected and compared to presence of drug in plasma, concerning four drugs with high toxic potential (tricyclic antidepressants, meprobamate, paracetamol and ethanol). Sensitivity, specificity, predictive positive and negative values of all sources of information pooled were assessed for each drug. 413 intentional drug overdoses were included, 66% with more than one drug. According to clinical information, 8% took tricyclic antidepressants, 11% meprobamate, 9% paracetamol and 41% ethanol. Systematic plasma assays confirmed this in 59% of cases for tricyclic antidepressants, 76% for meprobamate and ethanol, and 77% for paracetamol. Plasma concentrations were considered toxic in 28% of cases for tricyclic antidepressants, 65% for meprobamate, 43% for ethanol and never for paracetamol. Tricyclic antidepressants and meprobamate were found unexpectedly in 3%, paracetamol in 7% and ethanol in 6%. Toxic concentrations were found only with meprobamate. The risk of erroneous, clinically collected information was greater by excess (25 to 40% false positives) than by lack (3 to 7% false negatives). Thus, the consequences of erroneous, clinically collected information were probably more excess cost for the institution than medical risk for the patients. However these results found at the population level may not be true at an individual level.


Typeability of DNA in Touch Traces Deposited on Paper and Optical Data Discs.
Nucleated epithelial cells that are transferred by casual touching and handling of objects are the primary source of biological evidence that is found in high-volume crimes. Cellular material associated with touch traces usually contains low levels of DNA template making it challenging to acquire an informative profile. The main purpose of this study was to examine the efficacy of DNA typing in fingerprints deposited on optical data discs and the office paper. Latent fingerprints were made by 60 subjects of both sexes (30 males and 30 females). A highly effective DNA extraction method with QIAamp DNA Mini Kit (Qiagen) and an increased sensitivity PCR by AmpFlSTR® NGM™ Amplification Kit (Applied Biosystems) carried out at standard 30 cycles and at increased 34 cycles were used. The mean value of total DNA recovery was 0.4 ng from CDs/DVDs and 0.3 ng from the office paper. Amplification of Low Template DNA (LT-DNA) resulted in improved analytical success by increasing the number of PCR cycles from standard 30 to 34. On the other hand, the increased PCR cycles resulted in allele drop-ins showing additional peaks, the majority of which were outside the stutter positions. Rigorous procedures and interpretation guidelines are required during LT-DNA for producing reliable and reproducible DNA profiles for forensic purposes.


Inducible T7 RNA Polymerase-mediated Multigene Expression System, pMGX.
Co-expression of multiple proteins is increasingly essential for synthetic biology, studying protein-protein complexes, and characterizing and harnessing biosynthetic pathways. In this manuscript, the use of a highly effective system for the construction of multigene synthetic operons under the control of an inducible T7 RNA polymerase is described. This system allows many genes to be expressed simultaneously from one plasmid. Here, a set of four related vectors, pMGX-A, pMGX-hisA, pMGX-K, and pMGX-hisK, with either the ampicillin or kanamycin resistance selectable marker (A and K) and either possessing or lacking an N-terminal hexahistidine tag (his) are disclosed. Detailed protocols for the construction of synthetic operons using this vector system are provided along with the corresponding data, showing that a pMGX-based system containing five genes can be readily constructed and used to produce all five encoded proteins in Escherichia coli. This system and protocol enables researchers to routinely express complex multi-component modules and pathways in E. coli.


Effect on plasma cortisol level and urinary cortisol excretion, in healthy volunteers, after application of three different topical steroid ointments under occlusion.
The systemic effect of the topical glucocorticoid ointments budesonide 0.025% (Preferid), hydrocortisone-17-butyrate 0.1% (Locoid) and betamethasone-17,21-dipropionate 0.5% (Diproderm) was studied in 9 healthy volunteers. Five g ointment was applied on about 13% of the total body surface, using occlusive technique for three consecutive nights. The cortisol values in plasma and urine were measured before, during, and 3 days after applications. Although budesonide and betamethasone-17,21-dipropionate are equipotent drugs from a therapeutic point of view, the halogenated betamethasone-17,21-dipropionate caused significantly greater decrease in both plasma- and urinary cortisol levels. Between the two non-halogenated glucocorticosteroids, budesonide and hydrocortisone-17-butyrate, no significant difference was found despite the large difference in anti-inflammatory effects. The results indicate that it is possible to improve the ratio between the local therapeutic effect and the systemic activity of a glucocorticosteroid. Budesonide represents such an improvement.


