Structural lung changes, lung function, and non-invasive inflammatory markers in cystic fibrosis.
Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non-invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non-invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8-isoprostane, hydrogen peroxide, interferon-gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non-invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients <0.40). Patients with positive sputum Pseudomonas cultures had higher EBC nitrite levels and higher parenchymal HRCT subscores than patients with Pseudomonas-negative cultures (p < 0.05). Multiple linear regression models demonstrated that FVC was significantly predicted by hydrogen peroxide in EBC, and the scores of bronchiectasis and mosaic perfusion (Pearson correlation coefficient R = 0.78, p < 0.001). TLC was significantly predicted by 8-isoprostane, nitrate, hydrogen peroxide in EBC, and the mucous plugging subscore (R = 0.92, p < 0.01). Static and dynamic lung function indices in this CF group were predicted by the combination of non-invasive IM in EBC and structural lung changes on HRCT imaging. Future longitudinal studies should reveal whether non-invasive monitoring of airway inflammation in CF adds to better follow-up of patients.


Morbilliviruses in aquatic mammals: report on round table discussion.
A workshop was organised to ascertain the current situation with regard to morbillivirus infections in aquatic animals. The great interest generated by the discovery of these new virus infections in 1988 has to some extent abated but much high quality research has continued in this field as the workshop showed. There is some serological evidence that the viruses have continued to circulate in most areas since the initial epizootics. As to their origin, it appears that the most likely source of the European seal morbillivirus (PDV-1) is the North Atlantic and Artic seal populations. As to the origin of the Mediterranean dolphin morbillivirus and the morbilliviruses isolated from porpoises, there is serological evidence that the viruses are widespread in many cetacean species in the Atlantic and 93% of long-finned pilot whales (Globicephala melas) which mass stranded between 1982 and 1993 were morbillivirus seropositive. The epizootic in freshwater seals in Lake Baikal was unrelated to events in the European marine mammal populations. The virus which infected these animals (PDV-2) is indistinguishable from canine distemper field strains. Serological and molecular biological studies provided evidence for the presence of the virus in the seals, at least as late as the Summer of 1992 when the animals were last sampled.


3D analysis of the whole subcutaneous adipose tissue reveals a complex spatial network of interconnected lobules with heterogeneous browning ability.
Adipose tissue, as the main energy storage organ and through its endocrine activity, is interconnected with all physiological functions. It plays a fundamental role in energy homeostasis and in the development of metabolic disorders. Up to now, this tissue has been analysed as a pool of different cell types with very little attention paid to the organization and putative partitioning of cells. Considering the absence of a complete picture of the intimate architecture of this large soft tissue, we developed a method that combines tissue clearing, acquisition of autofluorescence or lectin signals by confocal microscopy, segmentation procedures based on contrast enhancement, and a new semi-automatic image analysis process, allowing accurate and quantitative characterization of the whole 3D fat pad organization. This approach revealed the unexpected anatomic complexity of the murine subcutaneous fat pad. Although the classical picture of adipose tissue corresponds to a superposition of simple and small ellipsoidal lobules of adipose cells separated by mesenchymal spans, our results show that segmented lobules display complex 3D poly-lobular shapes. Despite differences in shape and size, the number of these poly-lobular subunits is similar from one fat pad to another. Finally, investigation of the relationships of these subunits between each other revealed a never-described organization in two clusters with distinct molecular signatures and specific vascular and sympathetic nerve densities correlating with different browning abilities. This innovative procedure reveals that subcutaneous adipose tissue exhibits a subtle functional heterogeneity with partitioned areas, and opens new perspectives towards understanding its functioning and plasticity.


Synthesis and bioassay of 4-ipomeanol analogs as potential chemopreventive agents against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumorigenicity in A/J mice.
4-Ipomeanol (4-IPO) is an investigational drug with specific toxicity toward the lung. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen in several laboratory animals. Both IPO and NNK are toxic upon metabolic activation by cytochrome P450 enzyme(s) present in Clara cells of the lung. IPO and NNK are similar in structure and thus non-toxic analog of IPO could be competitive inhibitors of NNK metabolism in lung. 4-Hydroxyl-phenyl-1-pentanone (HPP), a non-toxic analog of IPO is a potent inhibitor of metabolic activation and tumorigenicity in A/J mouse lung. To extend these studies, we have synthesized 12 analogs of HPP, altering the terminal alkyl group in 6 of them. In another 2 analogs we have substituted electron-donating or electron-withdrawing groups in the benzene ring. Finally, we have altered the oxidation states of 1 and/or 4 position of HPP in the remaining 4 analogs. We have already examined the effect of in vitro inhibition of NNK metabolism by these 12 IPO analogs. In the present study, we have examined 4 IPO analogs that are potent inhibitors of in vitro NNK metabolism namely; 4-hydroxy-1-phenyl-1-octanone (4-HPO), 1,4-diphenyl-4-hydroxy-1-butanone (DPHB), 4-hydroxy-1-phenylpentane (HPPentane), and amyl benzene and tested their inhibitory effects toward the NNK-induced lung tumorigenicity in A/J mice.


Adolescent murderers.
Clinical, developmental and environmental factors were retrospectively studied in 14 adolescent murderers who had been referred to a forensic psychiatric clinic over an 11 year period. Results of these analyses were compared with findings from previous reports. The majority of subjects came from split families. There was a greater than expected degree of psychiatric illness in the adolescents. Previous psychiatric contact, antisocial behaviour and substance abuse were common among these adolescents. A tentative profile of adolescents who are likely to commit murder can therefore be drawn up, which may suggest direction for preventive action and rehabilitation.


