Dynamics of curved DNA molecules: prediction and experiment.
We have developed a quantitative predictive model capable of describing the dynamics of migration of intrinsically curved DNA fragments on polyacrylamide gels. The model takes into account structural features of DNA, end-to-end distance, screening of hydrodynamic interactions, ionic strength of buffer, electrostatic persistence length, structural fluctuations of the macromolecule, counter condensation, and variation of dielectric constant and viscosity of water with MPD. In doing so, we have also addressed a decade old issue on the effect of the organic solvent 2-methyl-2,4-pentanediol on gel migration of phased A-tracts. We show here that A-tract-solvent interactions are less favored compared with A-tract-A-tract and solvent-solvent interactions.


Lobular carcinoma in situ in a 15-year-old girl: a case report and review of the literature.
Lobular carcinoma in situ is a clinically occult lesion associated with subsequent development of invasive breast cancer in up to one-third of patients. Lobular carcinoma in situ may be viewed as a marker lesion indicating an increased risk for development of subsequent invasive disease in either breast. Regardless of patient age or diagnosis, excised breast tissue merits thorough pathologic examination. If lobular carcinoma in situ is identified, a thorough search for areas of invasion is warranted. Treatment options are based on the associated risk of invasive carcinoma. Thorough counseling of patients regarding risks and benefits of surgical and nonsurgical treatment options is essential, with marked emphasis on the need for continued lifelong surveillance of unexcised breast tissue.


Experimental demonstration of a flexible time-domain quantum channel.
We present an experimental realization of a flexible quantum channel where the Hilbert space dimensionality can be controlled electronically. Using electro-optical modulators (EOM) and narrow-band optical filters, quantum information is encoded and decoded in the temporal degrees of freedom of photons from a long-coherence-time single-photon source. Our results demonstrate the feasibility of a generic scheme for encoding and transmitting multidimensional quantum information over the existing fiber-optical telecommunications infrastructure.


Review of penile prosthetic reservoir: complications and presentation of a modified reservoir placement technique.
Multiple modifications have been made to the inflatable penile prosthesis (IPP) since its inception in the 1970s. These modifications have made reservoir-related mechanical malfunctions highly unlikely in current IPP models. Although these complications are rare, it would be incumbent upon the implanting surgeon to be aware of these potential complications, how they present, how they are best treated, and how to prevent them from occurring. The aim of this article was to present our experience with complications associated with penile prosthesis reservoirs, perform a review of the literature regarding reservoir-related complications, and present our modified technique to place the reservoir into the space of Retzius. Reservoir-related complications including inguinal herniation, erosion into bladder or bowel, intraperitoneal reservoir placement with subsequent visceral injury, vascular injury, autoinflation, and infection. We retrospectively reviewed our experience with penile prosthesis reservoir complications or procedures requiring an alternative implantation approach at our center over the past 10 years where over 400 devices were implanted. We also review reservoir-related complications published in the English literature since the 1980s. While exceedingly rare, reservoir complications do occur. Six cases from our institution are presented including one reservoir herniation, one postoperative direct inguinal hernia, one bladder laceration during revision surgery, one ectopic reservoir placement due to morbid obesity, one iliac vein compression syndrome, and one vascular laceration during reservoir revision. Reported reservoir complications include inguinal herniation, erosion into the bladder or bowel, intraperitoneal reservoir placement with subsequent injury to the ureter or bowel, vascular injury, autoinflation, and infection. Penile prosthesis reservoirs rarely fail mechanically but are associated with a variety of complications or may require alternate implantation technique. In our experience, the Jorgensen scissors technique allows safe entry into the space of Retzius with diminished risk of hernia as well as vascular, bladder, or bowel injury.


Anthrax: is there a risk of cross-infection during endoscopy?
Bacillus anthracis is a large, gram-positive, spore-forming bacterium responsible for human anthrax. Review of the medical literature indicates specific instrument reprocessing instructions addressing the prevention of B. anthracis transmission are limited. Although nosocomial anthrax infection has not been reported, strict adherence to well-established instrument reprocessing guidelines for cleaning and high-level disinfection is recommended to prevent patient-to-patient transmission of B. anthracis (or any other pathogen) via gastrointestinal endoscopes or bronchoscopes. All liquid chemical sterilants labeled for high-level disinfection of endoscopes would be expected to destroy B. anthracis. Additional instrument cleaning or disinfection procedures appear to be unnecessary. Reprocessing the endoscope immediately following the procedure is emphasized.


Characterization of polymers of adenosine diphosphate ribose generated in vitro and in vivo.
Methods have been developed and applied to determine the size and branching frequency of polymers of ADP-ribose synthesized in nucleotide-permeable cultured mouse cells and in intact cultured cells. Polymers were purified by affinity chromatography with a boronate resin and were fractionated according to size molecular sieve high-performance liquid chromatography. Fractions were enzymatically digested to nucleotides, which were separated by strong anion exchange high-performance liquid chromatography. From these data, average polymer size and branching frequency were calculated. A wide range of polymer sizes was observed. Polymers as large as 190 residues with at least five points of branching per molecule were generated in vitro. Polymers of up to 67 residues containing up to two points of branching per molecule were isolated from intact cells following treatment with the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Cells treated with hyperthermia prior to DNA damage contained polymers of an average maximum size of 244 residues containing up to six points of branching per molecule. The detection of large polymers of ADP-ribose in intact cells suggests that alterations in chromatin organization effected by poly(ADP-ribosylation) may extend beyond the covalently modified proteins and very likely involve noncovalent interactions of poly(ADP-ribose) with other components of chromatin.


Detection of late-onset adrenal hyperplasia in girls with peripubertal virilization.
We investigated the value of serum levels of adrenal steroids (dehydroepiandrosterone sulphate, testosterone, 17-hydroxyprogesterone, cortisol) in the identification in peripubertal females with late-onset congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Among 68 females (age 3-18 years) with virilization in childhood, peripubertally or postpubertally, we selected 21 girls for an ACTH test by measurement of basal blood-spot or serum 17-hydroxyprogesterone (17-OHP) levels. Eight of 21 patients had supranormal post-ACTH serum 17-OHP concentration (57-153 nmol/l) with low normal cortisol concentration. All of them had supranormal basal and post-ACTH 17-OHP to cortisol ratios. These data show a relatively high incidence (about 12%) of mild 21-hydroxylase deficiency among prepubertal and adolescent girls with virilization. It is concluded that the first step in the investigation of peripubertally virilized girls should be the determination of serum 17-OHP and cortisol. Patients with basal morning 17-OHP concentration and 17-OHP to cortisol ratio above reference range should be given an ACTH test.


[Analysis of clinical guidelines for oro-maxillofacial cone-beam CT].
Oro-maxillofacial cone-beam CT (CBCT) is the most widely used three-dimensional imaging method in the field of oral and maxillofacial radiology. It has been widely used in China, while radiation safety, examination indications and other issues still lack comprehensive regulations and standards. Over the years, clinical guidelines and position statements for the rational use of CBCT examinations have been issued in the world, providing standardized instructions for local practitioners. This paper reviewed these guidelines to provide reference for the formulation of relevant guidelines in China.


The potential contribution of social science to information technology implementation in healthcare.
Information technology systems in hospitals and other healthcare settings have sometimes proved difficult to implement successfully. Some of the problems encountered in the implementation of information technology systems in healthcare can be explained by the use of techniques and theoretical approaches derived from the social sciences, notably sociology and anthropology. Research from a variety of countries and healthcare systems confirms the explicative value of these techniques and approaches. These techniques can also be used to inform better the process of design and implementation of computer systems. Although they have been successfully applied in several industries and spread across several countries, these techniques have not yet been widely used in healthcare. This article suggests how these approaches can be fruitfully applied to the design and implementation of IT systems in healthcare and how this might be achieved.


Risk factors for Clostridium difficile infection in HIV-infected patients.
Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients. A retrospective, propensity score-matched case-control study design was employed, with patients selected from our institution's outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count. The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49-48.8, p < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81-8.94, p < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31-175.9, p = .021). As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies.


Evaluation of increases in stature, upper extremity length and hand length in children from school age to the cessation of growth in Ogi County, Japan: a longitudinal study.
Stature, upper extremity length (UEL) and hand length (HL) were measured once yearly in children (171 males and 180 females) in Ogi County, Saga, Japan, from the 1 st grade of primary school (6.5 years of age) for 12 years. Based on the age of growth cessation, the order of growth cessation of stature, UEL and HL was investigated, in addition to the relationship between this order and the measurements obtained at 6.5 years of age. With regard to the order of growth cessation of stature and UEL, growth cessation of UEL occurred earlier than that of stature in 73.68% of males and 71.67% of females, growth cessation occurred simultaneously in 23.98% of males and 25.56% of females, and growth cessation of UEL occurred later than that of stature in 2.34% of males and 2.78% of females. According, growth cessation of UEL occurred earlier than that of stature in most subjects. In males, no significant differences were observed between subjects in whom growth cessation of UEL and HL occurred simultaneously and those in whom growth cessation of UEL occurred later than that of HL. However, in females, significant differences were noted, since the latter case was observed 1.69 times more frequently than the former. Nevertheless, growth cessation of stature, UEL and HL occurred at almost the same age in both males and females when cross-sectional data was used for processing, in agreement with data reported by other researchers. We also investigated whether there was any relationship between stature and UEL at initial examination and the order of growth cessation. No significant relationship was observed. Each measured value at initial examination tended to be large in subjects in whom growth cessation of stature and UEL occurred earlier. In addition, final stature was significantly taller in both males and females in whom growth cessation of stature occurred later compared to those in whom growth cessation occurred earlier.


Covering surgical instruments with single- or double-layer drape pending surgery: an experimental study in a perioperative setting.
Surgical site infections (SSI) constitute a severe threat to surgery patients. The surgical environment must be as free of contaminating microorganisms as possible. Using sterile surgical instruments while performing surgery is an absolute necessity for ensuring quality of care in perioperative settings. To compare bacterial contamination of agar plates after 15 h on set surgical instrument tables covered with a single- or double-layer drape. An experimental design was used consisting of set instrument tables with six agar plates on each table: four instrument tables were covered with a single-layer drape and four instrument tables were covered with a double-layer drape. This set-up was repeated on nine occasions during the period of data collection, making 76 set instrument tables in total. As a control, one instrument table was uncovered on four of those occasions. The double-layer drape cover showed a significantly (P = 0.03) lower number of colony forming units (CFU) per agar plate than the single-layer drape covering. As expected, the uncovered instrument tables were highly contaminated. Our results indicate that it is good practice to cover instruments properly with at least a single-layer drape before a surgical procedure. If there is difficulty achieving optimal conditions while setting the instrument tables (e.g. positioning the patient for general anaesthesia), it is a better option to set the instrument tables earlier and cover them with a double-layer drape. These precautions will help protect the patient from harm and unnecessary SSI by lowering microbiological burden, a key factor in developing SSI.


Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study.
Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO(2) histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy.


Age-related decline in white matter tract integrity and cognitive performance: a DTI tractography and structural equation modeling study.
Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.


Effect of microsomal enzyme inducing agents on hepatic biotransformation in cotton rats (Sigmodon hispidus): comparison to that in Sprague-Dawley rats.
1. Activities of several biotransformation enzymes were determined in male and female Sigmodon hispidus. Benzphetamine N-demethylase and glutathione S-transferases toward 1-chloro-2,4-dinitrobenzene and sulfobromophthalein were higher in male Sigmodon hispidus than the female animals. 2. The study also determined the effect of microsomal enzyme inducing agents on hepatic biotransformation in male Sigmodon hispidus. 3. Cytochrome P-450 concentration was similar in cotton and Sprague-Dawley rats, and was increased after phenobarbital, pregnenolone-16 alpha-carbonitrile, or 3-methylcholanthrene treatment. 4. Benzphetamine N-demethylase was 4-fold higher in Sigmodon hispidus and was induced by 75-100% after phenobarbital. 5. UDP-Glucuronosyltransferase toward estrone, 1-naphthol, diethylstilbestrol and testosterone was 2- to 4-fold higher in cotton rats and was not altered by treatment with the inducing agents. 6. Conjugation of 1-chloro-2,4-dinitrobenzene, ethacrynic acid and sulfobromophthalein with glutathione was similar in both rodent species and was not inducible. 7. Sulfation of 2-naphthol was 15-30% of that in Sprague-Dawley rats and was not increased by inducer administration.


Resistance of Castanea mollissima Shuhe-WYL strain to Dryocosmus kuriphilus and its molecular mechanism.
The resistance of Castanea mollissima Shuhe-WYL strain to Dryocosmus kuriphilus and its molecular mechanism were examined. The larvae of D. kuriphilus were inoculated on the Shuhe-WYL and Qingzha strains, and mortality was observed and compared; the relative mRNA content of the OsCDPK2, receptor-like protein, OsNAC6 protein, KH domain protein, RNA-binding protein, and the bHLH genes was detected using real-time polymerase chain reaction, and then compared between the Shuhe-WYL and Qingzha strains. Phenylalanine ammonia-lyase content was detected by western blotting and compared between the inoculated Shuhe-WYL, non-inoculated Shuhe-WYL, and inoculated Qingzha strains. The mortalities of larvae inoculated on the bud, bracteal leaf, and cardiac lobe were lower in Shuhe-WYL than Qingzha at 48 and 96 h after inoculation; the contents of OsCDPK2, receptor-like protein, OsNAC6 protein, and bHLH in the cardiac lobe were higher in Shuhe-WYL than in Qingzha at 96 h after inoculation, but KH domain protein and RNA-binding protein were not significantly different. The content of phenylalanine ammonia-lyase in the cardiac lobe was higher in inoculated and non-inoculated Shuhe-WYL compared to inoculated Qingzha at 15, 30, 45, and 60 days, and higher in inoculated Shuhe-WYL than in non-inoculated Shuhe-WYL at 15, 30, 45, and 60 days. The content of phenylalanine ammonia-lyase in the cardiac lobe of inoculated Shuhe-WYL had no significant difference between at 60 and at 45 days; and was higher at 60 and 45 days than at 30 and 15 days; and was higher at 30 days than at 15 days (60≈45˃30˃15 days). The C. mollissima Shuhe-WYL strain was resistant to D. kuriphilus; high expression of OsCDPK2, receptor-like protein, OsNAC6 protein, and bHLH and phenylalanine ammonia-lyase may explain the mechanism.


Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.
Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32-0.41; P=0.0009-0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of germline biomarkers in predicting acute graft-versus-host disease. Further investigations are warranted to improve our understanding of these relationships to personalize immunosuppressive therapy and optimize outcomes.


Reply to comment on "Auditory-nerve first-spike latency and auditory absolute threshold: a computer model".
Krisha [J. Acoust. Soc. Am., in press (2006)] has commented that an explanation based on presynaptic calcium accumulation at the inner hair cell is an incorrect explanation for the success of a model of the auditory periphery [Meddis, R., J. Acoustic. Soc. Am. 119, 406-417 (2006)] in explaining data on first-spike auditory nerve latency. This reply accepts the criticism and accepts the strength of an alternative explanation based on expected latencies in random sequences of low-probability events. This reply also goes on briefly to explore the application of this argument to other phenomena, including the dependence of absolute auditory threshold on the duration of the stimulus. This has wide-ranging implications for the concept of "temporal integration" in psychophysics.


Interleukin 1 in rheumatoid arthritis: potentiation of immune responses within the joint.
Specific immunoassays were used to measure IL-1 peptides in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and in the serum of age-matched healthy controls. Patients with RA had raised levels of both IL-1 beta and IL-1 alpha in their sera compared to controls. Synovial fluid levels of IL-1 beta significantly correlated with immunoreactive IL-2 and soluble IL-2 receptor (sIL-2R). In addition, incubation of synovial fluid MNC with human recombinant (hr) IL-1 caused a dose-dependent increase in the level of sIL-2R in the cell supernatant. Finally, production of IL-1 beta and IL-6 from RA peripheral blood (PB) and synovial fluid (SF) MNC was examined. PBMNC spontaneously produced low levels of IL-1 beta and IL-6 that were augmented by the addition of hr IL-1 alpha. In contrast, SFMNC spontaneously produced high levels of IL-1 beta but only low levels of IL-6, again this production was augmented by the addition of hr IL-1 alpha. Taken together, the data suggests that IL-1 potentiates immune responses within the joint.


Effect of cycloheximide on in vitro development of electrically activated feline oocytes.
This study was conducted to improve parthenogenetic development in vitro of feline oocytes following a combined activation treatment of electrical stimulation and cycloheximide. In vitro matured (IVM) oocytes were stimulated electrically by a DC electrical pulse of 2 kV/cm for 50 micros. The stimulated oocytes were then incubated in MK-1 medium with or without cycloheximide and subsequently cultured in vitro for 6 days. No significant differences were observed between the two groups with respect to the proportions of cleavage, development to the morula stage, and the cell number of blastocysts. However, exposure of electrically stimulated oocytes to cycloheximide significantly increased the rate of development of the stimulated oocytes into the blastocyst stage compared with oocytes stimulated by electrical stimulation alone (31.0% vs 6.7%). The results from the present study suggested that a single electrical stimulation was insufficient to activate the IVM cat oocytes at 24 h of maturation and that exposure to cycloheximide following electrical stimulation improved the efficacy of the parthenogenetic development of domestic cat oocytes.


Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.
Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Here, we review the extensive preclinical and clinical development of anti-GD2 mAbs and the different mechanisms by which they mediate tumor cell killing. In addition, we discuss different mAb-based strategies that capitalize on the targeting ability of anti-GD2 mAbs to potentially deliver, as monotherapy, or in combination with other treatments, improved antitumor efficacy.


Medical education in palliative care.
There has been recent concern about both the care of dying patients and the adequacy of the preparation that most doctors receive for this task. The role of the doctor in palliative care is discussed and the educational needs of medical students in palliative care are suggested. A palliative care course for fifth-year students at the Austin Hospital-Repatriation General Hospital Clinical School, University of Melbourne, is described. This course recently has been adopted by the Victorian Palliative Care Council as a model for undergraduate palliative medicine education, and has been recommended to the University of Melbourne and Monash University Medical Schools for incorporation in each Clinical School curriculum.


