[Rosai-Dorfman disease presenting with multiple intracranial and intraspinal masses: a case report].
Rosai-Dorfman disease (RDD), a systemic histioproliferative disorder, was first described by Rosai and Dorfman in 1969. However, only 41 cases involving the central nervous system have been reported. The authors present a rare case of RDD with multiple intracranial and spinal lesions mimicking multiple meningioma. A 59-year-old woman was admitted to our hospital with a history of bilateral visual impairment. MRI demonstrated multiple central nervous system lesions in the suprasellar region, right temporal convexity, left frontal convexity, left cerebello-pontine angle and C5 level of the spinal cord. Preoperative neuro-imaging studies suggested multiple meningioma. Subtotal removal of the suprasellar lesion was performed, followed by gamma knife radiosurgery to the residual lesion and the other intracranial lesions. All intracranial lesions disappeared following gamma knife radiotherapy. The spinal lesion, however, was completely excised one year after the initial operation following the appearance of sensory disturbance. Both intracranial and spinal lesions were diagnosed as RDD on histological examination. No recurrences have been detected on MRI two years after the initial operation. Seeing the good results already achieved by surgical removal of RDD, this case suggests that the combination of surgery and gamma knife radiotherapy might improve further.


Specificity factors in cytoplasmic polyadenylation.
Poly(A) tail elongation after export of an messenger RNA (mRNA) to the cytoplasm is called cytoplasmic polyadenylation. It was first discovered in oocytes and embryos, where it has roles in meiosis and development. In recent years, however, has been implicated in many other processes, including synaptic plasticity and mitosis. This review aims to introduce cytoplasmic polyadenylation with an emphasis on the factors and elements mediating this process for different mRNAs and in different animal species. We will discuss the RNA sequence elements mediating cytoplasmic polyadenylation in the 3' untranslated regions of mRNAs, including the CPE, MBE, TCS, eCPE, and C-CPE. In addition to describing the role of general polyadenylation factors, we discuss the specific RNA binding protein families associated with cytoplasmic polyadenylation elements, including CPEB (CPEB1, CPEB2, CPEB3, and CPEB4), Pumilio (PUM2), Musashi (MSI1, MSI2), zygote arrest (ZAR2), ELAV like proteins (ELAVL1, HuR), poly(C) binding proteins (PCBP2, αCP2, hnRNP-E2), and Bicaudal C (BICC1). Some emerging themes in cytoplasmic polyadenylation will be highlighted. To facilitate understanding for those working in different organisms and fields, particularly those who are analyzing high throughput data, HUGO gene nomenclature for the human orthologs is used throughout. Where human orthologs have not been clearly identified, reference is made to protein families identified in man.


High level expression of recombinant chicken interferon-alpha using baculovirus.
Bioactive recombinant chicken interferon-alpha (ChIFN-alpha) was expressed in a baculovirus system. For easy purification, it was expressed as ChIFN-alpha bearing histidine hexamer (His-tag) at C-terminal, designated ChIFN-alphaHis. The expressed proteins were detected by SDS-PAGE analysis with Coomassie brilliant blue staining as around 23 and 19 kDa bands thought to be immature and matured ChIFN-alphaHis respectively. The purified ChIFN-alphaHis with a nickel chelated column showed anti-viral activity in vitro.


In situ biomonitoring of juvenile Chinook salmon (Onchorhynchus tshawytscha) using biomarkers of chemical exposures and effects in a partially remediated urbanized waterway of the Puget Sound, WA.
In situ biomonitoring has been used to assess the effects of pollution on aquatic species in heavily polluted waterways. In the current study, we used in situ biomonitoring in conjunction with molecular biomarker analysis to determine the effects of pollutant exposure in salmon caged in the Duwamish waterway, a Pacific Northwest Superfund site that has been subject to remediation. The Duwamish waterway is an important migratory route for Pacific salmon and has received historic inputs of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Juvenile pre-smolt Chinook salmon (Oncorhynchus tshawytscha) caged for 8 days in the three contaminated sites in close proximity within the Duwamish were analyzed for steady state hepatic mRNA expression of 7 exposure biomarker genes encompassing several gene families and known to be responsive to pollutants, including cytochrome P4501A (CYP1A) and CYP2K1, glutathione S-transferase pi class (GST-pi), microsomal GST (mGST), glutamylcysteine ligase catalytic subunit (GCLC), UDP-glucuronyltransferase family 1 (UDPGT), and type 2 deiodinase (type 2 DI, or D2). Quantitation of gene expression was accomplished by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in assays developed specifically for Chinook salmon genes. Gill PAH-DNA adducts were assessed as a chemical effects biomarker using (32)P-postlabeling. The biomarkers in the field-caged fish were analyzed with respect to caged animals maintained at the hatchery receiving flow-through water. Chemical analysis of sediment samples from three field sampling sites revealed relatively high concentrations of total PAHs in one site (site B2, 6711ng/g dry weight) and somewhat lower concentrations of PAHs in two adjacent sites (sites B3 and B4, 1482 and 1987ng/g, respectively). In contrast, waterborne PAHs at all of the sampling sites were relatively low (<1ng/L). Sediment PCBs at the sites ranged from a low of 421ng/g at site B3 to 1160ng/g at site B4, and there were no detectable waterborne PCBs at any of the sites (detection limit=10ng/L). There were no significant differences (p<0.05) in biomarker gene expression in the Duwamish-caged fish relative to controls, although there was a pattern of gene expression suppression at site B3, the most heavily PAH-enriched site. The lack of a marked perturbation of mRNA biomarkers was consistent with relatively low levels of gill PAH-DNA adduct levels that did not differ among caged reference and field fish, and which were also consistent with relatively low waterborne concentrations of chemicals. The results of our study suggest a low bioavailability of sediment pollutants in caged juvenile Chinook potentially reflecting low waterborne exposures occurring at contaminated sites within the Duwamish waterway that have undergone partial remediation.


[Diagnostic value of determining endogenous proteinase inhibitors in cancer patients].
Patients with stage III and IV cancers of different sites revealed a 47-76% increase in serum total antitrypsinic activity. A mean 40% increase was observed in cases of inflammatory pathology. Both study groups demonstrated raised alpha 1-antitrypsin levels, while that of alpha 2-macroglobulin did not show any significant changes. The level of alpha 1-antitrypsin accounted for 89 and 83% of total antitrypsinic activity in cases of inflammation and controls, respectively, while in cancer patients this index was significantly lower (70%). The diagnostic value of total antitrypsinic activity appeared to be higher than that of alpha 1-antitrypsin level determination. It is inferred that, apart from alpha 1-antitrypsin, malignant growth is associated with raised levels of more specific endogenous proteinase inhibitors, except alpha 2-macroglobulin.


Improving IUI success by performing modified slow-release insemination and a patient-centred approach in an insemination programme with partner semen: a prospective cohort study.
Pregnancy rates after in vitro fertilisation (IVF) treatment continue to improve, while intrauterine insemination (IUI) programmes show no such trend. There is a need to improve success rates with IUI to retain it as a viable option for couples who prefer avoiding IVF as a first line treatment. To investigate if a modified slow-release insemination (SRI) increases the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with partner semen. This was a prospective cohort study in a Belgian tertiary fertility centre. Between July 2011 and December 2018, we studied data from an ongoing prospective cohort study including 989 women undergoing 2565 IUI procedures for unexplained or mild/moderate male infertility. These data were analysed in order to study the importance of different covariates influencing IUI success. Generalised estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015, period 1 and 2016-2018, period 2) were examined and compared. From January 2016 (period 2) onwards, a standardised SRI procedure instead of bolus injection of sperm was applied. The primary outcome parameter was the difference in clinical pregnancy rate (CPR) per cycle between period 1 (bolus IUI) and period 2 (modified SRI). Secondary outcome results included all other parameters significantly influencing CPR after IUI. Following the application of modified SRI the CPR increased significantly, from 9.03% (period 1) to 13.52% (period 2) (p = 0.0016). Other covariates significantly influencing CPR were partner's age, smoking/non-smoking partner, BMI patient, ovarian stimulation protocol and Inseminating Motile Count (after semen processing). Conclusions: The intentional application of modified slow-release of processed semen appears to significantly increase CPRs after IUI with homologous semen. Future studies should investigate whether SRI, patient-centred measures, or a combination of both, are responsible for this improvement.


Change in defense mechanisms and coping patterns during the course of 2-year-long psychotherapy and psychoanalysis for recurrent depression: a pilot study of a randomized controlled trial.
Very little research has been conducted so far to study the potential mechanisms of change in long-term active psychological treatments of recurrent depression. The present pilot randomized controlled trial aimed to determine the feasibility of studying the change process occurring in patients during the course of 2-year-long dynamic psychotherapy, psychoanalysis, and cognitive therapy, as compared with clinical management. In total, eight outpatients presenting with recurrent depression, two patients per treatment arm, were included. All patients were randomly assigned to one of the four treatment conditions. Defense mechanisms and coping patterns were assessed using validated observer-rated methodology based on transcribed, semistructured follow-along independent dynamic interviews. The results indicated that, whereas some patients in the active treatments changed on the symptomatic levels, some others remained unchanged during the course of their 2-year-long treatment. However, with regard to potential mechanisms of change in these patients, changes in defense mechanisms and coping patterns were revealed to be important processes over time in successful therapies and, to a lesser extent, in less successful treatments. No change was found either on outcome or on the process measure for the control condition, that is, clinical management. These results are discussed along with previous data comparing change in defense mechanisms and coping during the course of treatments.