Neglected Type I Monteggia Fracture Dislocation in Adult.
Neglected Monteggia fracture dislocation is one of the challenging case and it becomes more of a therapeutic dilemma especially in adults. Several surgical techniques are described and in spite of this complication rate following surgery is high. This report concerns with management of three-month-old monteggia fracture dislocation in a 30-year-old male. Patient presented with complete loss of movement at elbow. Patient was managed surgically, with internal fixation of ulna and reduction of radial head with radio-capitellar Kirschner wires. Postoperatively at six months, ulna united and patient has achieved flexion from 50 to 115 degrees at elbow and supination pronation arc of 120 degrees. We do not see any indication for procedures directed at the reconstruction of annular ligament. The dilemma remains whether radial head preservation or excision gives better functional range of motion in adult neglected monteggia fracture dislocation.


Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy.
Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.


Paws + cause = pause? Memory load and memory blends in homophone recognition.
Previous research has shown that separate information sources, activated closely together in time, can induce errors suggestive of memory blends. In Experiment 1, homophones were used to induce such memory errors. In a study task, participants made relatedness judgments to word pairs that included homophones (e.g., PAWS-BEAR). During this task, one group (study-similar) maintained memory loads with words that were orthographically similar to the presented homophones (e.g., JAWS). Another group (test-similar) maintained memory loads similar to those obtained for the study homophone's alternate spelling (e.g., CAUSE). A third group maintained no memory load during the task. In a surprise recognition test, participants were presented both previously viewed homophones (PAWS) and non-presented alternate spellings (PAUSE). We hypothesized that partially activated alternate spellings, in conjunction with the orthographically similar memory words, would result in the creation of blended memories. The results followed suit: The test-similar condition produced significantly elevated false alarms, relative to both the study-similar and the no-load conditions. Experiment 2 replicated these results while including memory loads to control for potential orthographic confusions. The findings are discussed in terms of multiple, episodic memories later activated as single, blended memories.


Endothelin-1 receptor antagonist prevents deterioration of left ventricular function and coronary flow reserve in brain-dead canine heart.
Rapid hemodynamic deterioration is caused by induction of brain death, but the exact mechanism is still uncertain. The aim of this study was to investigate the contribution of endothelin-1 by using endothelin-1 receptor antagonist (TAK-044) in a canine brain-death model. Dogs were divided into 2 groups: (1) the TAK group, in which TAK-044 was intravenously injected 30 minutes before brain-death induction at a dose of 3 mg/kg; and (2) the control group. Brain death was induced by rapid inflation of a sub-durally placed balloon catheter. Left ventricular function and coronary flow reserve was compared between the 2 groups. Brain death caused a transient hyperdynamic response followed by hemodynamic deterioration after 60 minutes in both groups. Left ventricular function, evaluated by the slope of the end-systolic pressure-volume relation was significantly decreased from 7.7 +/- 0.6 to 3.7 +/- 0.3 mm Hg/ml (p < 0.01) in the control group, but was not decreased in the TAK group (7.7 +/- 0.8 to 7.3 +/- 0.9 mm Hg/ml, p = 0.75). Coronary flow reserve, measured by direct injection of acetylcholine (3 microg) into the coronary artery, was significantly reduced at 60 minutes after brain death in the control group (264.8% to 176.6%, p < 0.01), but not in the TAK group (291.2% to 301.3%, p = 0.84). Exactly the same results were obtained when sodium nitroprusside (SNP; 100 microg) was administered. TAK-044 can prevent the deterioration of left ventricular function and coronary flow reserve that follows induction of brain death, suggesting that endothelin-1 could play an important role in hemodynamic deterioration by impairment of coronary microcirculation after brain death.


Ludloff's medial approach for open reduction of congenital dislocation of the hip. A 20-year follow-up.
We reviewed 33 patients (35 hips) after open reduction of congenital dislocation of the hip using Ludloff's medial approach. The mean age at the time of operation was 14 months (5 to 29) and at the time of final follow-up 20.1 years (15 to 24) giving a mean duration of follow-up of 19.4 years (14 to 23). We evaluated the radiological results by the Severin classification and the extent of avascular necrosis using the criteria of Kalamchi. At the latest review 16 hips (45.7%) were in Severin groups I or II (acceptable results) and 19 (54.3%) in Severin groups III, IV or V (unacceptable results). There was evidence of avascular necrosis in 15 hips (42.9%). The radiological results began to become worse at about the age of ten years when type-II avascular changes presented. We conclude that Ludloff's medial approach for open reduction is unsatisfactory for the treatment of congenital dislocation since about half of our patients required additional operations.


[Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin].
Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19 (47.50%) were customers and 15 (37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion: This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.


Treatment of chronic lateral instability of the ankle with the Colville technique: a prospective analysis with minimum five years of follow-up.
This study aims to prospectively analyze of the long-term results of the Colville's technique for the treatment of chronic lateral ankle instabilities. Twenty-eight ankles of 28 male patients (mean age 24.6 years; range 20 to 35 years) which were treated using Colville's technique were evaluated with a mean follow-up of 76.1 months (range 60 to 106 months). Ankle instability, ankle functions and outcomes in the last visit were assessed and statistically compared. Stress radiographs with the TELOS device were repeated at six-months and five-years after surgery and compared with the stability of the uninjured ankle. Twenty-three of the results were excellent and five were good according to the criteria of Chrisman and Snook. All patients returned to normal daily activity levels at an average of eight months following surgery. Radiographic analysis revealed the significant preservation of stability at least five years after surgery with no sign of arthritis. The difference between preoperative and sixth-months postoperative values of both the talar tilt and the anterior draw tests were found statistically significant, indicating significant correction of the laxity. On contrary, difference between sixth months and five year values were not statistically significant, indicating the preservation of the correction. Anatomical augmented reconstruction procedure of Colville's is a long-lasting and good alternative compared to other more complex techniques of reconstruction with minimum long-term complications.