Plasma N-terminal pro-brain natriuretic peptide as a marker of right ventricular dysfunction in patients with tetralogy of Fallot after surgical repair.
Chronic heart failure is associated with neurohormonal activation that is not only related to outcome but is also a therapeutic target. We have attempted to demonstrate whether a similar pattern of neurohormonal activation exists in adult congenital heart disease (ACHD) and, if so, whether it relates to disease severity determined by cardiopulmonary exercise testing. Concentrations of N-terminal pro-atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin (ET)-1, renin, aldosterone, adrenalin, and noradrenalin were determined in 50 adults (mean age, 27.8 +/- 1.7 years [+/- SEM]; 26 women) with tetralogy of Fallot (TOF) after surgical repair (New York Heart Association functional class 1.1 +/- 0.1). One hundred age- and sex-matched healthy blood donors served as a control group for NT-proBNP determination. Dimensions of ventricles, left ventricular pump function, and estimated right ventricular (RV) systolic pressure were determined by echocardiography. Maximum oxygen uptake (V(O2max) was measured in all patients using spiroergometry. TOF patients had elevated levels of NT-proBNP compared with healthy individuals: NT-proBNP (women: 180 pg/mL vs 43 pg/mL, and men: 147 pg/mL vs 32 pg/mL; p < 0.0001) and ET-1 (2.5 fmol/L vs 0.7 fmol/L). There was a significant correlation of NT-proBNP to dimension and estimated peak systolic pressure of the RV as well as impairment of V(O2max). RV dysfunction detected by echocardiography and plasma NT-proBNP determination in asymptomatic or minimally symptomatic TOF patients correlates well with their cardiopulmonary exercise capacity. Thus, these simple and noninvasive screening methods can be used additionally to stratify ACHD patients with impaired cardiac function before they become clinically symptomatic.


[Effect of chinese herbs in enhancing prednisone for treatment of refractory rheumatoid arthritis].
To investigate the Chinese herbal medicine in enhancing effect of prednisone for treatment of refractory rheumatoid arthritis (RA). One hundred and twenty patients with refraetory RA were assigned to two groups, the treated group was orally administered with Qingbi Tablet, a patent Chinese herbal preparation formulated based on the clearing heat and removing toxic substances principle, and the control group was treated with intramuscular injection of amethopterin (MTX), oral intake of voltaren 75 mg and hydroxychloroquine 0.2 g once a day. Besides prednisone was given to all patients orally, the initiating dosage used in the treated group was lesser than that in the control group. The clinical index, dosage and adverse reaction of prednisone were recorded every 2 weeks. The curative effect evaluated by American College of Rheumatology (ACR) standard showed no statistical difference between the two groups (P > 0.05). Either clinical or laboratory indexes were improved significantly in both groups (P < 0.05), but the improvement in resting pain, patient's self-evaluation and doctor's evaluation in the treated group were better than those in the control group, showing statistical difference (P < 0.05). The 20-week total amount of prednisone used in the treated group was less than that in the control group (32,935 mg vs. 51,170 mg), while the dosage of prednisone used in various observation time points between the two groups was also significantly different respectively (P < 0.05), the former was less than the latter. Chinese herbal medicine can enhance the effect of prednisone in patients of refractory RA and alleviate the adverse reactions of prednisone.


The conserved and non-conserved regions of Rpb4 are involved in multiple phenotypes in Saccharomyces cerevisiae.
Rpb4, the fourth largest subunit of RNA polymerase II in Saccharomyces cerevisiae, is required for many phenotypes, including growth at high and low temperatures, sporulation, pseudohyphal growth, activated transcription of a subset of genes, and efficient carbon and energy metabolism. We have used deletion analysis to delineate the domains of the protein involved in these multiple phenotypes. The scRpb4 protein is conserved at the N and C termini but possesses certain non-conserved regions in the central portion. Our deletion analysis and molecular modeling results show that the N- and C-terminal conserved regions of Rpb4 are involved in interaction with Rpb7, the Rpb4 interacting partner in the RNA polymerase II. We further show that the conserved N terminus is required for efficient activated transcription from the INO1 promoter but not the GAL10- or the HSE-containing promoters. The N terminus is not required for any of the stress responses tested: growth at high temperatures, sporulation, and pseudohyphal growth. The conserved C-terminal 23 amino acids are not required for the role of Rpb4 in the pseudohyphal growth phenotype but might play a role in other stress responses and activated transcription. From the deletion analysis of the non-conserved regions, we report that they influence phenotypes involving both the N and C termini (interaction with Rpb7 and transcription from the INO1 promoter) but not any of the stress-responsive phenotypes tested suggesting that they might be involved in maintaining the two conserved domains in an appropriate conformation for interaction with Rpb7 and other proteins. Taken together, our results allow us to assign phenotype-specific roles for the different conserved and non-conserved regions of Rpb4.


Effect of upper and lower extremity control strategies on predicted injury risk during simulated forward falls: a study in healthy young adults.
Fall-related wrist fractures are common at any age. We used a seven-link, sagittally symmetric, biomechanical model to test the hypothesis that systematically alterations in the configuration of the body during a forward fall from standing height can significantly influence the impact force on the wrists. Movement of each joint was accomplished by a pair of agonist and antagonist joint muscle torque actuators with assigned torque-angle, torque-velocity, and neuromuscular latency properties. Proportional-derivative joint controllers were used to achieve desired target body segment configurations in the pre- andor postground contact phases of the fall. Outcome measures included wrist impact forces and whole-body kinetic energy at impact in the best, and worst, case impact injury risk scenarios. The results showed that peak wrist impact force ranged from less than 1 kN to more than 2.5 kN, reflecting a fourfold difference in whole-body kinetic energy at impact (from less than 40 J to more than 160 J) over the range of precontact hip and knee joint angles used at impact. A reduction in the whole-body kinetic energy at impact was primarily associated with increasing negative work associated with hip flexion. Altering upper extremity configuration prior to impact significantly reduced the peak wrist impact force by up to 58% (from 919 N to 2212 N). Increased peak wrist impact forces associated greater shoulder flexion and less elbow flexion. Increasing postcontact arm retraction can reduce the peak wrist impact force by 28% (from 1491 N to 1078 N), but postcontact hip and knee rotations had a relatively small effect on the peak wrist impact force (8% reduction; from 1411 N to 1303 N). In summary, the choice of the joint control strategy during a forward fall can significantly affect the risk of wrist injury. The most effective strategy was to increase the negative work during hip flexion in order to dissipate kinetic energy thereby reducing the loss in potential energy prior to first impact. Extended hip or elbow configurations should be avoided in order to reduce forearm impact forces.


Effect of needle gauge on pain and specimen quality of ultrasound-guided fine needle sampling without aspiration of the canine spleen.
Modifications of splenic parenchyma are common ultrasonographic findings in dogs. Splenic fine needle aspiration (FNA) is a rapid, safe procedure, routinely performed in veterinary institutions. However, 22-gauge (G) needle usually reported is selected according to general practice and the most appropriate needle size to be used remains unclear. The aim of this prospective, single-center, methods comparison study was to assess the effect of needle size on cytologic specimens' evaluation and animal welfare during the procedure. Dogs underwent ultrasound-guided splenic FNA using 23, 25, and 27G needles. Needles were compared based on initial and then detailed cytologic evaluation. The initial evaluation assessed overall cellularity, cell preservation, hemodilution, and detailed cytologic evaluation referred to exhaustive splenic components. Welfare evaluation was performed based on a scoring system. A total of 54 dogs were included in this study with 54 of 54 welfare evaluations and 35 of 54 cytologic evaluations by one or two European College of Veterinary Clinical Pathology-certified cytologists. The final cytologic diagnosis was unchanged regardless of the needle size. For the initial evaluation, 23G needles provided significantly higher cellularity than the 27G needles. For detailed cytologic evaluation, only the richness in mesothelial cells and stroma was affected by needle size. Pain induced by the procedures was considered low using 23, 25, and 27G needles with the 27G needle producing the least adverse reactions. Findings from the current study supported using needle gauges smaller than the previously published standard 22G needle for spleen ultrasound-guided fine needle nonaspiration in dogs. Due to higher cellularity and lower pain scores, authors recommend the use of 23G needles with a nonaspiration technique.


The role of GabaA receptors in the neural systems of the ventromedial hypothalamus-nucleus infundibular region in the control of GnRH release in ewes during follicular phase.
To examine the role of the GABAA receptor mediating systems in the control of gonadotropin releasing hormone (GnRH) release from the ventromedial-infundibular region (VEN/NI) of the hypothalamus of ewes during the follicular phase of the estrous cycle, the extracellular concentrations of GnRH, beta-endorphin (B-END), noradrenaline (NE), dopamine (DA), and their metabolites MHPG, DOPAC and concentration of luteinizing hormone (LH) in blood plasma were quantified during local stimulation or blockade of GABAA receptors with muscimol and bicuculline, respectively. Stimulation of GABAA receptors attenuated GnRH and LH release, increased beta-endorphin outflow and dopaminergic activity but had no evident effect on noradrenergic activity. Blockade of GABAA receptors decreased beta-endorphin release but had no evident effect on the extracellular concentration of GnRH, LH levels in the blood and catecholaminergic activity. It is suggested that suppression of GnRH/LH release under muscimol treatment may result from activation of GABAA receptors on GnRH nerve terminals and through GABAA receptor mechanism activated beta-endorphinergic and dopaminergic neurons in the VEN/NI. Lack of changes in NE and MHPG concentration during stimulation or blockade of GABAA receptors suggests, that during the follicular phase of the estrous cycle the noradrenergic system in the VEN/NI is not involved in the control of GnRH/LH release by GABA.


SOME MODELS FOR DEVELOPMENT, GROWTH, AND MORPHOMETRIC CORRELATION.
Genetic and phenotypic correlations between morphometric traits can be a direct consequence of shared developmental history and common systems of growth regulation. Correlation between traits, therefore, need not imply direct functional or adaptive constraints on those traits. Useful models of the developmental origins of correlations will consider mechanisms that can reduce initially high correlation of traits that arise from a single developmental precursor. Several models presented here predict such correlations for different modes of fission of a precursor. Timing of developmental events may also affect correlations and respond to selection on adult traits. The models may apply to development of the tetrapod limb bud, including variance and covariance induced by known developmental mutants.


Cholelithiasis in pediatric organ transplantation: detection and management.
The real incidence and the underlying causes of cholelithiasis in pediatric solid organ recipients is probably not exactly known. In addition to well-established risk factors for cholelithiasis, children after heart, kidney, or liver transplantation may develop gallstones due to drug therapy, sepsis, parenteral nutrition, or surgical complications. For pediatric patients, data are very limited and heterogeneous. However, the incidence in pediatric heart recipients seems to be substantially higher compared with kidney or liver graft recipients. In this review article the present data are discussed focusing on incidence, detection, and management of cholelithiasis in pediatric organ transplantation. In general, surgery is the therapy of choice in symptomatic patients; however, the pharmacological profile of ursodeoxycholic acid and the first results on its clinical impact are promising. The value of prophylactic therapy with ursodeoxycholic acid must be determined in further studies.


Quenching Capabilities of Long-Chain Carotenoids in Light-Harvesting-2 Complexes from Rhodobacter sphaeroides with an Engineered Carotenoid Synthesis Pathway.
Six light-harvesting-2 complexes (LH2) from genetically modified strains of the purple photosynthetic bacterium Rhodobacter (Rb.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. These strains were engineered to incorporate carotenoids for which the number of conjugated groups (N = NC═C + NC═O) varies from 9 to 15. The Rb. sphaeroides strains incorporate their native carotenoids spheroidene (N = 10) and spheroidenone (N = 11), as well as longer-chain analogues including spirilloxanthin (N = 13) and diketospirilloxantion (N = 15) normally found in Rhodospirillum rubrum. Measurements of the properties of the carotenoid first singlet excited state (S1) in antennas from the Rb. sphaeroides set show that carotenoid-bacteriochlorophyll a (BChl a) interactions are similar to those in LH2 complexes from various other bacterial species and thus are not significantly impacted by differences in polypeptide composition. Instead, variations in carotenoid-to-BChl a energy transfer are primarily regulated by the N-determined energy of the carotenoid S1 excited state, which for long-chain (N ≥ 13) carotenoids is not involved in energy transfer. Furthermore, the role of the long-chain carotenoids switches from a light-harvesting supporter (via energy transfer to BChl a) to a quencher of the BChl a S1 excited state B850*. This quenching is manifested as a substantial (∼2-fold) reduction of the B850* lifetime and the B850* fluorescence quantum yield for LH2 housing the longest carotenoids.


The Antimicrobial and Antibiofilm Potential of New Water-Soluble Tris-Quaternary Ammonium Compounds.
The invention and innovation of highly effective antimicrobials are always crucial tasks for medical and organic chemistry, especially at the current time, when there is a serious threat of shortages of effective antimicrobials following the pandemic. In the study presented in this article, we established a new approach to synthesizing three novel series of bioactive water-soluble tris-quaternary ammonium compounds using an optimized one-pot method, and we assessed their antimicrobial and antibiofilm potential. Five pathogenic microorganisms of the ESKAPE group, including highly resistant clinical isolates, were used as the test samples. Moreover, we highlighted the dependence of antibacterial activity from the hydrophilic-hydrophobic balance of the QACs and noted the significant performance of the desired products on biofilms with MBEC as low as 16 mg/L against bacteria and 8 mg/L against fungi. Particularly notable was the high activity against Pseudomonas aeruginosa and Acinetobacter baumannii, which are among the most resilient bacteria known. The presented work will provide useful insights for future research on the topic.


New insights into the proton pumping mechanism of ba3 cytochrome c oxidase: the functions of key residues and water.
As the terminal oxidase of cell respiration in mitochondria and aerobic bacteria, the proton pumping mechanism of ba3-type cytochrome c oxidase (CcO) of Thermus thermophiles is still not fully understood. Especially, the functions of key residues which were considered as the possible proton loading sites (PLSs) above the catalytic center, as well as water located above and within the catalytic center, remain unclear. In this work, molecular dynamic simulations were performed on a set of designed mutants of key residues (Asp287, Asp372, His376, and Glu126II). The results showed that Asp287 may not be a PLS, but it could modulate the ability of the proton transfer pathway to transfer protons through its salt bridge with Arg225. Maintaining the closed state of the water pool above the catalytic center is necessary for the participation of inside water molecules in proton transfer. Water molecules inside the water pool can form hydrogen bond chains with PLS to facilitate proton transfer. Additional quantum cluster models of the Fe-Cu metal catalytic center are established, indicating that when the proton is transferred from Tyr237, it is more likely to reach the OCu atom directly through only one water molecule. This work provides a more profound understanding of the functions of important residues and specific water molecules in the proton pumping mechanism of CcO.


Incorporating mini-implants within the general dental practice.
Dental implants represent a key business opportunity for today's practitioner. Demographically speaking, the number of candidates for implant dentistry continues to increase, and clinicians have in these patients a vast resource for practice expansion. Small-diameter implant therapy is thus a valuable service offering for clinicians challenged to remain abreast of current techniques and technologies. The following presentation highlights the associated demographics, clinical considerations and procedures, and practice marketing benefits of IMTEC's MDI to the contemporary practice.


Evaluation of the current status of operating and closed landfills in Russia, Finland and Ireland with regard to water pollution and methane emission.
The annual production of municipal solid wastes (MSW) in Russia, Finland and Ireland in the late 1990s accounts for 37.5, 2.5 and 2.05 min. tonnes or 252, 488 and 566 kg per capita, respectively. 96.5, 64 and 91% of these wastes (for Russia, Finland and Ireland, correspondingly) are currently disposed of via landfilling. However, nowadays, MSW management in these countries is undergoing drastic changes (source separation, closure of old landfills, reduction of the number of landfills etc.) forced by recent legislation set by the European Union and Russian authorities. This paper evaluates the current status of MSW landfills, as well as information on current leachate and methane emissions in the three above mentioned countries. Landfill leachates are highly variable in each country and between different countries due to different rainfall and climatic conditions and also due to poor landfill top insulation/cover. Leachates in poorly structured landfills are very dilute, whereas leachates with total COD and nitrogen contents as high as 33,700 mg COD/l and 4,030 mg N/l, respectively, have been detected from state-of-the-art sites. Currently, on-site treatment of leachates exists at only a few landfills in Russia, Finland and Ireland but this situation will be considerably improved during the next years. The annual methane emissions from landfills are estimated as 500-900 and 77 ktonnes for Russia and Finland, respectively. Recent estimates from Ireland suggest an annual landfill methane emission of c. 2.1 Mt CO2 equivalent. Several systems of methane recovery have been developed in all three countries and these are currently in different stages of implementation.


Species of Philometra (Nematoda, Philometridae) from fishes off the Mediterranean coast of Africa, with a description of Philometra rara n. sp. from Hyporthodus haifensis and a molecular analysis of Philometra saltatrix from Pomatomus saltatrix.
Two gonad-infecting species of Philometra Costa, 1845 (Nematoda, Philometridae) were recorded for the first time from marine perciform fishes off Tunisia and Libya: Philometra rara n. sp. from the rare, deep-water Haifa grouper Hyporthodus haifensis (Serranidae) off Libya and Philometra saltatrix Ramachandran, 1973 from the bluefish Pomatomus saltatrix (Pomatomidae) off Tunisia. Identification of both fish species was confirmed by molecular barcoding. Light and scanning electron microscope studies of Ph. rara n. sp. showed that it is characterized by the length of spicules (216-219 μm) and the gubernaculum (90-93 μm), the gubernaculum/spicules length ratio (1:2.32-2.43), and mainly by the shape and structure of the distal end of the gubernaculum (shovel-shaped with a wide median smooth field in dorsal view), appearing as having a dorsal protuberance in lateral view, and by the structure of the male caudal mound (dorsally interrupted); large subgravid females (70-137 mm long) are characterized by the presence of four oval submedian cephalic elevations, each of them bearing a pair of cephalic papillae of the outer circle. The finding of Ph. saltatrix off Tunisia confirms that this species is widespread throughout the Mediterranean region. A molecular analysis of our Ph. saltatrix specimens and other available philometrid cytochrome c oxidase 1 (COI) sequences showed that most species have robust clades. Sequences of Ph. saltatrix from Tunisia diverge from Ph. saltatrix from Brazil and the USA, suggesting that speciation is currently occurring between populations from both sides of the Atlantic Ocean.


The dopamine hypothesis of schizophrenia: current status, future prospects.
The dopamine hypothesis of schizophrenia is reviewed in the context of recent advances in dopamine research. These include the following: the discovery that there are several subtypes of dopamine receptor, the recognition that the activity of dopamine neurons is controlled by negative feedback systems; insights into the functions of different subsystems of dopamine neurons; the discovery that different subsystems of dopamine neurons interact with one another; and a growing understanding of the functions and mode of operation of the forebrain regions that the dopamine projections innervate. The paper reviews some of the complexities that the dopamine hypothesis has encountered, and continues to encounter, with a particular focus on three issues: the adequacy of our understanding of neuroleptic drug action, the heterogeneity of schizophrenic symptoms and the paucity of direct evidence to support the hypothesis. It is concluded that schizophrenia does not reflect primary abnormalities of dopamine transmission, but probably does reflect abnormalities in systems that have an intimate interaction with the dopamine system. The primary substrates for schizophrenia will probably be found within the major targets of the ascending dopamine projections: the fronto-striato-pallido-thalamic loops, and the limbic structures, such as amygdala and hippocampus, with which the fronto-striatal system interacts.


Ascending the learning curve--MSI testing experience of a six-laboratory consortium.
According to recently published guidelines, microsatellite instability (MSI) testing of colorectal cancers may be clinically indicated on a significant proportion of all colorectal tumors. To date, nothing has been published regarding the reproducibility of MSI testing between laboratories. We present MSI quality control activities experience of a six center multinational consortium, as laboratories developed competency with MSI testing and interpretation. The aim of this paper is to share lessons learned and to describe the final concordance rates in scoring MSI markers within this consortium.


Examining embedded validity indicators in Conners continuous performance test-3 (CPT-3).
Prior research has identified a variety of embedded performance validity indicators on the Conners' Continuous Performance Test-II (CPT-II). The purpose of this study was to examine embedded validity indicators within the updated third edition of the Conners Continuous Performance Test (CPT-3). This study used a retrospective chart review from an ADHD evaluation clinic at a Mid-Atlantic VA hospital. Participants were 197 military veterans who completed a clinical assessment for ADHD. All participants were consecutive referrals to the ADHD clinic who completed the CPT-3 and the Test of Memory Malingering, Trial 1 (TOMM1). Logistic regression analyses indicated that the following five variables were able to significantly predict validity status on the TOMM1: detectability (d'), omissions (OMI), commissions (COM), hit reaction time (HRT) standard deviation (SD), and HRT inter-stimulus interval (ISI) change. Among these measures, HRT SD and HRT ISI change were identified as the scores with the highest AUC values. Optimal cutoffs for all significant predictors were identified. A number of composite EVIs were created using various combinations of CPT-3 scores. All composite EVIs significantly differentiated between pass and fail status on the TOMM1. Several CPT-3 variables have clinical utility as embedded validity indicators; however, due to low sensitivity, they should not be used in isolation. These scores may be used as indicators of invalid performance but should not be used to rule out invalid performance. Identified CPT-3 scores may be useful as one component in a multivariate, multi-point continuous approach to performance validity sampling.


The Conundrum of Omega-3 Fatty Acids in Cancer Prevention Studies: Which One? How Much? What Biomarkers?
Marine omega-3 fatty acids promote resolution of inflammation and have potential to reduce risk of obesity-related breast cancer. For prevention trials in obese women, inflammatory cytokines, aromatase, and measures of breast immune cell infiltration are logical, as are biomarkers of growth factor, adipokine, and estrogen signaling. Where best to look for marker change: in the circulation (easiest), in benign breast tissue (most relevant), or in visceral adipose (inflammation often most marked)? A null biomarker modulation trial may reflect limitations in design, source and dose of fatty acids, or biomarkers and should not lead to premature abandonment of marine omega-3 fatty acids for cancer prevention. Cancer Prev Res; 11(4); 187-90. ©2018 AACRSee related article by Gucalp et al., p. 203.


Thioredoxin reductase 1 and NADPH directly protect protein tyrosine phosphatase 1B from inactivation during H2O2 exposure.
Regulation of growth factor signaling involves reversible inactivation of protein tyrosine phosphatases (PTPs) through the oxidation and reduction of their active site cysteine. However, there is limited mechanistic understanding of these redox events and their co-ordination in the presence of cellular antioxidant networks. Here we investigated interactions between PTP1B and the peroxiredoxin 2 (Prx2)/thioredoxin 1 (Trx1)/thioredoxin reductase 1 (TrxR1) network. We found that Prx2 becomes oxidized in PDGF-treated fibroblasts, but only when TrxR1 has first been inhibited. Using purified proteins, we also found that PTP1B is relatively insensitive to inactivation by H2O2 but found no evidence for a relay mechanism in which Prx2 or Trx1 facilitates PTP1B oxidation. Instead, these proteins prevented PTP1B inactivation by H2O2 Intriguingly, we discovered that TrxR1/NADPH directly protects PTP1B from inactivation when present during the H2O2 exposure. This protection was dependent on the concentration of TrxR1 and independent of Trx1 and Prx2. The protection was blocked by auranofin and required an intact selenocysteine residue in TrxR1. This activity likely involves reduction of the sulfenic acid intermediate form of PTP1B by TrxR1 and is therefore distinct from the previously described reactivation of end-point oxidized PTP1B, which requires both Trx1 and TrxR1. The ability of TrxR1 to directly reduce an oxidized phosphatase is a novel activity that can help explain previously observed increases in PTP1B oxidation and PDGF receptor phosphorylation in TrxR1 knockout cells. The activity of TrxR1 is therefore of potential relevance for understanding the mechanisms of redox regulation of growth factor signaling pathways.


Effect of metal permittivity on resonant properties of terahertz metamaterials.
We investigate the effect of metal permittivity on resonant transmission of metamaterials by terahertz time-domain spectroscopy. Our experimental results on double split-ring resonators made from different metals confirm the recent numerical simulations [Phys. Rev. E 65, 036622 (2002)] that metamaterials exhibit permittivity-dependent resonant properties. In the terahertz regime, the measured inductive-capacitive resonance is found to strengthen with a higher ratio of the real to the imaginary parts of metal permittivity, and this remains consistent at various metal thicknesses. Furthermore, we found that metamaterials made even from a generally poor metal become highly resonant owing to a drastic increase in the value of the permittivity at terahertz frequencies.


Combining reactive and configurational-bias Monte Carlo: confinement influence on the propene metathesis reaction system in various zeolites.
In order to efficiently calculate chemical equilibria of large molecules in a confined environment the reactive Monte Carlo technique is combined with the configurational-bias Monte Carlo approach. To prove that detailed balance is fulfilled the acceptance rule for this combination of particular Monte Carlo techniques is derived in detail. Notably, by using this derivation all other acceptance rules of any Monte Carlo trial moves usually carried out in combination with the configurational-bias Monte Carlo approach can be deduced from it. As an application of the combination of reactive and configurational-bias Monte Carlo the influence of different zeolitic confinements (MFI, TON, LTL, and FER) on the reaction equilibrium and the selectivity of the propene metathesis reaction system was investigated. Compared to the bulk phase the conversion is increased significantly. The authors study this reaction system in the temperature range between 300 and 600 K, and the pressure range from 1 to 7 bars. In contrast to the bulk phase, pressure and temperature have a strong influence on the composition of the reaction mixture in confinement. At low pressures and temperatures both conversion and selectivity are highest. Furthermore, the equilibrium composition is strongly dependent on the type of zeolite. This demonstrates the important role of the host structure in catalytic systems.


[Cytological studies in pneumonological diagnosis].
The following principles for the use of cytological examinations in pneumology are suggested: 1. The aim of cytological sputum examinations is diagnosis of tumors and not early detection of bronchial cancer in risk groups. 2. The diagnostic accuracy of cytological examinations depends mainly on the preparatory techniques. 3. Cytology and histology are complementary methods in the diagnosis of tumors and should always be combined. 4. Immunocytochemistry and electronmicroscopy are rarely indicated and are at best complementary to conventional microscopic diagnosis. 5. Cytological examinations for Pneumocystis carinii and other opportunistic germs in immuno-deficient patients should be confined to clinical centers with adequate experience.