[Meta-analysis on the effectiveness of pulmonary rehabilitation program on exercise capacity/tolerance and general health status].
This study was conducted to combine the effects of pulmonary rehabilitation program (PRP) on exercise capacity/tolerance and general health status of COPD patients based on the primary research results examined the effects of PRP. Seventeen studies were selected by the sampling criteria established to include the studies that reported enough statistics necessary to conduct meta-analysis. According to the study results, the most effective indicators for exercise capacity/tolerance were exercise time (such as cycling time or treadmill walking time) and ground walking distance within given time (6 minutes or 12 minutes), whereas effects on such indicators as VE and VO2 were not statistically significant. PRP induced significant effect on patients' general health status, frequently measured by physical, psycho-emotional, and holistic indicators, the enhancement on psycho-emotional dimension resulted from PRP was more prominent than those of the other dimensions. From the results, it was noted that the place where PRP was given and the contents of PRP exercised their influence on the outcome variables. Which body part was trained was also one of the important factors that influence on the patients' perception of dyspnea during exercise as well as on exercise capacity/tolerance. PRP including exercise training significantly improved the exercise capacity and general health status of COPD patients.


A worldwide bibliometric analysis of the research trends and hotspots of bruxism in adults during 1991-2021.
With the increasing attention to bruxism, the research on bruxism is increasing rapidly. However, there is still a lack of systematic bibliometric analysis in the field of bruxism in adults. This study aimed to comprehensively explore and visualize the global trends and research hotspots in the field of bruxism in adults during 1991-2021. The study searched the literature published during 1991-2021 in the Web of Science Core Collection database without language restrictions. VOSviewer, CiteSpace and Microsoft Excel were applied to analyse the authors, institutions, journals, countries, cited references, keywords and other information of the included publications, and construct visualized cooperation networks. A total of 878 articles were finally included. The top two most productive authors in the past 30 years were Lobbezoo F and Manfredini D. ACTA-Amsterdam, Univ Sao Paulo, Univ Helsinki, Univ Padua, Univ Montreal, et al. were prominent institutions in this field. Journal of Oral Rehabilitation made outstanding contributions in this field. The United States produced the most documents in this field, followed by Brazil. Both countries and authors cooperated closely around the world. The two most cited articles focused on the definition, assessment and classification of bruxism. In recent years, diagnostic criteria and stress have begun to receive a lot of attention. From 1991 to 2021, the attention to bruxism in adults continued to increase. Diagnostic criteria and stress may be potential research hotspots in this field. This study references relevant scholars on development trends and research hotspots.


A comparative dosimetric study on tangential photon beams, intensity-modulated radiation therapy (IMRT) and modulated electron radiotherapy (MERT) for breast cancer treatment.
Recently, energy- and intensity-modulated electron radiotherapy (MERT) has garnered a growing interest for the treatment of superficial targets. In this work. we carried out a comparative dosimetry study to evaluate MERT, photon beam intensity-modulated radiation therapy (IMRT) and conventional tangential photon beams for the treatment of breast cancer. A Monte Carlo based treatment planning system has been investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We have compared breast treatment plans generated using this home-grown treatment optimization and dose calculation software forthese treatment techniques. The MERT plans were planned with up to two gantry angles and four nominal energies (6, 9, 12 and 16 MeV). The tangential photon treatment plans were planned with 6 MV wedged photon beams. The IMRT plans were planned using both multiple-gantry 6 MV photon beams or two 6 MV tangential beams. Our results show that tangential IMRT can reduce the dose to the lung, heart and contralateral breast compared to conventional tangential wedged beams (up to 50% reduction in high dose volume or 5 Gy in the maximum dose). MERT can reduce the maximum dose to the lung by up to 20 Gy and to the heart by up to 35 Gy compared to conventional tangential wedged beams. Multiple beam angle IMRT can significantly reduce the maximum dose to the lung and heart (up to 20 Gy) but it induces low and medium doses to a large volume of normal tissues including lung, heart and contralateral breast. It is concluded that MERT has superior capabilities to achieve dose conformity both laterally and in the depth direction, which will be well suited for treating superficial targets such as breast cancer.


Analysis of protein phosphorylation and cellular signaling events by flow cytometry: techniques and clinical applications.
Analysis of protein phosphorylation with flow cytometric techniques has emerged as a powerful tool in the field of immunological signaling, allowing cellular subsets in complex populations to be analyzed accurately and rapidly. In this review, we examine the development of phospho-epitope, or phospho-specific, flow cytometry and the premises upon which the technique is based. Phospho-specific flow cytometry is compared to traditional biochemical methods, and its advantages, such as single cell analysis, multiparameter data acquisition, rapid protocols, and the ability to analyze rare cell subsets, are detailed. We also discuss the many technical considerations that must be addressed when developing new antibodies or analyzing new epitopes including antigen accessibility, stability of the phospho-epitope, fluorophore selection, surface phenotype integrity, and antibody suitability for staining epitopes inside fixed and permeabilized cells. The methods that have been used to date are described in light of these technical considerations. The importance of developing bioinformatic platforms in parallel with these techniques is emphasized due to the large, multiparameter datasets that are rapidly accumulated and which require more efficient data viewing and complex clustering methods than currently available for flow cytometric data. Finally, we discuss the potential clinical applications of phospho-specific flow cytometry in analyzing immune cell development and antigen-specific immune responses, as well as pharmacodynamic profiling of disease states or drug efficacy and specificity against particular signaling proteins.


Increased oxidative stress in patients with essential thrombocythemia.
Essential thrombocythemia (ET) is a clonal disease in which thrombotic and hemorrhagic complications are common. Our aim in this study was to investigate whether oxidative stress in ET patients increased compared to healthy volunteers and to investigate whether there is a relationship between vascular events and oxidative status parameters in ET patients. We determined the serum levels of oxidative status parameters, such as total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) in ET patients. Forty-three ET patients (20 males, 23 females) and 20 healthy volunteers were enrolled. Oxidative status parameters of the patients were compared with those of the controls at time of diagnosis and at 6th-month follow-up. Additionally, oxidative status parameters of patients with ET with a history of vascular event were compared with patients without a vascular event history during diagnosis. Rises in TOS, OSI, and MDA were statistically significant in the patients group; however, the TAS value was significantly lower compared to the control group. Furthermore, TOS was significantly higher in patients with history of vascular event compared to the patients without such a history. Following therapy, OSI and MDA values were significantly reduced in the patient group compared to the pre-treatment values. Our findings reveal that although oxidative stress parameters were increased, compensative total antioxidant status was significantly reduced in ET patients. Furthermore, TOS values were significantly high in patients with a history of vascular event.


Cell-produced viral inhibitor: possible mechanism of action and chemical composition.
A newly recognized cell-produced viral inhibitor appeared to be spontaneously released from most cells in tissue culture. It strongly inhibited the replication of a variety of viruses but did not exhibit species specificity as does interferon. These studies on the inhibitor's mechanism of action indicated that it inhibited attachment and penetration of virus by a readily reversible reaction requiring the presence of both virus and cells. Studies of inactivation by specific enzymes or chemicals indicated that for activity the inhibitor required intact protein but not lipid, carbohydrate, deoxyribonucleic acid, or ribonucleic acid.


Integrin αV mediated activation of myofibroblast via mechanoparacrine of transforming growth factor β1 in promoting fibrous scar formation after myocardial infarction.
Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor β1 (TGF-β1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-β1 in MFBs activation for fibrous reparation in mice with MI. Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-β1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-β1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-β1 and nuclear translocation of Smad2/3. This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-β1, especially in immature scar area, which ultimately promotes fibrous scar maturation.


The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression.
Histone monoubiquitylation is implicated in critical regulatory processes. We explored the roles of histone H2B ubiquitylation in human cells by reducing the expression of hBRE1/RNF20, the major H2B-specific E3 ubiquitin ligase. While H2B ubiquitylation is broadly associated with transcribed genes, only a subset of genes was transcriptionally affected by RNF20 depletion and abrogation of H2B ubiquitylation. Gene expression dependent on RNF20 includes histones H2A and H2B and the p53 tumor suppressor. In contrast, RNF20 suppresses the expression of several proto-oncogenes, which reside preferentially in closed chromatin and are modestly transcribed despite bearing marks usually associated with high transcription rates. Remarkably, RNF20 depletion augmented the transcriptional effects of epidermal growth factor (EGF), increased cell migration, and elicited transformation and tumorigenesis. Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes.


A Novel Approach to the Assessment of Fidelity to a Cognitive Behavioral Therapy for PTSD Using Clinical Worksheets: A Proof of Concept With Cognitive Processing Therapy.
Fidelity monitoring is a critical indicator of psychotherapy quality and is central to successful implementation. A major barrier to fidelity in routine care is the lack of feasible, scalable, and valid measurement strategies. A reliable, low-burden fidelity assessment would promote sustained implementation of cognitive behavioral therapies (CBTs). The current study examined fidelity measurement for cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) using clinical worksheets. External raters evaluated patient worksheets done as a part of treatment, both guided by the therapist and completed independently as homework. Results demonstrated that fidelity ratings from CPT session worksheets were feasible and efficient. Notably, they were strongly correlated with observer ratings of the fidelity of CPT strategies that were present on the worksheets. Agreement among ratings conducted by individuals with a range of experience with CPT was acceptable to high. There was not a main effect of therapist-guided, in-session worksheet ratings on PTSD symptom change. However, patient competence in completing worksheets independently was associated with greater PTSD symptom decline and in-session, therapist-guided worksheet completion was associated with larger symptom decreases among patients with high levels of competence. With further research and refinement, rating of worksheets may be an efficient way to examine therapist and patient skill in key CPT elements, and their interactions, compared to the gold standard of observer ratings of therapy video-recordings. Additional research is needed to determine if worksheets are an accurate and scalable alternative to gold standard observer ratings in settings in which time and resources are limited.