Control of ethylene epoxidation selectivity by surface oxametallacycles.
Surface science experiments, DFT calculations, and kinetic isotope effect data are utilized to understand the elementary steps that govern the selectivity of silver catalysts for the partial oxidation of ethylene to produce ethylene oxide. It is proposed that selective and unselective pathways proceed via a common intermediate, the surface oxametallacycle. The structures of the transition states leading from this intermediate to selective and unselective products are calculated. From the calculated Gibbs free energies of activation for competing pathways, it is possible to predict selectivity to ethylene oxide as well as the magnitude of the kinetic isotope effect. The proposed mechanism is qualitatively and quantitatively in accord with experimental results.


Disseminated histoplasmosis diagnosed on bone marrow aspirate cytology: report of four cases.
Histoplasmosis, caused by two varieties of dimorphic fungi, Histoplasma capsulatum variant capsulatum and Histoplasma capsulatum variant duboisii is a systemic fungal infection. It has a worldwide distribution and is shown to be more prevalent in North America and Central America. Both variants occur in Africa. Disease spectrum ranges from asymptomatic primary infection to disseminated disease in immunocompromised patients. Since the upsurge of acquired immune deficiency syndrome (AIDS) and despite the availability of high active anti-retroviral therapy (HAART) many patients still present with opportunistic infections of which histoplasmosis is one. Four cases are presented; two infants and two adults. All had disseminated disease with multiple organ involvement and the disease was not suspected clinically. Diagnosis was made incidentally on bone marrow aspirate cytology. The two adult cases were HIV positive, one with CD4 counts of 132 cells/microlitre and was not on HAART. The other was on HAART but the CD4 had not been determined. One of the infants tested HIV negative and the others status was unknown. A high index of suspicion is required for diagnosis as the disease may mimic tuberculosis(TB) and other causes of hepatosplenomegaly such as visceral leishmaniasis. Laboratory diagnosis includes culture, direct staining, antigen and antibody detection. Antibody detection may give false negative in the immunocompromised patient. The infection responds well to antifungal agents (amphotericin B is the drug of choice) and life long maintenance therapy may be required in AIDS especially if CD4 counts remain less than 150 cells/microlitre. Histoplasmosis should be a differential diagnosis in immunosuppressed patients with unexplained fever, weight loss, hepatosplenomegaly and chest findings especially if not responding to anti-TB treatment.


Impact of Multi-Night Experimentally Induced Short Sleep on Adolescent Performance in a Simulated Classroom.
Investigate whether a realistic "dose" of shortened sleep, relative to a well-rested state, causes a decline in adolescents' learning and an increase in inattentive and sleepy behaviors in a simulated classroom setting. Eighty-seven healthy 14.0- to 16.9-year olds underwent a 3-week sleep manipulation protocol, including two 5-night sleep manipulation conditions presented in a randomly counterbalanced within-subjects cross-over design. Wake time was held constant. Bedtimes were set to induce Short Sleep (SS; 6.5 hours in bed) versus Healthy Sleep (HS; 10 hours in bed). During the morning at the end of each condition, participants underwent a simulated classroom procedure in which they viewed lecture-based educational videotapes and completed relevant quizzes. Their behaviors in the simulated classroom were later coded by condition-blind raters for evidence of inattention and sleepiness. Adolescents had a longer average sleep period during HS (9.1 hours) than SS (6.5 hours). Compared to scores during HS, adolescents scored significantly lower on the quiz, showed more behaviors suggestive of inattention and sleepiness in the simulated classroom, and were reported by adolescents themselves and by their parents to be more inattentive and sleepy during SS. However, the impact of the manipulation on quiz scores was not mediated by changes in attention or sleepiness. Although effect sizes were modest, these findings suggest that previously-reported correlations between sleep duration and academic performance reflect true cause-effect relationships. Findings add to the growing evidence that the chronically shortened sleep experienced by many adolescents on school nights adversely impacts their functioning and health.


A pilot study of a family cognitive adaptation training guide for individuals with schizophrenia.
There is a paucity of accessible, evidence-based tools for caregivers of individuals with schizophrenia. This study examines changes in the self-assessed and caregiver-assessed outcomes of people with schizophrenia after exposure to a cognitive adaptation training (CAT) guide that addressed pragmatic, in-home approaches to offset the cognitive impacts of the illness. This study examined the 4-month, pre-post outcomes of a CAT guide, as compared with a popular, general manual, for families of individuals with schizophrenia. A total of 17 caregiver-supported individual dyads completed all measures, having been randomized to either a CAT-guide group or a support-manual group. Measures included medication adherence, adaptive functioning, quality of life, and caregiver burden. Semistructured interviews assessed use and utility questions. Caregiver-assessed improvements in community functioning with medium-high effect sizes were observed in both study conditions. Self-report ratings by supported individuals did not change from baseline to 4 months and no change was observed in medication adherence or quality of life for either condition. Caregiver-burden ratings significantly declined with a large effect size, again with no difference as a function of manual type. These findings suggest that there is some promise in providing families with evidence-based information in manual form. Further research informed by this study's findings should include assessments of whether and how environmental cognitive supports can be of specific benefit to families affected by schizophrenia. (PsycINFO Database Record


Developing imaging strategies for castration resistant prostate cancer.
Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for "radiographic" progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na(18)F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as (18)F-FDHT and (89)Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to accelerate drug development in CRPC. The development and use of analytically valid imaging biomarkers will increase the likelihood of clinical qualification, and ultimately lead to improved patient outcomes.


Genomic Analysis and Antimicrobial Resistance of Campylobacter jejuni and Campylobacter coli in Peru.
Campylobacter is the leading cause of human bacterial gastroenteritis worldwide and has a major impact on global public health. Whole Genome Sequencing (WGS) is a powerful tool applied in the study of foodborne pathogens. The objective of the present study was to apply WGS to determine the genetic diversity, virulence factors and determinants of antimicrobial resistance of the populations of C. jejuni and C. coli in Peru. A total of 129 Campylobacter strains (108 C. jejuni and 21 C. coli) were sequenced using Illumina Miseq platform. In silico MLST analysis identified a high genetic diversity among those strains with 30 sequence types (STs), several of them within 11 clonal complexes (CC) for C. jejuni, while the strains of C. coli belonged to a single CC with 8 different STs. Phylogeny analysis showed that Peruvian C. jejuni strains were divided into 2 clades with 5 populations, while C. coli formed a single clade with 4 populations. Furthermore, in silico analyses showed the presence of several genes associated with adherence, colonization and invasion among both species: cadF (83.7%), jlpA (81.4%), racR (100%), dnaJ (83.7%), pebA (83.7%), pldA (82.1%), porA (84.5%), ceuE (82.9%), ciaB (78.3%), iamB (86.8%), and flaC (100%). The majority (82.9%) of the Campylobacter strains carried the cdtABC operon which code for cytolethal distending toxin (CDT). Half of them (50.4%) carried genes associated with the presence of T6SS, while the frequency of genes associated with T4SS were relatively low (11.6%). Genetic markers associated with resistance to quinolones, tetracycline (tetO, tetW/N/W), beta-lactamases (blaoxa-61 ), macrolides (A2075G in 23S rRNA) were found in 94.5, 21.7, 66.7, 6.2, 69.8, and 18.6% of strains, respectively. The cmeABC multidrug efflux operon was present in 78.3% of strains. This study highlights the importance of using WGS in the surveillance of emerging pathogens associated with foodborne diseases, providing genomic information on genetic diversity, virulence mechanisms and determinants of antimicrobial resistance. The description of several Campylobacter genotypes having many virulence factors and resistance to quinolones and tetracyclines circulating in Peru provides important information which helps in the monitoring, control and prevention strategies of this emerging pathogen in our country.


A new approach towards volumetric assessment of left ventricular function with MSCT.
Cardiovascular CT is considered the diagnostic standard for establishing the presence of a functional and dynamic imaging system. It is difficult, however, to estimate the ventricular motion and volumes that are processed using hundreds and thousands of CT images, in a few moments.The main concept and design of our work are two fold - the development of effective semi-automatic tools for measuring the sequential left ventricular volumes from the hundreds or thousands of cardiac trans-axial images, and providing a simple interface with an interactive diagnostic tool for the volumetry of left ventricle and valuable cardiac 4D visualisation.We converted ten and more sequential volume data sets of the heart acquired from retrospective ECG-gating helical scan into 3D images by volume rendering. These sequential 3D images could be displayed as a movie (4D cardiac image) file. Furthermore, we developed a method for semi-automatic calculation of ejection fraction (EF) and cardiac cycle (%)-volume (ml) curve for estimation of the motion and the volume of the left ventricle. This method involved the use an interactive selection tool in the region of interest (ROI). All 3D processing methods, such as, cutting objects, segmentation, and image fusion were based on mask processing data. We now describe the software developed for cardiac 4D imaging and the estimation of ventricular volume.


Glass bottle sampling solid phase microextraction gas chromatography mass spectrometry for breath analysis of drug metabolites.
Breath analysis is a non-invasive approach which may be applied to disease diagnosis and pharmacokinetic study. In the case of offline analysis, the exhaled gas needs to be collected and the sampling bag is often used as the storage vessel. However, the sampling bag usually releases some extra compounds, which may interfere with the result of the breath test. In this study, a novel breath sampling glass bottle was developed with a syringe needle sampling port for solid phase microextraction (SPME). Such a glass bottle scarcely liberates compounds and can be used to collect exhaled gas for ensuing analysis by gas chromatography-mass spectrometry (GC-MS). The glass bottle sampling SPME-GC-MS analysis was carried out to investigate the breath metabolites of myrtol, a multicompound drug normally used in the treatment of bronchitis and sinusitis. Four compounds, α-pinene, 2,3-dehydro-1,8-cineole, d-limonene and 1,8-cineole were found in the exhaled breath of all eight volunteers who had taken the myrtol. While for other ten subjects who had not used the myrtol, these compounds were undetectable. In the SPME-GC-MS analysis of the headspace of myrtol, three compounds were detected including α-pinene, d-limonene and 1,8-cineole. Comparing the results of breath and headspace analysis, it indicates that 2,3-dehydro-1,8-cineole in the breath is the metabolite of 1,8-cineole. It is the first time that this metabolite was identified in human breath. The study demonstrates that the glass bottle sampling SPME-GC-MS method is applicable to exhaled gas analysis including breath metabolites investigation of drugs like myrtol.


Joint Function and Arthropathy Severity in Patients with Hemophilia.
The Arnold-Hilgartner classification is one of the most popular evaluation systems for the progression hemophilic arthropathy. A previous study reported an association between arthropathy severity and arc range of motion (ROM). However, associations between arthropathy severity and angular ROM and muscle strength remain unclear. The purpose of this study was to clarify the association between joint function and arthropathy severity in hemophilia. We studied the knee, ankle, and elbow joints of 31 patients with hemophilia (PWH). The condition of the affected joints was evaluated on the basis of the interview data, joint function measurements, and roentgenography of the affected joints. In assessment of joint function, we evaluated knee strength (flexor, extensor) and grip strength as well as the passive ROM of the elbow, knee, and ankle. During the interview, all patients were asked about the history of intra-articular bleeding over the past year and pain. As arthropathy severity worsened, knee flexor strength, knee extensor strength, grip strength, and ROM (elbow flexion, elbow extension, knee flexion, knee extension, and ankle extension) significantly decreased. Even patients with mild arthropathies experienced knee extensor weakness and extension limitation. In addition, joint function of severe ankle arthropathy was significantly related to the history of intra-articular bleeding and pain. Our results suggest that physical therapy is necessary to improve joint function in PWH and mild or no arthropathy. Pain control and prophylactic hematological management are necessary for patients with severe arthropathy because intra-articular bleeding and pain significantly decrease joint function.


Nerve Conduction Abnormalities and Neuromyotonia in Genetically Engineered Mouse Models of Human Hereditary Neuropathies.
We performed electrophysiological studies in myelin protein mutant mice in order to characterize nerve conduction changes. We performed neurographic studies on the facial and sciatic nerves and needle electromyography (EMG). Mice homozygously deficient for the peripheral myelin protein 22 gene (Pmp22-/-) exhibited increased motor latencies, reduced nerve conduction velocities, and polyphasia of the M-response, which are the typical electrophysiological signs of dysmyelination. PMP22 +/- mice developed only mild conduction slowing at an old age and a mild reduction of the M-amplitude, which indicates mild axonal dysfunction. Mice overexpressing Pmp22 developed severe electrophysiological signs of dysmyelination. In myelin protein zero-deficient mice (P0-/-), we found alterations similar to those found in Pmp22-/- mice, whereas P0+/- mice developed mildly increased sciatic nerve F-wave latencies only late in life, which indicates only mild dysmyelination. Connexin 32-deficient mice showed electrophysiological evidence of mild axonal damage. By EMG, we found the clinical and electrophysiological signs of neuromyotonia, that is, continuous spontaneous motor unit discharges, often in rhythmic patterns (myokymia), in P0-/-, Pmp22-/-, Trembler, Trembler-J, and Pmp22-overexpressing mice. This indicates abnormal impulse generation in these dysmyelinated nerves. In summary, our studies demonstrate nerve conduction changes in mice with myelin protein gene defects that are similar to those found in patients with Charcot-Marie-Tooth disorders. In addition, we identified new mouse models of hereditary neuromyotonia.


[Modification of the agarose drop micromethod for studying mouse macrophage migration inhibition factor].
A modification of the drop agarose micromethod for the study of the factor inhibiting the migration of mouse macrophages is proposed. The syngeneic system was used instead of type RPMI-1640 complex culture media and calf embryonal serum, commonly used in the work with mouse macrophages. The production of the factor inhibiting the migration of macrophages by sensitized lymphocytes from mice of different strains has been shown to occur in vitro under the influence of pertussis corpuscular antigen. The method of obtaining supernatant containing macrophage migration inhibiting factor, from immune mouse lymphocyte culture is proposed. This supernatant may be used for, the analysis of the above-mentioned factor and other lymphokins.


Key factors for child participation - an empowerment model for active inclusion in participatory processes.
Child participation is advocated for in many contexts related to children, such as in education and health services, but also in everyday life settings. To facilitate children's real opportunities for participation, it is proposed that children need to be adequately empowered to liberate the child's autonomous voice and activate their powers of action. This involves an understanding of children as opinion-forming and social individuals, who play an active part in social relationships. This article aims at a theoretical exploration of empowerment in the organization of ethically justifiable participation situations with children. With a semantic view of theory, an eclectic research design has been used to search for a theoretical framework based on basic human needs to be an active agent in one's own life. The purpose is to define key factors that promote the sense of empowerment as a prerequisite for being an active participant in interaction with adults. This conceptualization aims to raise clearer guidelines for the implementation of child participation and presents an empowerment model with four dimensions for the active inclusion of children in participatory processes with adults. These dimensions are information, autonomy, recognition, and alliance.


Alternative methods for measurement of membrane potentials in epithelia.
Methods for the measurement of membrane potentials in cells not easily penetrated by microelectrodes were assessed for use in epithelia. The lipophilic cation triphenylmethylphosphonium appeared to distribute in a Nernstian fashion in the epithelial cells of Necturus gallbladder as judged by parallel microelectrode measurements. In the toad urinary bladder, the distribution of this cation gave a value for the membrane potential of epithelial cells under short-circuit conditions of -62 mV in normal Ringer's solution and -51 mV after 2 h treatment with ouabain. In our laboratory the dye 3,3'-dipropylthiadicarbocyanine iodide, when used with cell suspensions, yielded results comparable to those of other workers, but we were unable to record a redistributional signal from epithelial sheets or scraped cells. The dye appeared to enter cells and become irreversibly bound. The membrane-bound merocyanine dyes have not been used on epithelial cells. They appear to hold the greatest promise for dynamic experiments on epithelial membrane potentials.


Reanimating the paralyzed face.
Facial animation is an essential part of human communication and one of the main means of expressing emotions, indexing our physiologic state and providing nonverbal cues. The loss of this important human quality due to facial paralysis can be devastating and is often associated with depression, social isolation and poor quality of life. Interruption of the neuromuscular pathway from the facial motor cortex to the facial muscles is the common causative factor in facial paralysis resulting from various etiologies. Restoring tone, symmetry and movement to the paralyzed face requires timely nerve grafting intervention in cases of reversible paralysis and the transfer of functional muscle units in irreversible paralysis. We review recent advances in these techniques.


Experimenter- and Infrared Thermography-Derived Measures of Capsaicin-Induced Neurogenic Flare Among Non-Hispanic White and Black Adults.
Capsaicin is a widely utilized experimental pain stimulus; however, few studies have reported on ethnic differences in pain responses to capsaicin. The present study used infrared thermography to 1) measure differences in capsaicin-induced neurogenic flare between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults and 2) determine the association between neurogenic flare and secondary hyperalgesia. Fifty-four participants (NHB N = 28) underwent heat/capsaicin sensitization model procedures. Neurogenic flare was examined using experimenter (i.e., subjective) and thermography (i.e., objective) measurements. A typically nonpainful mechanical punctate probe was used to measure secondary hyperalgesia. Ethnic groups did not significantly differ in age, sex, marital status, or personal income. Although experimenters rated a significantly wider area of capsaicin-related neurogenic flare among NHW compared with NHB participants (F1, 52 = 8.33, P = 0.006), thermography results showed no differences between groups in neurogenic flares (F1, 52 = 0.01, P = 0.93). Further, although NHB individuals reported greater average pain during the capsaicin procedures compared with NHW individuals (NHB = 58.57 [3.67], NHW = 46.46 [3.81]; F2, 51 = 5.19, P = 0.03), the groups did not differ in secondary hyperalgesia (F2, 51 = 0.03, P = 0.86), and ethnicity did not moderate the association between neurogenic flare and secondary hyperalgesia (F3, 50 = 0.24, P = 0.87). Findings cautiously support the use of infrared thermography over subjective experimenter report when measuring neurogenic inflammation in diverse samples. However, infrared thermography should not be used as a diagnostic tool for pain, given the lack of association between these factors. Future research is warranted to replicate these findings in a larger and more diverse sample to determine accurate neurogenic inflammation measures across other ethnic minority populations.


EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332.
Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the development of an invasive and metastatic carcinoma cell phenotype. Therefore, the definition of this phenotype is of great clinical interest. We recently evidenced vimentin positive cells in oral squamous cell carcinoma (OSCC) invasive front expressing laminin γ2 chain mRNA implicating an EMT origin of these cells. To further elucidate the nature of these cells, we have investigated the relation between EMT criteria and laminin-332 expression in a cell culture model of transforming growth factor beta-1 (TGFβ1)/epithelial growth factor (EGF) long time co-stimulation. We demonstrate that in contrast to TGFβ1 or EGF alone, co-stimulation induces phenotype transition in OSCC cells which fulfils the criteria of EMT in terms of vimentin up-regulation and E-cadherin down-regulation on protein level as well as cell scattering. Furthermore, cells displayed a strongly enhanced invasiveness and adhesion to type I-IV collagens. Phenotype transition is accompanied by an enhanced expression of laminin-332, especially of its γ2 chain. We further analyse the expression of extracellular matrix related genes by RT-PCR profiling. With respect to strongly enhanced proteins, data confirm the EMT phenotype of co-stimulated OSCC cells and expression of laminin-332. Furthermore, alpha catenin, collagen type 16, the integrin α7 and β1 chains, and MMP11 are suggested as candidates with potential role in EMT in OSCC. In summary we are able to show that EMT in OSCC is mediated by multiple growth factors and is accompanied by laminin γ2 chain up-regulation evidencing the existence of an intermediate Vim(+) /Ln332(+) EMT phenotype as seen in situ.


The Behavioral Inhibition System and Engagement With, and Influence By, COVID-19 and Election-Based Misinformation.
The negative impact of misinformation on public discourse and public safety is increasingly a focus of attention. From the COVID-19 pandemic to national elections, exposure to misinformation has been linked to conflicting perceptions of social, economic, and political issues, which has been found to lead to polarization, radicalization, and acts of violence at the individual and group level. While a large body of research has emerged examining the development and spread of misinformation, little has been done to examine the human processes of being exposed to, and influenced by, misinformation material online. This article uses reinforcement sensitivity theory to examine the effect of individual differences in the Behavioral Inhibition System (BIS) on the behavioral and cognitive intentions to engage in violence after exposure to misinformation online. Using an online panel sample (Mechanical Turk), and a behavioral study that involved exposure to, and interaction with, misinformation, this study found that trait BIS score impacted how much individuals engaged with misinformation, as well as their ensuing activism and radicalism toward the narratives that were depicted. This study identified that engagement with misinformation impacted intentions for activism and radicalism, as did trait BIS. However, these effects were present for both misinformation and correct information conditions. These findings highlight the importance of BIS-related processes and raise important questions about the degree to which we need to think about online influence as a general process versus specific processes that directly relate to the effect of misinformation.


Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential.
Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.


Evaluation of the interaction of cyclin-dependent kinase 5 with activator p25 and with p25-derived inhibitor CIP.
A high-affinity inhibitor protein called CIP, produced by small truncations of p35, was experimentally identified. P35 is a physiological activator of the cyclin-dependent kinase cdk5. P25 is derived from proteolytic truncation of p35 within "stressed" neurons, and it is associated with the hyperphosphorylation of specific neuronal proteins, typically occurring in neurodegenerative diseases such as Alzheimer's. Here, we report a study of the binding mechanisms of the cdk5-p25 and cdk5-CIP complexes. This provides a better understanding of the source of the inhibitory activity of the protein CIP. We use a geometry-based technique to test the hypothesis that p25's truncation increases the flexibility of CIP and thus prevents cdk5 from reaching its active conformation. Our study is based on a geometry-based alignment algorithm, which aligns two given protein conformations with respect to their interfaces. Our results support the flexibility hypothesis and will be used as a basis for targeted molecular dynamics simulations.


Relative location of alpha- and beta-adrenoceptors to sites of release of sympathetic transmitter in the rabbit facial vein.
We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated relaxation responses in rings pretreated with phentolamine (6 x 10(-7)M). These responses were significantly greater than the corresponding alpha-receptor-mediated contractions in rings pretreated with propranolol (10(-6)M). Blockade of neuronal uptake with desmethylimipramine (DMI, 10(-7)M) increased significantly the neurogenic relaxation but had little effect on neurogenic contractility. DMI pretreatment caused a shift to the left (x 5.6) in the relaxant dose-response curve to exogenous l-norepinephrine (NE). The NE contractile dose-response curve was also shifted to the left after DMI pretreatment but by a significantly smaller amount (x 3.1). Neurogenic activation of beta-receptors evoked almost maximal relaxations in facial vein rings (85% at 2 Hz), whereas the maximum neurogenic contraction was approximately half the maximum contraction with exogenous NE (40% at 6 Hz). These results imply that the beta-adrenoceptors in the rabbit facial vein are located in close proximity to sites of adrenergic transmitter release and neuronal reuptake, whereas the alpha-receptors are more distant.


Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity.
A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent as trolox), but in the LPO assay IC(50) values ranged from 0.2 to 37 microM. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents.


Factors Affecting the Development of an Antibody Response to Hepatitis B Immunization in Children With Intestinal Failure: Before and After Small Bowel Transplantation (With and Without Liver Graft).
Small bowel transplant with or without a liver graft (SBTx ± LTx) for children with intestinal failure involves checking their immunity to a range of microorganisms, including hepatitis B virus (HBV), at the time of assessment. HBV vaccination in the United Kingdom is recommended for transplant candidates. The aim of this audit was to find out how many SBTx ± LTx candidates received HBV vaccination before transplantation and how the timing of vaccination influenced the development of immunity. Retrospective review of case notes and hospital microbiology database formed the basis of the study. Vaccination history and serology were available in 56 of 87 subjects who had SBTx ± LTx. All patients were seronegative for HBV when assessed for transplant. HBV vaccination was started before transplant in 25 children and after transplant in 31. Eight children died posttransplant before their immunity could be checked, but of the 48 survivors, 20 children developed immunity, of whom 13 (65%) received at least 1 vaccination before SBTx ± LTx ( P = .008). Lack of response to HBV vaccine was significantly associated with isolated bowel transplantation and intensification of immune suppression. Of 11 children, 5 lost hepatitis B surface antibody (HbsAb), and 28 never made HBsAb, despite repeated vaccinations. Our study clearly shows that HBV vaccine before transplant is more effective. In line with renal failure patients, we suggest that children with chronic intestinal failure receive HBV vaccine when clinically stable, before referral for transplant. Higher-dose vaccines, accelerated schedules, and more frequent booster vaccinations are also strategies that may improve HBsAb levels after transplant.


Decrease in the protein kinase C-catalyzed phosphorylation of an endogenous lung protein (Mr 36,000) following treatment of mice with the tumor-modulatory agent butylated hydroxytoluene.
Butylated hydroxytoluene (BHT) causes transient lung damage in mice, and it can either inhibit or enhance carcinogen induction of tumors in internal organs, such as urethan-induced lung adenomas. Since protein kinase C (Pk-C) may mediate the action of one class of tumor-modulatory agents, the phorbol esters which promote skin tumorigenesis, we are examining the hypothesis that Pk-C is involved in the modulatory effects of BHT on internal organs. Endogenous phosphorylation of a Mr 36,000 cytosolic protein (p36) with a pI of 5.7 was demonstrable in extracts from lung and spleen but not from brain or heart. Phosphorylation required the presence of both Ca2+ and phosphatidylserine, and phosphate was incorporated into seryl and threonyl residues but not into tyrosyl residues. This reaction thus has the characteristics of Pk-C-dependent catalysis. A single i.p. injection of BHT (400 mg/kg body weight) decreased p36 phosphorylation severalfold in both BALB/cByJ and A/J mice. This decrease correlated with the extent of BHT-induced lung damage with regard to both the time course following BHT administration and the dose dependence of BHT. All of the pulmonary effects of BHT are abolished if the mice are pretreated with cedrene, an inducer of drug-detoxifying enzymes. Such treatment with cedrene prevented any BHT-induced decrease in p36 phosphorylation. A decrease in Pk-C specific activity, as measured using histone as an exogenous substrate, which resulted upon BHT treatment may provide a mechanism for decreased p36 phosphorylation. The specificity of this toxicity-related effect of BHT is emphasized by the fact that urethan injection did not detectably affect the phosphorylation of any lung proteins. Both p36 phosphorylation and Pk-C specific activity increased as a function of postnatal age. Thus the extent of p36 phosphorylation was inversely related to the extent of lung cell proliferation in two different physiological states, postnatal growth and regenerative repair following BHT-induced toxic injury. A single BHT injection is sufficient to cause lung toxicity, tumor prophylaxis, or cocarcinogenesis, while tumor promotion requires chronic treatment. P36 phosphorylation also decreased when mice were given multiple BHT injections over a period of 5 weeks. These results are consistent with a hypothesis that decreased Pk-C-dependent phosphorylation of p36 is involved in lung tumor modulation by BHT.


Emerging investigator series: microplastic sources, fate, toxicity, detection, and interactions with micropollutants in aquatic ecosystems - a review of reviews.
Hundreds of review studies have been published focusing on microplastics (MPs) and their environmental impacts. With the microbiota colonization of MPs being firmly established, MPs became an important carrier for contaminants to step inside the food web all the way up to humans. Thus, the continuous feed of MPs into the ecosystem has sparked a multitude of scientific concerns about their toxicity, characterization, and interactions with microorganisms and other contaminants. The reports of common subthemes have agreed about many findings and research gaps but also showed contradictions about others. To unravel these equivocal conflicts, we herein compile all the major findings and analyze the paramount discrepancies among these review papers. Furthermore, we systematically reviewed all the highlights, research gaps, concerns, and future needs. The covered focus areas of MPs' literature include the sources, occurrence, fate, existence, and removal in wastewater treatment plants (WWTPs), toxicity, interaction with microbiota, sampling, characterization, data quality, and interaction with other co-contaminants. This study reveals that many mechanisms of MPs' behavior in aquatic environments like degradation and interaction with microbiota are yet to be comprehended. Furthermore, we emphasize the critical need to standardize methods and parameters for MP characterization to improve the comparability and reproducibility of the incoming research.


How salt causes hypertension: the natriuretic hormone-Na/Ca exchange--hypertension hypothesis.
The hypothesis outlined below shows how an underlying functional (genetic or acquired) defect in renal excretion (undetectable by standard renal function tests) can, in the presence of an excessive salt load, lead to the development of hypertension. The initial tendency toward salt and water retention and extracellular fluid volume expansion is compensated by the secretion of a natriuretic hormone that promotes Na excretion by inhibiting Na pumps in renal tubule cells. The hormone also inhibits Na pumps in other types of cells, however, including vascular smooth muscle cells, so that the intracellular Na concentration rises in these cells. Then, because the vascular smooth muscle cells contain a Na/Ca exchange transport system in their plasma membranes, more Ca than normal will be delivered to these cells. This will cause the increased contractility and reactivity that underlies increased vascular tone and peripheral vascular resistance which is the direct cause of the elevated blood pressure.


Survey of Salmonella contamination of raw shell eggs used in food service premises in the United Kingdom, 2005 through 2006.
This survey was launched after an unusual number of Salmonella Enteritidis outbreaks associated with the use of eggs in food service premises in England and Wales. Between November 2005 and December 2006, 9,528 eggs (1,588 pooled samples of 6 eggs) were collected from 1,567 food service premises in the United Kingdom, most of which (89%) were produced in the United Kingdom. Salmonella was isolated from 6 (0.38%) pools of eggs. Of these, 5 (0.31%) were Salmonella Enteritidis, which were further characterized to phage types (PTs): PT 4 (0.19%), PT 8 (0.06%), and PT 12 (0.06%). Salmonella Mbandaka was also isolated (0.06%). Salmonella was detected from five and one of pooled eggs samples that were produced in the United Kingdom and Germany, respectively; these were from different producers. The study showed evidence of poor egg storage and handling practices in food service premises, in that 55% did not store eggs under refrigerated conditions; 20.7% of eggs had expired "best before" dates or were in use after 3 weeks of lay, indicating poor stock rotation; and 37.1% pooled eggs not intended for immediate service. Eggs are a commonly consumed food that may occasionally be contaminated with Salmonella at different rates, according to their country of origin. The food service sector needs to be aware of this continuing hazard, receive appropriate food safety and hygiene training on storage and usage of raw shell eggs, adopt appropriate control measures, and follow advice provided by national food agencies in order to reduce the risk of infection.


Fabrication of electrospun poly(ethylene oxide)-poly(capro lactone) composite nanofibers for co-delivery of niclosamide and silver nanoparticles exhibits enhanced anti-cancer effects in vitro.
An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, which hindered their translation from laboratory to clinics. In an effort to enhance their water solubility and bioavailability, we have developed simplistic strategies based on the solvent evaporation and amorphous solid dispersion methods. Among various solvent evaporation methods, electrospinning was adopted in the present work. Poly(ethylene oxide) (PEO) was selected as the polymeric solid dispersion matrix of the drug based on various advantageous properties of PEO. Moreover PEO could also serve as a template for the in situ synthesis of silver nanoparticles (Ag NPs). Furthermore the co-delivery of multiple anticancer drugs within a nanocarrier is a promising approach to overcome the drug resistance and to achieve synergistic therapy. To achieve this goal, the drugs (niclosamide (nic)) and Ag NPs were loaded separately and together (nic@Ag NPs) into the nanofiber. The as-prepared various formulations of composite nanofibers were well-characterized by different techniques. The in vitro release and kinetic studies suggest the sustained release of niclosamide which followed Fickian diffusion kinetics. The anticancer potential of the drugs alone and the nic@Ag NPs loaded nanofibers were evaluated by MTT assay against A549 (lung carcinoma) and MCF-7 (breast carcinoma) cell lines. The co-delivery of anticancer drugs nic@Ag NPs from nanofibers displayed superior anticancer potential in vitro when compared to nic alone or Ag NPs composite nanofibers. Additionally nic@Ag NPs showed better therapeutic efficacy against MCF-7 cells. To confirm the mechanism of cell death by nic@Ag NP composite nanofibers on MCF-7 cells, various cell based assays were done. Our finding clearly explains that a combination of drugs with the diverse anticancer mechanism remarkably improved the therapeutic potential of drugs. Therefore, the nic@Ag NPs composite nanofiber as a co-delivery system might have potential applications in combination cancer therapy.


Efficacy of different carriers for the triple antibiotic powder during regenerative endodontic procedures.
Chemical debridement during Regenerative Endodontic procedures is important. Previous research studies have evaluated various antibiotics and their concentrations but none have addressed the concern of delivering these materials. Hence, the purpose of this study was to determine what carrier could be used effectively in a clinical setting. Sixty caries-free maxillary incisors were used and inoculated with Enterococcus faecalis and divided into positive and irrigation controls and experimental groups that had triple antibiotic powder (1:1:1 ciprofloxacin:metronidazole:minocycline) delivered using various carriers: saline, cotton, sponge and methylcellulose. Current AAE regenerative protocols were followed. S2 sampling was performed and tested for bacterial presence via culturing and SEM. The results demonstrated that saline was the most effective carrier for the triple antibiotic powder while cotton and sponge were most ineffective. