Efficacy and Safety of an mHealth App and Wearable Device in Physical Performance for Patients With Hepatocellular Carcinoma: Development and Usability Study.
Exercise is predicted to have a positive effect among hepatocellular carcinoma (HCC) patients. However, these patients are hesitant to start and build up an exercise program for one major reason: the vague fear of developing hepatic decompensation, a potentially fatal condition that can lead to death. Integrating mobile health (mHealth) with individualized exercise programs could be a possible option for promoting physical capacity among HCC patients. The aim of this study was to evaluate the efficacy and safety of rehabilitation exercises, which have been individually prescribed via an mHealth app, on physical fitness, body composition, biochemical profile, and quality of life among HCC patients. A total of 37 HCC patients were enrolled in a 12-week course with an mHealth app program targeted to HCC patients. The wearable wristband device Neofit (Partron Co) was provided to participants, and recorded daily physical data, such as the number of steps, calorie expenditure, exercise time, and heart rate. Each participant was given an individualized rehabilitation exercise program that was prescribed and adjusted at the 6-week midintervention period based on the assessment results. At baseline, 6-week, and 12-week sessions, participants' physical fitness levels (ie, 6-minute walk test, grip strength test, and 30-second chair stand test) were measured. Physical activity levels, as measured by the International Physical Activity Questionnaire-Short Form (IPAQ-SF); body composition (ie, body mass index, body fat percentage, and muscle mass); biochemical profiles; and quality of life, as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30, were assessed at baseline and at the end point. At the 6-week midpoint, exercise intensity was individually adjusted. Of the 37 patients, 31 (84%) completed the 12-week intervention. Grip strength improved significantly after 12 weeks of the intervention. The 30-second chair stand test and the 6-minute walk test showed significant improvement from 0 to 6 weeks, from 0 to 12 weeks, and from 6 to 12 weeks. Muscle mass and the IPAQ-SF score increased significantly after 12 weeks of the intervention without biochemical deterioration. Following 12 weeks of mHealth care, including an individually prescribed rehabilitation exercise program, we saw significant improvements in physical fitness, body composition, and physical activity without any complication or biochemical deterioration among compensated HCC patients who had completed therapy.


Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin.
Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p < 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p < 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.


"Space means Science, unless it's about Star Wars": A qualitative assessment of science communication audience segments.
Scholars of science communication have identified population segments that differ in their perceptions of and attitudes toward science as well as in their patterns of science-related information and media use. So far, however, most of these studies employed quantitative, standardized methods and their descriptions could not go into qualitative detail. This study fills this gap: It delivers an in-depth description of members of four audience segments that were identified in a prior, representative survey in Switzerland. Forty-one of these survey respondents, representing different segments, were asked to note their encounters with science in smartphone-based diaries, and diary entries were discussed in qualitative follow-up interviews. Results show that the segments differ in their criteria for identifying science, expectations toward science, and their reasons to use science communication.


[A pancreatobiliary malformation causing spontaneous perforation of the extrahepatic bile duct].
Biliaryascitis usually results from a spontaneous or traumatic perforation of the common bile duct, usually at the junction with the cystic duct. Distal duct obstruction, pancreatic fluid reflux up the common bile duct, congenital weakness or a localized mural malformation of the wall of the common duct have been proposed as possible causes. We present an 11-months-old infant girl who developed a biliary ascitis as a consequence of biliary rupture. Perforation was due to malformation of the pancreatico-biliary junction. An uneventful external derivation by tube was performed.


Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma.
Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.


The forgotten condyle: the appearance, morphology, and classification of occipital condyle fractures.
To evaluate the appearance, morphology, and treatment of occipital condyle fractures (OCF). Cases were collected by a retrospective and prospective analysis of teaching files and case logs. Patients' charts, when available, were reviewed for age, sex, mode of injury, physical examination, Glascow Coma Scale score, and associated injuries. Plain films and CT images were reviewed to determine OCF type and to assess for the presence of associated cervical spine and/or intracranial trauma. Fifteen patients with OCF, 13 occurring in a 43-month period, were identified. Ten patients were involved in motor vehicle accidents. Severity of closed head injury and associated clinical findings were variable. Three patients had associated cervical spine fracture. According to the Anderson and Montesano classification, two patients (13%) had type I OCF, eight patients (54%) had type II OCF, and five (33%) had type III OCF. Fourteen of the fractures were identified on screening trauma head CT scans. Treatment varied according to the presence of associated injuries and stability of the cervical spine. Although OCFs are rare, they will be encountered by most radiologists who see a significant amount of trauma. Type II OCFs were the most common fracture type in our series. Type III fractures were the second most common and potentially unstable. CT should be initiated at the level of the C-1 ring to screen for the presence of OCF in all patients who have suffered trauma.


Positive association of child involvement and treatment outcome within a manual-based cognitive-behavioral treatment for children with anxiety.
Ratings of child involvement in manual-based cognitive-behavioral treatment for anxiety were associated with the absence of primary anxiety diagnosis and reductions in impairment ratings at posttreatment for 59 children with anxiety (ages 8-14 years). Good-to-excellent interrater reliability was established for the independent ratings of 237 therapy sessions, and strong psychometrics were established for the involvement measure. Child involvement at midtreatment, just prior to in vivo exposures, was positively associated with treatment gains but earlier involvement was not. Increased involvement during therapy (positive involvement shifts) may provide a useful index of change and may also predict outcomes. Involvement was not associated with client demographics or diagnostic category. Implications for treatment and measurement of psychotherapy process within manual-based treatments are discussed.


Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the alpha-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.


Biphasic transient kinetics are a property of a single site in horse liver alcohol dehydrogenase.
The transient kinetics under single turnover conditions of the dimeric enzyme horse liver alcohol dehydrogenase (LADH) are often biphasic with nearly equal amplitudes in the fast and slow components of the reaction. These observations have been the basis for the suggestion that this enzyme displays half of the sites reactivity or kinetic site-site interactions in its catalytic cycle [Bernhard, S.A., Dunn, M.F., Luisi, P.L., & Shack, P. (1970) Biochemistry 9, 185]. Alternatively, the biphasic kinetics could be the result of a complex mechanistic path at a single site with no kinetic interactions between the active sites [Kvassman, J., & Pettersson, G. (1976) Eur. J. Biochem. 62, 279; Kvassman, J., & Pettersson, G. (1978) Eur. J. Biochem. 87, 417]. To resolve this question, we have prepared LADH in which one of the two active sites is occupied by the strongly bound, slowly exchanging ternary complex inhibitors NAD with trifluoroethanol or NAD with pyrazole. These half-inhibited dimers show essentially the same biphasic transient kinetics as the native enzyme. These results strongly support mechanisms in which the observed kinetics are a property of each independently functioning site of the dimer. The possibility of half of the sites reactivity or kinetic site-site interaction appears to be ruled out.


Robotic dismembered pyeloplasty: a 6-year, multi-institutional experience.
The introduction of the da Vinci Surgical System to perform complex reconstructive procedures, such as repair of ureteropelvic junction obstruction, has helped to overcome some of the technical challenges associated with laparoscopy. We review our large multi-institutional experience with long-term followup of robotic dismembered pyeloplasty. A total of 140 patients from 3 university medical centers underwent robotic dismembered pyeloplasty. An institutional review board approved retrospective chart review was performed to collect demographic, preoperative, operative and postoperative data. Patients were analyzed as an entire cohort and then divided into various subgroups. Of the cases 117 (84.6%) were primary repairs and 23 (16.4%) were secondary repairs. There were 13 (9.3%) patients who underwent concomitant stone extraction and 5 (3.6%) procedures were performed on patients with solitary kidneys. A crossing vessel was found in 77 (55%) patients. Mean operative time was 217 minutes (range 80 to 510), estimated blood loss was 59.4 ml (range 10 to 600), mean length of hospital stay 2.1 days (range 0.75 to 7) and mean followup was 29 months (range 3 to 63). Radiographic resolution of obstruction on first postoperative diuretic renal scan or excretory urogram was noted in 134 patients (95.7%). There was a 7.1% major complication rate and a 2.9% minor complication rate. No statistically significant differences were found in any parameters among patients from the various cohorts. To our knowledge this review represents the largest multi-institutional experience of robotic dismembered pyeloplasty with long-term followup. Robotic pyeloplasty appears to be safe, durable and efficacious for primary and secondary ureteropelvic junction obstruction with or without concomitant stone extraction, and for patients with a solitary kidney.


Influence of antifungal polyenes on the adhesion of Candida albicans and Candida glabrata to human epithelial cells in vitro.
Candidal adherence to mucosal surfaces is considered as the first step in the pathogenesis of oral candidiasis. We examined the effect of antifungal polyenes, amphotericin B, nystatin and natamycin, at sublethal and minimum inhibitory concentrations (MICs) on the adherence of Candida albicans and Candida glabrata to HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. A total of six oral Candida isolates were used throughout the study. Two Candida strains, C. albicans (44990) and C. glabrata (MYA-275) were obtained from ATCC. Four Candida strains, C. albicans 19 and 24 and C. glabrata 15 and 21, were isolated from patients with documented Candida-associated denture stomatitis. Cells were either incubated with Candida in the presence of the drug, or pre-incubated with yeasts and exposed subsequently to the drug. In the drug-free controls, the mean number of C. albicans yeasts associated with HeLa cells obtained from all experiments (130.1+/-10.1 yeasts/mm(2)) was significantly greater than that for HSC-3 cells (114.7+/-10.1 yeasts/mm(2); P<0.025). For C. glabrata, the mean adherence to HeLa and HSC-3 cells was 84.4+/-5.5 and 84.4+/-3.3 yeasts/mm(2), respectively, and these values were not statistically different (P>0.4). Candidal adherence was significantly reduced when the tested polyenes were present during the "adherence phase". The obtained values were significantly different from the controls, except for the effect of nystatin at the MIC on the adherence of C. glabrata strain MYA-275 to HeLa cells (P<0.375). Amphotericin B had the highest effect against both Candida species, reducing adherence by approximately 50 and approximately 60%, at the MIC and sublethal concentrations, respectively. The susceptibility of cell-associated Candida to polyenes was decreased markedly and the treatment did not result in significant detachment of adherent yeasts. The reduction in adherence was between 2 and 10%, when compared to the drug-free controls. These findings suggest that sub-therapeutic levels of polyenes that are likely to persist in the oral cavity following topical treatment may modulate candidal colonization when present during the "adherence phase".


Bilateral impacted femoral neck fracture in a renal disease patient.
Spontaneous bilateral femoral neck facture in a renal disease patient is not common. We report a case of 47-year-old female patient with chronic renal failure and on regular hemodialysis for the past 5 years who sustained bilateral impacted femoral neck fracture without history of trauma and injury and refused any surgical intervention. The patient was mobilised on wheel chair one year after the fractures. The cause of the fracture and the literature review of the bilateral femoral neck fracture in renal disease are discussed.


Molecular ecology and selection in the drought-related Asr gene polymorphisms in wild and cultivated common bean (Phaseolus vulgaris L.).
The abscisic acid (ABA) pathway plays an important role in the plants' reaction to drought stress and ABA-stress response (Asr) genes are important in controlling this process. In this sense, we accessed nucleotide diversity at two candidate genes for drought tolerance (Asr1 and Asr2), involved in an ABA signaling pathway, in the reference collection of cultivated common bean (Phaseolus vulgaris L.) and a core collection of wild common bean accessions. Our wild population samples covered a range of mesic (semi-arid) to very dry (desert) habitats, while our cultivated samples presented a wide spectrum of drought tolerance. Both genes showed very different patterns of nucleotide variation. Asr1 exhibited very low nucleotide diversity relative to the neutral reference loci that were previously surveyed in these populations. This suggests that strong purifying selection has been acting on this gene. In contrast, Asr2 exhibited higher levels of nucleotide diversity, which is indicative of adaptive selection. These patterns were more notable in wild beans than in cultivated common beans indicting that natural selection has played a role over long time periods compared to farmer selection since domestication. Together these results suggested the importance of Asr1 in the context of drought tolerance, and constitute the first steps towards an association study between genetic polymorphism of this gene family and variation in drought tolerance traits. Furthermore, one of our major successes was to find that wild common bean is a reservoir of genetic variation and selection signatures at Asr genes, which may be useful for breeding drought tolerance in cultivated common bean.


High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model.
With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study's objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1-13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1-13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (HT+V; n = 7); (iii) HT + Melatonin (HT+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after HI. Comparing HT+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/exchangeable phosphate were higher at 48 h in HT+M versus HT (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in HT+M (47.1 cells/mm2) compared to HT (123.8 cells/mm2) (p = 0.0003) and HT+V (97.5 cells/mm2) compared to HT (p = 0.012). Localized protection was seen in white matter for HT+M versus HT (p = 0.036) and internal capsule for HT+M compared to HT (p = 0.001) and HT+V versus HT (p = 0.006). Therapeutic melatonin levels (15-30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.


ACOG Committee opinion no. 553: multifetal pregnancy reduction.
Fertility treatments have contributed significantly to the increase in multifetal pregnancies. The first approach to the problem of multifetal pregnancies should be prevention, and strategies to limit multifetal pregnancies, especially high-order multifetal pregnancies, should be practiced by all physicians who treat women for infertility. Incorporating the ethical frameworks presented in this Committee Opinion will help physicians counsel and guide patients when making decisions regarding multifetal pregnancy reduction. In cases of high-order multifetal pregnancies, counseling should include the availability of multifetal pregnancy reduction. Fellows should be knowledgeable about the medical risks of multifetal pregnancy, the possible medical benefits of multifetal pregnancy reduction, and the complex ethical issues inherent in decisions regarding the use of multifetal pregnancy reduction. Physicians should not be required to act in ways that conflict with their value systems but should be prepared to react in a professional and ethical manner to patient requests for both information and intervention.


Interleukin-2 receptor blockade in cardiac transplantation: influence of HLA-DR locus incompatibility on treatment efficacy.
Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation. A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA-DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls. IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.


Exploring the anthelmintic properties of Australian native shrubs with respect to their potential role in livestock grazing systems.
We measured in vitro anthelmintic activity in extracts from 85 species of Australian native shrub, with a view to identifying species able to provide a degree of worm control in grazing systems. Approximately 40% of the species showed significant activity in inhibiting development of Haemonchus contortus larvae. The most active extracts showed IC50 values of 60-300 microg/ml. Pre-incubation with polyvinylpolypyrrolidine removed the activity from some extracts, implicating tannins as the bioactive agent, while in other cases the pre-incubation had no effect, indicating the presence of other anthelmintic compounds. Plant reproductive maturity (onset of flowering or fruiting) was associated with increasing anthelmintic activity in some species. Variability was observed between plants of the same species growing in different environments, while variation between individual plants of the same species within a single field suggests the existence of distinct chemotypes. Significant activity against adult H. contortus worms in vitro was also demonstrated in a limited number of extracts tested against this life stage. Our study indicates that there is potential for Australian native shrubs to play an anthelmintic role in grazing systems, and highlights some plant biology factors which will need to be considered in order to maximize any anthelmintic effects.


Thoracic complications of amebiasis.
The most recent statistics clearly show that the incidence of amebiasis in Canada has increased progressively over the past 10 years. The authors review the incidence, pathophysiology and management of thoracic complications of amebiasis, including the experience from endemic countries. Complications include amebic liver abscess, best treated with metronidazole, and the resulting thoracic complications of pleural and pericardial effusion, atelectasis and rupture into the thoracic cavity. Since amebic liver abscess always precedes the thoracic complications, its early diagnosis and treatment will prevent these complications in most cases of amebiasis.


Definitions of recurrence of an episode of low back pain: a systematic review.
Systematic review. To identify the definitions of recurrence (and related recovery definitions) currently used in the literature. Recurrence of low back pain (LBP) is a common and costly problem and the goal of many treatments is to prevent future recurrences. However, it is unclear whether standardized recurrence definitions are being used in the research literature evaluating the risk of recurrence and the effectiveness of treatments to prevent recurrence. A literature search was performed of MEDLINE, EMBASE, CINAHL, AMED, and PEDro, and from chosen systematic reviews investigating treatments that could plausibly affect recurrence of LBP. Studies were considered eligible if they investigated recurrence of LBP in a cohort of patients with LBP. Inclusion was assessed by 2 reviewers and definitions of recurrence (and related recovery) were extracted. Fifty-three studies were identified by the review. Only 32% of studies gave explicit definitions of recurrence and only 10% gave a definition for both recurrence and recovery. Less than 10% of studies shared a common definition of recurrence. Because of a lack of an agreed terminology it is very difficult to compare results between studies reporting recurrence rates or evaluating strategies to prevent recurrence. Steps to achieve consensus on recurrence and recovery definitions are required. In the interim, it is recommended that a minimum pain duration of 24 hours with a minimum pain intensity equivalent to the appropriate minimal important change for the chosen scale, be used for defining a recurrence. If disability measures are used, it is also recommended that the appropriate minimal important change be used. For recovery, a minimum duration of 1 month pain-free should be used.


Trends in cancer mortality in the European Union and accession countries, 1980-2000.
Cancer mortality rates and trends over the period 1980-2000 for accession countries to the European Union (EU) in May 2004, which include a total of 75 million inhabitants, were abstracted from the World Health Organization (WHO) database, together with, for comparative purposes, those of the current EU. Total cancer mortality for men was 166/100,000 in the EU, but ranged between 195 (Lithuania) and 269/100,000 (Hungary) in central and eastern European accession countries. This excess related to most cancer sites, including lung and other tobacco-related neoplasms, but also stomach, intestines and liver, and a few neoplasms amenable to treatment, such as testis, Hodgkin's disease and leukaemias. Overall cancer mortality for women was 95/100,000 in the EU, and ranged between 100 and 110/100,000 in several central and eastern European countries, and up to 120/100,000 in the Czech Republic and 138/100,000 in Hungary. The latter two countries had a substantial excess in female mortality for lung cancer, but also for several other sites. Furthermore, for stomach and especially (cervix) uteri, female rates were substantially higher in central and eastern European accession countries. Over the last two decades, trends in mortality were systematically less favourable in accession countries than in the EU. Most of the unfavourable patterns and trends in cancer mortality in accession countries are due to recognised, and hence potentially avoidable, causes of cancer, including tobacco, alcohol, dietary habits, pollution and hepatitis B, plus inadequate screening, diagnosis and treatment. Consequently, the application of available knowledge on cancer prevention, diagnosis and treatment may substantially reduce the disadvantage now registered in the cancer mortality of central and eastern European accession countries.


Crosstalk between kinases and Nedd4 family ubiquitin ligases.
A dazzling array of human biological processes achieves coordination and balance through the posttranslational modification of protein residues with phosphate (95 Da) or ubiquitin (8565 Da). Over the past years, a reciprocal communication has become recognized between phosphorylating (kinases) and ubiquitinating (E3 ligases) enzymes. Such crosstalk occurs when a kinase acts on a ligase or vice versa to modify the catalytic activity, substrate specificity, or subcellular localization of the modified enzyme. In this review, we focus on the crosstalk between the nine members of the Nedd4 family E3 ubiquitin ligases with kinase signal transducers such as cell surface receptors, cytosolic kinases, phosphatases, and transcription factors. Since protein kinases are well explored and established therapeutic targets, we hypothesize that mapping E3 ligases onto kinase signalling networks will provide clues to the full therapeutic potential of pharmacologically targeting E3 ligases.


[Implementation design of the HEARTS healthy-lifestyle counselling module at the first level of care in MexicoDelineamento da implementação do módulo de hábitos e estilos de vida saudáveis da Iniciativa HEARTS na atenção primária do México].
The number of people with cardiovascular diseases is a leading public health problem. The Ministry of Health of Mexico and the local representative office of the Pan American Health Organization have joined forces to implement the "HEARTS: technical package for cardiovascular disease management in primary health care." The objective of this article is to describe the implementation design of the "Healthy-lifestyle counselling" module, which is part of the HEARTS technical package. To this end, an interdisciplinary and inter-institutional group was formed to discuss implementation, the topics to be addressed in each brief intervention, and follow-up and monitoring. In conclusion, working with the advisory group from various health disciplines contributed to a broad vision of the person-centered approach, and helped with the implementation design of the module. The objective is to achieve active communication between patients and health professionals, helping to generate interventions that result in informed patients who are active in their health care, and health teams that enable patients to obtain better health outcomes.


Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.
Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.


Identification of a novel saturable endoplasmic reticulum localization mechanism mediated by the C-terminus of a Dictyostelium protein disulfide isomerase.
Localization of soluble endoplasmic reticulum (ER) resident proteins is likely achieved by the complementary action of retrieval and retention mechanisms. Whereas the machinery involving the H/KDEL and related retrieval signals in targeting escapees back to the ER is well characterized, other mechanisms including retention are still poorly understood. We have identified a protein disulfide isomerase (Dd-PDI) lacking the HDEL retrieval signal normally found at the C terminus of ER residents in Dictyostelium discoideum. Here we demonstrate that its 57 residue C-terminal domain is necessary for intracellular retention of Dd-PDI and sufficient to localize a green fluorescent protein (GFP) chimera to the ER, especially to the nuclear envelope. Dd-PDI and GFP-PDI57 are recovered in similar cation-dependent complexes. The overexpression of GFP-PDI57 leads to disruption of endogenous PDI complexes and induces the secretion of PDI, whereas overexpression of a GFP-HDEL chimera induces the secretion of endogenous calreticulin, revealing the presence of two independent and saturable mechanisms. Finally, low-level expression of Dd-PDI but not of PDI truncated of its 57 C-terminal residues complements the otherwise lethal yeast TRG1/PDI1 null mutation, demonstrating functional disulfide isomerase activity and ER localization. Altogether, these results indicate that the PDI57 peptide contains ER localization determinants recognized by a conserved machinery present in D. discoideum and Saccharomyces cerevisiae.


Meals on Wheels? A Decade of Megafaunal Visual and Acoustic Observations from Offshore Oil & Gas Rigs and Platforms in the North and Irish Seas.
A decade of visual and acoustic detections of marine megafauna around offshore Oil & Gas (O&G) installations in the North and Irish Seas are presented. Marine megafauna activity was monitored visually and acoustically by Joint Nature Conservation Committee (JNCC) qualified and experienced Marine Mammal Observers (MMO) and Passive Acoustic Monitoring (PAM) Operators respectively, with real-time towed PAM in combination with industry standard software, PAMGuard. Monitoring was performed during routine O&G industrial operations for underwater noise mitigation purposes, and to ensure adherence to regulatory guidelines. Incidental sightings by off-effort MMOs and installation crew were also reported. Visual and acoustic monitoring spanned 55 non-consecutive days between 2004 and 2014. A total of 47 marine mammal sightings were recorded by MMOs on dedicated watch, and 10 incidental sightings of marine megafauna were reported over 10 years. Species included: harbour porpoise (Phocoena phocoena), Atlantic white-sided dolphin (Lagenorhynchus acutus), white beaked dolphin (Lagenorhynchus albirostris), common dolphin (Delphinus delphis), minke whale (Balaenoptera acutorostrata), common seal (Phoca vitulina), grey seal (Halichoerus grypus) and, basking shark (Cetorhinus maximus). Passive Acoustic Monitoring was conducted on two occasions in 2014; 160 PAM hours over 12 days recorded a total of 308 individual clicks identified as harbour porpoises. These appear to be the first such acoustic detections obtained from a North Sea drilling rig whilst using a typically configured hydrophone array designed for towing in combination with real-time PAMGuard software. This study provides evidence that marine megafauna are present around mobile and stationary offshore O&G installations during routine operational activities. On this basis, Environmental Impact Assessments (EIAs) for decommissioning O&G platforms should be carried-out on a case-by-case basis, and must include provisions for hitherto overlooked marine megafauna.


Thrombophilia and pregnancy.
Preeclampsia, intrauterine growth restriction and placental abruption greatly contribute to maternal and fetal morbidity and mortality. Thrombophilia is an inherited or acquired condition that predisposes individuals to venous and/or arterial thrombosis. Recently, three important inherited thrombophilias have been discovered. An inherited mutation in the gene coding for coagulation factor V (factor V Leiden), and a mutation in prothrombin that is associated with higher plasma levels of prothrombin. Both mutations result in an increased susceptibility to develop venous thrombosis. Hyperhomocysteinemia, which is associated with mutations in the gene for methylenetetrahydrofolate reductase, is a risk factor for venous and arterial thrombosis. The presence of antiphospholipid antibodies, an acquired thrombophilic condition, is associated with venous and arterial thrombosis. The term placental vasculopathy, is used to describe pathological placental changes that have been associated with preeclampsia, intrauterine growth restriction, placental abruption and fetal loss. The known thrombotic nature of the placental vasculopathy and the increased thrombotic risk with the presence of thrombophilias suggest, a cause-and-effect relationship between inherited and acquired thrombophilias and a number of severe obstetric complications. Testing patients with these complications for thrombophilias may have therapeutic implications for future pregnancies.


Image Quality of ECG-Triggered High-Pitch, Dual-Source Computed Tomography Angiography for Cardiovascular Assessment in Children.
Evaluate the feasibility and determinants of image quality of ECG-triggered High-Pitch Dual-Source Computed Tomography Angiography (CTA) for cardiovascular assessment in Children. All children that underwent ECG-triggered High-Pitch Dual-Source CTA between August 2014 and September 2017 were identified. Scanner parameters and patients' information were retrieved. Objective image quality was evaluated measuring the Hounsfield units (HU) and standard deviation of regions of interests in the left ventricle, ascending and descending aorta. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Qualitative image quality was recorded independently by two pediatric radiologist blinded using a three-point scale: 1 - good image quality, 2 - mild artifacts, 3 - poor image quality. Continuous variables were presented as mean ± standard deviation. The interobserver agreement and non-parametric test were used. 93 patients (mean age 5.6 ± 7.1 years) were selected. Average cardiovascular attenuation, SNR and CNR were 406.2 ± 146.3 HU, 24.2 ± 16.0 HU and 52.1 ± 38.6 HU, respectively. Average image quality was 1.51 ± 0.48 and the inter-observer agreement was excellent (k = 0.8). Worse subjective quality scores were associated with lower age, height, weight, BSA, lower contrast dose and slower injection rates (p < 0.05). Higher heart rate was associated with high attenuation (p < 0.05), however, SNR and CNR did not show an association with heart rate (p = 0.80). ECG-triggered High-Pitch Dual-Source cardiac CTA is feasible and provides good or excellent image quality for the evaluation of cardiovascular diseases in children.


Comparison on the Efficacy and Safety of Different Surgical Treatments for Benign Prostatic Hyperplasia With Volume >60 mL: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.
The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.


Sentinel node detection and radioguided occult lesion localization in breast cancer.
Sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 breast cancer patients and represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. In our Institute, Radioguided Occult Lesion Localization is the standard method to locate non-palpable breast lesions and the gamma probes is very effective in assisting intra-operative localization and removal, as in sentinel node biopsy. The rapid spread of sentinel lymph node biopsy has led to its use in clinical settings previously considered contraindications to sentinel lymph node biopsy. In this contest, we evaluated in a large group of patients possible factors affecting sentinel node detection and the reliability of sentinel lymph node biopsy carried out after large excisional breast biopsy. Our data confirm that a previous breast surgery does not prohibit efficient sentinel lymph node localization and sentinel lymph node biopsy can correctly stage the axialla in these patients.


Heat-induced cell death and radiosensitization: molecular mechanisms.
Although several lines of evidence suggest that the cellular membrane plays a role in heat-induced cell death, a basic question remains unanswered. Namely, how does membrane damage lead to reproductive death which is traditionally thought to reflect DNA damage? Recent results suggest that membrane damage in the absence of heat can cause an increase in chromatin protein content similar to that induced by hyperthermia. The increased protein content in chromatin could cause structural alterations that lead to inhibition of enzyme-mediated DNA function. These alterations appear to play a major role in heat-induced radiosensitization by inhibiting the repair of X-ray-induced DNA strand breaks and thymine damage. The correlation between cell killing by heat alone and the increase in chromatin content imply that structural alterations in chromatin are part of the killing mechanism. Recently, heat-induced DNA damage has been observed. Therefore, the molecular mechanism by which hyperthermia kills cells could involve DNA damage resulting from alterations in chromatin structure.


Drug-eluting stent thrombosis in patients undergoing non-cardiac surgery: is it always a problem?
Recent publications have reported high incidence of perioperative complications in patients with drug-eluting stent (DES). The recommendations for bare-metal stents (BMS) are not applicable to DES. In fact, large evidence-based studies are lacking on which to base a consensus for the perioperative management of patients with DES. The aim of the present study is to evaluate the postoperative cardiac risk associated with DES. Prospectively collected data were examined for the rate of postoperative cardiac complications in 96 consecutive patients with DES who underwent digestive, urologic, orthopaedic, or vascular surgery. The average delay between revascularization and non-cardiac surgery was 14 (11) months (extremes 1 week and 36 months). The occurrence of postoperative troponin release (troponin I > or =0.15 ng ml(-1)) and the rate of in-stent thrombosis were analysed. Twelve patients (12%) presented a postoperative troponin release, without EKG abnormalities in 10 cases (83%). Two patients (2%) developed an in-stent thrombosis. None of the patients had excessive postoperative blood loss. Patients with DES are at higher risk of postoperative cardiac complications. Nevertheless, the specific thrombotic complications of the DES were uncommon in this series and this is in contrast to previous alarming reports. A balanced perioperative management of anti-platelet agents, considering both risk for bleeding and risk of thrombotic complications, in patients with DES, is associated with a low risk of thrombosis in the postoperative period. The rate of cardiac complications remains high in these patients due to co-morbidities.


Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients.
Ninety patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant prognostic associations. At diagnosis of blast crisis the main clinical, laboratory, and cytogenetic data were recorded and evaluated for prognostic significance. At the time of the analysis 89 patients had died, with a median survival of 11 weeks from diagnosis of blast crisis. Patient characteristics demonstrated in the univariate analysis to have significant association with shorter survival were: thrombocythemia, leukocyte count above 20 x 10(9), Karnofsky index < 50%, nonlymphoid blast cell morphology, cytogenetic clonal evolution, the presence of a double Philadelphia chromosome or trisomy 8, and no response to therapy. In 17 of 59 patients (29%) evaluable for response to therapy a complete or partial remission was achieved. These responders had a significantly longer median survival (25 weeks) as compared with nonresponders (9 weeks). Response to therapy was significantly better in lymphoid blast crisis and in patients without clonal evolution. In a multivariate analysis containing all significant variables of the univariate analysis two parameters retained their prognostic significance: response to therapy and trisomy 8. In spite of the short overall survival in blast crisis, the determination of prognostic factors may be a useful tool for the clinician planning therapy, especially new therapeutic approaches.


Laboratory evaluation of two commercial repellants against Leptotrombidium fletcheri (Acari: Trombiculidae).
Two commercial repellants were evaluated in the laboratory against Leptotrombidium fletcheri chiggers. The active ingredient in one was DEET and in the other was citrus oil. Excito-toxicity effect was studied and it was determined by the time ("escape time") chiggers took to move off filter papers treated with the repellants. All chiggers exposed on filter papers treated with DEET died and did not move off the treated papers. None of the chiggers that were placed on papers treated with citrus oil were killed. Escape times on papers treated with a 2-sec spray of citrus oil were longer than those for the 4- and 8-sec sprays. The weights of citrus oil deposited increased with increasing spray times. Electron microscopy showed that the repellants had no effect on the texture of the filter papers. It was concluded that the spray containing DEET was more effective; however, both repellants should be further evaluated under field conditions for protection against chigger bites.


LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians.
Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial 'LIM code' to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that lim homeobox (lhx) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2 and -lmx1a/b-3 are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while Smed-lhx1/5.2 and -lhx2/9.2 are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (lhx6/8), axial patterning (islet1, lhx1/5-1, lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.


Recent advances in chemotherapy for advanced gastric cancer.
Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the choice of optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration, with a median survival of approximately 7-11 mo and survival at 2 years rarely more than 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, several molecular targeting agents are now under evaluation in international randomized studies, and trastuzumab, an anti-HER2 monoclonal antibody, has shown antitumor activity against HER-2 positive AGC. However, this benefit is limited to only about 20% of patients with AGC (patients with HER-2 positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of predictive and prognostic molecular markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.


Inhibition of human T lymphocyte E rosette formation by neutrophils and hydrogen peroxide. Differential sensitivity between helper and suppressor T lymphocytes.
Co-incubation of human mononuclear cells with small numbers of autologous polymorphonuclear leukocytes resulted in a ratio-dependent inhibition of T lymphocyte rosette formation with sheep erythrocytes (SRBC). Inhibition by polymorphonuclear leukocytes was reversed with catalase, implicating H2O2 or associated products as the suppressive agent(s). Exposing T lymphocytes directly to micromolar concentrations of H2O2 also inhibited subsequent rosette formation. Inhibition was dose-dependent between 40 and 320 microM H2O2 and was not due to cytotoxicity at those H2O2 concentrations. Kinetic studies demonstrated that after exposing T lymphocytes to H2O2 a proportion of cells appeared to be relatively resistant in that they retained their ability to form E rosettes. T cell phenotype analysis of these cells showed that, in contrast to untreated T cells, H2O2-treated T rosette-forming cells were almost exclusively of the helper/inducer phenotype. Analysis with the monoclonal antibody 4B4 revealed that H2O2-resistant T rosette-forming cells contained significantly fewer 4B4-positive cells than predicted for the T helper population, indicating that H2O2-resistant T cells might be a subset of helper/inducer T lymphocytes. The interaction between H2O2 and T cells was rapid but did not lead to loss of Leu-5b binding sites. Preliminary functional analysis indicates that interleukin 2 production and phytohemagglutinin-induced proliferation by the relatively H2O2-resistant T cells is similar to untreated T cells. In contrast, H2O2-treated T cells which lost their ability to form E rosettes produced undetectable levels of interleukin 2 and proliferated poorly in response to phytohemagglutinin. Finally, mononuclear cells pretreated with H2O2 and subsequently stimulated with mitogens demonstrated a preferential expansion of the T helper population with concomitant loss of T suppressors. Our results show that, although neutrophil-released H2O2 inhibits effective interactions between SRBC and T lymphocyte sheep erythrocyte receptors, there appears to be a population of T helper cells which is relatively resistant to H2O2 both in terms of SRBC rosette formation and response to mitogens. These data suggest that at sites of inflammation phagocyte-released H2O2 could exert immunoregulatory effects on T cells by altering T cell subset survival and allowing the function of a particular lymphocyte population to predominate.


Metagenomics reveals effects of fluctuating water conditions on functional pathways in plant litter microbial community.
Climate change modifies environmental conditions, resulting in altered precipitation patterns, moisture availability and nutrient distribution for microbial communities. Changes in water availability are projected to affect a range of ecological processes, including the decomposition of plant litter and carbon cycling. However, a detailed understanding of microbial stress response to drought/flooding is missing. In this study, an intermittent lake is taken up as a model for changes in water availability and how they affect the functional pathways in microbial communities of the decomposing Phragmites australis litter. The results show that most enriched functions in both habitats belonged to the classes of Carbohydrates and Clustering-based subsystems (terms with unknown function) from SEED subsystems classification. We confirmed that changes in water availability resulted in altered functional makeup of microbial communities. Our results indicate that microbial communities under more frequent water stress (due to fluctuating conditions) could sustain an additional metabolic cost due to the production or uptake of compatible solutes to maintain cellular osmotic balance. Nevertheless, although prolonged submergence seemed to have a negative impact on several functional traits in the fungal community, the decomposition rate was not affected.


Multiscale modeling of charge transfer in polymers with flexible backbones.
In order to evaluate the carrier transfer properties in polymers with flexible backbones, we have proposed a simplified multi-scale modeling approach combining molecular dynamics simulations, first-principles calculations and kinetic Monte Carlo simulations. Hole transfer in amorphous polyethylene (PE) is studied as a model system. It is shown that the characteristic length scale of hole localized states in PE is comparable to the Kuhn length of PE, which is the characteristic length scale in terms of the geometric structure. Because a PE oligomer whose length is equivalent to the Kuhn length (C12H26) has a similar electronic structure to amorphous PE, C12H26 is considered as an approximate model of amorphous PE. In line with experimental findings, computed hole mobility in the amorphous PE oligomer is several orders of magnitude smaller than that in crystalline PE. We show that this difference originates from strong hole localization and large site energy variation in amorphous PE due to the conformational disorder of PE oligomer chains. The agreement between experimental and calculated hole mobilities strongly supports the rationale of our modeling approach. The modeling approach proposed in this paper is considered capable of predicting carrier mobilities in polymers with flexible backbones with reasonable computational load.


Stimulation of nicotine demethylation by NaHCO(3) treatment using greenhouse-grown burley tobacco.
Experiments were conducted in tobacco (Nicotiana tabacum L.) to investigate the effect of sodium bicarbonate (NaHCO(3)) on the conversion of nicotine to nornicotine, a secondary alkaloid that can form the tobacco-specific nitrosamine N-nitrosonornicotine (NNN). The results showed that, under optimum conditions, NaHCO(3) stimulated nicotine conversion in converter plants to the maximum level predetermined by the genetic background. The conversion level in NaHCO(3)-treated leaves was 2-3 times higher than that in control leaves. For young seedlings the optimum concentration of sodium bicarbonate was 0.8% aqueous solution, and for adult plants the optimum concentration was 1%. Lower concentrations resulted in partial stimulation, whereas higher concentration damaged leaf tissue and resulted in a lower conversion level. Studies with different temperatures (from 22 to 43 degrees C) showed that 37 degrees C was optimal. This temperature allowed the least amount of time, 2-3 days for mature leaves and 4-6 days for green leaves, for the major converters to reach >95% of nicotine conversion. An examination of leaves from different growth stages and stalk positions showed that the amount of time needed for conversion was longer for young leaves and shorter for mature leaves. Treatment of leaves with NaHCO(3) affords a rapid and convenient means of identifying and removing nornicotine converter plants during growth in the greenhouse or field.


Presence of a Gs alpha mutation in an adrenal tumor expressing LH/hCG receptors and clinically associated with Cushing's syndrome.
We describe the case of a patient with Cushing's syndrome due to a functioning adrenal adenoma. There was a pronounced increase in serum and urinary cortisol after administration of human chorionic gonadotropin. Immunocytochemistry revealed positive immunostaining for LH/hCG receptors. Molecular analysis documented the presence of a gsp mutation at codon 201 (CGT to TGT). The existence of this type of hCG-responsive adrenal tumor may help explain the higher prevalence of cortisol-secreting adrenal tumors versus pituitary-dependent disease in pregnant women with Cushing's syndrome as well as some reported cases of remission following delivery.


Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction.
Circulating monocytes have different subsets, including classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2-14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06-13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07-10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4-18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0-28.5, p = 0.002). CD14++CD16-, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings.


Aluminosilicate-Supported Catalysts for the Synthesis of Cyclic Carbonates by Reaction of CO2 with the Corresponding Epoxides.
Functionalized aluminosilicate materials were studied as catalysts for the conversion of different cyclic carbonates to the corresponding epoxides by the addition of CO2. Aluminum was incorporated in the mesostructured SBA-15 silica network. Thereafter, functionalization with imidazolium chloride or magnesium oxide was performed on the Al_SBA-15 supports. The isomorphic substitution of Si with Al and the resulting acidity of the supports were investigated via 27Al magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and NH3 adsorption microcalorimetry. The Al content and the amount of MgO were quantified via inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis. The anchoring of the imidazolium salt was assessed by 29Si and 13C MAS NMR spectroscopy and quantified by combustion chemical analysis. Textural and structural properties of supports and catalysts were studied by N2 physisorption and X-ray diffraction (XRD). The functionalized systems were then tested as catalysts for the conversion of CO2 and epoxides to cyclic carbonates in a batch reactor at 100 or 125 °C, with an initial CO2 pressure (at room temperature) of 25 bar. Whereas the activity of the MgO/xAl_SBA-15 systems was moderate for the conversion of glycidol to the corresponding cyclic carbonate, the Al_SBA-15-supported imidazolium chloride catalysts gave excellent results over different epoxides (conversion of glycidol, epichlorohydrin, and styrene oxide up to 89%, 78%, and 18%, respectively). Reusability tests were also performed. Even when some deactivation from one run to the other was observed, a comparison with the literature showed the Al-containing imidazolium systems to be promising catalysts. The fully heterogeneous nature of the present catalysts, where the inorganic support on which the imidazolium species are immobilized also contains the Lewis acid sites, gives them a further advantage with respect to most of the catalytic systems reported in the literature so far.


Interchanges of spatially neighbouring residues in structurally conserved environments.
The question of whether interchanges of spatially neighboring residues are coupled, or whether they change independently of each other, has been addressed repeatedly over the last few years. Utilizing a residue order-independent structural comparison tool, we investigated interchanges of spatially adjacent residue pairs in conserved 3D environments in globally dissimilar protein structures. We define spatially adjacent pairs to be non-local neighboring residues which are in spatial contact, though separated along the backbone, to exclude backbone effects. A dataset of unrelated structures is extensively compared, constructing a matrix of all 400x400 interchanges of residue pairs. Our study indicates that (i) interchanges of residues which are spatial neighbors are independent of each other. With the exception of a few pairs, the pattern of interchanges of pairs of adjacent residues resembles that expected from interchanges of single residues. However, clustering residues of similar characteristics, serves to enhance secondary trends. Hence, (ii) clustering the hydrophobic, aliphatic and, separately, the aromatic, and comparing them with the charged, and the polar, indicates that hydrophobic pairs are favorably replaced by hydrophobic, and charged/ polar by charged/polar. The most strongly conserved are the charged. Interestingly, the type of charge (like or opposite) plays no role. Interchanges between the hydrophobic and hydrophilic classes are unfavorable. (iii) Clustering by volume indicates that the most highly conserved are the (Small, Small) pairs. The least favorable are interchanges of the type (Small, Small) <--> (Large, Large). Interchanges of the type (Large, Small) <--> (Large, Large) are less favorable than (Large, Small) <--> (Small, Small). Compensatory interchanges of the type (Large, Small) <--> (Small, Large) are unfavorable. (iv) Inspection of the trends in the interchanges of the clustered small residues versus clustered large rigid, and separately versus clustered large flexible, illustrates clear differences. Consistently, within all hydrophobic, large and small, the flexible aliphatic differ from the more rigid aromatic. The flexible aliphatic residue pairs are unfavorably replaced by other residue types. Furthermore, (v) the unique properties of the aromatics, conferred by the electronic configuration of their benzene rings, are transformed into clear trends. Replacements of polar residues by aromatics, while unfavorable, are nevertheless consistently more favorable than into aliphatics. We address these issues and their direct implications to protein design and to fold recognition.


Deaths in the Turkish hamam (hot bath).
Hamam (Hot Bath) culture is prevalent worldwide. The high temperature and humidity of these places have multiple effects on human health. The aim of this study was to investigate the demographic characteristics, autopsy findings and causes of death of cases who died in hamam and underwent medicolegal autopsies. The study was performed on 15 cases who experienced sudden death or died suspiciously in hamam and autopsied between January 1999 and December 2004. Eleven cases were men and 4 were women. Mean age was 69.5 +/- 3.1 and median age was 74. Eight cases were found dead in a bathtub or pool whereas seven were found out of water. Six of the cases older than 65 died in winter months. The causes of death were recorded as acute cardiac failure in 13 cases, pneumonia and cardiac failure in one, pneumonia and acute pancreatitis in the last case. Elderly patients with cardiac failure and coronary heart disease experience significant health problems in saunas and hamams. They should avoid this tradition unless approved by their physicians (Ref. 35). Full Text (Free, PDF) www.bmj.sk.


Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management.
To report changes in grade and stage between initial diagnostic and repeat biopsies or resection for urothelial carcinoma (UTUC) and investigate the consequences for endoscopic management. Ureteroscopic management of upper tract UTUC is an alternative to nephroureterectomy, which is less invasive and preserves renal function. However, concerns about potential understaging, inaccurate grading, incomplete resection, lack of effective tertiary chemoprevention, and need for ureteroscopic surveillance limits it appeal. Clinicopathological records of patients with UTUC treated at our institution were reviewed. Fifty-six patients with a histologic diagnosis of UTUC and 2 or more consecutive biopsies or biopsy followed by surgical resection were included, resulting in 65 biopsy specimens. The median interval between diagnostic biopsy and subsequent biopsy or resection was 6 weeks (range, 1 week to 60 months). Change in grade from the diagnostic biopsy occurred in 24 of 65 biopsies (37%), including 9 in which diagnosis changed from low to high grade. Change in the stage from the diagnostic biopsy occurred in 25 of 65 biopsies (38%). Overall, 24 (43%) patients were reclassified from low-grade, noninvasive disease to high-grade and/or invasive disease. A change in grade and/or stage from the diagnostic biopsy occurred in more than one third of patients with UTUC managed conservatively. Because of the short median time interval between biopsies, this finding likely represents variability in tumor sampling on biopsy. Because of the concerns of undergrading and understaging, appropriate patient selection and vigilant endoscopic surveillance are mandatory for UTUC managed endoscopically.


Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members.
The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of "diversity" (total number of activities), "intensity" (hours per month), and "percentage intensity" (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20-39) to middle adulthood (40-60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.


Effect of back-pressure on absorption efficiency of impingers used for air sampling.
The gas-liquid absorption method, using an impinger as an extracting device, is the most common method for quantifying most gaseous pollutants. The performance of conventional impingers was studied, and several modified impingers were tested. It was found that the sampling efficiency varied from impinger to impinger, which resulted from back-pressure differences between impingers. The back-pressure of ten tested impingers ranged between 160 mm to 520 mm water gage when a 50 mL absorbing solution was used, which caused the ammonia concentration coefficients of variations to be up to 15%. It was also verified that an open bubble distribution tube could be used to eliminate back-pressure variations between impingers. Nearly identical back-pressure (44 +/- 4 mm water gage) could be obtained. This modification can improve measurement repeatability significantly and reduce the coefficient of variation of measurements to 1.2%. With this modification to the impingers, greater accuracy, repeatability and comparison of results can be achieved in the measurement of gaseous pollutants in air.


Interpreting infant vocal distress: the ameliorative effect of musical training in depression.
An infant's cry is one of the most emotionally salient sounds in our environment. Depression is known to disrupt a mother's ability to respond to her infant, but it is not well-understood why such difficulties arise. One reason might be that depression disrupts the perceptual abilities necessary to interpret infant's affective cues. Given that musicians are known to have enhanced auditory perception, we assessed whether depression and previous musical training can impact on the ability to interpret distress in infant cries, as manipulated by changes in pitch. Depressed participants with musical training demonstrated better discriminative acuity of distress in infant cry bursts compared to those without. Non-depressed participants, with and without musical training, had levels comparable to musicians with depression. We suggest that previous musical training may act as a protective factor that maintains auditory perceptual abilities in the context of depression. These findings have potential implications for the development of novel training interventions to maintain sensitivity to infant vocal cues in individuals with postnatal depression.


Evaluating peer-influence processes in a prison-based therapeutic community: a dynamic network approach.
The Therapeutic Community (TC) is a common treatment modality for incarcerated individuals with substance use disorders. TCs rely on peer group processes to promote lasting behavioral and identity change, yet prior research has not adequately tested the peer influence mechanisms underlying the theoretical model. This study applied dynamic network analysis to estimate peer influence processes central to TC philosophy. A stochastic actor-oriented model (SAOM) was applied to ten months of social network data collected from prisoner surveys within a TC unit (N = 62) in a medium-security Pennsylvania prison. Respondents (N = 177, 84% of unit) completed at least one prison survey and provided network and community role model nominations. Although residents' levels of treatment engagement were significantly correlated with their nominated peers, estimates of peer influence for treatment engagement were non-significant in longitudinal network models. Nor were estimates of peer influence significantly greater for peers perceived as community role models. Rather, inmates connected with peers who were of similar treatment engagement as themselves (i.e., a peer selection process), and the latter primarily resulted from racial homophily in the TC social network. Inconsistent with the desired treatment model, treatment engagement diffusion was not evident in the sampled TC. Results suggested that highly-engaged residents clustered together at the center of the TC's social structure but had little impact on less-engaged and peripheral inmates. The relatively short (i.e., four-month) program length and moderate-to-low treatment fidelity likely contributed to the lack of peer influence processes.


[Consensus for infliximab treatment of patients with Crohn's disease].
Very recently infliximab--a tumour necrosis factor blocking antibody--was registered as an important novel immunomodulating therapy for active Crohn's disease in the Netherlands. Although this treatment can have a very significant and sometimes dramatic effect (on remission induction), its longterm effects are still uncertain and the high cost is a major drawback. An expert committee of specialists in inflammatory bowel disease (IBD) in the Netherlands therefore produced a consensus report on specific treatment indications for its use. It is stated that only immunosuppressive-resistant patients or patients with incompatibilities and allergies to prednisone, azathioprine and methotrexate should be candidates, a second indication being patients with serious enterocutaneous fistulae not reacting to a full course of conventional therapy. Its use is not indicated in patients with stenosing disease. It is also stated that the effect of longterm repeated therapy in active Crohn's disease still has to be established. Since budget limitations for medications are a major disadvantage, the formation of expert committees (with an expert in the treatment of complicated inflammatory bowel disease) in each hospital should be stimulated to limit the treatment to only cases with real immunosuppressive-resistant disease.


Surgery and electrochemotherapy for the treatment of cutaneous squamous cell carcinoma in a yellow-bellied slider (Trachemys scripta scripta).
A 5-year-old female yellow-bellied slider (Trachemys scripta scripta) was referred for evaluation of a 2-month nonhealing ulcerated mass on the dorsal aspect of the neck. The turtle was quiet, alert, and responsive, with a 2 × 1.5-cm ulcerated lesion on the neck. Signs of discomfort were observed during manipulation of the neck; no other abnormalities were detected during physical evaluation. Following total body radiography and hematologic and serum biochemical analysis, the turtle was anesthetized and the mass was surgically removed. The excised tissue was submitted for histologic evaluation. A histopathologic diagnosis of squamous cell carcinoma (SCC) was made. Further surgical revision was not an option because of the extensive nature of the lesion; therefore, the tumor bed was treated with electrochemotherapy (ECT). Two sessions of ECT were performed with a 2-week interval between treatments. Electrochemotherapy involved intratumoral administration of bleomycin followed by trains of biphasic electric pulses. The treatment was well tolerated, and the turtle was disease free after 12 months. ECT resulted in good local control of SCC and should be considered as a possible postsurgical adjuvant treatment in reptiles with cutaneous tumors.


In vivo imaging and therapeutic treatments in an orthotopic mouse model of ovarian cancer.
Human cancer and response to therapy is better represented in orthotopic animal models. This paper describes the development of an orthotopic mouse model of ovarian cancer, treatment of cancer via oral delivery of drugs, and monitoring of tumor cell behavior in response to drug treatment in real time using in vivo imaging system. In this orthotopic model, ovarian tumor cells expressing luciferase are applied topically by injecting them directly into the mouse bursa where each ovary is enclosed. Upon injection of D-luciferin, a substrate of firefly luciferase, luciferase-expressing cells generate bioluminescence signals. This signal is detected by the in vivo imaging system and allows for a non-invasive means of monitoring tumor growth, distribution, and regression in individual animals. Drug administration via oral gavage allows for a maximum dosing volume of 10 mL/kg body weight to be delivered directly to the stomach and closely resembles delivery of drugs in clinical treatments. Therefore, techniques described here, development of an orthotopic mouse model of ovarian cancer, oral delivery of drugs, and in vivo imaging, are useful for better understanding of human ovarian cancer and treatment and will improve targeting this disease.


Microstructural Properties of Human Brain Revealed by Fractional Anisotropy Can Predict the After-Effect of Intermittent Theta Burst Stimulation.
Intermittent theta burst stimulation (iTBS) delivered by transcranial magnetic stimulation (TMS) produces a long-term potentiation-like after-effect useful for investigations of cortical function and of potential therapeutic value. However, the iTBS after-effect over the primary motor cortex (M1) as measured by changes in motor evoked potential (MEP) amplitude exhibits a largely unexplained variability across individuals. Here, we present evidence that individual differences in white matter (WM) and gray matter (GM) microstructural properties revealed by fractional anisotropy (FA) predict the magnitude of the iTBS-induced after-effect over M1. The MEP amplitude change in the early phase (5-10 min post-iTBS) was associated with FA values in WM tracts such as right superior longitudinal fasciculus and corpus callosum. By contrast, the MEP amplitude change in the late phase (15-30 min post-iTBS) was associated with FA in GM, primarily in right frontal cortex. These results suggest that the microstructural properties of regions connected directly or indirectly to the target region (M1) are crucial determinants of the iTBS after-effect. FA values indicative of these microstructural differences can predict the potential effectiveness of repetitive TMS for both investigational use and clinical application.


Designing national IP/MPLS networks with flexgrid optical technology.
We propose a two-step procedure to design flexgrid-based national networks. Locations are first partitioned into a set of metro areas interconnected through a flexgrid optical network. The problem is modeled as a Mixed Integer Linear Programming (ILP). Next, each network is designed separately. Optimal results show a future large (>200 nodes) flexgrid core network inter-connecting small (~10 nodes) metro regions.


Not Always Sticky: Specificity of Protein Stabilization by Sugars Is Conferred by Protein-Water Hydrogen Bonds.
Solutes added to buffered solutions directly impact protein folding. Protein stabilization by cosolutes or crowders has been shown to be largely driven by protein-cosolute volume exclusion complemented by chemical and soft interactions. By contrast to previous studies that indicate the invariably destabilizing role of soft protein-sugar attractions, we show here that soft interactions with sugar cosolutes are protein-specific and can be stabilizing or destabilizing. We experimentally follow the folding of two model miniproteins that are only marginally stable but in the presence of sugars and polyols fold into representative and distinct secondary structures: β-hairpin or α-helix. Our mean-field model reveals that while protein-sugar excluded volume interactions have a similar stabilizing effect on both proteins, the soft interactions add a destabilizing contribution to one miniprotein but further stabilize the other. Using molecular dynamics simulations, we link the soft protein-cosolute interactions to the weakening of direct protein-water hydrogen bonding due to the presence of sugars. Although these weakened hydrogen bonds destabilize both the native and denatured states of the two proteins, the resulting contribution to the folding free energy can be positive or negative depending on the amino acid sequence. This study indicates that the significant variation between proteins in their soft interactions with sugar determines the specific response of different proteins, even to the same sugar.


Combined utility of Ki-67 index and tumor grade to stratify patients with pancreatic ductal adenocarcinoma who underwent upfront surgery.
To investigate the prognostic prediction of a new indicator, combined by tumor grade and Ki-67, in patients with resected pancreatic ductal adenocarcinoma (PDAC). Data were retrospectively collected from consecutive patients who underwent primary resection of pancreas from December 2012 to December 2017. Tumor grade and Ki-67 were reviewed from routine pathological reports. G-Ki67 was classified as three categories as I (G1/2 and Ki-67 < 40%), II (G1/2 and Ki-67 ≥ 40%), and III(G3/4 and all Ki-67). Cox regression analyses revealed that tumor stage (II vs. I: hazard ratio (HR), 3.781; 95% confidence index (CI), 2.844-5.025; P < 0.001; III vs. I: HR, 7.476; 95% CI, 5.481-10.20; P < 0.001) and G-Ki67 (II vs. I: HR, 1.299; 95% CI, 1.038-1.624; P = 0.022; III vs. I: HR, 1.942; 95% CI, 1.477-2.554; P < 0.001) were independent prognostic factors in the developing cohort. The result was rectified in the validation cohort. In subgroups analysis, G-Ki67 (II vs. I: HR, 1.866 ; 95% CI, 1.045-3.334; P = 0.035; III vs. I: HR, 2.333 ; 95% CI, 1.156-4.705; P = 0.018) also had a high differentiation for survival prediction. Our findings indicate that three-categories of G-Ki67 in resectable PDAC according to the routine pathological descriptions provided additional prognostic information complementary to the TNM staging system.


Prevention of diabetes in BB/Wor rats by intrathymic islet injection.
The objective of this study was to determine whether the intrathymic injection of islets can prevent the development of diabetes in BB/Wor rats. Evidence suggests that a failure to induce islet thymic tolerance may be an etiological factor in the development of the disease. It was theorized that the introduction of islets into the thymus might directly induce islet tolerance and thus prevent disease. Islets from diabetes-resistant BB/Wor rats were injected into the thymuses of 23 young diabetes-prone BB/Wor rats; 25 sham-operated animals served as controls. Results showed that 22 of the 25 control rats became diabetic while only 8 of the 23 experimental rats became diabetic (P less than 0.0002). The specific lysis of islet cells by spleen cells from nondiabetic experimental and control rats was comparable and less than the lysis induced by spleen cells from diabetic rats. These data demonstrate that the intrathymic injection of islets into diabetes-prone BB/Wor rats is an effective method for preventing the development of autoimmune type I diabetes.


Normal values for left ventricular volumes obtained using gated PET.
Accurate assessment of left ventricular (LV) volumes provides important insights into myocardial function, being particularly important for diseases of the heart in which there is progressive dilatation of the LV, such as remodeling after myocardial infarction. We have recently validated a method for measuring LV volumes using gated positron emission tomography (PET) with oxygen-15 labeled carbon monoxide (C15O). The present study was performed to establish normal values for LV volumes, in absolute units, using this technique. Forty subjects [21 males and 19 females; age 49 +/- 13 years (mean +/- SD), range 24-80; body surface area (BSA) range 1.50-2.18 m2] were studied. End diastolic (EDV) and end systolic volumes (ESV) were calculated by determining the edge of the end diastolic and end systolic blood pool images (obtained using PET with C15O) and summing the volume of the voxels comprising the blood pool. For the overall study population, EDV was 109 +/- 20 ml and ESV 37 +/- 12 ml. When stratified according to gender, these values were: in males, EDV was 117 +/- 18 ml and ESV 42 +/- 18 ml; in females, EDV was 100 +/- 19 ml and ESV 32 +/- 8 ml. The differences between gender groups (EDV: p = 0.0027, ESV: p = 0.0029) were eliminated when volumes were corrected for BSA. These data will form a database of normal values for comparison with pathological conditions of the heart. PET quantification of LV volumes offers a means of measurement of function using an imaging modality that can also assess regional myocardial perfusion and metabolism during the same study session.


A spontaneous Fatp4/Scl27a4 splice site mutation in a new murine model for congenital ichthyosis.
Congenital ichthyoses are life-threatening conditions in humans. We describe here the identification and molecular characterization of a novel recessive mutation in mice that results in newborn lethality with severe congenital lamellar ichthyosis. Mutant newborns have a taut, shiny, non-expandable epidermis that resembles cornified manifestations of autosomal-recessive congenital ichthyosis in humans. The skin is stretched so tightly that the newborn mice are immobilized. The genetic defect was mapped to a region near the proximal end of chromosome 2 by SNP analysis, suggesting Fatp4/Slc27a4 as a candidate gene. FATP4 mutations in humans cause ichthyosis prematurity syndrome (IPS), and mutations of Fatp4 in mice have previously been found to cause a phenotype that resembles human congenital ichthyoses. Characterization of the Fatp4 cDNA revealed a fusion of exon 8 to exon 10, with deletion of exon 9. Genomic sequencing identified an A to T mutation in the splice donor sequence at the 3'-end of exon 9. Loss of exon 9 results in a frame shift mutation upstream from the conserved very long-chain acyl-CoA synthase (VLACS) domain. Histological studies revealed that the mutant mice have defects in keratinocyte differentiation, along with hyperproliferation of the stratum basale of the epidermis, a hyperkeratotic stratum corneum, and reduced numbers of secondary hair follicles. Since Fatp4 protein is present primarily at the stratum granulosum and the stratum spinosum, the hyperproliferation and the alterations in hair follicle induction suggest that very long chain fatty acids, in addition to being required for normal cornification, may influence signals from the stratum corneum to the basal cells that help to orchestrate normal skin differentiation.


Turkish version of the SPAN questionnaire for highschool students: reproducibility and validity.
This study aimed to generate a Turkish version of the School Physical Activity and Nutrition (SPAN) (2009) questionnaire for high-school students and to test its validity and reproducibility. The questionnaire was translated and back translated and the language validity was assessed. It was tested and re-tested on 318 highschool students to evaluate its validity and reproducibility. Validity was determined by comparing the parts of the questionnaire about what was eaten in the previous day with that of 24-hour food consumption lists. Statistical analysis was performed by using Spearman correlation analysis, kappa statistics and percentage of agreement. The highest test-re-test results were on foods consumed the day before, with an agreement percentage range of 56%-96% and a kappa range of 0.43-0.95. The items related to physical activity had an agreement range of 38%-88% and a kappa range of 0.24-0.82. The reproducibility and validity of the Turkish version of SPAN questionnaire is acceptable and it is a rapid, easily used tool for the assessment of nutrition and physical activity in schoolchildren.


Comparison of a new test for agility and skill in soccer with other agility tests.
The purpose of this study was both to develop a novel test to measure run, shuttle run and directional change agility, and soccer shots on goal with decision making and to compare it with other agility tests. Multiple comparisons and assessments were conducted, including test-retest, Illinois, Zig-Zag, 30 m, Bosco, T-drill agility, and Wingate peak power tests. A total of 113 Turkish amateur and professional soccer players and tertiary-level students participated in the study. Test-retest and inter-tester reliability testing measures were conducted with athletes. The correlation coefficient of the new test was .88, with no significant difference (p> 0.01> 0.01) between the test results obtained in the first and second test sessions. The results of an analysis of variance revealed a significant (p < 0.01) difference between the T-drill agility and power test results for soccer players. The new agility and skill test is an acceptable and reliable test when considering test-retest reliability and inter-rater reliability. The findings in this study suggest that the novel soccer-specific agility and shooting test can be utilized in the testing and identification of soccer players' talents.


Relation of Resting Heart Rate to Incident Atrial Fibrillation (from the Henry Ford Hospital Exercise Testing Project).
Autonomic nervous system (ANS) dysfunction plays a role in atrial fibrillation (AF) initiation. Cardiorespiratory fitness modulates ANS function and is inversely associated with resting heart rate (RHR) and risk of AF. Thus, we sought to study the association between RHR, as a surrogate for ANS function, and incident AF independent of exercise capacity (EC). We analyzed 51,436 subjects without previous AF who underwent a clinically indicated exercise stress test. Incident AF was ascertained through claims files. RHR was measured before stress testing, and EC was estimated by peak metabolic equivalents of task. We studied the association between RHR categories (<70, 70 to 85 [reference], and >85 beats/min) and incident AF using Cox models adjusted for risk factors and for EC. We tested for interaction between RHR and age, gender, smoking, and EC. Mean (SD) age was 53 (13) years, 53% were men, and 28% were black. Participants with RHR <70 beats/min were older, more likely to be men, have higher EC, and more likely to smoke but less likely to have diabetes and hypertension. Over a median of 5.5 years, RHR <70 beats/min was associated with 14% increased risk of AF (95 CI 6% to 25%) in fully adjusted models, whereas RHR >85 beats/min was not associated with AF risk after adjusting for EC. Results for RHR analyzed continuously and by quartile were similar. No interaction was seen. In conclusion, subjects with low RHR at all levels of EC are at increased risk of AF and may benefit from heart rhythm surveillance, particularly in the presence of other AF risk factors.


[Study of the impact of breeding sites on the infectivity of P. falciparum gametocytes to An. gambiae s.l in malaria-endemic area of Nanguilabougou.-Mali].
Numerous studies have shown the influence of some bacteria colonizing the breeding sites on the development of the parasite in Anopheles malaria vectors. The aim of this study was to evaluate the impact of the breeding sites of Plasmodium falciparum on the gametocytes infectivity of Anopheles gambiae sl using the membrane feeding method. We carried out an experimental infestation study from September 2010 to January 2011 in a village located in the southern savanna of Mali. Cross sectional surveys were conducted to collect larvae and to select gametocyte carriers. Female offspring of L3 and L4 stage larvae were used for the experimental infestation. The gametocyte carriers were children aged within 4 to 12 years. Bacteria identified in breeding water of larvae and adult mosquitoes were: Escherichia coli, Salmonella spp, Klebsiella oxytoca, Pseudomonas spp, Staphylococcus spp, Shigella sp. The oocyst load of infected mosquitoes did not significantly vary according to the samples (F = 1.517, P = 0.230). Low infection rates (5.4% and 2.8%) were observed in the larval bedding and in mosquitoes containing K. oxytoca and Shigella. The blood feeding rates (62.4%; 60.9%; 67.7%) and mortality (66.4%; 64.9%; 61.9%) of An. gambiae did not significantly vary depending on the breeding sites [(P = 0.15); (P = 0.22)].


Arabidopsis BRANCHED1 acts as an integrator of branching signals within axillary buds.
Shoot branching patterns depend on a key developmental decision: whether axillary buds grow out to give a branch or whether they remain dormant in the axils of leaves. This decision is controlled by endogenous and environmental stimuli mediated by hormonal signals. Although genes involved in the long-distance signaling of this process have been identified, the genes responding inside the buds to cause growth arrest remained unknown in Arabidopsis thaliana. Here, we describe an Arabidopsis gene encoding a TCP transcription factor closely related to teosinte branched1 (tb1) from maize (Zea mays), BRANCHED1 (BRC1), which represents a key point at which signals controlling branching are integrated within axillary buds. BRC1 is expressed in developing buds, where it arrests bud development. BRC1 downregulation leads to branch outgrowth. BRC1 responds to developmental and environmental stimuli controlling branching and mediates the response to these stimuli. Mutant and expression analyses suggest that BRC1 is downstream of the MORE AXILLARY GROWTH pathway and that it is required for auxin-induced apical dominance. Therefore, BRC1 acts inside the buds as an integrator of signals controlling bud outgrowth and translates them into a response of cell growth arrest. The conservation of BRC1/tb1 function among distantly related angiosperm species suggests that a single ancestral mechanism of branching control integration evolved before the radiation of flowering plants.