A multi-state outbreak of Salmonella Saintpaul in Australia associated with cantaloupe consumption.
A multi-state outbreak of Salmonella enterica serovar Saintpaul infection occurred in Australia during October 2006. A case-control study conducted in three affected jurisdictions, New South Wales, Victoria and Australian Capital Territory, included 36 cases with the outbreak-specific strain of S. Saintpaul identified by multiple locus variable-number tandem repeat analysis (MLVA) in a faecal specimen and 106 controls. Consumption of cantaloupe (rockmelon) was strongly associated with illness (adjusted OR 23.9 95%, 95% CI 5.1-112.4). S. Saintpaul, with the outbreak MLVA profile, was detected on the skin of two cantaloupes obtained from an implicated retailer. Trace-back investigations did not identify the specific source of the outbreak strain of S. Saintpaul, but multiple Salmonella spp. were detected in environmental samples from farms and packing plants investigated during the trace-back operation. Cantaloupe production and processing practices pose a potential public health threat requiring regulatory and community educational interventions.


Comparison of Suture-Augmented Ligamentplasty to Transarticular Screws in a Lisfranc Cadaveric Model.
Lisfranc injuries represent a spectrum of trauma from high-energy lesions, with significant instability of the midfoot, to low-energy lesions, with subtle subluxations or instability without gross displacement. Recently, treatment options that allow for physiologic fixation of this multiplanar joint are being evaluated. The purpose of this study was to analyze the stability of a cadaveric Lisfranc injury model fixed with a novel suture-augmented neoligamentplasty in comparison with a traditional transarticular screw fixation construct. Twenty-four fresh-frozen, matched cadaveric leg and foot specimens (12 individuals younger than 65 years of age) were used for this study. Two different types of Lisfranc ligament injuries were tested: partial and complete. Two different methods of fixation were compared: transarticular screws and augmented suture ligamentplasty with FiberTape. Specimens were fixed to a rotation platform in order to stress the joints while applying 400 N of axial load and internal and external rotation. Six distances were measured and compared between the intact, injured, and fixed states with a 3D Digitizer arm, in order to evaluate the stability between them. Analysis of variance was used with P < .05 considered significant. Using distribution graphs and analyzing the grouped data, it was observed that there was no difference between the 2 stabilization methods, but the augmented suture ligamentplasty presented lower variability and observed distance shortenings were more likely to be around the mean. The variability of the stabilization with screws was 2.9 times higher than that with tape (P < .001). We suggest that augmented suture ligamentplasty can achieve similar stability to classic transarticular screws, with less variability. This cadaveric study adds new information on the debate about Lisfranc lesions treatment. Flexible fixations, such as the synthethic ligamentplasty used, can restore good stability such as conventional transarticular screws.


Obesity and Endometrial Cancer: A Lack of Knowledge but Opportunity for Intervention.
The causal link between obesity and endometrial cancer is well established; however obese women's knowledge of this relationship is unknown. Our objective was to explore patients' understanding of this relationship and assess the acceptability of a technology-based weight loss intervention. Obese women with Type I endometrial cancer/hyperplasia were surveyed about their assessment of their body mass, knowledge of the relationship of obesity and endometrial cancer, and eating and activity habits. Interest in participation in an intervention also was assessed. Eighty-one women with early stage (71.6% stage I) and grade (41.7% grade 1) disease completed the survey. The median BMI was 35.4 kg/m2 (IQR 32.2-43.5 kg/m2) and the average age was 59.3 (SD 11.1) yr. 76.25% of women were unable to categorize their BMI correctly and 86.9% of those incorrectly underestimated their BMI category. One-third (35.9%) were unaware of any association between obesity and endometrial cancer and 33.3% responded that obesity decreased or did not significantly increase the risk of endometrial cancer. 59% expressed interest in a weight loss intervention. Endometrial cancer survivors with obesity underestimated their obesity and lacked knowledge regarding the link between obesity and endometrial cancer. However, the majority expressed interest in electronically delivered weight loss interventions.


Growth factors and endothelial dysfunction.
Endothelial dysfunction has been implicated in the pathogenesis of many cardiovascular diseases; experimental and clinical studies have shown that endothelial dysfunction may be a key factor in various processes, including abnormal arterial vasomotion, thrombosis or neointimal proliferation. Endothelial dysfunction has been shown to be a characteristic feature of atherosclerotic vessels, sites subject to mechanical injury or collateral vessels that develop in response to severe ischaemia. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) are important growth factors for endothelial cells in vitro. While VEGF is specific for endothelial cells, FGFs are also potent growth factors for other cell types such as smooth muscle cells. Recent studies have demonstrated the feasibility of using endothelial cell growth factors in vivo. Basic FGF (bFGF) and VEGF have been shown to increase the development of collateral vessels in ischaemic models and to enhance the extent of endothelial regrowth following arterial injury. The marked anatomical improvement associated with the administration of endothelial cell growth factors has promoted questions concerning a possible role for these factors in endothelial dysfunction. In vivo administration of endothelial cell growth factors is associated with significant improvement in endothelium-dependent responses. This effect is observed with bFGF and VEGF in various animal models of endothelial dysfunction such as the collateral circulation, the regenerated endothelium following arterial injury and experimental atherosclerosis. While the precise mechanisms underlying this ubiquitous beneficial effect of endothelial cell growth factors are still to be determined, these results do support the concept of using such factors as a new therapeutic strategy in patients with vascular diseases.


[New molecular and clinical information about collagens].
Collagen is one of the most abundant proteins in human tissues. Together with other connective tissue components (non-collagenous glycoproteins, proteoglycans, laminins, thrombospondins, entactin and tenascin), collagen promotes cellular adhesion, activates intracellular signals, and regulates the biological activities of growth factors and other proteins. During the past 20 years at least 19 genetically different collagenous proteins coded by 30 distinct genes have been identified. Here, we review some new aspects of the collagens that form fibrils, sheets, or beaded filaments, and of the so-called multiplexin collagens. Whenever possible, we give insights regarding the association of the structural abnormalities of these proteins as they relate with human disease(s).


A feasibility study of a novel, task-specific movement training intervention for women with patellofemoral pain.
To investigate whether a novel, task-specific training intervention that focused on correcting pain-producing movement patterns was feasible and whether it would improve hip and knee kinematics, pain, and function in women with patellofemoral pain. Prospective, non-randomized, within-group, double baseline, feasibility intervention study. A total of 25 women with patellofemoral pain were enrolled. The intervention, delivered 2×/week for six weeks, consisted of supervised, high-repetition practice of daily weight-bearing and recreational activities. Activities were selected and progressed based on participants' interest and ability to maintain optimal alignment without increasing pain. Primary feasibility outcomes were recruitment, retention, adherence, and treatment credibility (Credibility/Expectancy Questionnaire). Secondary outcomes assessing intervention effects were hip and knee kinematics, pain (visual analog scale: current, average in past week, maximum in past week), and function (Patient-Specific Functional Scale). A total of 25 participants were recruited and 23 were retained (92% retention). Self-reported average daily adherence was 79% and participants were able to perform their prescribed home program correctly (reduced hip and knee frontal plane angles) by the second intervention visit. On average, treatment credibility was rated 25 (out of 27) and expectancy was rated 22 (out of 27). Hip and knee kinematics, pain, and function improved following the intervention when compared to the control phase. Based on the feasibility outcomes and preliminary intervention effects, this task-specific training intervention warrants further investigation and should be evaluated in a larger, randomized clinical trial.


Chloride transport.
Chloride transport along the nephron is one of the key actions of the kidney that regulates extracellular volume and blood pressure. To maintain steady state, the kidney needs to reabsorb the vast majority of the filtered load of chloride. This is accomplished by the integrated function of sequential chloride transport activities along the nephron. The detailed mechanisms of transport in each segment generate unique patterns of interactions between chloride and numerous other individual components that are transported by the kidney. Consequently, chloride transport is inextricably intertwined with that of sodium, potassium, protons, calcium, and water. These interactions not only allow for exquisitely precise regulation but also determine the particular patterns in which the system can fail in disease states.


