Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial.
Docetaxel and cabazitaxel improve overall survival compared with mitoxantrone in patients with metastatic castration-resistant prostate cancer. Custirsen (OGX011) is a second generation highly specific antisense oligonucleotide that inhibits the production of clusterin, an antiapoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance. We aimed to assess whether custirsen in combination with cabazitaxel and prednisone increases overall survival in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. In this randomised, open-label, international, phase 3 trial, men with radiographically documented metastatic castration-resistant prostate cancer that had progressed after docetaxel treatment with a Karnofsky performance status of more than 70% and who were fit for chemotherapy, were recruited from 95 cancer treatment centres in eight countries. Patients were randomly assigned (1:1) centrally using permuted blocks (block size 8) to receive cabazitaxel plus prednisone (cabazitaxel 25 mg/m2 intravenously every 21 days plus oral prednisone 10 mg daily) with or without custirsen (640 mg intravenously on days 1, 8, and 15, plus three previous loading doses) until disease progression, unacceptable toxicity, or the completion of ten treatment cycles. Randomisation was stratified by use of opioids for prostate cancer-related pain at screening, disease progression following first-line docetaxel treatment established by radiographic evidence, and previous treatment with abiraterone or enzalutamide. The co-primary endpoints were overall survival in all randomly assigned patients and in a poor-prognosis subgroup. All analyses were intention to treat with the exception of safety, which was reported for patients who received any assigned treatment. The trial has been completed and the results presented here are the final analysis. This trial is registered with Clinicaltrials.gov, number NCT01578655. Between Sept 9, 2012, and Sept 29, 2014, 795 patients were screened for enrolment. 635 men were eligible for inclusion and were randomly assigned (n=317 in the cabazitaxel and prednisone plus custirsen group and n=318 in the cabazitaxel and prednisone group). Median follow up was 28·3 months (IQR 24·4-34·5) for the custirsen group and 29·8 months (IQR 25·3-35·2) for the control group. Median overall survival in all randomly assigned patients did not differ between the two groups (14·1 months [95% CI 12·7-15·9] in the curtisen group vs 13·4 months [12·1-14·9] in the control group; hazard ratio [HR] 0·95 [95% CI 0·80-1·12]; log-rank p=0·53). In the poor prognosis subgroup, median overall survival also did not differ between the two treatment groups (11·0 months [95% CI 9·3-13·3] in the custursin group vs 10·9 months [8·2-12·4] in the control group; HR 0·97 [95% CI 0·80-1·21]; two-sided p=0·80). The most frequently reported grade 3 or worse adverse events in the custirsen versus control groups were neutropenia (70 [22%] of 315 vs 61 [20%] of 312), anaemia (68 [22%] vs 49 [16%]), fatigue (23 [7%] vs 18 [6%]), asthenia (16 [5%] vs 8 [3%]), bone pain (16 [5%] vs 5 [2%]), and febrile neutropenia (16 [5%] vs 9 [3%]). Serious adverse events were reported in 155 (49%) versus 132 (42%). 27 patients died within 30 days of treatment in the cabazitaxel and prednisone plus custirsen group, seven of which were deemed to be treatment related, versus 17 in the cabazitaxel and prednisone group, eight of which were deemed to be treatment related. Of the 21 deaths reported, 15 were reported as complications related to study treatment, either chemotherapy (eight and three, respectively) or study drug (none and four, respectively). We noted no survival benefit in men with metastatic castration-resistant prostate cancer with the addition of custirsen to cabazitaxel and prednisone treatment. Cabazitaxel and prednisone remains the standard of care for patients with metastatic castration-resistant prostate cancer progressing after docetaxel chemotherapy. OncoGenex Pharmaceuticals.


Separation, concentration and determination of trace chloramphenicol in shrimp from different waters by using polyoxyethylene lauryl ether-salt aqueous two-phase system coupled with high-performance liquid chromatography.
Polyoxyethylene lauryl ether (POELE10)-NaH2PO4 aqueous two-phase extraction system (ATPES) is coupled with HPLC to analyze chloramphenicol (CAP) in aquatic product. Response surface methodology (RSM) was adopted in the multi-factor experiment to determine the optimized conditions. The extraction efficiency of CAP (E%) is up to 99.42% under the optimal conditions, namely, the concentration of NaH2PO4, the concentration of POELE10, pH and temperature were 0.186 g · mL(-1), 0.033 g · mL(-1), 3.8 and 25 °C respectively. The optimal value of enrichment factor of CAP (F) was 22.56 when the concentration of NaH2PO4 was 0.192 g · mL(-1), the concentration of POELE10 was 0.024 g/ml, pH was 4.2 and temperature was 30 °C. The limit of detection (LOD) and limit of quantification (LOQ) of this method are 0.8 μg · kg(-1) and 1 μg · kg(-1), which meet the needs of determining trace or ultratrace CAP in food. The E% and F of this technique are much better than other extraction methods.


Extracellular matrix gene expression by human bone marrow stroma and by marrow fibroblasts.
In the marrow space hemopoietic progenitors interact with stromal cells allowing homing, migration and the expression of developmental programs. Some of these interactions are mediated by extracellular matrix molecules (ECM) which are produced by marrow stromal cells. In the murine system the nature of these interactions and its biological significance have been studied in vitro by using indistinctly, either whole stroma (obtained from long-term marrow cultures) or isolated stromal (fibroblast-like) cells. In an attempt to analyze whether in the human system both sources of stromal cells are equivalent in terms of production of ECM components, we measured the expression of genes encoding for several ECM proteins. The results obtained show that whole stroma as well as marrow fibroblasts express genes for collagen types I, III, IV, V and VI as well as for fibronectin and laminin. However, the relative abundance of mRNA transcripts for some of these proteins was higher in marrow fibroblasts as compared to whole stroma. The latter was further supported by an increased collagen synthesis observed in marrow fibroblasts as compared to whole stroma.


Computerized games to study the development of attention in childhood.
Children enjoy playing games. We can take advantage of this in the designs of computerized tasks that will engage their interest. These designs also serve to advance the study of chronometric measures, such as manual and saccadic reaction times and event related potentials, with young children. The goals of our method development are (1) to allow for comparable tasks across a wide variety of ages, (2) to make possible comparisons of child performance with data gathered in adult cognitive studies, and (3) to help to support inferences about the development of underlying mechanisms. We have designed a battery of computerized tasks in order to study the development of attention functions of alertness, orienting, and executive control during childhood. Our purpose is to describe each of these tasks in detail and present the results that have been obtained so far. The battery was tested using a sample of 5-year-old children as subjects.


Intrathecal baclofen: a useful agent in the treatment of well-established complex regional pain syndrome.
We present 2 case reports that illustrate that chronic intrathecal (IT) baclofen administration may be efficacious in treating patients with long-standing complex regional pain syndrome, type I (CRPS I) who have failed treatment with multiple drugs and procedures. Both cases presented were women who developed CRPS I following multiple lower extremity surgeries. One patient had had symptoms for 5 years and had continued symptoms despite multiple sympathetic blocks, sympathectomy, spinal cord stimulation, and various medication trials. The other patient had had chronic lower extremity pain for 30 years and symptoms of CRPS for about 5 years. Her symptoms continued despite multiple sympathetic blocks, sympathectomy, and many medications. Neither patient had motor dysfunction (dystonia, tremors, spasticity) associated with their painful disorder. One patient experienced good control of pain, allodynia, and autonomic dysfunction with a combination of IT baclofen and clonidine after failing treatment with IT morphine. Baclofen alone produced intolerable side effects at the doses required to produce adequate analgesia. The other patient experienced long-term control of pain, allodynia, and autonomic symptoms with IT baclofen alone. IT baclofen appears to be an option for patients with intractable CRPS who have failed other modalities, including IT morphine.


Determination of Singlet Exciton Diffusion Length in Thin Evaporated C60 Films for Photovoltaics.
C60 is used as an electron acceptor in small molecule photovoltaic devices in combination with various electron donors. The transport of excitons, i.e., bound electron/hole pairs, is an important factor determining the efficiency of such devices. Here we investigate the exciton diffusion length in C60 with the electrodeless time-resolved microwave conductance (TRMC) technique. Bilayers of 30 nm Zn-phthalocyanine with a C60 layer with variable thickness are prepared by physical vapor deposition. Analysis of the photoconductance with an exciton diffusion model yields a diffusion length of 7 nm, and the mobility of holes along Zn-Phthalocyanine stacks is close to 1 cm(2)/(V s). From analysis of the rise and decay of the TRMC transients, we attribute the photoconductance to diffusion and dissociation of singlet excitons rather than triplets. The energy transfer rate between C60 molecules exceeds 8 × 10(10) s(-1). Exciton diffusion cannot be described by the Förster model due to the close proximity of the molecules.


Survey on organochlorine pesticides, PCDD/Fs, dioxin-like PCBs and HCB in sediments from the Han river, Korea.
The contamination status of twelve persistent organic pollutants (POPs) on the Stockholm convention in the surface sediments of Han river, which is one of the largest river in the South Korea were investigated. Five organochlorine pesticides (OCPs) such as aldrin, dieldrin, endrin, mirex, and SigmaCHLs (alpha-chlordane, gamma-chlordane, cis-nonachlor, trans-nonachlor, and heptachlor) were not detected in all sediment samples. The overall concentrations of DDTs, HCB, dioxin-like PCBs (DL-PCBs) and PCDD/Fs were in the range of 1.05-8.94microgkg(-1) (average value: 3.93microgkg(-1)), 0.485-3.73microgkg(-1) (1.48microgkg(-1)), 41.5-4,530ngkg(-1) (548ngkg(-1)), and 23.1-368ngkg(-1) (131ngkg(-1)), respectively. The principal source of HCB, DL-PCBs and PCDD/Fs was identified as a deposition in this study. For the DL-PCBs, it was also shown that commercial PCBs product (Kanechlor 500 and/or Aroclor 1254) plays a role as a source in sediment.


Mass spectrometric fragmentation analysis of oligosialic and polysialic acids.
Oligosialic and polysialic acids (oligo/polySia) are characterized by high structural diversity, because of different types of sialic acids and glycosidic linkages. Although several methods have been described for the analysis of oligo/polySia, only high-performance liquid chromatography (HPLC) analysis in conjunction with 1,2-diamino-4,5-methylenedioxybenzene labeling, fluorometric C7/C9 detection, Western blotting, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF-MS) of lactonized oligo/polySia species, require submicrogram amounts of analyte. Since these methods do not provide detailed structural information, this study is focused on the characterization of oligo/polySia by tandem mass spectrometry (MS/MS). MALDI-TOF-MS/MS and electrospray ionization tandem mass spectrometry (ESI-MS/MS), employing up to three cycles of ion isolation and fragmentation in an ion trap, have been used for the characterization of nonderivatized glycans, oligoSia species modified at their reducing or nonreducing ends, as well as partially O-acetylated oligoSia derivatives. The obtained spectra were dominated by simultaneous cleavage of glycosidic linkages and the corresponding lactone ring, whereas classical cross-ring fragments were of minor abundance. However, the combined use of the two different types of fragmentation analysis allowed a sensitive and detailed characterization of both short-chained oligoSia and long polySia species. Furthermore, oxidation of the nonreducing end sugar moiety enabled sequence determination and localization of acetylated and nonacetylated sialic acid residues.


Risk adjustment for in-hospital mortality of contemporary patients with acute myocardial infarction: the acute coronary treatment and intervention outcomes network (ACTION) registry-get with the guidelines (GWTG) acute myocardial infarction mortality model and risk score.
accurate risk adjustment is needed to guide quality improvement initiatives and research to improve care of patients with acute myocardial infarction (MI). We developed and validated a model to predict the risk of in-hospital mortality for contemporary patients with acute MI treated in routine clinical practice. the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry-Get With The Guidelines (GWTG) database of patients with acute MI was used to derive (n = 65,668 from 248 US sites) and validate (n = 16,336) a multivariable logistic regression model to predict the likelihood of in-hospital mortality (4.9% in each cohort). factors with the highest independent significance in terms of mortality prediction included age, baseline serum creatinine, systolic blood pressure, troponin elevation, heart failure and/or cardiogenic shock at presentation, ST-segment changes, heart rate, and prior peripheral arterial disease. The model showed very good discrimination, with c statistics of 0.85 and 0.84 in the derivation and validation cohorts, respectively. The model calibrated well overall and in key patient subgroups including males versus females, age <75 versus ≥ 75 years, diabetes versus no diabetes, and ST-elevation MI versus non-ST-elevation MI. The ACTION Registry-GWTG in-hospital mortality risk score was also developed from the model. Patients with a risk score of ≤ 40 had an observed mortality rate of <4% compared with those with a risk score of 41-50 (12%) and risk scores >50 (34%). the ACTION Registry-GWTG™ in-hospital mortality model and risk score represent simple, accurate risk adjustment tools for contemporary patients with acute MI.


Intracellular applications of analytical SERS spectroscopy and multispectral imaging.
The aim of this tutorial review is to give an overview of the state of the art of intracellular applications of analytical SERS spectroscopy. We pay particular attention to nanoparticle-based SERS spectroscopy since this currently dominates the published literature on non-disturbing analysis of live cells. We describe recent advances in this domain due to the development of multispectral imaging and to the combined use of SERRS (surface-enhanced resonance Raman scattering) and fluorescence spectroscopy. Finally, a perspective view is given on the tip-based approaches like tip-enhanced Raman spectroscopy (TERS) which allow micrometric and nanometric resolution.


Bullying Victimization and Perpetration Among Adolescent Sport Teammates.
Bullying is a specific pattern of repeated victimization explored with great frequency in school-based literature, but receiving little attention within sport. The current study explored the prevalence of bullying in sport, and examined whether bullying experiences were associated with perceptions about relationships with peers and coaches. Adolescent sport team members (n = 359, 64% female) with an average age of 14.47 years (SD = 1.34) completed a pen-and-paper or online questionnaire assessing how frequently they perpetrated or were victimized by bullying during school and sport generally, as well as recent experiences with 16 bullying behaviors on their sport team. Participants also reported on relationships with their coach and teammates. Bullying was less prevalent in sport compared with school, and occurred at a relatively low frequency overall. However, by identifying participants who reported experiencing one or more act of bullying on their team recently, results revealed that those victimized through bullying reported weaker connections with peers, whereas those perpetrating bullying only reported weaker coach relationships. With the underlying message that bullying may occur in adolescent sport through negative teammate interactions, sport researchers should build upon these findings to develop approaches to mitigate peer victimization in sport.


The effect of endometriosis, cycle stage, lymphocyte suppression and pregnancy on CA-125 levels in peritoneal fluid and serum in baboons.
Serum CA-125 during the mid-follicular phase has been reported to be a clinically useful and reproducible marker in the diagnosis of advanced endometriosis in women. This study was undertaken to document the effect of the menstrual cycle, pregnancy and lymphocyte suppression on CA-125 levels in peritoneal fluid (PF) and serum in baboons with a normal pelvis and baboons with endometriosis. CA-125 levels were measured in 264 serum samples that were serially obtained during one menstrual cycle from 10 animals with and without endometriosis. In addition, CA-125 levels were determined in 204 archived samples (serum, n = 112 and PF, n = 92) obtained from 32 female baboons with or without endometriosis. The CA-125 assays were performed by radioimmunoassay using kits from Centocor (Malvern, PA, USA). Serum CA-125 levels were at their highest during menstruation and decreased progressively during the follicular and luteal phase. PF CA-125 levels were increased during the follicular phase in baboons with a normal pelvis, but no cyclic changes were observed in animals with endometriosis. Serum CA-125 levels were unaffected by induction, lymphocyte suppression or pregnancy. Induction of endometriosis resulted in increased PF CA-125 levels, whereas lymphocyte suppression or pregnancy had no effect. In baboons, serum CA-125 originates mainly from eutopic endometrium whereas the main source of PF CA-125 seems to be the peritoneum or ectopic endometrium. The baboon appears to be a valid model to further study the relationship between endometriosis and CA-125.


HIV-related knowledge, beliefs, and behaviors among high school students in the United States: results from a national survey.
The Secondary School Student Health Risk Survey measured the prevalence of sexual intercourse and illegal drug injection among a national probability sample of U.S. high school students and assessed their HIV-related knowledge and beliefs. Ninety-nine (81%) of the 122 selected schools and 8,098 (83%) of the eligible students participated. Nearly all high school students knew the major modes of HIV transmission. Three percent reported injecting illegal drugs, and 1% reported sharing needles used to inject drugs. In addition, 59% of students reported having sexual intercourse and, of students who reported having sexual intercourse, 40% reported having four or more sexual partners. HIV-related knowledge, beliefs, and behaviors among high school students suggest the need for school-based HIV education programs that help young people acquire the knowledge and skills to adopt and maintain behaviors that reduce risk of HIV infection and other related health problems.


Cell competition in tumor evolution and heterogeneity: Merging past and present.
In many cases, cancers are difficult to eliminate because they develop resistance to a primary chemotherapy or targeted therapy. Tumors grow into diverse cell subpopulations, increasing the ability to resist elimination. The phenomenon of 'cell competition' describes our body's natural surveillance system to optimize tissue fitness by forcing viable but aberrant cells to undergo cell death. Cell competition is not simply comparison of cell division potential. Competition factors signal for 'loser' cell elimination and 'winner' cell dominance. New evidence demonstrates it is possible to restrict cancer growth by strengthening the cell fitness of surrounding healthy tissue via anti-apoptotic pathways. Hence, cell competition provides strong conceptual explanation for oncogenesis, tumor growth and suppression. Tumor heterogeneity is a hallmark of many cancers and establishes gradients in which competitive interactions are able to occur among tumor cell subpopulations as well as neighboring stromal tissue. Here we review cellular/molecular competition pathways in the context of tumor evolution, heterogeneity and response to interventions. We propose strategies to exploit these mediators and design novel broad-spectrum therapeutic approaches that eliminate cancer and enhance fitness of neighboring tissue to improve patient outcomes.


Design of Metal-Organic Framework-Based Nanoprobes for Multicolor Detection of DNA Targets with Improved Sensitivity.
Metal-organic frameworks (MOFs) receive more and more interest in the field of analytical chemistry for their diverse structures and multifunctionality. In this study, we have designed and fabricated nanoscale MOF-based nanoprobes for multicolor detection of DNA targets with improved sensitivity. To do so, MOF-based nanoprobes, constructed by using porous MOFs as a scaffold to load signal dyes and a DNA hairpin structure as capping shell, have been prepared. Once the target has been introduced, a competitive displacement reaction triggers the release of fluorophores from the MOFs' pores. Consequently, a significantly enhanced fluorescence signal can be observed owing to the high loading capacity of MOFs. Therefore, the stimuli-responsive nanoprobes can enable sensitive detection of DNA targets with a low detection limit of 20 fM and selective identification to discriminate single-base mismatch. Moreover, the MOFs can encapsulate different fluorophores with different DNA gatekeepers designed according to the sequence of the target DNA, resulting in more kinds of stimuli-responsive nanoprobes for multiplexed DNA analysis in the same solution. Furthermore, these smart nanoprobes reported in this paper may provide a unique MOF-based tool for detection of various targets via stimuli-responsive systems in the future to widen the applications of MOFs.


Atypical antipsychotics in the treatment of affective symptoms: a review.
Atypical antipsychotics have demonstrated beneficial effects on affective symptoms, in addition to antipsychotic activity. Consequently, their role in the treatment of bipolar disorder and treatment-resistant or psychotic depression has been explored. Adjunctive atypical antipsychotic therapy appears to benefit patients experiencing manic episodes of bipolar disorder, and some studies suggest that monotherapy may also be efficacious. Clinical studies of patients with schizoaffective disorder and major depression support the use of atypical antipsychotics to treat depression. This review focuses on risperidone, olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs demonstrate activity against manic episodes of bipolar disorder when used as adjunctive therapy and possibly as monotherapy and that depression in patients with schizoaffective disorder also responds to these agents.


Plasma fibronectin deficiency during chemotherapy of acute myeloid leukaemia.
Plasma fibronectin was determined using a laser nephelometric method in 10 patients with acute myeloid leukaemia undergoing chemotherapy. There was a continuous fall during the first 3 weeks to about 50% of the normal level. The decrease of fibronectin may contribute to the lowered resistance against infection characteristic of these patients.


Characteristics of gut specific monoclonal antibodies.
Eight distinct murine monoclonal antibodies that are directed to normal human mouse small intestinal epithelial cells have been characterized. Three of these called TPNG 2, 20 and 43 were directed to goblet cells and mucin components. One antibody, TPNC 10, was directed to basilar crypt cell inclusions and was specific for the small bowel and possible progenitor cells. Another antibody, TPNC 30, was directed to the microvilli of the brush border. Finally, three antibodies, TPNC 50, 51 and 52 reacted with epithelial cell membranes. These three antibodies reacted with intestinal epithelial cell membranes but also cross-reacted with hepatocyte cytoplasm. The availability of intestinal specific monoclonal reagents will be of significant interest in studies of normal and abnormal intestinal physiology.


Revising the British Occupational Hygiene Society asbestos standard: 1968-1982.
In 1968 the British Occupational Hygiene Society (BOHS) published a chrysotile asbestos hygiene standard. As a consequence of acknowledged inadequacies of the data, it underestimated the risks of exposure, but its influence was international and operated for longer than it merited. Five years later, BOHS reported the standard not to be in need of amending, despite its own doubts and no cognizance having been taken of the cancer hazard. Within months, stung by criticism from Dr. Irving J. Selikoff, industry required it to review the standard, which BOHS continued to do for a number of years before giving up. Material obtained for the American Courts by means of legal discovery from an asbestos company's archive, provided information on the membership of the new BOHS committees, and on its operation. Alterations in the composition of the new committees included importantly the introduction of certain independent scientists, whose rigor militated against the ready production of a new hygiene standard acceptable to industry. There was a time in Britain when a learned society might with impunity omit to consult the views of workers or their representatives when making value judgments about their health and safety, but consider it proper to accede to industry's decision as to what hygiene standard it would accept. Health and Safety at Work legislation in 1974, established an organization on which industry and labor were represented, with the onus for recommending hygiene standards. For several years the BOHS Asbestos Sub-Committee continued attempting to reconcile the interests of industry, until finally abandoning hygiene standard setting as its mission.


An audit of emergency medicine responses to children injured in violence.
To audit emergency department (ED) responses to violence in which children are injured in violence in a European capital city. A prospective survey of children (aged <16 years) was conducted in Cardiff's only ED using ED software adapted for this purpose. All clinical records were scrutinised for evidence of discussion with and referral to agencies concerned with child protection. 123 children reportedly injured in violence (92 boys) were treated in 2004, six aged 5-9 years; one under 5 years. Overall, 24 (19%) incidents had been reported to the police prior to ED arrival. Only four (3%) prompted documented referral or discussions with other agencies while in the ED. 78% prompted no action apart from treatment of injuries. 13 (10%) children had fractures or were admitted, but only two of these incidents had been drawn to police attention. Only five (4%) were injured at home; a large majority were injured in the street or at school with fists or feet (12 with a weapon) by other children or adults. In this audit, most violence in which children were injured took place in schools and in the street. For children of secondary school age, ED treatment rarely prompted referral or discussion with agencies responsible for child safety. Particularly since youth and child violence are major national issues, policy and practice in this area were developed and built on disclosure of all such cases to a single referral point in the local authority education department.


Value of ultrasound elastography in the diagnosis of native kidney fibrosis.
In the last decade, ultrasound elastography, an already widely used technique in the diagnosis of hepatic fibrosis, has raised the attention of nephrologists as a potential valuable noninvasive tool for the diagnosis of renal fibrosis. Due to renal deep location and anatomic complexity, the shear wave techniques are the most appropriate elastography methods for exploring native kidneys. Recent research offers promising results, but further larger studies are required for a better standardization of this method and also for establishing reference values of normal kidney elasticity. This article reviews the studies conducted for exploring the native kidney, highlighting the advantages and limitations of ultrasound elastography for assessing fibrosis development in chronic kidney diseases.


Double-blind comparison of oral transmucosal fentanyl citrate with oral meperidine, diazepam, and atropine as preanesthetic medication in children with congenital heart disease.
The effectiveness of oral transmucosal fentanyl citrate (OTFC) as preanesthetic medication was compared with oral meperidine, diazepam, and atropine (MDA) in 40 pediatric patients scheduled to undergo repair of congenital heart defects. In a double-blinded manner, patients received a fentanyl lollipop (20-25 micrograms/kg) and a placebo oral solution (0.4 ml/kg) (n = 20) or a placebo lollipop and an oral solution (0.4 ml/kg) of meperidine (1.5 mg/kg), diazepam (0.2 mg/kg), and atropine (0.02 mg/kg) (n = 20). The patient's vital signs, systolic and diastolic blood pressures, heart rate, respiratory rate, and oxyhemoglobin saturation (SpO2), as well as activity and apprehension scores were evaluated and recorded at baseline and at 10-min intervals. The patient's emotional status at the time of parental separation and at induction of anesthesia were also assessed. Side effects and onset of action were observed. After OTFC, onset of sedation was significantly faster than with the oral solution of meperidine, diazepam, and atropine. In both groups there was no significant change in heart rate. Although systolic blood pressure, diastolic blood pressure, and respiratory rate showed statistically significant decreases, these changes were not clinically significant. The child's emotional status at the time of separation from the parents and during induction was similar in both groups. Side effects with OTFC were more frequent: nose itching occurred in 65%, body itching in 10%, and vomiting in 30%. Two patients (10%) in the OTFC-treated group became hypoxemic (SpO2 less than 90) and required supplemental oxygen. In the group receiving oral meperidine, diazepam, and atropine, 10% had mild facial pruritus and 5% complained of a dry mouth.(ABSTRACT TRUNCATED AT 250 WORDS)


AIDS in Europe: current trends and short-term predictions estimated from surveillance data, January 1981-June 1986.
European AIDS surveillance data, reported to the World Health Organization (WHO) Collaborating Centre on AIDS, Paris by 30 June 1986, have been analysed statistically to assess current trends and to provide short-term predictions. Reported case numbers were first adjusted to allow for the estimated time delays between diagnosis and reporting. The adjusted data (cases per half-year of diagnosis) were then fitted using exponential functions over selected time intervals to monitor and compare the evolution of the epidemic in individual countries and in the European Community (EC) as a whole. Predictions to mid-1988 were made by extrapolation. Results are presented for the EC and for the following individual countries: Belgium, Denmark, France, Federal Republic of Germany, Italy, The Netherlands, Spain, Sweden, Switzerland and the United Kingdom.


Firearms and adolescent suicide. A community case-control study.
To assess the association between firearms in the home and adolescent suicide. Matched, case-control. Population-based community sample. Sixty-seven adolescent suicide victims and a demographically matched group of 67 living community controls. The series of adolescent suicide victims was consecutive, with an overall participation rate of 74% (67/91). The presence, type (hand-gun vs long-gun), number, and method of storage (locked vs unlocked, loaded vs unloaded) of firearms in the home were compared between the suicide victims and controls. Even after adjusting for differences in rates of psychiatric disorders between suicide victims and controls, the association between suicide and both any gun (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 1.1 to 17.5) and handguns (OR = 9.4, 95% CI = 1.7 to 53.9) in the home were both highly significant. Long-guns in the home were associated with suicide only in rural areas, whereas handguns were more closely associated with suicide in urban areas. Handguns (OR = 12.9, 95% CI = 1.5 to 110.9) and loaded guns (OR = 32.3, 95% CI = 2.5 to 413.4) in the home were particularly significant risk factors for suicide in those with no apparent psychiatric disorder. When pediatricians are faced with a suicidal adolescent, they should insist on the removal of firearms from the home. Pediatricians should also inform parents that the presence of firearms may be associated with adolescent suicide even in the absence of clear psychiatric illness.


[Proteomic analysis of proteins related to retinoid acid resistance].
To evaluate the applicability of proteomic methods for shedding light on the mechanisms of All-trans retinoic acid resistance. The expression of cellular proteins in the retinoid acid sensitive cell line NB4 and retinoid acid resistant cell line MR2 was analyzed using the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Differentially expressed proteins were analyzed by mass spectrometry for peptide mass finger and identified by SWISS-PROT protein database. Approximately 600 spots appeared in an sodium dod(SDS-GEL). The match of the expression of cellular proteins between NB4 and MR2 was better. Three significantly differentially expressed proteins were screened and identified to DJ-1 and HSP70, as well as KIAA1289 of which the function is not yet known. The utilization of 2D-PAGE, coupled with mass spectrometry is effective in screening the drug resistance-associated proteins and could provide molecular targets for the elucidation of resistance mechanisms.


C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site.
USP7, also known as the hepes simplex virus associated ubiquitin-specific protease (HAUSP), deubiquitinates both mdm2 and p53, and plays an important role in regulating the level and activity of p53. Here, we report that deletion of the TRAF-like domain at the N-terminus of USP7, previously reported to contain the mdm2/p53 binding site, has no effect on USP7 mediated deubiquitination of Ub(n)-mdm2 and Ub(n)-p53. Amino acids 208-1102 were identified to be the minimal length of USP7 that retains proteolytic activity, similar to full length enzyme, towards not only a truncated model substrate Ub-AFC, but also Ub(n)-mdm2, Ub(n)-p53. In contrast, the catalytic domain of USP7 (amino acids 208-560) has 50-700 fold less proteolytic activity towards different substrates. Moreover, inhibition of the catalytic domain of USP7 by Ubal is also different from the full length or TRAF-like domain deleted proteins. Using glutathione pull-down methods, we demonstrate that the C-terminal domain of USP7 contains additional binding sites, a.a. 801-1050 and a.a. 880-1050 for mdm2 and p53, respectively. The additional USP7 binding site on mdm2 is mapped to be the C-terminal RING finger domain (a.a. 425-491). We propose that the C-terminal domain of USP7 is responsible for maintaining the active conformation for catalysis and inhibitor binding, and contains the prime side of the proteolytic active site.


Immunoreactive trypsin and the prenatal diagnosis of cystic fibrosis.
Immunoreactive trypsin (IRT) was measured by radioimmunoassay in a series of amniotic fluids obtained at between 15 and 19 weeks from pregnancies with a 1-in-4 risk of fetal cystic fibrosis. IRT concentrations were significantly depressed in nine affected pregnancies, but the degree of overlap with the normal range was too great for this to be useful in early prenatal diagnosis. Furthermore, in one fetus, presumed to have cystic fibrosis, the fetal plasma IRT concentration was within the normal range.


Trousseau's syndrome in the head and neck.
Thromboses in Trousseau's syndrome are typically confined to the vascular system of the extremities and viscera. The authors report a case of sequential bilateral internal and external jugular-vein thromboses secondary to this paraneoplastic hypercoagulable state. The etiologies of commonly encountered head and neck venous thromboses are infection, trauma, and obstruction. This article purports that head and neck venous thromboses without a proximal inflammatory or mechanical cause may be the initial manifestation of an occult malignancy. Upon establishing the presence of a hypercoagulable state, further evaluation may lead to the early diagnosis of such an occult malignancy.


A novel study of antibacterial activity of copper iodide nanoparticle mediated by DNA and membrane damage.
In this article potential activity of nanoparticles (NPs) of copper iodide (CuI) as an antibacterial agent has been presented. The nano particles are synthesized by co-precipitation method with an average size of 8 nm as determined by Transmission Electron Microscope (TEM). The average charge of the NPs is -21.5 mV at pH 7 as obtained by zeta potential measurement and purity is determined by XRD. These NPs are able to kill both gram positive and gram negative bacteria. Among the bacteria tested, DH5α is more sensitive but Bacillus subtilis is more resistant to NPs of CuI. Consequently, the MIC and MBC values of DH5α is least (0.066 mg/ml and 0.083 mg/ml respectively) and B. subtilis is highest (0.15 mg/ml and 0.18 mg/ml respectively) among the tested bacterial strains. From our studies it is inferred that CuI NPs produce reactive oxygen species (ROS) in both gram negative and gram positive bacteria and it also causes ROS mediated DNA damage for the suppression of transcription as revealed by reporter gene assay. Probably ROS is formed on the surface of NPs of CuI in presence of amine functional groups of various biological molecules. Furthermore they induce membrane damage as determined by atomic force microscopy (AFM). Thus production of ROS and membrane damage are major mechanisms of the bactericidal activity of these NPs of CuI.


[Recovery of nigrostriatal and mesolimbic dopaminergic system following administration of ganglioside in MPTP-treated mice].
The effects of systemic injection of GM 1 ganglioside on dopaminergic (DA) nigrostriatal and mesolimbic system following 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) have been studied in C 57 BL/6 mice. MPTP treatment (4 x 20 mg/kg i.p. given 12 hr apart) resulted in significant depletion of DA concentration in the major terminal fields of the nigrostriatal and mesolimbic DA systems, i.e. dorsal striatum, ventral striatum, nucleus accumbens and olfactory tubercle 5 weeks after treatment in young (2 month old) mice. In aging (12 month old) mice treated with MPTP, significant depletion of DA concentration was observed in the cell body regions, i.e. substantia nigra and ventral tegmental area in addition to the major terminal fields, suggesting that the effect of MPTP is more widespread in aging mice. Although GM 1 ganglioside treatment (30 mg/kg, i.p. daily for 5 weeks) partially restored DA concentration in every major terminal field in young mice, such an apparent recovery was not seen in aging mice. GM 1 ganglioside treatment also reduced the increased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio following MPTP injection in the striatum of young mice, but such an effect was not observed in aging mice. We conclude that DA nigrostriatal and mesolimbic system in aging mice demonstrates reduced regenerative capacity following MPTP depletion compared with young mice, and the beneficial effect of GM 1 ganglioside for the recovery of DA nigrostriatal and mesolimbic system neurons declines with age.


The pH dependence of CD2 domain 1 self-association and 15N chemical exchange broadening is correlated with the anomalous pKa of Glu41.
We have previously shown using (15)N nuclear relaxation measurements that the concentration-dependent rotational correlation time and chemical exchange broadening for selected resonances of rat CD2 domain 1 (CD2d1) are consistent with a model of low-affinity self-association of the protein molecules. The exchange broadening data, which at high protein concentrations highlight selected nuclei in the major C'-C-F-G beta-sheet face of the immunoglobulin fold, implicate a surface reminiscent of the major lattice contact within crystals of the intact CD2 ectodomain. In a separate study, we have also demonstrated that the beta-strand C' surface-exposed residue Glu41 possesses an anomalously elevated acidity constant (pK(a) = 6.7 at a protein concentration of 1.2 mM). Mutagenesis studies showed that the close contact of residue Glu41 with Glu29 (beta-strand C) is the primary cause of the high pK(a). However, the measured pK(a) of Glu41 also shows a weak dependence on protein concentration, implicating Glu41 in the mechanism of CD2d1 self-association. In the study presented here, we demonstrate a correlation of the pH dependence of the chemical shift and (15)N nuclear relaxation parameters measured for wild-type and mutant forms of CD2d1 with pH and the protonation state of Glu41. Self-association of CD2d1 molecules is promoted whenever the side chain charge of residue 41 is neutralized. These observations are consistent with a model for CD2d1 self-association that corresponds to the crystal structure lattice contact where the interatomic distances are consistent with Glu41 being in the protonated state. This study reinforces the conclusion that residue-specific chemical exchange broadening of protein resonances can arise from weak self-association phenomena. In addition, the electrostatic profile of rat CD2 interfacial residues parallels that of the homologous human CD2 in a manner that suggests a rationalization of similar exchange broadening observations.


Routes of administration of antibiotic prophylaxis for preventing infection after caesarean section.
Post-caesarean section infection is a cause of maternal morbidity and mortality. Administration of antibiotic prophylaxis is recommended for preventing infection after caesarean delivery. The route of administration of antibiotic prophylaxis should be effective, safe and convenient. Currently, there is a lack of synthesised evidence regarding the benefits and harms of different routes of antibiotic prophylaxis for preventing infection after caesarean section. The aim of this review was to assess the benefits and harms of different routes of prophylactic antibiotics given for preventing infectious morbidity in women undergoing caesarean section. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 January 2016) and reference lists of retrieved studies. We included randomised controlled trials (RCTs) comparing at least two alternative routes of antibiotic prophylaxis for caesarean section (both elective and emergency). Cross-over trials and quasi-RCTs were not eligible for inclusion. Two review authors independently assessed trials for inclusion, assessed the risk of bias and extracted data from the included studies. These steps were checked by a third review author. We included 10 studies (1354 women). The risk of bias was unclear or high in most of the included studies.All of the included trials involved women undergoing caesarean section whether elective or non-elective. Intravenous antibiotics versus antibiotic irrigation (nine studies, 1274 women) Nine studies (1274 women) compared the administration of intravenous antibiotics with antibiotic irrigation. There were no clear differences between groups in terms of this review's maternal primary outcomes: endometritis (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.29; eight studies (966 women) (low-quality evidence)); wound infection (RR 0.49, 95% CI 0.17 to 1.43; seven studies (859 women) (very low-quality evidence)). The outcome of infant sepsis was not reported in the included studies.In terms of this review's maternal secondary outcomes, there were no clear differences between intravenous antibiotic or irrigation antibiotic groups in terms of postpartum febrile morbidity (RR 0.87, 95% CI 0.48 to 1.60; three studies (264 women) (very low-quality evidence)); or urinary tract infection (RR 0.74, 95% CI 0.25 to 2.15; five studies (660 women) (very low-quality evidence)). In terms of adverse effects of the treatment on the women, no drug allergic reactions were reported in three studies (284 women) (very low-quality evidence), and there were no cases of serious infectious complications reported (very low-quality evidence). There was no clear difference between groups in terms of maternal length of hospital stay (mean difference (MD) 0.28 days, 95% CI -0.22 to 0.79 days, (random-effects analysis), four studies (512 women). No data were reported for the number of women readmitted to hospital. For the baby, there were no data reported in relation to oral thrush, infant length of hospital stay or immediate adverse effects of the antibiotics on the infant. Intravenous antibiotic prophylaxis versus oral antibiotic prophylaxis (one study, 80 women) One study (80 women) compared an intravenous versus an oral route of administration of prophylactic antibiotics, but did not report any of this review's primary or secondary outcomes. There was no clear difference between irrigation and intravenous antibiotic prophylaxis in reducing the risk of post-caesarean endometritis. For other outcomes, there is insufficient evidence regarding which route of administration of prophylactic antibiotics is most effective at preventing post-caesarean infections. The quality of evidence was very low to low, mainly due to limitations in study design and imprecision. Furthermore, most of the included studies were underpowered (small sample sizes with few events). Therefore, we advise caution in the interpretation and generalisability of the results.For future research, there is a need for well-designed, properly-conducted, and clearly-reported RCTs. Such studies should evaluate the more recently available antibiotics, elaborating on the various available routes of administration, and exploring potential neonatal side effects of such interventions.


Androgen receptor in rat Harderian and submandibular glands.
Androgens regulate the development and sexual dimorphism of rodent Harderian and submandibular glands. This effect is believed to be mediated by the androgen receptor. Immunohistochemistry and immunoblotting were carried out to study the receptor in normal, castrated and dihydrotestosterone-supplemented rat Harderian and submandibular glands. Immunohistochemically, the most intense nuclear staining was observed in the acinar cells of the submandibular glands, followed by intercalated duct cells. The granular convoluted tubules showed weak immunostaining and the striated ducts were negative. In the Harderian gland, nuclear staining was seen in both type I and II secretory cells. Castration and treatment had no effect on the expression of the androgen receptor protein in either gland. A 110 K androgen receptor signal was detected by immunoblotting in the Harderian gland but not in the submandibular gland. An experiment was designed to explore the possible effect of proteinases on the receptor protein in the homogenate of submandibular gland. Our results demonstrate the cell-specific location of the receptor in Harderian and submandibular glands, and show that the expression of the receptor protein is androgen-independent.


Incidence of chronic bilirubin encephalopathy in Canada, 2007-2008.
Despite the implementation of screening guidelines to identify infants at risk for hyperbilirubinemia, chronic bilirubin encephalopathy (CBE) continues to be reported worldwide in otherwise healthy infants. The incidence of CBE in Canada is unknown. The objectives of this study were to establish the incidence of CBE in Canada and identify epidemiological and medical risk factors associated with its occurrence. Data on infants were collected prospectively through the Canadian Pediatric Surveillance Program. Infants born between January 1, 2007 and December 31, 2008 were included if they either had symptoms of CBE and a history of hyperbilirubinemia, or if they presented in the newborn period with severe hyperbilirubinemia and an abnormal MRI finding as per the reporting physician. During the study period, 20 cases were identified; follow-up data were available for 14 of these. The causes for the hyperbilirubinemia included glucose-6-phosphate dehydrogenase deficiency (n = 5), sepsis (n = 2), ABO incompatibility and other red blood cell antibodies (n = 7). Fifteen infants had abnormal brain MRI findings during the neonatal period. At follow-up, 5 infants developed classic choreoathetoid cerebral palsy, 6 had spectrum of neurologic dysfunction and developmental delay (as described by the reporting physician), and 3 were healthy. CBE continues to occur in Canada at an incidence that appears to be higher than previously reported.


Non-peptide angiotensin receptor antagonists bind to tachykinin NK3 receptors of rat and guinea pig brain.
[3H]Senktide, a highly selective tachykinin NK3 receptor agonist, was used to study tachykinin NK3 receptors of rat and guinea pig brain. Guinea pig brain membranes had a Kd of 3.9 +/- 0.5 nM and a Bmax of 42 fmol/mg. Dose-displacement experiments with neurokinins and selective tachykinin receptor agonists revealed the following order of potency: [MePhe7]neurokinin B > neurokinin B > substance P > neurokinin A. This order is typical for a tachykinin NK3 receptor. To further characterize the specificity of this receptor, the effects of unrelated compounds such as: bradykinin, angiotensin II, bombesin and their structural analogs were also evaluated on the binding of [3H]senktide. Unexpectedly, the angiotensin AT1 receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole potassium salt), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl) methyl]-3H-imidazo[4,5-beta]pyridine H2O) and EXP 3174 (2-n-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]i midazole- 5-carboxylic acid), inhibited the binding of [3H]senktide to its receptor in the guinea pig brain membranes with IC50 values of 18 microM, 25 microM and 50 microM, respectively. Similar effects were also observed with rat brain membranes. Angiotensin II, saralasin ([Sar1,Val5,Ala8]angiotensin II, a peptide angiotensin AT1 receptor antagonist) and PD 123,319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)-4,5, 6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, a known non-peptide angiotensin AT2 receptor antagonist) did not inhibit the binding of [3H]senktide to either type of membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


Degradation of vitamin B12 in dietary supplements.
Beverages and solid dietary supplements rich in various added vitamins and minerals have recently become available. It seems reasonable to consider that the intake of these foods is convenient for easy ingestion of nutrients, but problems caused by blending different nutrients in high concentrations have arisen. We focused on vitamin B12 (B12) among vitamins and determined the B12 contents of beverages and solid dietary supplements purchased from a retail shop. The B12 contents of three of five beverages were less than stated on the labels. On the other hand, certain beverages unexpectedly contained much more B12 than stated on the labels. In these beverages the amount of B12 decreased rapidly with time, whereas B12 content was lower than stated on the label in only one of four solid dietary supplements. The content of B12 was affected by storage time, light exposure, temperature and vitamin C. From experimental analysis with a competitive binding assay method employing a ACS Chemiluminescent B12 kit, examining differential binding by intrinsic factors and spectral analysis of B12, it was determined that some of the B12 might have been converted into B12 analogues or small degradation products by multinutrient interaction during storage.


The cerebral function monitor during open-heart surgery.
Open-heart surgery has entered the third decade of its existence. The period has demonstrated increased patient safety during and after open-heart surgery due to the employment of simple and reliable monitoring techniques. The monitoring of the function of the brain has not kept pace with these advances. Electroencephalographic (EEG) method is impractical for routine use in the operating room and in the intensive care unit. The cerebral function monitor (CFM) offers simplified continuous monitoring and interpretation of cerebral electrical activity (integrated EEG) in the clinical situation. The unit displays a two channel tracing, one representing cerebral activity and a second indicating electrode impedance artefacts. The early changes seen in addition to other conventional monitoring of the electrocardiogram, blood pressures, pulse rate, etc. offers information especially pertinent to open-heart surgery. It would appear that there is a place in anesthetic practice during and after cardiopulmonary bypass for the routine use of the CFM to supplement existing monitoring for the safer conduct of open-heart surgery. This study analyzes the value of a cerebral function monitor in 112 patients undergoing open-heart surgery.


Improved renal recovery with postresuscitation N-acetylcysteine treatment in asphyxiated newborn pigs.
Renal injury is one of the severe and common complications that occurs early in neonates with asphyxia, and reactive oxygen species have been implicated to play an important role on its pathogenesis. Improved renal recovery has been shown previously with N-acetyl-l-cysteine (NAC) in various acute kidney injuries. Using a subacute swine model of neonatal hypoxia-reoxygenation (H/R), we examined whether NAC can sustain its beneficial effect on renal recovery for 48 h. Newborn piglets were randomly assigned into a sham-operated group (without H/R, n = 6) and two H/R experimental groups (n = 8 each) with 2 h normocapnic alveolar hypoxia and 1 h 100% oxygen of reoxygenation followed by 21% oxygen for 47 h. Five minutes after reoxygenation, piglets received either normal saline (H/R control) or NAC (150-mg/kg bolus and 20 mg/kg per hour i.v. for 24 h) in a blinded, randomized fashion. All piglets were acidotic and in cardiogenic shock after hypoxia. Treating the piglets with NAC significantly increased both renal blood flow and oxygen delivery throughout the reoxygenation period. N-acetyl-l-cysteine treatment also improved the renal function with the attenuation of elevated urinary N-acetyl-β-d-glucosaminidase activity and plasma creatinine concentration observed in H/R controls (both P < 0.05). The tissue levels of lipid hydroperoxides and caspase 3 in the kidney of NAC-treated animals were significantly lower than those of H/R controls. Conclusively, postresuscitation administration of NAC elicits a prolonged beneficial effect in improving renal functional recovery and reducing oxidative stress in newborn piglets with H/R insults for 48 h.


Ischemic reperfusion brain injury in fetal transgenic mice with elevated levels of copper-zinc superoxide dismutase.
To examine the effect of overexpression of human intracellular copper-zinc superoxide dismutase (CuZnSOD1) gene on fetal mice brain exposed to in-utero ischemic reperfusion injury. Transient in-utero ischemia (7 min) was induced in pregnant transgenic mice overexpressing human CuZnSOD1 and wild-type mice by occluding the blood supply to the uterine artery on day 17 of pregnancy, followed by 24 hours of reperfusion. The level of lipid peroxidation in fetal mice brains was compared between the transgenic and non-transgenic (control) fetal mice. Motor and coordination skills of transgenic and control adult mice (six to eight months old) which were exposed to ischemic reperfusion injury in-utero were compared by the rope grip test and visible platform task. We first measured CuZnSOD1 activity in the brains of the transgenic fetal mice and confirmed that the enzyme activity is 4.2-fold higher than control. We also established that ischemia reperfusion on day 17 of pregnancy led to increased level of TBARS (Thiobarbituric acid reactive substance) in brains of wild-type fetal mice when compared to sham operated mice (72.5 +/- 3.4 vs. 49.4 +/- 1.5 nmol/mg. p < 0.001). The increase was markedly accentuated in the CuZnSOD1 transgenic mice, and significantly higher compared to control mice exposed to ischemia-reperfusion (85.6 +/- 4.0 vs. 69.5 +/- 2.3 nmol/mg, p < 0.001). Moreover, we found that the transgenic mice that were subjected to in-utero ischemia reperfusion exhibited a significantly higher rate of failures in the rope grip test and poorer performance in the visible platform task, when compared to non-transgenic mice exposed to identical insult. Oxygen free radicals play an important role in the pathogenesis of perinatal hypoxia. Overexpression of the enzyme CuZnSOD1 in transgenic mice exposed their brains to increased damage during ischemic-reperfusion insult.


Calcium channel blocker use reduces incident dementia risk in elderly hypertensive patients: A meta-analysis of prospective studies.
Calcium channel blockers (CCBs) are an established class of drug for the management of hypertension. Observational studies have found that CCB use is associated with a reduction in the risk of developing dementia; however, studies have variably linked the CCBs use with the risk of dementia. This meta-analysis aims to assess whether, in elderly hypertensive patients, the use of CCBs alters the risk of developing dementia. We searched PubMed, Embase and Cochrane from August 2013 to 21st August 2017. Studies were screened on the basis of title and abstract. Quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcome was an estimate of the risk of dementia in elderly hypertensive CCBs users. The pooled relative risk (RR) was calculated using a generic inverse variance method. A subgroup analysis was also performed based on CCB class. Statistical analyses were performed using Review Manager Version 5.3. The meta-analysis included ten studies comprising 75,239 patients (53.16% female) with a median age and follow-up duration of 72.24 years and 8.21 years respectively. All of the studies were of high quality. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients (RR 0.70 [95% CI: 0.58-0.85] p = 0.0003) compared to those not using CCBs. In subgroup analysis we found that the dihydropyridine class was associated with a 44% [RR 0.56 (95% CI: 0.40-0.78) p = 0.0005] reduction in the dementia risk. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients.


[The role of developmental HOX genes in cervical cancer].
Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.


[Involvement of PIWI-interacting RNAs in Cancerogenesis via the Regulation of Gene Expression].
In the past few years, a number of studies have suggested that small non-coding RNAs could be promising diagnostic, prognostic and predictive biomarkers in oncology. Recently, small RNAs interacting with PIWI proteins (piRNAs) have been described. These small RNAs regulate gene expression at transcriptional and post-transcriptional levels; however, they appear to be specifically involved in silencing the transposable elements LINE and SINE and are thus considered to contribute to genomic stability. Furthermore, piRNAs participate also in other important biological processes, such as gametogenesis, chromosome segregation, and stem cell self-renewal. Although their expression was first noted in germ line cells, they are now known to be present in all tissue types and their expression is highly tissue-specific. In addition, piRNA expression is dysregulated in tumor tissues. Nevertheless, the exact function of these molecules in cancerogenesis is not known. Recently, free circulating piRNAs were reported to be stably present in body fluids, suggesting that they could serve as promising noninvasive biomarkers to enable early diagnosis, therapy response prediction, and accurate prognosis prediction of cancer patients. The aim of this review is to summarize current knowledge about piRNA biogenesis and their functions in the regulation of gene expression and transposons silencing. In addition, the review focuses on piRNAs that show dysregulated expression in different types of cancers and that could serve as potential diagnostic biomarkers and/or therapeutic targets.Key words: PIWI-interacting RNAs - piRNA - biogenesis - cancer - transposon silencing - biomarkers - therapeutic targetsThe results of this research have been acquired within CEITEC 2020 (LQ1601) project with financial contribution made by the Ministry of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 23. 11. 2016Accepted: 5. 12. 2016.


Instability of microsatellites is an infrequent event in uveal melanoma.
Microsatellite instability (MSI) is a distinct tumour phenotype that is associated with alterations of DNA mismatch repair and is being increasingly reported in a number of hereditary and sporadic tumours. Numerous reports have suggested that melanocytic neoplasms, including cutaneous melanomas, frequently demonstrate low frequency MSI, whilst a small number of tumours exhibit high frequency MSI. Furthermore, loss of expression of DNA mismatch repair proteins has been associated with progression from benign to malignant disease in melanocytic neoplasms, but the presence or absence of mismatch repair defects in uveal melanomas has yet to be determined. This study was designed to establish whether MSI is a feature of these ocular melanomas. To investigate the prevalence of MSI in uveal melanomas, 52 tumours were analysed by polymerase chain reaction amplification of a panel of microsatellite markers selected for their ability to detect tumours exhibiting defects in DNA mismatch repair mechanisms. MSI was rarely detected in the 52 uveal melanomas analysed. All tumours demonstrated stable microsatellites at five of the six microsatellite markers tested (BAT26, BAT40, APC, D2S123 and Mfd15CA). Only one tumour showed the presence of a single unstable allele at a tetranucleotide marker (MYCL1). These data suggest that high frequency MSI does not occur in these tumours, and that low frequency MSI, in contrast to cutaneous melanoma, is a rare event in malignant melanomas of the uveal tract.


Interplasmidic and intraplasmidic recombination in Escherichia coli K-12.
The construction of plasmids which facilitate the study of interplasmidic and intraplasmidic recombination is described. In this system, a single recombination event between two mutated Tcr genes on separate plasmids or on one plasmid leads to a change in the host phenotype from sensitivity to resistance to tetracycline. Recombination proficiencies have been determined for different E. coli K-12 strains: both interplasmidic and intraplasmidic recombination are independent of the recBC gene product. RecA mutations decrease the proficiency of plasmidic recombination 40 - 100 fold. Intraplasmidic and interplasmidic recombination via the recE pathway are more efficient than via the recBC pathway. Intraplasmidic recombination, but not interplasmidic recombination via the recE pathway is independent of a functional recA product.


Regulation of HIV-1 infection in astrocytes: expression of Nef, TNF-alpha and IL-6 is enhanced in coculture of astrocytes with macrophages.
'Restricted' human immunodeficiency virus type (HIV-1) infection of astrocytes is recognized in vivo in some pediatric and adult AIDS brains and in vitro in a small proportion of transfected primary fetal astrocytes. We investigated the extent of HIV-1JR-FL expression in fetal astrocytes and macrophages cultivated alone or together. Peak HIV-1 p24 antigen titres in supernatant fluids of macrophage cultures were increased with monocyte/macrophages from certain donors and were higher when macrophages were cocultivated with astrocytes. Structural HIV-1 gene (gp 41 and pol) products (protein and mRNA) were observed only in macrophages. Ten days after HIV-1JR-FL infection, astrocytes in a monoculture were stained negative or only weakly positive (1-2+) for Nef, whereas in a coculture up to 100% of astrocytes displayed Nef staining (up to 4+) in the cytoplasm. The streptavidine-biotine-peroxidase technique with certain monoclonal antibodies to Nef (Ovod et al, 1992) was specific for infected astrocytes. The intensity of Nef staining was higher in astrocytes cultivated with monocyte/macrophages from certain donors. In the coculture, tumor necrosis factor-alpha (TNF-alpha) was expressed in the astrocyte cytoplasm earlier after coinfection with HIV-1 and cytomegalovirus (CMV) compared to infection with HIV-1 alone. Interleukin-6 (IL-6) was secreted spontaneously and transiently in uninfected cocultures, but in a prolonged fashion following HIV-1 and HIV-1/CMV infections. The interactions between HIV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-alpha and IL-6 and enhancement of productive HIV-1 infection of macrophages and of 'restricted' HIV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.


T cells and cancer - why do the killers become exhausted?
Nascent tumors are mostly eliminated by the immune system. During carcinogenesis mutated cells find a way to escape from the immune system´s surveillance. As the tumor microenvironment evolves it becomes increasingly difficult for T cells to recognize and kill cancer cells. Recently, novel immunological targets have been recognized and potent immunomodulatory drugs discovered in clinical trials. This has resulted in the emergence of immunotherapy as a novel potent therapy for cancer in addition to chemotherapy, targeted therapy, operative therapy and radiotherapy.


Understanding the origin of asthma and its relationship to breastfeeding.
Asthma is a chronic disease of the lung that has been increasing at an alarming rate in industrialized countries around the world over the last few decades. Although considerable progress has been made in our understanding of the underlying pathogenesis of the disease, the exact causes of the increasing prevalence are unknown. Studies suggest that most asthma develops in early childhood and that environmental factors present early in life may be crucial in the development of disease. One potential explanation for the recent epidemic referred to as the "hygiene hypothesis" postulates that factors that have resulted in a reduction in exposure to microbial products and/or infections in the western world may be contributing to this rise in disease prevalence. As early life influences are known to play an important role in establishment of asthma, studies have focused on the interface between mother and child that occurs during gestation and through breastfeeding. In this regard, the body of evidence regarding the relationship between breastfeeding and asthma indicates benefit but with the potential for risk. While providing population-level protection from infections and atopy in infancy and early childhood, breastfeeding might also pose an increased risk of atopic asthma among children with asthmatic mothers. In order to put this controversy in context, we discuss our current understanding of asthma pathogenesis, current theories on the factors driving the rising prevalence of asthma, and then discuss the potential influence of breastfeeding on asthma pathogenesis.


Aldosterone and renin inhibition by physiological levels of atrial natriuretic factor.
This study was designed to examine, in the rat, the inhibition of renin release and aldosterone secretion by physiological plasma levels of atrial natriuretic factor (ANF). Intravascular volume expansion over 30 min with donor blood equal to 3% body weight increased plasma ANF concentration from a base line of 216 +/- 28 to 1,590 +/- 240 pg/ml (P less than 0.001) in sodium-replete rats. Basal plasma ANF levels were decreased to 125 +/- 9 pg/ml in animals fed a low-sodium diet, and the infusion of synthetic ANF into separate groups of these rats at doses of 15 or 45 ng.kg-1.min-1 elevated plasma ANF to 346 +/- 38 and 720 +/- 96 pg/ml, respectively (P less than 0.001 for both values). Infusion of ANF at 15 ng.kg-1.min-1 resulted in a significantly lower plasma renin activity [30 +/- 3 vs. 69 +/- 5 ng angiotensin I (ANG I).ml-1.h-1, P less than 0.05], but there was no difference in aldosterone secretion between control and infused groups (7.00 +/- 0.49 vs. 7.29 +/- 0.95 ng/min, P greater than 0.05). However, the higher ANF dose of 45 ng.kg-1.min-1 did reduce aldosterone secretion approximately 40% to 4.18 +/- 0.36 ng/min (P less than 0.001) with no further suppression in plasma renin activity. In sodium-replete rats, infusion of ANF at 45 ng.kg-1.min-1 resulted in lower plasma renin activity compared with the control noninfused group (14 +/- 4 vs. 22 +/- 2 ng ANG I.ml-1.h-1, P less than 0.05), but aldosterone secretion was not different (P greater than 0.05) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Cognitive deficit is related to immune-cell beta-NGF in multiple sclerosis patients.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), causing cognitive impairment in 45-65% of patients. Beta-NGF facilitates proper cholinergic transmission in the healthy CNS. In MS-damaged tissue there is a relative deficit of neurotrophins that might be compensated by peripheral blood mononuclear cells (PBMCs) synthesis. Our aim was to evaluate the relationship between PBMCs neurotrophins' expression and cognitive performance in relapsing-remitting MS (RRMS) patients. Beta-NGF, NT-3 and NT-4/5 levels were measured in sera and in PBMCs by ELISA method in 41 RRMS patients in remission. All patients underwent neuropsychological assessment with a battery of 10 tests evaluating a wide range of cognitive functions. PBMCs beta-NGF concentration correlated significantly with spontaneous word list generation test (Pearson R=0.37, p=0.02) and 15-Word List Recall Test results (Pearson R=0.40, p<0.00). Both tests assessing semantic memory correlated significantly with the cognitive composite score, defined as a number of tests in which patients performed below group median for the given test. In RRMS beta-NGF is strongly linked to cognitive performance, which makes it an attractive therapeutic target. It might play a neuroprotective role in MS, especially in the cognitive domain.


[The clinical picture, diagnosis and treatment of postinjection cicatricial contractures of the mandible].
Causes, clinical and X-ray manifestations of postinjection mandibular contractures are discussed as exemplified by 10 cases and methods of eliminating these contractures are offered.


Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions.
We treated a 57-year-old woman for refractory inflammatory bowel disease with a humanized anti-tumor necrosis factor alpha monoclonal antibody (Infliximab). The patient also had a 15-year history of Crohn's disease and a 20-year history of moderate to severe psoriasis. She received a single infusion of Infliximab (5 mg/kg). Two weeks after the infusion her psoriasis had dramatically improved in appearance. To our knowledge, our case is the first reported instance of successful anti-tumor necrosis factor alpha therapy in psoriasis.


Accelerating the coping process.
On the basis of previous work, freshmen should evidence improved health after writing about their thoughts and feelings associated with entering college. One hundred thirty subjects were assigned to write either about coming to college or about superficial topics for 20 min on 3 days. One fourth of the subjects in each group wrote during the 1st, 5th, 9th, or 14th week of classes. Physician visits for illness in the months after writing were lower for the experimental than for the control subjects. Self-reports of homesickness and anxiety were higher in the experimental group 2-3 months after writing. By year's end, experimental subjects were either superior or similar to control subjects in grade average and in positive moods. No effects emerged as a function of when people wrote, suggesting that the coping process can be accelerated. Implications for comparing insight treatments with catharsis and for distinguishing between objective and self-report indicators of distress are discussed.


Effect of wind velocity on ethylene release from lettuce plants.
Effect of wind velocity on ethylene release rate of intact lettuce plant was investigated. Lettuce plants were grown at wind velocities of 0.1, 0.4, 0.8, and 1.4 m s-1 for 25 to 33 days and then used for ethylene measurement. When ethylene release rate of the plants grown at a wind velocity of 0.1m s-1 was measured at wind velocities of 0.2, 0.6 and 1.0m s-1 the rate was not affected by wind velocity. This result indicates that ethylene diffusion from lettuce leaf to atmosphere is not affected by boundary layer conditions. When ethylene release rate of the plants grown at wind velocities of 0.1, 0.4, 0.8 and 1.4 m s-1 was measured at the same wind velocity as growing conditions, the rate was scarcely increased by high velocity of wind. A strong wind (4.0 m s-1), which induced wounding damage in small areas of the leaves, had no measurable effect on a ethylene release of the whole plant.


Phenomenological approaches to collective behavior in epithelial cell migration.
Collective cell migration in epithelial tissues resembles fluid-like behavior in time-lapse recordings. In the last years, hydrodynamic velocity fields in living matter have been studied intensely. The emergent properties were remarkably similar to phenomena known from active soft matter systems. Here, we review migration experiments of large cellular ensembles as well as of mesoscopic cohorts in micro-structured environments. Concepts such as diffusion, velocity correlations, swirl strength and polarization are metrics to quantify the cellular dynamics both in experiments as well as in computational simulations. We discuss challenges relating collective migration to single cell and oligocellular behavior as well as linking the phenotypic parameters to the underlying cytoskeleton dynamics and signaling networks. This article is part of a Special Issue entitled: Mechanobiology.


[The history of antitobacco actions in the last 500 years. part. 1. Non-medical actions].
Tobacco was brought to Europe by Christopher Columbus, who discovered it in Cuba in October, 1492. Spread of tobacco consumption was initiated by the French diplomat Jean Nicot de Villemain, who in 1560 recommended it in the form of powdered tobacco leaves to the French Queen Catherine de Medice to combat her migraine headaches, and introduced the term Nicotiana tobaccum. Tobacco consumption greatly rose after the I World War, and after the II World War it became very common, especially among man. In the first half of the 20th century the sale of tobacco products rose by 61%, and cigarettes dominated the market of tobacco products. At the beginning of the 20th century cigarettes constituted only 2% of the total sale of tobacco products, while in the middle of the 20th century--more than 80%. Although the first epidemiological papers indicating that "smoking is connected with the shortening of life span" were published in the first half of the 20th century, not until 1950 did Hill and Doll in Great Britain, and Wynder and Graham in USA in 1951 show a statistically significant correlation between cigarettes smoking and lung cancer occurrence. Many controversies according the use of tobacco accompanied it from the beginning of its presence in Europe. The conflicting opinions according to its influence to health coexisted in the 16th to 19th centuries. In this period, especially in the 19th century dominated moral and religious arguments against tobacco. In the 20th century however, and particularly in its second part, development in medical research was enhanced by civil voluntary actions against advertisement and passive smoking. This lead to the significant limitation of tobacco expansion in Europe, USA and Canada in the end of the 20th century.


Differentiating Adults With Mixed Age Victims From Those Who Exclusively Sexually Assault Children or Adults.
Although adults who have sexually offended against both child and adult victims (i.e., adults with mixed aged sexual offense victims [MASOVs]) have been found at increased risk to reoffend, they have been a neglected and rarely studied group of individuals who have sexually offended. The present study explored their differentiating characteristics by comparing them with adults who had sexually offended exclusively against children (child sex offense victims [CSOVs]) or adults (adult sex offense victims [ASOVs]). Using an extensive database gathered on offenders examined for civil commitment, we found that although MASOVs were not distinguished from the other types of offenders by any specific developmental trauma, they cumulatively tended to be higher across traumas. They evidenced lower self-esteem relative to both other offender types. In addition, MASOVs, like ASOVs, exhibited higher levels of psychopathy relative to CSOVs. The implications of these findings for etiology and treatment are discussed.


Efficacious delivery of protein drugs to prostate cancer cells by PSMA-targeted pH-responsive chimaeric polymersomes.
Protein drugs as one of the most potent biotherapeutics have a tremendous potential in cancer therapy. Their application is, nevertheless, restricted by absence of efficacious, biocompatible, and cancer-targeting nanosystems. In this paper, we report that 2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (Acupa)-decorated pH-responsive chimaeric polymersomes (Acupa-CPs) efficiently deliver therapeutic proteins into prostate cancer cells. Acupa-CPs had a unimodal distribution with average sizes ranging from 157-175 nm depending on amounts of Acupa. They displayed highly efficient loading of both model proteins, bovine serum albumin (BSA) and cytochrome C (CC), affording high protein loading contents of 9.1-24.5 wt.%. The in vitro release results showed that protein release was markedly accelerated at mildly acidic pH due to the hydrolysis of acetal bonds in the vesicular membrane. CLSM and MTT studies demonstrated that CC-loaded Acupa10-CPs mediated efficient delivery of protein drugs into PSMA positive LNCaP cells leading to pronounced antitumor effect, in contrast to their non-targeting counterparts and free CC. Remarkably, granzyme B (GrB)-loaded Acupa10-CPs caused effective apoptosis of LNCaP cells with a low half-maximal inhibitory concentration (IC50) of 1.6 nM. Flow cytometry and CLSM studies using MitoCapture™ revealed obvious depletion of mitochondria membrane potential in LNCaP cells treated with GrB-loaded Acupa10-CPs. The preliminary in vivo experiments showed that Acupa-CPs had a long circulation time with an elimination phase half-life of 3.3h in nude mice. PSMA-targeted, pH-responsive, and chimaeric polymersomes have appeared as efficient protein nanocarriers for targeted prostate cancer therapy.


Experimental Brugia pahangi and B. malayi infections of callitrichid primates.
The callitrichid primates, Callithrix jacchus jacchus (the marmoset) and Saguinus labiatus (the tamarin) were inoculated with infective larvae of Brugia malayi and B. pahangi. Microfilaraemia at low levels developed in 3 out of 4 C.j. jacchus infected with B. malayi and living or dead adult worms found in all 4. Only one of 4 C.j. jacchus became microfilaraemic (mf + ve) when given B. pahangi and adults were found in two. Of 4 S. labiatus given B. pahangi one became very lightly mf + ve and adults were found in 3. It is concluded that these animals are not suitable hosts for chemotherapeutic experiments.


The anatomical basis for cervicogenic headache.
The neuroanatomical basis for cervicogenic headache is convergence in the trigeminocervical nucleus between nociceptive afferents from the field of the trigeminal nerve and the receptive fields of the first three cervical nerves. Only structures innervated by C1-C3 have been shown to be capable of causing headache. These are the muscles, joints and ligaments of the upper three cervical segments, but also include the dura mater of the spinal cord and posterior cranial fossa and the vertebral artery.


Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signaling.
Many hormonal signals from peripheral tissues contribute to the regulation of energy homeostasis and food intake. These regulators including leptin, insulin, and ghrelin, modulate the orexigenic and anorexigenic neuropeptide expression in hypothalamic nuclei. The anti-aging effects of caloric restriction have been explained from an evolutional viewpoint of the adaptive response of the neuroendocrine and metabolic response systems to maximize survival during periods of food shortage. In organisms, excess energy is stored in adipose tissues as a triglyceride preparation for such survival situations. Adipose tissue has recently been recognized as an endocrine organ, and leptin, as secreted by adipocyte, seems to be an especially important factor for the adaptive response to fasting and neuroendocrine alterations under caloric restriction. In this review, we discuss the potential involvement of neuroendocrine modulators in longevity and the anti-aging effects of caloric restriction.


Rhabdomyosarcoma of the right ventricle.
A case of a 66-year-old male with rhabdomyosarcoma of the right ventricle who presented first with a pleuritic chest pain and later developed congestive heart failure with A-V block is described. The total period of the disease was about 9 months. At autopsy the right ventricle and wall were found to be replaced by tumor tissue which was diagnosed histologically as rhabdomyosarcoma of the alveolar type. We described one case and 52 rhabdomyosarcomas of the heart from the literature; the ages ranged from 3 months to 92 years with 29 men and 23 women (unknown 1). The primary lesions were right ventricle 29%, right atrium 26%, left atrium 24%, left ventricle 6%, and others 15%.


Identification of agents targeting FtsZ assembly.
Filamenting temperature-sensitive mutant Z (FtsZ), an essential cell division protein in bacteria, has recently emerged as an important and exploitable antibacterial target. Cytokinesis in bacteria is regulated by the assembly dynamics of this protein, which is ubiquitously present in eubacteria. The perturbation of FtsZ assembly has been found to have a deleterious effect on the cytokinetic machinery and, in turn, upon cell survival. FtsZ is highly conserved among prokaryotes, offering the possibility of broad-spectrum antibacterial agents, while its limited sequence homology with tubulin (an essential protein in eukaryotic mitosis) offers the possibility of selective toxicity. This review aims to summarize current knowledge regarding the mechanism of action of FtsZ, and to highlight existing attempts toward the development of clinically useful inhibitors.


Vanadium 7,7,8,8-tetracyano-p-quinodimethane (V[TCNQ]2)-based magnets.
A new family of molecule-based magnets of general formula V[TCNQR(2)](2).zCH(2)Cl(2) has been synthesized and characterized (TCNQ = 7,7,8,8-tetracyano-p-quinodimethane; R = H, Br, Me, Et, i-Pr, OMe, OEt, and OPh). In addition, solid solutions of V[TCNQ](x)()[TCNQ(OEt)(2)](2)(-)(x)().zCH(2)Cl(2) composition have been prepared. Except R = Br, magnetic ordering was observed for all materials, with T(c) values between 7.5 K (R = Me) and 106 K (R = OEt), with R = H at 52 K. The substitution of electron-donating OMe and OEt groups for H in TCNQ increased T(c), whereas the substitution of less electron-donating alkyl groups (with respect to alkoxy groups) decreased T(c). The results of MO calculations indicate that neither the spin nor charge densities of the disubstituted TCNQs are sufficiently different to explain the wide range of critical temperatures. Although the structures of the amorphous materials are not known, it is proposed that the oxygen atom of the [TCNQR(2)](*)(-) acceptor (R = OMe and OEt) and the V(II) interact to form a seven-membered ring. This interaction could stabilize the structure and enhance the magnetic coupling, leading to an increased T(c). The magnetic properties of V[TCNQ](x)()[TCNQ(OEt)(2)](2)(-)(x)().zCH(2)Cl(2) deviated from the expected linear relationship with respect to x, exhibiting magnetic behavior more characteristic of a step function in a plot of T(c) versus x.


Advanced detection of recent changing trends in gastric cancer survival: up-to-date comparison by period analysis.
To establish a comprehensive cancer treatment and prevention policy, data collection should be performed in a timely manner, and survival analysis needs to reflect changes in treatment strategy. Therefore, we introduced the concept of period analysis for gastric cancer, the most prevalent cancer in Korea. We estimated 5- and 10-year survival trend of gastric cancer, based on data from the Yonsei Cancer Center Tumor Registry between 1990 and 2004. We compared the differences in survival between cohort, complete and period analyses for two different periods, 1995-99 and 2000-04. A total of 11 724 cases were included. The median age of cancer diagnosis gradually increased over time, and more patients were diagnosed with Stage I disease in recent years. In the basic comparison of three estimated analytic methods (cohort, complete and period), period analysis (45.8%) was most similar to the actual 5-year observed survival rate (48.5%), when compared with cohort (43.6%) and complete (44.8%) analyses. When we compared survival between different 10-year periods (1990-99 and 1995-2004), period analysis demonstrated a greater difference than complete analysis (9.0 versus 3.9%). Subgroup analysis indicated that the survival improvement was determined by period analysis, and it was more pronounced for the age group <74 years and in Stages III-IV patients. We observed that period analysis demonstrates the most similar results to the actual observed survival and is, therefore, a useful method to derive precise cancer survival in gastric cancer. This information is useful to understand survival differences that are influenced by changing treatment strategy.


Influence of an oxygen-inhibited layer on enamel bonding of dental adhesive systems: surface free-energy perspectives.
The influence of an oxygen-inhibited layer (OIL) on the shear bond strength (SBS) to enamel and surface free-energy (SFE) of adhesive systems was investigated. The adhesive systems tested were Scotchbond Multipurpose (SM), Clearfil SE Bond (CS), and Scotchbond Universal (SU). Resin composite was bonded to bovine enamel surfaces to determine the SBS, with and without an OIL, of adhesives. The SFE of cured adhesives with and without an OIL were determined by measuring the contact angles of three test liquids. There were no significant differences in the mean SBS of SM and CS specimens with or without an OIL; however, the mean SBS of SU specimens with an OIL was significantly higher than that of SU specimens without an OIL. For all three systems, the mean total SFE (γS), polarity force (γSp), and hydrogen bonding force (γSh) values of cured adhesives with an OIL were significantly higher than those of cured adhesives without an OIL. The results of this study indicate that the presence of an OIL promotes higher SBS of a single-step self-etch adhesive system, but not of a three-step or a two-step self-etch primer system. The SFE values of cured adhesives with an OIL were significantly higher than those without an OIL. The SFE characteristics of the OIL of adhesives differed depending on the type of adhesive.


Taiwan guideline on oral pre-exposure prophylaxis for HIV prevention - 2018 update.
Pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus infection is proved to be effective and has been implemented worldwide. This article introduces the guideline development and revised recommendations and guidance on PrEP provision in the updated Taiwan PrEP guideline. The Taiwan PrEP guideline writing group searched randomized controlled trials and guidelines published before October 2017 through Medline/PubMed, Cochrane Database, Embase and ClinicalTrials.gov database. Keywords included pre(-)exposure prophylaxis, PrEP, Truvada, tenofovir, HIV, and AIDS. Each selected article was assessed by two authors using the Grading of Recommendations Assessment, Development and Evaluation. External reviewers were invited to independently evaluate the revised manuscript per the Appraisal of Guidelines for Research and Evaluation II. Before publication, a public consultation was held to reach consensus on the updated guideline among providers, civil society, and Taiwan Centers for Disease Control. Four systematic reviews and 28 original articles were reviewed by Taiwan PrEP writing group. The second version of the Taiwan PrEP guideline was released in March 2018. We recommended daily PrEP use for the following populations: strong recommendation and high quality of evidence for men who have sex with men (MSM) and transgender women (TGW), as well as heterosexual serodiscordant couples; weak recommendation and high quality of evidence for people who inject drugs, while weak recommendation and moderate quality of evidence for at-risk heterosexual men and women. There is high-quality evidence for event-driven PrEP in MSM and likely TGW, and we additionally recognized these key populations could benefit from such dosing regimen.


Using standardized patients as teachers: a concurrent controlled trial.
To compare two methods of teaching physical assessment, a traditional faculty-taught course and a course with components taught by specially trained standardized patients (SPs), with respect to students' performances and costs. Medical students in their second year and without preliminary course work in physical assessment were taught by faculty-led small groups. Students in their first year were taught by faculty-led lecture-demonstrations and exercises led by physical examination teaching associates (PETAs). Both groups of students were tested with a performance-based examination that involved six identical stations. The costs of both courses were calculated using faculty and SP salaries. There was no difference in students' performances on two of the stations, those involving the eye and abdominal examinations. The class that had been taught by PETAs, however, demonstrated a statistically significant performance advantage on the remaining four stations. The cost saving from using the PETAs was conservatively estimated at $24,155. Specially trained SPs can effectively teach the normal physical examination to medical students and are a less expensive alternative to traditional faculty small-group teaching methods.


The value of the stentless biovalve prosthesis. An experimental study.
Clinical use of the stentless bioprosthesis has not yet been accepted world-wide. Experimental studies are scarce. In a study in growing pigs, 23 aortic valve replacements were performed (7 stented bioprostheses (STB), 10 stentless bioprostheses (SLB) and 6 cryopreserved homografts (CAH)). Valves were studied macroscopically and microscopically after explantation. Five animals died between 1.5 and 4 months after implantation. Two STBs showed extreme calcific degeneration. A third STB animal died suddenly: this STB showed only minimal leaflet calcification. One SLB was stenosed with a large fibrin deposit in one cusp, a second SLB showed slight cusp calcification and three were paracommissural tears in one cusp. In all other animals the valves were explanted after 5 to 6.5 months. All STBs showed severe calcific degeneration. Five SLBs showed mild calcific degeneration, while three others were unaltered after 6 months. All CAHs were free of calcific degeneration, three were perfect, two had a tear in a commisure and another was prolapsed with a fibrin degeneration. The speed and extent of valve degeneration were less than in the STB group. The stentless design is an important contribution which may result in a higher durability of bioprosthetic valves.


Urinary functional outcomes in female neobladder patients.
The ratio between orthotopic and non-orthotopic diversions in women is far lower than in male patients. Data on urinary function in female patients with neobladders are therefore sparse. We investigated the urinary function of female neobladder patients utilizing the Bladder Cancer Index, a validated and reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we tried to identify preoperative factors that may influence functional results. All living female patients with an orthotopic neobladder (N = 82) from the University of Southern California Bladder Cancer Database were sent a questionnaire including the University of Michigan Bladder Cancer Index. Univariate analyses were performed using the Kruskal-Wallis test followed by a multivariate stepwise regression model. Fifty-six patients (68.3%) responded and were included in the analysis. Thirty-five (62.5%) of these patients had to catheterize their neobladder to a certain amount, while 25 patients (44.6%) depend on catheterization to empty their neobladder. Univariate analyses showed that patient age (>65 years) was the only variable associated with a statistically significant lower rate of neobladder catheterization. Better urinary bother scores were associated with organ-confined disease (p = 0.038) and education level (p = 0.01). However, these variables were not significant in a multivariate stepwise linear regression model. Considerably more women require urinary catheterization to void than previously reported. In this study, representing the largest investigated cohort in this topic, we were unable to identify any predictors of this outcome or any other urinary HRQOL in this cohort.


Investigation of the nasal cycle function through endoscopy, rhinoresistometry and acoustic rhinomety.
The cyclic congestion and decongestion in both nasal cavities systematically accompany the nose respiratory function. The turbulent behavior of the nasal airflow seems to be a prerequisite of the adequate contact of inspired air particles with a nasal mucosa. The aim of the present study was to gain further information regarding the turbulent airflow behavior just during the nasal cycle dynamics. The nasal cycles in 10 healthy human subjects were investigated applying endoscopic imaging, rhinoresistometry, and acoustic rhinometry methods. The nasal function has been estimated at the regular intervals of 20 minutes over a time period of 15 hours. The following parameters were calculated in each case: airflow resistance, hydraulic diameter, friction coefficient , transition from the laminar flow to the turbulent one, and minimal cross-sectional areas. In addition to the previously known cyclic changes of the flow resistance and of the nasal width, periodic alterations in the turbulence function were noted. Under the resting phase, the laminar flow was usually demonstrated. Under the working phase, the turbulences arouse already at low flow velocities. The increases of turbulences that supplemented the working phase were caused by the enlargement of the cross-sectional area in the anterior nasal cavum. The latter followed to the decongestion of the mucosa of the head of the inferior turbinate as well as of the septal tuberculum. Rhinoresistometry and acoustic rhinometry predominantly complement each other. Application of both methods provides therefore valuable information on the functional nasal cycle changes. A combination of these two methods is recommended thus for the proper evaluation of the nasal cavity behavior.