Anticholinesterase effect on motor kinematic measures and brain activation in Parkinson's disease.
Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson's disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity.


An economic perspective on Malawi's medical "brain drain".
The medical "brain drain" has been described as rich countries "looting" doctors and nurses from developing countries undermining their health systems and public health. However this "brain-drain" might also be seen as a success in the training and "export" of health professionals and the benefits this provides. This paper illustrates the arguments and possible policy options by focusing on the situation in one of the poorest countries in the world, Malawi. Many see this "brain drain" of medical staff as wrong with developed countries exploiting poorer ones. The effects are considerable with Malawi facing high vacancy rates in its public health system, and with migration threatening to outstrip training despite efforts to improve pay and conditions. This shortage of staff has made it more challenging for Malawi to deliver on its Essential Health Package and to absorb new international health funding.Yet, without any policy effort Malawi has been able to demonstrate its global competitiveness in the training ("production") of skilled health professionals. Remittances from migration are a large and growing source of foreign exchange for poor countries and tend to go directly to households. Whilst the data for Malawi is limited, studies from other poor countries demonstrate the power of remittances in significantly reducing poverty. Malawi can benefit from the export of health professionals provided there is a resolution of the situation whereby the state pays for training and the benefits are gained by the individual professional working abroad. Solutions include migrating staff paying back training costs, or rich host governments remitting part of a tax (e.g. income or national insurance) to the Malawi government. These schemes would allow Malawi to scale up training of health professionals for local needs and to work abroad. There is concern about the negative impacts of the medical "brain-drain". However a closer look at the evidence for and against the medical "brain-drain" in Malawi suggests that there are potential gains in managing medical migration to produce outcomes that are beneficial to individuals, households and the country. Finally we present several policy options.


Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma.
Galectin-1 (Gal1) is a member of a highly conserved family of carbohydrate-binding proteins. It modulates innate and adaptive immune responses and fosters tumor-immune escape. Hodgkin lymphoma (HL) Reed-Sternberg cells overexpress and secrete Gal1, which selectively kills T helper (Th)1 and Th17 cells and cytotoxic T cells and promotes the immunosuppressive Th2/regulatory T-cell-predominant HL microenvironment. We developed a sandwich enzyme-linked immunosorbent assay and assessed serum Gal1 levels in 293 newly diagnosed, previously untreated patients with classical HL (cHL) enrolled in 3 risk-adapted clinical trials. Serum Gal1 levels were significantly higher in patients with cHL than in normal controls (P < .0001). Gal1 serum levels also increased with Ann Arbor stage (P = .012), areas of nodal involvement (P < .0001), and the International Prognostic Score (2-7, P = .019). We conclude that Gal1 serum levels are significantly associated with tumor burden and related clinical features in newly diagnosed cHL patients.


Ethnic minority baccalaureate nursing student academic dismissal: a description of the antecedent academic characteristics.
Dismissal for academic reasons from a baccalaureate nursing (BSN) program is a phenomenon that has rarely been discussed in the literature, and, as a result, little is known about the academic characteristics of the students who are dismissed. Presently, minority students that have been admitted to BSN programs are less likely to graduate from their respective nursing programs than White BSN students are, but whether or not ethnic minority student attrition is due to academic dismissal has not been clearly described. In addition, the antecedent academic characteristics that may identify minority BSN students at high risk for academic dismissal are not fully understood. Thus, the primary purpose of this study was to describe the academic characteristics ofa sample of minority BSN students who experienced academic dismissal. A secondary purpose was to compare ethnic minority BSN students who were dismissed with a sample of ethnic minority BSN students who were academically successful. The results revealed that ethnic minority BSN students who were dismissed for academic reasons tended to have low scholastic and nursing aptitudes, and that nursing aptitudes were higher among ethnic minority BSN students who were academically successful.


Metal-free C-H Borylation and Hydroboration of Indoles.
The C-H borylation and hydroboration reactions have emerged as promising synthetic tools to construct organoboron compounds. Organoboron compounds of N-heterocycles, particularly indole derivatives, have found widespread application in a variety of fields. As a result, considerable advancement in the area of C-H borylation and hydroboration reactions of indoles was observed in the last few decades. Among the various synthetic methods applied, the metal-free approach has received special attention. This mini-review discusses the recent progress in the area of C-H borylation and hydroboration reactions of indoles under metal-free conditions, their scope, and brief mechanistic studies.


Reflex changes in breathing pattern evoked by inhalation of wood smoke in rats.
The acute ventilatory response to inhalation of wood smoke was studied in 58 anesthetized Sprague-Dawley rats. Wood smoke (approximately 6 ml) was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, either a slowing of respiration (SR) (n = 39) or an augmented inspiration (AI) (n = 19) was elicited consistently in each rat. The SR was primarily due to a prolongation of expiratory duration, whereas the AI was characterized by a two-step inspiratory flow leading to an exceedingly large tidal volume. Both initial responses, usually accompanied by bradycardia and hypotension, were reduced by inhaling smoke at a decreased concentration. After these initial responses, a delayed tachypnea developed and reached its peak 6-10 breaths after inhalation of smoke. Both the SR and AI were completely abolished by bilateral cervical vagotomy. In contrast, the delayed tachypneic response was not prevented by vagotomy but was significantly attenuated by denervation of peripheral chemoreceptors. We conclude that the initial responses to inhalation of several tidal breaths of wood smoke are mediated through vagal bronchopulmonary afferents, whereas the delayed tachypnea may involve nonvagal mechanisms that include a stimulation of peripheral chemoreceptors.


Spontaneous bovine respiratory syncytial virus infection in goats: pathological findings.
This paper presents the results of a study of eight cases of natural bovine respiratory syncytial virus (BRSV) infection in a herd of 50 Murciana kids from a intensive goat-farm in Spain. Clinical and pathological analysis confirmed the existence of natural BRSV infection in eight kids. In two of the eight animals there was also evidence of concurrent infection with P. haemolytica A.


Protective effects of estrogen on gender-specific development of diet-induced hypertension.
Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2 replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2 replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.


Toward reliable operative assessment: the reliability and feasibility of videotaped assessment of laparoscopic technical skills.
Decision making on the competency of surgical trainees to perform laparoscopic procedures has been hampered by the lack of reliable methods to evaluate operative performance. The goal of this study was to develop a feasible and reliable method of evaluation. Twenty-nine senior surgical residents were videotaped performing a low anterior resection and a Nissen fundoplication in a pig. Ten blinded laparoscopists rated the videos independently on two scales. Rating time was minimized by allowing raters to fast-forward through the tapes at their discretion. Interrater reliability and the time required to rate a procedure were assessed. Rating time per procedure was a median of 15 min (range, 6-40). The mean interrater reliability for the two scales was 0.74. The use of videotapes of operations enabled multiple raters to assess a performance reliably and shortened assessment times by 80%. This assessment technique shows potential as a means of evaluating the performance of advanced laparoscopic procedures by surgical trainees.


Annual changes in fecal estradiol-17beta concentrations of the sun bear (Helarctos malayanus) in Sarawak, Malaysia.
Fecal estradiol concentrations were measured in three captive unmated female sun bears (Helarctos malayanus) from August 1998 to July 1999 in Sarawak, Malaysia and vaginal smears from one of the females was observed in August 1998 and March 1999. A single peak in fecal estradiol concentration was obvious for each bear in August or September 1998, and there was a much higher percentage of superficial vaginal anuclear cells in August 1998 than in March 1999. These results suggest that sun bears in Sarawak are likely to be a seasonal breeder associated with a peak of estrogen production in August or September.


Acute scrotal pain in children--ten years' experience.
Acute scrotal pain sometimes requires prompt surgical intervention and therefore accurate diagnosis of different etiologies of acute scrotal pain has great therapeutical and prognostic significance. The aim of this study was to analyze the incidence, symptomatology and results of treatment of acute scrotal pain in children. The study included patients hospitalized at the Pediatric Surgery Clinic with a diagnosis of acute scrotal pain. We retrospectively analyzed anamnestic data (age of patient and duration of anamnesis prior to admission), clinical parameters obtained during physical examination, mode of treatment (operative or medical), intraoperative findings and (postoperative) treatment. The study included 256 patients with acute scrotal pain, aged from several hours up to 17 years of age (average 9.73 years). The average duration of symptoms prior to admission was 56.74 h. Acute epididymitis was diagnosed in 110 patients (43.0%), torsion of the testicular appendage in 104 patients (40.6%), torsion of the testis in 30 patients (11.7%) and other pathologies in another 12 patients. 166 patients (64.8%) underwent surgery, 42 patients with orchiepididymitis (38.2%), 92 patients with torsion of the testicular appendage (88.5%), and 16.6% of the patients with other pathologies. 22 patients with torsion of the testis underwent surgery (73.3%), while the rest of the 8 patients underwent manual detorquation of the testis. Regardless of the etiology of the acute scrotal pain, it is of great importance that the patient seeks medical assistance promptly. It is therefore important to educate the parents and patients about the problems related to acute scrotal pain.


The potassium channel KAT1 is activated by plant and animal 14-3-3 proteins.
14-3-3 proteins modulate the plant inward rectifier K+ channel KAT1 heterologously expressed in Xenopus oocytes. Injection of recombinant plant 14-3-3 proteins into oocytes shifted the activation curve of KAT1 by +11 mV and increased the tau(on). KAT1 was also modulated by 14-3-3 proteins of Xenopus oocytes. Titration of the endogenous 14-3-3 proteins by injection of the peptide Raf 621p resulted in a strong decrease in KAT1 current (approximately 70% at -150 mV). The mutation K56E performed on plant protein 14-3-3 in a highly conserved recognition site prevented channel activation. Because the maximal conductance of KAT1 was unaffected by 14-3-3, we can exclude that they act by increasing the number of channels, thus ruling out any effect of these proteins on channel trafficking and/or insertion into the oocyte membrane. 14-3-3 proteins also increased KAT1 current in inside-out patches, suggesting a direct interaction with the channel. Direct interaction was confirmed by overlay experiments with radioactive 14-3-3 on oocyte membranes expressing KAT1.


Paying people to participate in research: why not? A response to Wilkinson and Moore.
This paper argues against paying people to participate in research. Volunteering to participate as a subject in a research program is not like taking a job. The main difference is to do with the risks inherent in research. Experimentation on human beings is, by definition, trying out something with an unknown consequence and exposes people to risks of harm which cannot be known in advance. This is the main reason for independent review by committee of research programs. It is based on a recognition that researchers are not always capable of putting the interests of their subjects ahead of their research objectives. It is not simply a matter of individual autonomy. Society has an obligation, prior to the protection of individual freedom and autonomy, to establish basic safeguards that are equitable in their operation. Any inducement for participating in research would add to the difficulty subjects have in adequately assessing the risks of participating in research. An acceptance of inducement to participate in research would further increase the inequity of research conducted on the impecunious for the benefit of the well-off.


Machine Learning Analysis of Immune Cells for Diagnosis and Prognosis of Cutaneous Melanoma.
Tumor infiltration, known to associate with various cancer initiations and progressions, is a promising therapeutic target for aggressive cutaneous melanoma. Then, the relative infiltration of 24 kinds of immune cells in melanoma was assessed by a single sample gene set enrichment analysis (ssGSEA) program from a public database. The multiple machine learning algorithms were applied to evaluate the efficiency of immune cells in diagnosing and predicting the prognosis of melanoma. In comparison with the expression of immune cell in tumor and normal control, we built the immune diagnostic models in training dataset, which can accurately classify melanoma patients from normal (LR AUC = 0.965, RF AUC = 0.99, SVM AUC = 0.963, LASSO AUC = 0.964, and NNET AUC = 0.989). These diagnostic models were also validated in three outside datasets and suggested over 90% AUC to distinguish melanomas from normal patients. Moreover, we also developed a robust immune cell biomarker that could estimate the prognosis of melanoma. This biomarker was also further validated in internal and external datasets. Following that, we created a nomogram with a composition of risk score and clinical parameters, which had high accuracies in predicting survival over three and five years. The nomogram's decision curve revealed a bigger net benefit than the tumor stage. Furthermore, a risk score system was used to categorize melanoma patients into high- and low-risk subgroups. The high-risk group has a significantly lower life expectancy than the low-risk subgroup. Finally, we observed that complement, epithelial-mesenchymal transition, and inflammatory response were significantly activated in the high-risk group. Therefore, the findings provide new insights for understanding the tumor infiltration relevant to clinical applications as a diagnostic or prognostic biomarker for melanoma.


Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.
Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.


Incidence and sites of bone lesions detected by 99mTc-polyphosphate scans in patients with tumors.
The value of bone scanning with 99mTc-polyphosphate was assessed in 186 patients with various types of tumors. The sensitivity of this technique was greater than that of metastatic roentgenographic series and the reported results of 85-Sr-bone scans, in the detection of osseous involvement by tumors. Three cases with normal bone scans and abnormal roentgenographic studies illustrated the necessity and complementary value of comparing bone scan findings with radiographic studies. Patients with carcinoma of the breast, lung, or prostate displayed characteristic patterns of bone involvement by their tumors. The importance of clinical information, including bone symptoms, antecedent bone disease, and serum calcium and alkaline phosphatase, was stressed in the detection and interpretation of bone scan abnormalities.


Case report: A case of ocular infection caused by Corynespora cassiicola.
The aim of this study is to identify the pathogen causing ocular infection in a Chinese patient and to describe its morphological characteristics. Samples from the patient's intraoperative pus were collected for microscopic examination and culture. Morphology and drug sensitivities of the isolated fungus were analyzed. Ribosomal DNA (rDNA) sequencing was performed and blasted in GenBank. A strain of fungi was repeatedly isolated from pus samples in different types of medium. No conidia were shown when the isolate cultured on normal PDA medium, whereas pseudoseptate thick-walled conidia were shown when cultured on medium containing leaf leachate. The results of BLAST and phylogenetic trees based on internal transcribed spacer, beta-tubulin, translation elongation factor 1-alpha, and RNA polymerase II gene demonstrated that the isolated fungus was Corynespora cassiicola. Minimum inhibitory concentration results of this organism were as follows: anidulafungin, 0.06 μg/ml; amphotericin B, 0.12 μg/ml; micafungin, 0.06 μg/ml; caspofungin, 0.5 μg/ml; 5-fluorocytosine, >64 μg/ml; posaconazole, 2 μg/ml; voriconazole, 0.25 μg/ml; itraconazole, 0.5 μg/ml; fluconazole, 64 μg/ml. The case was infected with Corynespora cassiicola and led to eye suppurative endophthalmitis and blindness. Combined applications of morphological and molecular biology techniques facilitate accurate diagnosis of fungal infections.


Diffusion-limited aggregation in channel geometry.
We performed extensive numerical simulation of diffusion-limited aggregation in two-dimensional channel geometry. Contrary to earlier claims, the measured fractal dimension D=1.712+/-0.002 and its leading correction to scaling are the same as in the radial case. The average cluster, defined as the average conformal map, is similar but not identical to Saffman-Taylor fingers.


Some features of DNA-tRNA hybrids in the rat.
1. Sequences complementary to rRNA in rat DNA amount to 0.04% which corresponds to about 300 rRNA genes per haploid genome. 2. Purified DNA-rRNA hybrids had a DNA: rRNA weight ratio of about 1.1:1. Their melting temperature estimated on hydroxyapatite column was 75-80 degrees C. In CsCl gradients hybrids banded at 1.728 g/cm3 as compared to 1.699 g/cm3 for bulk DNA. 3. Length distribution histogram of DNA-rRNA hybrid molecules visualized by electron microscopy revealed that most of them possessed a length of 0.2-0.5 mum which corresponds to 4 X 10(5)-1 X 10(6) daltons, i.e. 670-1600 nucleotide pairs. 4. DNA sequences complementary to rRNA are localized on the heavy shoulder of the main band at a CsCl density of 1.709 g/cm3, and in a DNA fraction which re-associates at a Cot=10(-1)-10(2).


Histopathologic Characteristics of Upper Tract Urothelial Carcinoma With an Emphasis on Their Effect on Cancer Survival: A Single-Institute Experience With 305 Patients With Long-Term Follow-Up.
Tumor stage and grade represent the best established predictors for the prognosis of upper tract urothelial carcinoma (UTUC). However, controversies still exist regarding the role of tumor necrosis, location, and multifocality in the prognosis of UTUC. We share our experience with 305 patients, reporting on the pathologic features in detail, cancer characteristics, and survival. We retrospectively reviewed the data from patients who had undergone surgery for UTUC from 1983 to 2013. The tumors were staged according to the 1997 TNM classification and the 3-tiered World Health Organization grading system. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. A total of 305 patients were eligible for analysis. The 5-year CSS for grade 1, 2, and 3 was 88%, 84%, and 60%, respectively. The CSS for stage pT1, T2, T3, and T4 was 82%, 70%, 62%, and 0%, respectively. On univariate analysis, tumor stage, tumor grade, positive lymph node status, and micropapillary invasion had adverse effects on survival (P = .006, P = .045, P = .01, and P = .005, respectively). On multivariate analysis, only stage and micropapillary variant maintained significance (P = .01). Multicentricity and tumor location affected CSS in the early follow-up period but did not in the late follow-up period. Neither carcinoma in situ nor adverse pathologic variants affected survival. The tumor stage and presence of a micropapillary variant are of paramount prognostic significance for survival in patients with UTUC. The tumor grade and lymph node status are also good predictors. In our series, multifocality and tumor location affected early and mid-term survival with no significant effects on late survival.


Trauma Data Quality Improvement: One Center's Experience With Telecommuting and Paperless Data Management.
The American College of Surgeons requires that trauma centers collect and enter data into the National Trauma Data Registry in compliance with the National Trauma Data Standard. ProMedica supports employment of 4 trauma data analysts who are responsible for entering information in a timely manner, validating the data, and analyzing data to evaluate established benchmarks and support the performance improvement and patient safety process. Historically, these analysts were located on-site at ProMedica Toledo Hospital. In 2017, a proposal was developed including modifications to data collection to streamline processes, move toward paperless documentation, and allow for the analysts to telecommute. To measure the effect of these changes, the timeliness of data entry, rate of data validation, productivity, and staff satisfaction were measured. After the transition to electronic data management and home-based workstations, registry data were being entered within 30 days and 100% of cases were being validated, without sacrificing effective and efficient communication between in-hospital and home-based staff. The institution also benefitted from reduced expense for physical space, employee turnover, and decreased employee absenteeism. The analysts appreciated benefits related to time, travel, environment, and job satisfaction.It is feasible to transition trauma data analysts to a work-from-home situation. An all-electronic system of data management and communication makes such an arrangement possible and sustainable. This quality improvement project solved a workspace issue and was beneficial to the trauma program overall, with the timeliness and validation of data entry vastly improved.


The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.
We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.