Antizyme overexpression in transgenic mice reduces cell proliferation, increases apoptosis, and reduces N-nitrosomethylbenzylamine-induced forestomach carcinogenesis.
Antizyme (AZ) is known to be a regulator of polyamine metabolism that inhibits ornithine decarboxylase activity and polyamine transport, thus restricting polyamine levels. Transgenic mice with AZ expression targeted to the basal cell layer of the forestomach epithelium by the keratin 5 promoter were used to investigate whether AZ overexpression inhibited uncontrolled cell proliferation in zinc-deficient (ZD) mice and reduced their susceptibility to forestomach carcinogenesis by N-nitrosomethylbenzylamine (NMBA). Four-week-old keratin 5/AZ and wild-type (Wt) littermates were placed on ZD or zinc-sufficient (ZS) diets to form four groups: ZD:AZ, ZD:Wt, ZS:AZ, and ZS:Wt. After 5 weeks, 27-45 mice in each group were treated twice with NMBA and sacrificed 14 weeks later. Independent of zinc intake, AZ mice had significantly lower forestomach tumor incidence and tumor multiplicity than respective Wt littermates (P < 0.001): 21% of ZD:AZ versus 76% of ZD:Wt mice and 3% of ZS:AZ versus 33% of ZS:Wt mice developed tumors. Spermidine content was reduced in NMBA-treated ZD:AZ forestomachs. Zinc deficiency increased the forestomach cell proliferation in Wt mice, but this effect was blocked by AZ. Conversely, apoptosis was substantially higher in control and NMBA-treated ZD:AZ than respective ZD:Wt forestomachs. The restored ZD:AZ forestomach epithelium displayed strong expression of Bax, a proapoptotic protein, and weak staining of cyclin D1 and its catalytic partner Cdk4, key regulatory proteins controlling G(1) to S progression. In contrast, proliferative ZD:Wt forestomach showed strong expression of Bcl-2, an antiapoptotic protein, and overexpression of cyclin D1/Cdk4. Treatment of ZD:Wt mice with alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase, had similar results to AZ in reducing tumor incidence, spermidine content, decreasing cell proliferation, and increasing apoptosis. These results demonstrate that AZ may act as a tumor suppressor gene stimulating apoptosis and restraining cell proliferation, thereby inhibiting forestomach tumor development. Although effects of AZ on functions other than polyamine metabolism are possible, alterations in polyamines are the most likely explanation for the reduction in tumors, supporting the use of strategies to modulate polyamine levels for cancer chemoprevention in individuals at high risk of developing malignancies of the gastrointestinal tract.


Socioeconomic inequalities in cancer incidence in Europe: a comprehensive review of population-based epidemiological studies.
Background Since the end of the previous century, there has not been a comprehensive review of European studies on socioeconomic inequality in cancer incidence. In view of recent advances in data source linkage and analytical methods, we aimed to update the knowledge base on associations between location-specific cancer incidence and individual or area-level measures of socio-economic status (SES) among European adults. Materials and methods We systematically searched three databases (PubMed, Scopus and Web of Science) for articles on cancer incidence and SES. Qualitative synthesis was performed on the 91 included English language studies, published between 2000 and 2019 in Europe, which focused on adults, relied on cancer registry data and reported on relative risk (RR) estimates. Results Adults with low SES have increased risk of head and neck, oesophagogastric, liver and gallbladder, pancreatic, lung, kidney, bladder, penile and cervical cancers (highest RRs for lung, head and neck, stomach and cervix). Conversely, high SES is linked with increased risk of thyroid, breast, prostate and skin cancers. Central nervous system and haematological cancers are not associated with SES. The positive gap in testicular cancer has narrowed, while colorectal cancer shows a varying pattern in different countries. Negative associations are generally stronger for men compared to women. Conclusions In Europe, cancers in almost all common locations are associated with SES and the inequalities can be explained to a varying degree by known life-style related factors, most notably smoking. Independent effects of many individual and area SES measures which capture different aspects of SES can also be observed.


A tale of two genomes: contrasting patterns of phylogeographic structure in a widely distributed bat.
One of the most widely distributed bats in the New World, the big brown bat (Eptesicus fuscus) exhibits well-documented geographic variation in morphology and life history traits, suggesting the potential for significant phylogeographic structure as well as adaptive differentiation among populations. In a pattern broadly consistent with morphologically defined subspecies, we found deeply divergent mitochondrial lineages restricted to different geographic regions. In contrast, sequence data from two nuclear loci suggest a general lack of regional genetic structure except for peripheral populations in the Caribbean and Mexico/South America. Coalescent analyses suggest that the striking difference in population structure between genomes cannot be attributed solely to different rates of lineage sorting, but is likely due to male-mediated gene flow homogenizing nuclear genetic diversity across most of the continental range. Despite this ongoing gene flow, selection has apparently been effective in producing and maintaining adaptive differentiation among populations, while strong female site fidelity, maintained over the course of millions of years, has produced remarkably deep divergence among geographically isolated matrilines. Our results highlight the importance of evaluating multiple genetic markers for a more complete understanding of population structure and history.


[Molecular mechanism of exocytosis in neural and immune system].
Exocytosis is a common process for the secretion of physiologically active substances such as neurotransmitter, hormone, and inflammatory mediators. Exocytosis is triggered by an increase in intracellular calcium ion concentration. At the nerve terminal, voltage dependent calcium channels (VDCCs) are responsible for this calcium increase. There are several types of VDCC which are different from each other in their electro-physiological and pharmacological characteristics. In order to identify the types of VDCC at the cholinergic nerve terminal, acetylcholine (ACh) release from the electric organ synaptosomes was measured in the presence of type-specific channel blockers. At least three types of VDCC were involved in the ACh release, and N- and P/Q-type VDCC had a major contribution. Adenosine receptor A1 was coupled with N-type VDCC and had negative feedback regulation of ACh release, while A2 receptor coupled with P/Q-type VDCC enhanced the ACh release. Investigation of the inhibitory effects of antibodies from patients of autoimmune disease Lambert-Eaton syndrome on ACh release revealed that P/Q-type channel was a target for the autoantibodies. Unlike the nerve terminal, little is known about the mechanism and molecules involved in the exocytosis of immune cells. Ion channel activities of secretory granule proteins of mast cells were observed. The calcium dependency of the open probability of the channel was similar to that of histamine release from mast cells. We also showed the expression of some SNARE proteins in RBL-2H3 cells. Localization and dynamics of VAMP-7 and syntaxin-3 after antigen stimulation suggested the involvement of SNARE proteins in the exocytosis of mast cells.


[Tumorogenesis and mdm2 protein].
Tumorogenesis is associated with several events by which a normal cell transforms itself into a tumour cell with an increased proliferation rate. One of the most important research initiatives in this area is the characterization of the molecular mechanisms involved in tumorogenesis and cancer. Oncogenes and tumour suppressor genes are directly involved in the cell cycle, differentiation, and apoptosis. The cellular oncogene MDM2 seems to be abnormally elevated in several human tumours, specially in sarcomas. The MDM2 gene product, mdm2 protein, pS3 and retinoblastoma (Rb) proteins, play crucial roles in the control of the cell cycle. The molecular interactions between mdm2, pS3 and Rb in cancer, are associated with a loss of control in the G1 phase of the cell cycle leading to uncontrolled cell proliferation. Studies by gene amplification appear to show an incomplete picture of mdm2 protein levels in tumour cells. The simultaneous determination of mdm2 protein and mRNA levels seems to give a more accurate interpretation of the abnormal function of the mdm2 protein. Thus, in addition to gene amplification, different mechanisms by which mdm2 is overexpressed in cancer cells also play an important role in tumorogenesis.


Bench surgery and liver autotransplantation. Personal experience and technical considerations.
Advances in hepatic transplantation have opened the possibility of bench surgery for liver disease. Thus, nonconventional methods such as the ex vivo approach (bench procedure) or the in vivo ex situ preserved liver surgery have been performed in selected cases. These methods have been confined to situations and tumour stages otherwise deemed untreatable, or to situations where resection may not be sufficiently radical. To date, primary liver tumours (hepatocellular, cholangiocellular) and colo-rectal metastases are considered to be suitable conditions. The technique used is that of liver grafting. Hypothermic liver perfusion (U.W., 4 degrees C) and pump-driven veno-venous bypass from portal vein and inferior vena cava to the superior vena cava are performed. The principal aim of bench surgery is to avoid the unnecessary removal of a large amount of normal parenchyma. Resection lines follow the segmental structure of the liver. Sometimes, an atypical hepatectomy with a parenchymal exeresis "à la demande" is required. Authors' experience with four patients undergoing ex vivo operation of the liver (three patients) or surgery on an ex situ hypothermic perfused liver (one patient) is reported. The patients had liver metastases from colonic carcinoma (1 M, 2 F) and from renal carcinoma (1 M). Major hepatic resections were performed. One patient (M) died from neoplastic intestinal recurrence after 16 months. Two patients (F) died after 24 and 9 days for sepsis and pulmonary embolism. One patient (M) died intraoperatively from a massive retroperitoneal bleeding. Being able to remove otherwise unresectable hepatic neoplasms is a worthy objective. In the presence of diffuse chemoresistant colo-rectal hepatic metastases, liver bench surgery is a promising therapeutic hope. At the basis of a good hepatic function there are a correct organ preservation, a perfect bench surgical technique with respect for vascularization and biliary drainage of the hepatic remnant, and an accurate hemostasis of the resection surface.


[Innovations in biomarker development: a pathway towards individualized cancer therapy?].
Despite multiple medical and scientific achievements, cancer remains a leading cause of death worldwide. Next to imaging technologies, molecular methods for early detection and for monitoring of the course of disease are of increasing interest. Thus, over the past years numerous studies have focused on the identification of biomarkers for cancer diagnosis, prognosis and response to therapy. The study of biomarkers seems to pose a high degree of complexity because many different types of molecules may, in principle, serve as potential biomarkers. In addition, these molecules can be produced either by the tumor or by the tumor-host in response to the presence of cancer. In this review the authors will address several major topics encompassed by the field of biomarker research. They will discuss the primary sources from which biomarker candidates can be 'mined' as well as the technological or methodological challenges associated with identification of biomarkers. Furthermore, the review will focus on current biomarker candidates for head and neck squamous cell carcinoma (HNSCC), with particular interest on several molecules yielding potential relevance for detection and prognosis of this type of cancer. Finally, several biomarker candidates with predictive potential for the response to therapy of HNSCC patients will be discussed, since identifying such molecules is crucial for developing individually-tailored and improved therapeutic strategies.