Caragasinin C: a new oligostilbene from the roots of Caragana sinica.
A new oligostilbene, caragasinin C (1), and seven known compounds, betulinic acid (2), 4-hydroxybenzaldehyde (3), (‒)-medicarpin (4), wistin (5), (2E,4S)-4-hydroxy-2-nonenoic acid (6), pallidol (7), and (+)-α-viniferin (8), were isolated from the roots of Caragana sinica. The structure of caragasinin C was established on the basis of spectroscopic techniques, including HRESIMS, 1D and 2D-NMR.


Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation.
For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.


A usability study of a mobile health application for rural Ghanaian midwives.
Midwives in rural Ghana work at the frontline of the health care system, where they have access to essential data about the patient population. However, current methods of data capture, primarily pen and paper, make the data neither accessible nor usable for monitoring patient care or program evaluation. Electronic health (eHealth) systems present a potential mechanism for enhancing the roles of midwives by providing tools for collecting, exchanging, and viewing patient data as well as offering midwives the possibility for receiving information and decision support. Introducing such technology in low-resource settings has been challenging because of low levels of user acceptance, software design that does not match the end-user environment, and/or unforeseen challenges such as irregular power availability. These challenges are often attributable to a lack of understanding by the software developers of the end users' needs and work environment. A mobile health (mHealth) application known as mClinic was designed to support midwife access to the Millennium Village-Global Network, an eHealth delivery platform that captures data for managing patient care as well as program evaluation and monitoring, decision making, and management. We conducted a descriptive usability study composed of 3 phases to evaluate an mClinic prototype: 1) hybrid lab-live software evaluation of mClinic to identify usability issues; 2) completion of a usability questionnaire; and 3) interviews that included low-fidelity prototyping of new functionality proposed by midwives. The heuristic evaluation identified usability problems related to 4 of 8 usability categories. Analysis of usability questionnaire data indicated that the midwives perceived mClinic as useful but were more neutral about the ease of use. Analysis of midwives' reactions to low-fidelity prototypes during the interview process supported the applicability of mClinic to midwives' work and identified the need for additional functionality. User acceptance is essential for the success of any mHealth implementation. Usability testing identified mClinic development flaws and needed software enhancements.


Multicomponent Oxidative Trifluoromethylation of Alkynes with Photoredox Catalysis: Synthesis of α-Trifluoromethyl Ketones.
The direct oxidative addition of CF3 and H2O to alkynes was achieved with photoredox catalysis to obtain α-trifluoromethyl ketones via rapid enol-keto tautomerization. The reaction exhibits high functional group tolerance and regioselectivity. Heterocycles of various sizes containing CF3 were synthesized from the α-CF3-substituted diketones obtained through the protocol, thereby demonstrating the versatile applicability of the method. Mechanistic studies of the reaction with isotopes provided insight into the reaction pathway.


Effects of control techniques on therapeutic outcome in a controlled clinical trial.
Undertaken in the context of a controlled drug trial involving newly admitted psychiatric hospital patients, this study compared the effectiveness of a "Doctor's Choice" (DC) method of administering psychotropic drugs versus an experimentally determined treatment regimen employing random assignment and double-bline procedures. The 32-day drug trial sought to determine the comparative effectiveness of thioridazine-placebo, thioridazine-chlordiazepoxide, and thioridazine-imipramine, with the daily dosage of openly administered thioridazine ranging from 100 to 900 mg and dosages for chlordiazepoxide and imipramine, administered in a double-blind fashion, fixed at daily dosages of 30 and 75 mg, respectively. DC medication, consisting of a choice (by a research physician) of any of the three experimental medications determined on the basis of judged clinical need, was added as a fourth treatment category for present purposes. Criteria of effectiveness included standarized psychiatric rating scales and global measures of imporvement completed by research team members and ward physicians. Outcome results for the DC group compared to those for a single control group made up of individuals matched with DC patients on the basis of drug assignment indicated an essentially similar clinical effectiveness under both DC and control treatment conditions. Generalization of the finding was limited by the fact that the main treatment effect, attributable to thioridazine, overshadowed the more subtle action of the ancillary drugs.


Tissue angiotensin II concentration in the heart and kidneys in transgenic Tsukuba hypertensive mice.
Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and angiotensinogen genes, and possessing an overexpressing human renin-angiotensin system. The aim of this study is to evaluate the angiotensin II concentration in the heart and kidney in THM. Twenty-week-old male THM and control C57BL/6 mice (C57) were used. Each group consisted of 3 mice. For each mouse, systolic blood pressure, heart to body weight ratio, renal glomerular sclerosis index and angiotensin II concentration in the heart and kidney were measured. Systolic blood pressure of THM was about 40 mmHg higher than that of C57. Heart to body weight ratio and renal glomerular sclerosis index were significantly higher in THM than those in C57. The angiotensin II concentration in THM was about 4 times higher in the heart and about 5 times higher in the kidney compared with that in C57. These results suggest that accelerated tissue angiotensin II production, significant cardiac hypertrophy and renal glomerular sclerosis all occur because of hypertension.


Appropriate use of D-dimer testing can minimize over-utilization of venous duplex ultrasound in a contemporary high-volume hospital.
The sensitivity of d-dimer (DD) in detecting deep venous thrombosis (DVT) is remarkably high; however, many institutions send patients immediately for a venous duplex ultrasound (VDU). This study was designed to examine the appropriate utilization of DD and VDU in a high-volume hospital. A retrospective study was conducted on consecutive patients who presented to a high-volume emergency department (ED) with lower extremity limb swelling/pain over a 30-day period, who were sent for VDU during an evaluation for DVT. VDU data were merged with electronic DD laboratory results. The enzyme-linked immunosorbent assay method was used to provide DD values and thresholds. Values above 0.60 mg/fibrinogen equivalent unit (FEU) were considered abnormal. We reviewed the medical records of 517 ED patients in the month of June 2013. After applying the Wells criteria, 157 patients (30.4%) were excluded because of a history of DVT or pulmonary embolism, having been screened for shortness of breath, or sent for surveillance-leaving 360 for analysis. The average age was 59.3 ± 16.5 years with more women (210, 58.3%) and the majority reported limb pain or swelling (73.9%). DD was performed on 51 patients with an average value of 3.6 ± 5.4 mg/FEU, of which 43 (84.3%) were positive. DD identified all positive and negative DVT patients (100% sensitivity and negative predictive value), but also included 40 false positives (16.7% specificity). On the other hand, 309 patients were sent directly to VDU without DD; of those, 43 (13.9%) were positive for DVT. However, 266 (86.1%) patients were negative for DVT by VDU without DD and these were deemed improper by our current study protocol. Potential charge savings were calculated as VDU for all (360 × $1000 = $360,000), DD for all (360 × $145 = $52,200), and VDU for both true and false positives (estimated to be about 25% of the cases; 90 × $1000 = $90,000); this equals a charge savings of $217,800 and would avoid unnecessary VDUs. Based on the results of our study, we suggest that the DD test be utilized during the initial work-up for patients with limb swelling/pain in the emergency room. Appropriate utilization of DD, as well as other clinical criteria, may limit the over-utilization and added cost of VDU, without a negative impact on patient care. The results of DD tests should be utilized to limit the number of patients sent for VDU to only those patients with a positive DD or other significant underlying concerns.


Comparison between exploratory factor-analytic and SEM-based approaches to constructing SF-36 summary scores.
To compare the two higher order factor structures of the Short-Form 36 (SF-36) Health Survey, using exploratory factor analytic methods and structural equation modeling (SEM). Two population data sets were used. A stratified representative sample (n = 1,005) of the Greek general population was approached for interview. This survey containing the SF-36 was used to obtain component score coefficients from principal components analysis and orthogonal rotation. These coefficients were then used in the second data set (n = 1,007) of the Greek adult general population to compute scores for the physical component summary and the mental component summary of the SF-36. The second data set was also used to obtain factor scores for physical and mental health measures, applying SEM. Exploratory factor analysis supported the existence of two principal components that are the basis for summary physical and mental health measures. SEM showed that models assuming that physical and mental health are correlated provided a better fit to the data than models assuming independence between physical and mental health. However, all eight dimensions of SF-36 should be included in the construction of summary scores. These results confirm the multidimensional structure of the SF-36, the correlational equivalence between standard summary measures and SEM-based second-order factor scores, and underscore the feasibility of multinational comparisons of health status using this instrument.


Thawed Porcine Model for Surgical Training: A Novel Conservative Procedure.
Background: General Surgery course is a mandatory in medical schools and continuing surgery training is important even to experienced surgeons which they need to maintain and/or improve their surgical skills. Additionally, the models used for that practice are human cadavers, anesthetized porcine, or simulators and are not accessible for medicine schools or physicians in many countries. Therefore, we present a new technical procedure for preparation of frozen experimental animal's cadavers for medical surgical training. Materials and Methods: To perform the study, one porcine slaughtered and frozen at -20°C was used. The porcine cadaver was thawed at room temperature (25°C) and then the pneumoperitoneum test was performed and viscera inspection carried out. Results: The porcine cadaver took 20 hours to completely thaw. The pneumoperitoneum was successfully performed with total distention of the abdominal cavity. All viscera were well preserved maintaining important in vivo characteristics for consistency. Conclusion: The use of thawed porcine cadaver as a model to train many surgical procedures including videolaparoscopy is feasible. The tissues were well preserved by this method and was financially accessible and could be used for different techniques, equipment, and material tests.


Potential biomedical applications of marine algae.
Functional components extracted from algal biomass are widely used as dietary and health supplements with a variety of applications in food science and technology. In contrast, the applications of algae in dermal-related products have received much less attention, despite that algae also possess high potential for the uses in anti-infection, anti-aging, skin-whitening, and skin tumor treatments. This review, therefore, focuses on integrating studies on algae pertinent to human skin care, health and therapy. The active compounds in algae related to human skin treatments are mentioned and the possible mechanisms involved are described. The main purpose of this review is to identify serviceable algae functions in skin treatments to facilitate practical applications in this high-potential area.


Mechanism of oxidative stress in neurodegeneration.
Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.


Two Cases of Guillain-Barré Syndrome Variants Presenting With Dysautonomia.
We describe 2 pediatric cases presenting with posterior reversible encephalopathy syndrome secondary to autonomic dysfunction preceding the onset of motor symptoms in Guillain-Barré syndrome variants. Patient 1 presented acutely with encephalopathy, cerebellar signs, hypertension, lower limb weakness, and respiratory decompensation. Magnetic resonance imaging (MRI) brain showed occipital lesions consistent with posterior reversible encephalopathy syndrome. Nerve conduction studies were consistent with Miller-Fisher syndrome. After intravenous immunoglobulin and plasmapheresis, he improved clinically with radiological resolution. Patient 2 presented with headache, leg pain, seizures, and significant hypertension. Brain MRI was normal but spine MRI revealed enhancement of the cauda equina ventral nerve roots. She was areflexic with lower limb weakness a few days after intensive care unit admission and made a significant improvement after treatment with intravenous immunoglobulin. In children presenting with posterior reversible encephalopathy syndrome in the absent of other causes of primary hypertension, Guillain-Barré syndrome variants are an important differential etiology, presenting with autonomic dysfunction, even before signs of motor weakness become evident.


Treatment of hypertension with captopril: preservation of regional blood flow and reduced platelet aggregation.
The BP of 12 patients with essential hypertension was controlled with captopril over a period of three months. Cerebral blood flow, muscle blood flow (anterior tibialis muscle), platelet aggregation and platelet thromboxane A2 release were measured during a baseline drug-free period, and measurements repeated during the treatment phase on achieving BP control, after one and three months. Cerebral blood flow rose during the early phase of treatment and then dropped to baseline levels during chronic therapy. Muscle blood flow, both at rest and following maximal exercise, was unaffected by captopril therapy. Platelet aggregation was diminished during therapy, and this finding was paralleled by a reduction in platelet thromboxane A2 generation. Control of hypertension with maintenance of regional blood flow and beneficial changes in platelet function during treatment with captopril may improve the overall risk profile of hypertensive patients. Inhibition of platelet aggregation and thromboxane A2 release may contribute to the antihypertensive action of captopril and the maintenance of regional blood flow.


Possible association between HPV16 E7 protein level and cytokeratin 19.
The mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19.


Individual surgeon is an independent risk factor for leak after double-stapled colorectal anastomosis: An institutional analysis of 800 patients.
Our aim was to assess whether the individual surgeon is an independent risk factor for anastomotic leak in double-stapled colorectal anastomosis after left colon and rectal cancer resection. This retrospective analysis of a prospectively collected database consists of a consecutive series of 800 patients who underwent an elective left colon and rectal resection with a colorectal, double-stapled anastomosis between 1993 and 2009 in a specialized colorectal unit of a tertiary hospital with 7 participating surgeons. The main outcome variable was anastomotic leak, defined as leak of luminal contents from a colorectal anastomosis between 2 hollow viscera diagnosed radiologically, clinically, endoscopically, or intraoperatively. Pelvic abscesses were also considered to be an anastomotic leak. Radiologic examination was performed when there was clinical suspicion of leak. Anastomotic leak occurred in 6.1% of patients, of which 33 (67%) were treated operatively, 6 (12%) with radiologic drains, and 10 (21%) by medical treatment. Postoperative mortality rate was 2.9% for the whole group of 800 patients. In patients with anastomotic leak, mortality rate increased up to 16% vs 2.0% in patients without anastomotic leak (P < .0001). At multivariate analysis, rectal location of tumor, male sex, bowel obstruction preoperatively, tobacco use, diabetes, perioperative transfusion, and the individual surgeon were independent risk factors for anastomotic leak. The surgeon was the most important factor (mean odds ratio 4.9; range 1.0 to 13.5). The variance of anastomotic leak between the different surgeons was 0.56 in the logit scale. The individual surgeon is an independent risk factor for leakage in double-stapled, colorectal, end-to-end anastomosis after oncologic left-sided colorectal resection.


Pulmonary hamartoma: Cytological study of a case and literature review.
Pulmonary hamartomas are the most common but rare benign tumor-like lesions of the lung arising from the embryonic rest. They are more common in males and in aged. Majority are asymptomatic and seen as coin lesions with popcorn calcification in the chest radiograph. Fine needle aspiration cytology (FNAC) helps to diagnose and distinguish them from the cancerous lesions of the lung. The cytological material is characterized by fibromyxoid stroma, cartilage, bronchial cells, adipose tissue and bone. Bronchial cells with reactive atypia may be a source of false-positive result. Symptomatic cases need surgical intervention such as enucleation or segmental resection. We report a case of a 74-year-old male who had a lung mass that did not progress over 4-year on chest radiograph. The CT-guided FNAC smears showed benign bronchial epithelial cells, fibro-myxoid spindle cell stroma and fat spaces that aided the diagnosis of pulmonary hamartoma avoiding surgical intervention.


DNA substrate recognition and processing by the full-length human UPF1 helicase.
UPF1 is a conserved helicase required for nonsense-mediated decay (NMD) regulating mRNA stability in the cytoplasm. Human UPF1 (hUPF1) is also needed for nuclear DNA replication. While loss of NMD is tolerated, loss of hUPF1 induces a DNA damage response and cell cycle arrest. We have analysed nucleic acid (NA) binding and processing by full-length hUPF1. hUPF1 unwinds non-B and B-form DNA and RNA substrates in vitro. Unlike many helicases involved in genome stability no hUPF1 binding to DNA structures stabilized by inter-base-pair hydrogen bonding was observed. Alternatively, hUPF1 binds to single-stranded NAs (ssNA) with apparent affinity increasing with substrate length and with no preference for binding RNA or DNA or purine compared to pyrimidine polynucleotides. However, the data show a pronounced nucleobase bias with a preference for binding poly (U) or d(T) while d(A) polymers bind with low affinity. Although the data indicate that hUPF1 must bind a ssNA segments to initiate unwinding they also raise the possibility that hUPF1 has significantly reduced affinity for ssNA structures with stacked bases. Overall, the NA processing activities of hUPF1 are consistent with its function in mRNA regulation and suggest that roles in DNA replication could also be influenced by base sequence.


Examination of a bifactor model of the Three Domains of Disgust Scale: specificity in relation to obsessive-compulsive symptoms.
The current research evaluated a bifactor model for the Three Domains of Disgust Scale (TDDS) in 2 undergraduate samples. The goals were (a) to evaluate whether the TDDS should be scored as a unidimensional scale or whether subscales of pathogen, sex, and moral disgust should be additionally interpreted, and (b) to examine the utility of the TDDS subscales above and beyond the total score in predicting obsessive-compulsive disorder (OCD) symptoms. Results in Study 1 and Study 2 revealed that a bifactor model fit the TDDS data well and that all items were influenced by a general disgust dimension and by 1 of 3 content dimensions. However, model-based reliability estimated via omega hierarchical for the total score suggested that TDDS items are highly multidimensional. That is, the general disgust dimension only accounts for about half of the variability in the items of the total score, with the remaining variability accounted for by the specific disgust domains and other sources of variance. Despite the high degree of multidimensionality underlying the TDDS items, the pathogen and sex subscale scores were found to be relatively unreliable after controlling for the general disgust factor. Among the 3 domains, pathogen disgust had the most consistently significant relationship with an OCD symptom latent factor above and beyond the general disgust factor. The strengths and limitations of the TDDS are discussed in the context of these findings, and the implications for better understanding the structure of disgust and its relationship with OCD are outlined.


Do infectious agents cause interstitial cystitis?
The possibility that infectious agents play a role in the etiology of interstitial cystitis (IC) has been investigated for a number of years. Early studies were directed toward attempts to cultivate bacteria and fungi on routine culture media and microscopic examinations of urine or bladder tissue specimens for the presence of microorganisms. In more recent years, this approach has been expanded to include sophisticated culture techniques to search for the presence of fastidious and unusual organisms that would not be detected by routine culture methods. Similarly, the presence of viruses has been sought by incubating specimens from interstitial cystitis patients in mammalian cell cultures to detect cytopathic effects. None of these approaches has provided convincing evidence that micro-organisms or viruses are associated with IC. The latest attempts to search for the presence of bacteria have made use of the polymerase chain reaction (PCR) to amplify bacterial 16S rRNA genes that would be present if bacteria were present in bladder tissue or urine of IC patients. This approach allows bacteria to be detected and even identified without culture. However, the results from the great majority of bladder biopsy samples analyzed by these molecular techniques have been negative. PCR strategies have also been used to search for the presence of certain viruses in IC specimens, again without success. At this time, the results from laboratory culture, light and electron microscopy, and various molecular strategies to detect micro-organisms and viruses in IC specimens all argue against an infectious etiology for IC.


Proximal subscapularis release for the treatment of adduction-internal rotation shoulder contracture in obstetric brachial plexus palsy.
The purpose of this paper was to evaluate the results on shoulder function following isolated proximal subscapularis release in children with Erb's palsy. A retrospective study was conducted on 64 consecutive children with Erb's palsy who underwent a Carlioz proximal subscapularis release between 2001 and 2012. Fifty children with complete records and a minimum follow-up of 2 years were included for evaluation. Age at surgery ranged from 1.3 to 4.5 years (average 2.6 years). Preoperative active shoulder abduction/anterior elevation, active external and internal rotations as well as the Mallet score were compared with those found at 6 and 24 months postoperatively using the Student paired t test, with a confidence interval of 95 %. The results were compared between children <3 years of age at surgery and those older, and between children who had an isolated C5-C6 and those with greater involvement. p < 0.05 was considered statistically significant. Active abduction improved 21° at 6 months and 31° (total) at 2 years (p < 0.01) with an overall Mallet abduction score improvement of 0.58 at 6 months and 0.6 (overall) at 2 years (p < 0.01). Active external rotation improved 52° at 6 months and 35° (total) at 2 years (p < 0.01) with an overall Mallet external rotation score improvement of 1.3 at 6 months (p < 0.01) and 0.52 (overall) at 2 years (p = 0.013). There was no statistically significant change in internal rotation (p = 0.37). We found no correlation between the child's age or the severity of involvement at surgery and the end result. Proximal subscapularis release according to Carlioz is simple and effective in improving overall shoulder function in children with obstetric brachial plexus palsy, mainly abduction and external rotation. Improvement tends to reach a plateau around 6-12 months postoperatively.


Brome mosaic virus detected in Kansas wheat co-infected with other common wheat viruses.
Wheat breeders are developing new virus-resistant varieties; however, it is assumed that only a few viruses or well-known viruses are present in the field. New sequencing technology is allowing for better determination of natural field virus populations. For three years, 2019-2021, Kansas wheat field surveys were conducted to determine the constituents of natural field virus populations using nanopore sequencing. During analysis, brome mosaic virus (BMV) was identified for the first time in Kansas but was in association with other wheat viruses. Brome mosaic virus was identified from 29 out of 47 different Kansas counties sampled and 44% of the total samples. BMV was found co-infected with wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) in 27.8% of the samples, with WSMV only (13.9%) and co-infected with WSMV + TriMV + High Plains wheat mosaic emaravirus (HPWMoV) (13.9%). RNA genomes of Kansas BMV isolates had 99.4 to 100% nucleotide and amino acid sequence identity, respectively, to each other. RNA2a possessed relatively high divergence (π = 0.01) compared to RNA1a and RNA3a (π = 0.004). Coding regions of all BMV RNAs were considered negative for purifying selection pressure as nonsynonymous and synonymous nucleotide ratio was less than one (dNs/dS >1). The identification of BMV in Kansas virus populations adds another layer of complexity to plant breeding. This work provides information to improve tools to aid in monitoring, detecting, and determining the variation within BMV.


Posterior Cingulate Epilepsy: A Systematic Review.
In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic review of posterior middle and posterior cingulate epilepsy cases was conducted to present a summary of current knowledge about this localization-based type of epilepsy. The literature search identified 32 articles, for a total of 69 patients (34 with posterior middle cingulate epilepsy [pMCE] and 35 with posterior cingulate epilepsy [PCE]). Most patients were children and young adults with drug-resistant lesional epilepsy with high seizure burden. In both groups, most patients reported auras, mainly sensory, but various types were reported, including autonomic, behavioral, and cognitive manifestations. Most pMCE and PCE showed motor manifestations (mainly respectively asymmetric tonic posturing and automotor features). Impaired awareness during seizures was more frequently reported in PCE than in pMCE. As for ictal scalp EEG, epileptogenic abnormalities were poorly lateralized and did not localize the seizure onset zone. An ictal temporal involvement was only observed in PCE. Interictal EEG findings were nonspecific. As for other presurgical noninvasive investigations, data are limited, and no studies have adequately assessed their value. Partly explained by our inclusion criteria, most patients underwent a surgical procedure (either lesionectomy or resection of epileptogenic zone as defined by intracranial EEG study results), which overall yielded good outcomes.


Defining good candidates for extraperitoneal cystectomy: results from random peritoneum biopsies of 136 cases.
To define who are good candidates for extraperitoneal cystectomy. Between April 2009 and April 2012, 136 consecutive patients (median age 63.8 years, range 35-87 years) scheduled for transperitoneal radical cystectomy were included in this study. After the bladder was removed, the peritoneum covering the bladder was detached. Any suspicious macroscopic abnormalities on the peritoneum were sampled and examined. A 6-8 point random biopsy of the peritoneum was performed for patients without gross macroscopic abnormality. The study group consisted of 41 patients with pT1, 48 patients with pT2, 34 patients with pT3, and 13 patients with pT4. The transitional cell carcinoma (TCC) group consisted of 123 of 136 patients (90.4%) and nonurothelial histologies of 13 of 136 patients (9.6%). In general, 8 of 136 patients (5.9%) and 14 of 816 biopsies (1.7%) were confirmed positive for peritoneum biopsies. Among them, 0 of 89 patients with pT1/2, 5 of 34 patients with pT3 (14.7%), and 3 of 13 patients with pT4 (23.1%) had positive biopsies (P <.001). In addition, 5 of 123 patients (4.9%) with TCC, 1 of 7 patients (14.3%) with adenocarcinoma, 1 of 2 patients (50%) with sarcomatoid carcinoma, and 1 of 2 patients (50%) with small cell tumors had positive peritoneum biopsies (P = .006). Among patients with positive lymph nodes, 5 of 34 patients (14.7%) had positive biopsies, compared with 3 of 102 patients (2.9%) in the lymph node-negative group (P = .012). We found that tumor stage and lymph node status are independent predictors of peritoneal involvement. Extraperitoneal cystectomy should be performed with great caution, only indicated for those patients who have a high likelihood of stage pT1 and pT2. However, patients with cT2-4, positive lymph nodes, or nonurothelial histologies should not have the peritoneum covering the bladder preserved.


A lifestage approach to assessing children's exposure.
Understanding and characterizing risks to children has been the focus of considerable research efforts at the U.S. Environmental Protection Agency (EPA). Potential health risks resulting from environmental exposures before conception and during pre- and postnatal development are often difficult to recognize and assess because of a potential time lag between the relevant periods of exposure during development and associated outcomes that may be expressed at later lifestages. Recognizing this challenge, a lifestage approach for assessing exposure and risk is presented in the recent EPA report titled A Framework for Assessing Health Risks of Environmental Exposures to Children (U.S. EPA, 2006). This EPA report emphasizes the need to account for the potential exposures to environmental agents during all stages of development, and consideration of the relevant adverse health outcomes that may occur as a result of such exposures. It identifies lifestage-specific issues associated with exposure characterization for regulatory risk assessment, summarizes the lifestage-specific approach to exposure characterization presented in the Framework, and discusses emerging research needs for exposure characterization in the larger public-health context. This lifestage approach for characterizing children's exposures to environmental contaminants ensures a more complete evaluation of the potential for vulnerability and exposure of sensitive populations throughout the life cycle.


Pentagastrin testing in patients with renal insufficiency: normal responsivity of mature calcitonin.
Calcitonin (CT) is the most sensitive tumor marker for medullary thyroid carcinoma available, but it lacks specificity. Chronic renal failure (CRF) is known to be associated with elevations of serum immunoreactive calcitonin. Using an immunoradiometric assay to detect only mature CT, we evaluated the basal CT level and its response to pentagastrin in 30 patients with CRF and compared these data with those obtained in 71 controls. Basal mature CT was significantly higher (p < 0.05) in patients with CRF (3.55 pg/mL) than in controls (2.00). Among these patients, 20% had basal CT levels more than 10 pg/mL with a maximum of 51 pg/mL. Peak CT values (highest value obtained 3 or 5 minutes after pentagastrin) were comparable in the two groups. Among patients with CRF, 10% had peak CT values greater than 30 pg/mL with a maximum of 53 pg/mL. In this group of patients, no correlation was found between CT (at any time during the test) and parathyroid hormone, calcium, phosphate, or creatinine clearance. Men had significantly higher CT values compared with women at each time point tested, including peak values. Patients with CRF, who have not yet undergone dialysis, have moderately elevated basal CT levels, but have normal pentagastrin-stimulated peak CT levels.