Naravelia zeylanica [corrected] occurrence of primary benzamides in flowering plants.
Extract of Naravelia zeylanica (Ranunculaceae) yielded three simple benzamides, 3,4-methylenedioxybenzamide, 4-methoxybenzamide and 4-hydroxy-3-methoxybenzamide. These simple C6C1 metabolites have been encountered as natural products for the first time. The compounds were identified by direct comparison of their spectral (1H- and 13C-NMR) and chromatographic (GCMS) data with those of authentic samples. Authentic 4-hydroxy-3-methoxybenzamide was synthesized in one step by treatment of 4-hydroxy-3-methoxybenzonitrile with sodium perborate. Authentic 3,4-methylenedioxybenzamide was synthesized from the corresponding acid.


Persistent renal and extrarenal immune changes after severe ischemic injury.
Renal ischemia/reperfusion (I/R) injury is associated with delayed graft function and decreased long-term allograft function. However, most experimental studies evaluating renal I/R injury have focused on acute events after ischemia. T cells are potential candidates to link preservation injury, alloimmunity, and fibrosis. We hypothesized that severe renal I/R injury would generate long-term kidney damage and immune changes. C57BL/6 mice underwent 60 minutes of warm unilateral I/R injury or sham surgery and were studied for 6 weeks. Serum creatinine, renal histology, and albumin excretion were measured. Phagocyte infiltration, CD4+ infiltration, renal cytokine expression, and splenic lymphocyte intracellular cytokine production were also measured in mice at 6 weeks. Serum creatinine levels rose following 60 minutes of unilateral I/R injury compared to sham mice. Histologic analysis of ischemic kidneys at 6 weeks revealed a pronounced loss of tubular architecture and infiltration of inflammatory cells. Phagocyte and CD4+ T-cell infiltration were significantly increased in ischemic kidneys. This was accompanied by a significant increase in interleukin (IL)-1beta and regulated upon activation, normal T-cell expressed and secreted (RANTES) expression. Despite similar splenic CD4 and CD8 numbers, intracellular cytokine staining of T cells revealed a significant increase in interferon-gamma (IFN-gamma) in I/R injury mice compared to sham mice. Persistent renal and extrarenal immune responses occur after a single episode of severe I/R injury. These immune processes resulting from injury could in turn have long-term consequences on progression of renal disease in transplanted and native kidneys.


Defects in human methionine synthase in cblG patients.
Inborn errors resulting in isolated functional methionine synthase deficiency fall into two complementation groups, cblG and cblE. Using biochemical approaches we demonstrate that one cblG patient has greatly reduced levels of methionine synthase while in another, the enzyme is specifically impaired in the reductive activation cycle. The biochemical data suggested that low levels of methionine synthase activity in the first patient may result from mutations in the catalytic domains of the enzyme, reduced transcription, or generation of unstable message or protein. Using Northern analysis, we demonstrate that the molecular basis for the biochemical phenotype in this patient is associated with greatly diminished steady-state levels of methionine synthase mRNA. The biochemical data on the second patient cell line implicated mutations specific to reductive activation, a function that is housed in the C-terminal AdoMet-binding domain and the intermediate B12-binding domain, in the highly homologous bacterial enzyme. We have detected two mutations in a compound heterozygous state, one that results in conversion of a conserved proline (1173) to a leucine residue and the other a deletion of an isoleucine residue (881). The crystal structure of the C-terminal domain of the Escherichia coli MS predicts that the Pro to Leu mutation could disrupt activation since it is embedded in a sequence that makes direct contacts with the bound AdoMet. Deletion of isoleucine in the B12-binding domain would result in shortening of a beta-sheet. Our data provide the first evidence for mutations in the methionine synthase gene being culpable for the cblG phenotype. In addition, they suggest directly that mutations in methionine synthase can lead to elevated homocysteine, implicated both in neural tube defects and in cardiovascular diseases.


Facilitating co-existence by tracking gene dispersal in conventional potato systems with microsatellite markers.
Based on international findings, Irish co-existence guidelines for the cultivation of GM potato stipulate that an isolation distance of 20 m is required to minimize the spread of transgenic pollen in accordance with required labeling thresholds. As potato tolerant to Phytophthora infestans is the most applicable GM crop from an Irish context, we tested the efficacy of this isolation distance under Irish environmental conditions using the conventional variety Désirée as a pollen donor and the male-sterile variety British Queen as a pollen receptor. Gene flow was determined by scoring for berry presence on receptor plants and confirmed using a microsatellite marker system designed to assess paternity in F(1) seedlings. 99.1% of seedlings recovered were identified as having Désirée paternity. Whereas 19.9% (140/708) of total berries formed on receptor plants occurred at a distance of 21 m from the pollen source, only 4 of these berries bore viable true potato seed (TPS), from which 23 TPS germinated. TPS-bearing berry formation was negatively correlated with distance from the pollen source, and although overall distribution of berries and seeds was non-random across the plot, no significant correlation was evident with respect to wind direction. Microsatellite markers were also used to confirm that the foraging beetle Meligethes aeneus is a vector for the transmission of potato pollen, but a more detailed statistical analysis of this dataset was limited by inclement weather during the trial. To conclude, we recommend that a two-tiered system be established in regard to establishing isolation distances for the experimental trial and commercial cultivation of GM potato in Ireland, and that responsible crop management be adopted to minimize the establishment of TPS-derived volunteers, which we have noted will emerge through a rotation as a result of pollen-mediated gene flow.


Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial.
Rapid bone loss and high rates of fractures occur following liver transplantation. To analyze the effect of intravenous pamidronate on bone loss after liver transplantation. A randomized, double-blind, placebo-controlled study was performed. Seventy-nine patients were randomized to two groups of treatment: the pamidronate group (n = 38) was treated with 90 mg/IV of pamidronate within the first 2 weeks and at 3 months after transplantation; the placebo group (n = 41) received glucose infusions at the same time points. All patients received calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine (L(2)-L(4)) and proximal femur using dual energy X-ray absorptiometry and also spinal X-rays were performed before, and at 6 and 12 months after liver transplantation. Biochemical and hormonal determinations were performed previous to transplantation, at 24 h before and after treatment, as well as at 6 and 12 months after liver transplantation. At 12 months after transplantation, there were significant differences in lumbar BMD changes (6 months: pamidronate 1.6% vs. placebo 0.8%, P = NS; 12 months: pamidronate 2.9% vs. placebo 1%, P < 0.05). Femoral neck BMD decreased in the pamidronate- and placebo groups during the first 6 months (6 months: pamidronate -3.1% vs. placebo -2.9%, P = NS; 12 months: pamidronate -3.2% vs. placebo -3.1%, P = NS). BMD at the trochanter remained stable in the pamidronate group, whilst a reduction was observed in the placebo group at 6 months (6 months: pamidronate -0.7% vs. placebo -3.7%, P < 0.05; 12 months: pamidronate -0.5% vs. placebo -1.2%, P = NS). Moreover, no significant differences in the incidence of fractures, serum parathyroid hormone and serum 25-hydroxyvitamin D values between both groups were found. Pamidronate did not increase the risk of serious adverse events. The results of this study show that 90 mg of intravenous pamidronate within the first 2 weeks and at 3 months following liver transplantation preserve lumbar bone mass during the first year, without significant adverse events. However, pamidronate does not reduce bone loss at the femoral neck and furthermore it does not reduce skeletal fractures.


The influence of hepatitis B and C virus infections on patient and allograft outcomes in kidney transplantation.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most important causes of chronic liver diseases among end-stage kidney disease patients. Our aim was to evaluate the influence of HBV and HCV infections on patient and allograft outcomes after successful kidney transplantation. We retrospectively analyzed 592 kidney transplantations performed between December 2008 and August 2010. We compared patient and graft survivals as well as age, gender, immunosuppression status, pretransplant dialysis duration, chronic allograft dysfunction, and causes of death. Thirty-two patients (5.4%; group 1) were positive for HCV antibody, whereas 16 (2.7%) were positive for hepatitis B surface antigen (HBsAg) (group 2). Two patients (0.3%) were positive concurrently for both HCV antibody and HBsAg. Five hundred forty-two patients (91.6%; group 3) were negative for both. Patients were divided into groups with respect to viral infection. The groups were analyzed for age, gender, immunosuppression, pretransplant dialysis duration, chronic allograft dysfunction, and causes of death, as well as patient and graft outcomes. There were no differences in patient and graft survivals among the groups. None of the patients showed signs of hepatic failure. No patient or graft loss was observed among hepatitis groups when compared with disease-free patients. Graft and patient survivals were not influenced by HBV and/or HCV infections. HBV and HCV infections are not contraindications for kidney transplantation.


Controlling Legionella in hospital drinking water: an evidence-based review of disinfection methods.
Hospital-acquired Legionnaires' disease is directly linked to the presence of Legionella in hospital drinking water. Disinfecting the drinking water system is an effective preventive measure. The efficacy of any disinfection measures should be validated in a stepwise fashion from laboratory assessment to a controlled multiple-hospital evaluation over a prolonged period of time. In this review, we evaluate systemic disinfection methods (copper-silver ionization, chlorine dioxide, monochloramine, ultraviolet light, and hyperchlorination), a focal disinfection method (point-of-use filtration), and short-term disinfection methods in outbreak situations (superheat-and-flush with or without hyperchlorination). The infection control practitioner should take the lead in selection of the disinfection system and the vendor. Formal appraisals by other hospitals with experience of the system under consideration is indicated. Routine performance of surveillance cultures of drinking water to detect Legionella and monitoring of disinfectant concentrations are necessary to ensure long-term efficacy.


T-dependent B cell responses to Plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein.
The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little is known about this interaction. We used isothermal titration calorimetry, X-ray crystallography and mutagenesis-validated modeling to analyze the binding of a murine neutralizing antibody to Plasmodium falciparum CSP. Strikingly, we found that the repeat region of CSP is bound by multiple antibodies. This repeating pattern allows multiple weak interactions of single FAB domains to accumulate and yield a complex with a dissociation constant in the low nM range. Because the CSP protein can potentially cross-link multiple B cell receptors (BCRs) we hypothesized that the B cell response might be T cell independent. However, while there was a modest response in mice deficient in T cell help, the bulk of the response was T cell dependent. By sequencing the BCRs of CSP-repeat specific B cells in inbred mice we found that these cells underwent somatic hypermutation and affinity maturation indicative of a T-dependent response. Last, we found that the BCR repertoire of responding B cells was limited suggesting that the structural simplicity of the repeat may limit the breadth of the immune response.


Antibodies in the Treatment of Psoriasis: IL-12/23 p40 and IL-17a.
The anti-tumor necrosis factor (TNF)-α agents represent the second generation of psoriasis therapy. Research has produced a third generation of biologic treatments, some of which offer greater efficacy than the TNF-α inhibitors. This article reviews the data documenting the efficacy and safety of three types of biologics. Semin Cutan Med Surg 35(supp4):S74-S77.


Relationship of Strength, Weight, Age, and Function in Ambulatory Children With Cerebral Palsy.
The natural history of ambulatory function in individuals with cerebral palsy (CP) consists of deterioration over time. This is thought to be due, in part, to the relationship between strength and weight, which is postulated to become less favorable for ambulation with age. The study design was prospective, case series of 255 subjects, aged 8 to 19 years, with diplegic type of CP. The data analyzed for the study were cross-sectional. Linear regression was used to predict the rate of change in lower extremity muscle strength, body weight, and strength normalized to weight (STR-N) with age. The cohort was analyzed as a whole and in groups based on functional impairment as reflected by Gross Motor Function Classification System (GMFCS) level. Strength increased significantly over time for the entire cohort at a rate of 20.83 N/y (P=0.01). Weight increased significantly over time for the entire cohort at a rate of 3.5 kg/y (P<0.0001). Lower extremity STR-N decreased significantly over time for the entire cohort at a rate of 0.84 N/kg/y (P<0.0001). The rate of decline in STR-N (N/kg/y) was comparable among age groups of the children in the study group. There were no significant differences in the rate of decline of STR-N (N/kg/y) among GMFCS levels. There was a 90% chance of independent ambulation (GMFCS levels I and II) when STR-N was 21 N/kg (49% predicted relative to typically developing children). The results of this study support the longstanding clinically based observation that STR-N decreases with age in children with CP. This decrease occurs throughout the growing years, and across GMFCS levels I to III. Independent ambulation becomes less likely as STR-N decreases. This information can be used to support the rationale, and provide guidelines, for a range of interventions designed to promote ambulation in children with CP.


[Hormones and aging. 2].
The main hormonal disturbances in ageing are: 1) a slight decrease in the secretion of all hormones, with the exception of gonadotropins in women whose production increases sharply as a result of the almost complete suppression of ovarian activity; 2) a slight but substantial resistance of tissues to the action of most hormones; 3) the cessation of estrogen secretion with an important decrease in androgen secretion in the ovaries; 4) a decrease in androgen secretion with a lesser reduction in estrogen secretion in the testicles; 5) an important decrease in adrenal androgen secretion in both sexes. These findings are the consequence and not the cause of ageing which, to some degree, they do promote, especially in bone, muscle, skin and mucous membranes. Therapeutic incidences of the hormonal disturbances in ageing, though not negligeable, are still limited.


Links between hydrothermal environments, pyrophosphate, na(+), and early evolution.
The discovery that photosynthetic bacterial membrane-bound inorganic pyrophosphatase (PPase) catalyzed light-induced phosphorylation of orthophosphate (Pi) to pyrophosphate (PPi) and the capability of PPi to drive energy requiring dark reactions supported PPi as a possible early alternative to ATP. Like the proton-pumping ATPase, the corresponding membrane-bound PPase also is a H(+)-pump, and like the Na(+)-pumping ATPase, it can be a Na(+)-pump, both in archaeal and bacterial membranes. We suggest that PPi and Na(+) transport preceded ATP and H(+) transport in association with geochemistry of the Earth at the time of the origin and early evolution of life. Life may have started in connection with early plate tectonic processes coupled to alkaline hydrothermal activity. A hydrothermal environment in which Na(+) is abundant exists in sediment-starved subduction zones, like the Mariana forearc in the W Pacific Ocean. It is considered to mimic the Archean Earth. The forearc pore fluids have a pH up to 12.6, a Na(+)-concentration of 0.7 mol/kg seawater. PPi could have been formed during early subduction of oceanic lithosphere by dehydration of protonated orthophosphates. A key to PPi formation in these geological environments is a low local activity of water.


Physical Properties of the Second Type of Aciniform Spidroin (AcSp2) from Neoscona theisi Reveal a pH-Dependent Self-Assembly Repetitive Domain.
Orb-weaving spiders can use an array of specialized silks with diverse mechanical properties and functions for daily survival. Of all spider silk types, aciniform silk is the toughest silk fiber that combines high strength and elasticity. Although aciniform spidroins (AcSp) are the main protein in aciniform silks, their complete genes have rarely been characterized until now. Moreover, the structural and physical properties of AcSp variant proteins within the species are also unclear. Here, we present three full-length AcSp genes (named AcSp1A, AcSp1B, and AcSp2) from the orb-weaving spider Neoscona theisi and investigate the structural and mechanical features of these three AcSp repetitive domains. We demonstrate that all three AcSp proteins have mainly α-helical structural features in neutral solution and high thermal stability. Significantly, the AcSp2 repetitive domain shows a pH-dependent structural transition from α to β conformations and can self-assemble into amyloid fibrils under acidic conditions, which is the first reported AcSp repetitive domain with pH-dependent self-assembly capacity. Compared with the other two AcSp spidroins, AcSp2 demonstrated the lowest expression level in the aciniform gland but had the highest strength for its silk fiber. Collectively, our findings provide new insight into the physical properties of each component of aciniform silk and expand the repertoire of known spidroin sequences for the synthesis of artificial silk materials.


Comparative Assessment of Conventional Composites and Coloured Compomers in Permanent Molars of Children with Mixed Dentition: A Pilot Study.
Early treatment of carious lesions in children is important for the maintenance of oral health. Multicoloured restorations could be the impetus for an extremely nervous or defiant child to take dental treatment. The aim of this study was to assess and compare the clinical success of conventional composites and coloured compomer material in first permanent molars of children with mixed dentition. A total of sixty sites, divided into two groups, with thirty subjects in each group using split mouth design were chosen amongst patients reporting to Department of Pedodontics and Preventive Dentistry. In control group conventional composites were placed, similarly coloured compomers were placed in experimental group under standard operating protocol. Patients were recalled for assessment of clinical success amongst control as well as experimental group at regular intervals of one; three and six months follow up based on Modified Ryge's Criteria. Statistical analysis was done using Chi-square test using SPSS version 20.0 (Chicago, USA). Both conventional composites and coloured compomers had comparable retention rates in terms of anatomical form, marginal integrity, secondary caries and marginal discolouration. The coloured compomer material showed promising results in this six month follow up study in permanent molars and had properties comparable to that of conventional composites.


Return-to-play in sport: a decision-based model.
Return-to-play (RTP) decisions are fundamental to the practice of sports medicine but vary greatly for the same medical condition and circumstance. Although there are published articles that identify individual components that go into these decisions, there exists neither quantitative criteria nor a model for the sequence or weighting of these components within the medical decision-making process. Our objective was to develop a decision-based model for clinical use by sports medicine practitioners. English literature related to RTP decision making. We developed a 3-step decision-based RTP model for an injury or illness that is specific to the individual practitioner making the RTP decision: health status, participation risk, and decision modification. In Step 1, the Health Status of the athlete is assessed through the evaluation of Medical Factors related to how much healing has occurred. In Step 2, the clinician evaluates the Participation Risk associated with participation, which is informed by not only the current health status but also by the Sport Risk Modifiers (eg, ability to protect the injury with padding, athlete position). Different individuals are expected to have different thresholds for "acceptable level of risk," and these thresholds will change based on context. In Step 3, Decision Modifiers are considered and the decision to RTP or not is made. Our model helps clarify the processes that clinicians use consciously and subconsciously when making RTP decisions. Providing such a structure should decrease controversy, assist physicians, and identify important gaps in practice areas where research evidence is lacking.


Role of ¹⁸F 2-fluoro-2-deoxyglucose positron emission tomography in upper gastrointestinal malignancies.
The role of whole-body FDG [((18)F) 2-fluoro-2-deoxyglucose] positron emission tomography (PET) scanning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two decades. FDG-PET has demonstrated significant efficacy in the staging, prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract, in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging tools. The sensitivity and specificity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases, but also on histological cell type, reflecting underlying disparities in glucose metabolism. The metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate significantly with both the histological tumor response to treatment and with consequent improvements in overall survival. This may offer a future paradigm of personalized treatment based on the PET response to chemotherapy. FDG-PET has been less successful in efforts to screen for and detect recurrent upper gastrointestinal malignancies, and in the detection of low volume metastatic peritoneal disease. Efforts to improve the accuracy of PET include the use of novel radiotracers such as ((18)F) FLT (3-deoxy-3-fluorothymidine) or (11)C-choline, or fusion PET-CT with concurrent high-resolution computed tomography. This review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointestinal tract, specifically gastric, esophageal and pancreas carcinoma.


Transgenic zebrafish for ratiometric imaging of cytosolic and mitochondrial Ca2+ response in teleost embryo.
Intracellular Ca2+ imaging has widely been used to visualize intracellular signals, but the application in an intact animal is still limited due to difficulty of the indicator loading. In addition, the motion of the living animal produces artifacts. To investigate Ca2+ signaling at early embryonic stage, we established transgenic zebrafish line expressing a genetically encoded Ca2+ indicator, cameleon YC2.60, driven by a constitutively active promoter, hspa8. Although the embryo dynamically changes its morphology, the motion artifact could be canceled out by taking the advantage of YC2.60 as a ratiometric indicator. The transgenic zebrafish was used to visualize the propagation of cytosolic Ca2+ during the early embryonic stage upon fertilization and along cleavage furrow, and the rise in Ca2+ in the myocytes contracting spontaneously in the embryo. We also established a transgenic zebrafish line expressing YC2.60 targeted to the mitochondria. The rise in mitochondrial Ca2+ was rather sustained (≈2 min), which is consistent with the requirement of ATP refilling since the mitochondrial Ca2+ upregulates rate-limiting enzymes of Krebs cycle. This is in contrast with the transient rise in the cytosol Ca2+ that directly evokes the muscle contraction. These transgenic zebrafish lines are expected to serve as useful tools further Ca2+ imaging in vivo.


Growth stimulating activity associated with an altered cell renewal pattern in the small intestine.
A growth stimulating activity has been recently identified in the rat proximal intestine during the transient stages of adaptation after small bowel resection. This study shows that the growth stimulating activity is associated with all the cells of the crypt-villus axis. At the same time the thymidine kinase activity is detectable in all the cells implying a more extensive proliferative zone during the transient stages of adaptation. The presence of the growth stimulating activity along with the more extensive proliferative zone suggests that the activity modulates the proliferation capacity of intestinal epithelial cells.


[Genetics of the immune response of Karakul sheep immunized with E. coli and Salmonella vaccines. An analysis of the intensity of the immune response in 2d-generation and reverse-cross hybrids].
For the genetic analysis of the character of inheriting the immune response and the study of the possibility of immunoselection in astrakhan sheep, the test crossing of the previously selected and raised animals in different genetic combinations has been made. Regularities in inheriting the intensity of immune response in hybrids F2 and BC1 of astrakhan sheep, highly responsive to E. coli and Salmonella vaccines, confirm the dominant character of the capacity for intensive immune response. The second-generation hybrids obtained by the crossing of the animals, either highly responsive or weakly responsive to E. coli or Salmonella vaccine, show a high degree of concordance in their capacity for response to this antigen. This confirms the possibility for the immunoselection of sheep by their capacity for response to a given vaccine.


Transcriptional activities of reovirus RNA polymerase in recoated cores. Initiation and elongation are regulated by separate mechanisms.
The particle-associated reovirus polymerase synthesizes mRNA within only certain viral particle types. Reovirus cores, subviral particles lacking outer capsid proteins mu1, sigma3, and sigma1, produce mRNA and abortive transcripts. Reovirus virions, which contain complete outer capsids, cannot produce mRNA and produce few abortive transcripts. Recoated cores are virion-like particles generated by the addition of recombinant outer capsid proteins to cores. We used recoated cores to analyze transcriptional regulation by reovirus outer capsid proteins. Partially recoated particles, containing less than virion amounts of mu1 and sigma3, synthesized mRNA at levels inversely proportional to outer capsid protein levels. Fully recoated cores exhibited undetectable mRNA synthesis levels, as did virions. However, recoated cores produced high levels of abortive transcripts. Recoated core abortive transcripts remained particle-associated and appeared to inhibit further abortive transcript production. Proteolysis of recoated cores removing mu1 and sigma3 released accumulated abortive transcripts and relieved inhibition of mRNA and abortive transcript synthesis. These results suggest transcriptional elongation, but not initiation, is blocked by virion-like amounts of mu1 and sigma3. Particle-associated abortive transcripts may down-regulate transcriptional initiation. Minor outer capsid protein sigma1 had no demonstrable effect on transcriptional activities. Transcriptional regulation may ensure progeny virions do not compete with transcribing particles for ribonucleoside triphosphates.


[Apropos of V.M. Kolomiĭts's article "Administrator-phthisiologist in current conditions"].
The editorial board of the journal presented for discussion the paper by V. M. Kolomiyits "A phthisiological curator under the present-day conditions". Four review papers have been received which are concerned with pro and contra of the activity of a phthisiological curator. All the participants of the discussion supported the idea of remaining curator's activities in either form.


Skin-Microbiome Assembly in Preterm Infants during the First Three Weeks of Life and Impact of Topical Coconut Oil Application.
The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.


Automated detection of regional wall motion abnormalities based on a statistical model applied to multislice short-axis cardiac MR images.
In this paper, a statistical shape analysis method for myocardial contraction is presented that was built to detect and locate regional wall motion abnormalities (RWMA). For each slice level (base, middle, and apex), 44 short-axis magnetic resonance images were selected from healthy volunteers to train a statistical model of normal myocardial contraction using independent component analysis (ICA). A classification algorithm was constructed from the ICA components to automatically detect and localize abnormally contracting regions of the myocardium. The algorithm was validated on 45 patients suffering from ischemic heart disease. Two validations were performed; one with visual wall motion scores (VWMS) and the other with wall thickening (WT) used as references. Accuracy of the ICA-based method on each slice level was 69.93% (base), 89.63% (middle), and 72.78% (apex) when WT was used as reference, and 63.70% (base), 67.41% (middle), and 66.67% (apex) when VWMS was used as reference. From this we conclude that the proposed method is a promising diagnostic support tool to assist clinicians in reducing the subjectivity in VWMS.


Teneligliptin as an initial therapy for newly diagnosed, drug naive subjects with type 2 diabetes.
Teneligliptin is a novel, highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of this study is to explore the glycemic and non-glycemic efficacies of teneligliptin as an initial therapy. Newly diagnosed, drug naive Japanese subjects with type 2 diabetes (T2DM) were assigned to 20 mg/day teneligliptin monotherapy (n = 31). At 3 months, levels of glycemic and other parameters were compared with those at baseline. Significant reductions of HbA1c (from 10.34 ± 2.06 to 8.38 ± 2.23%) and fasting blood glucose (FGB, from 211.3 ± 68.4 to 167.3 ± 70.2 mg/dL) levels were observed without any clinically significant adverse events. However, significant increases of uric acids (UA) levels were observed and two subjects reported mild hypoglycemic events. Homeostasis model assessment-B (HOMA-B) levels significantly increased, while high HOMA-R levels significantly decreased. Significant correlations were observed between the changes (Δ) of HbA1c and those of HOMA-B, and between ΔFBG and ΔHOMA-R. No changes in lipid and body weight were noted. Teneligliptin might be effectively and safely used as an initial therapy for newly diagnosed T2DM. Glycemic efficacy of teneligliptin is obtained through activating beta-cell function as well as decreasing insulin resistance.


Potential Ceiling Effect of Healthcare Worker Influenza Vaccination on the Incidence of Nosocomial Influenza Infection.
OBJECTIVE To evaluate the effect of healthcare worker (HCW) influenza vaccination on the incidence of nosocomial influenza DESIGN Retrospective cross-sectional study SETTING A 550-bed tertiary-care academic medical center METHODS All admitted patients with a direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) assay positive for influenza ordered between October 1 and May 31 from 2010 to 2015 were eligible for inclusion. Nosocomial influenza was defined as a positive influenza test collected ≥48 hours after admission in patients without influenza-like illness present within 24 hours of admission. Relative nosocomial influenza frequency was calculated by dividing the number of nosocomial cases by the total number of admitted patients with influenza for each season. A univariate logistic regression was used to determine the association between HCW influenza vaccination coverage and nosocomial influenza. RESULTS Over 5 seasons, 533 patients had positive influenza tests during their hospitalization; 29 of these patients (5.4%) acquired influenza during their hospitalization. HCW vaccination coverage increased over the 5 seasons from 47% to 90% (P<.001). Despite an initial decrease in relative nosocomial influenza frequency during the first year (9% to 4.9%), subsequent seasons failed to show an additional decrease in nosocomial infections (4.3%, 5.2%, and 4.8%, respectively); the overall decrease in nosocomial influenza from the first season to the final season was not significant (P=.282). No association was detected between HCW vaccination coverage and nosocomial influenza (odds ratio [OR], 0.990; 95% confidence interval [CI], 0.970-1.011). CONCLUSION HCW vaccination >50% may not have a significant effect on nosocomial influenza. Infect Control Hosp Epidemiol 2016;37:840-844.


Recombination and DNA replication in the Drosophila melanogaster oocyte.
A method is described that permits the recovery of a well-synchronized population of oocytes. Utilizing this pupal system, the heat-responsive period for increasing crossing-over in the Drosophila genome has been defined for the X chromosome and a portion of chromosome 2. The response is initiated close to the time of oocyte formation (premeiotic interphase) and is terminated after approximately 36 hr. During the 36-hr period different regions show characteristic responses, which vary in degree, in duration, and in initiation and termination points, so as to generate the beginning of a thermal recombination map for the Drosophila genome. Centromere regions exhibit the greatest increases in crossing-over for their respective chromosomes but are distinctly asynchronous in time; interstitial regions respond the least. Correlated autoradiographic studies have localized DNA replication in the oocyte to a approximately 24-hr period, which also begins close to oocyte formation (premeiotic interphase); late labeling in restricted regions, undetectable with the present method, could extend the period, as could prolonged synthesis in the oocyte. The results demonstrate that DNA replication and the heat-sensitive period for enhancement of crossing-over are coincident processes over most and possibly all of their length.


Extreme hypofractionation for high-risk prostate cancer: Dosimetric correlations with rectal bleeding.
We explored the association of dosimetric parameters with late rectal bleeding among high-risk prostate cancer patients treated with hypofractionated simultaneous in-field boost (H-SIB) to prostate with nodal treatment. Rectal toxicity results and dose-volume histogram (DVH) information from patients treated on FASTR and SATURN were combined. Patients in both trials received long-term androgen deprivation and H-SIB with prescription dose 40 Gy to the prostate and proximal seminal vesicles and 25 Gy to the lymph nodes delivered over 5 weekly fractions using image guidance with cone beam computed tomography. Mean rectal DVH values at 5-Gy intervals and mean DVH curves were compared between patients with rectal bleeding (B) versus no bleeding (NB). There were 12 B and 33 NB patients in the pooled group. Rectal bleeding was more frequent and of higher grade among FASTR patients (8/15, 5 grade 2 or higher) than among SATURN patients (4/30, all grade 1). For any bleeding (grade ≥1), individual dose-volume points in the 20 to 40 Gy range were significantly different (2-sided P < .05) between the B and NB groups, with the 40 Gy point being the most significant (B: V40 = 1.53%, standard deviation (SD), 1.32; NB: V40 = 0.69%, SD, 1.46; P = .006). For grade ≥2 bleeding, the V20 Gy was most significant (B: 68.4%, SD, 4.76; NB: 40.45%, SD, 13.9; P < .001). The higher relative dose volumes to the rectum (V20-V40) were most strongly associated with clinically significant bleeding in this analysis and are consistent with findings of series that used H-SIB to treat prostate only. Differences in the prostate target volumes and planning margins likely account for the differences in the rates and grades of rectal bleeding observed between trials.


Effect of non-crop vegetation types on conservation biological control of pests in olive groves.
Conservation biological control (CBC) is an environmentally sound potential alternative to the use of chemical insecticides. It involves modifications of the environment to promote natural enemy activity on pests. Despite many CBC studies increasing abundance of natural enemies, there are far fewer demonstrations of reduced pest density and very little work has been conducted in olive crops. In this study we investigated the effects of four forms of non-crop vegetation on the abundance of two important pests: the olive psyllid (Euphyllura olivina) and the olive moth (Prays oleae). Areas of herbaceous vegetation and areas of woody vegetation near olive crops, and smaller patches of woody vegetation within olive groves, decreased pest abundance in the crop. Inter-row ground covers that are known to increase the abundance of some predators and parasitoids had no effect on the pests, possibly as a result of lack of synchrony between pests and natural enemies, lack of specificity or intra-guild predation. This study identifies examples of the right types of diversity for use in conservation biological control in olive production systems.


[Tactics of the patients management in continuing acute thrombosis of deep veins].
Experience of active tactics of treatment application in 18 patients, suffering an acute thrombosis in system of lower vena cava, is presented. Possibilities were estimated and efficacy of active surgical tactics proved in continuing deep vein thrombosis on early stage were estimated. Active tactics, using catheter--governed thrombolysis, permits to escape pulmonary thromboembolism and to reduce a severity of further chronic venous insufficiency.


Renal effects of selective adenosine receptor agonists in anesthetized rats.
Exogenous adenosine affects renal hemodynamics, renal tubular transport processes, and the secretion of renin. However, adenosine is not a selective agonist; it activates both A1 and A2 cell-surface receptors and it binds to an intracellular P-site that inhibits adenylate cyclase activity. Recent in vitro studies have suggested that activation of A1- and A2- adenosine receptors results in opposite effects on renin secretion. The purpose of these experiments was to examine the renal effects of A1- and A2-adenosine receptor agonists in vivo. 5'-N-ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-CLA), and N6-cyclohexyladenosine (CHA) were infused intravenously at rates that produced comparable decreases in systemic arterial blood pressure. All three of these adenosine analogues produced comparable decreases in para-aminohippurate (PAH) and inulin clearances and in Na and K excretion rates. CHA, an A1-selective agonist, markedly decreased plasma renin concentration (PRC), whereas NECA, an A2-selective agonist, markedly increased PRC; 2-CLA, a nonselective agonist, produced a smaller increase in PRC. Taken together, these results suggest that occupation of A1- and A2-receptors inhibits and stimulates renin secretion in vivo, independently of the effects of these adenosine receptor agonists on arterial blood pressure, renal hemodynamics, and tubular Na and K transport.


Methane and NOx Emissions from Natural Gas Stoves, Cooktops, and Ovens in Residential Homes.
Natural gas stoves in >40 million U.S. residences release methane (CH4)─a potent greenhouse gas─through post-meter leaks and incomplete combustion. We quantified methane released in 53 homes during all phases of stove use: steady-state-off (appliance not in use), steady-state-on (during combustion), and transitory periods of ignition and extinguishment. We estimated that natural gas stoves emit 0.8-1.3% of the gas they use as unburned methane and that total U.S. stove emissions are 28.1 [95% confidence interval: 18.5, 41.2] Gg CH4 year-1. More than three-quarters of methane emissions we measured originated during steady-state-off. Using a 20-year timeframe for methane, annual methane emissions from all gas stoves in U.S. homes have a climate impact comparable to the annual carbon dioxide emissions of 500 000 cars. In addition to methane emissions, co-emitted health-damaging air pollutants such as nitrogen oxides (NOx) are released into home air and can trigger respiratory diseases. In 32 homes, we measured NOx (NO and NO2) emissions and found them to be linearly related to the amount of natural gas burned (r2 = 0.76; p ≪ 0.01). Emissions averaged 21.7 [20.5, 22.9] ng NOx J-1, comprised of 7.8 [7.1, 8.4] ng NO2 J-1 and 14.0 [12.8, 15.1] ng NO J-1. Our data suggest that families who don't use their range hoods or who have poor ventilation can surpass the 1-h national standard of NO2 (100 ppb) within a few minutes of stove usage, particularly in smaller kitchens.


Patterns of intracellular calcium oscillations in horse oocytes fertilized by intracytoplasmic sperm injection: possible explanations for the low success of this assisted reproduction technique in the horse.
In all species studied, fertilization induces intracellular Ca2+ ([Ca2+]i) oscillations required for oocyte activation and embryonic development. This species-specific pattern has not been studied in the equine, partly due to the difficulties linked to in vitro fertilization in this species. Therefore, the objective of this study was to use intracytoplasmic sperm injection (ICSI) to investigate fertilization-induced [Ca2+]i signaling and, possibly, ascertain problems linked to the success of this technology in the horse. In vivo- and in vitro-matured mare oocytes were injected with a single motile stallion sperm. Few oocytes displayed [Ca2+]i responses regardless of oocyte source and we hypothesized that this may result from insufficient release of the sperm-borne active molecule (sperm factor) into the oocyte. However, permeabilization of sperm membranes with Triton-X or by sonication did not alleviate the deficient [Ca2+]i responses in mare oocytes. Thus, we hypothesized that a step downstream of release, possibly required for sperm factor function, is not appropriately accomplished in horse oocytes. To test this, ICSI-fertilized horse oocytes were fused to unfertilized mouse oocytes, which are known to respond with [Ca2+]i oscillations to injection of stallion sperm, and [Ca2+]i monitoring was performed. Such pairs consistently displayed [Ca2+]i responses demonstrating that the sperm factor is appropriately released into the ooplasm of horse oocytes, but that these are unable to activate and/or provide the appropriate substrate that is required for the sperm factor delivered by ICSI to initiate oscillations. These findings may have implications to improve the success of ICSI in the equine and other livestock species.


Optical lens design based on metallic nanoslits with variant widths.
Designs of optical lenses based on metallic nanoslits are carried out based on the phase and amplitude modulation by tuning the slit widths. The slits are perforated on thin metallic film, and the width of each slit is achieved by simulated annealing algorithms, which is connected with both the amplitude and phase modulation. Two kinds of focal lenses, which can realize one or two focus points, have been designed. The finite-difference time-domain method is employed to check the performance of the designed lenses. Simulation results show that the designed lenses can perform the preset functions well. Using this method, multiple optical elements with different functions can be conveniently achieved in subwavelength scale.


Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya.
The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya. A total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV). Out of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value < 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV. Genomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.


Congenital ureteropelvic junction obstruction: human disease and animal models.
Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin-angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short-coming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans.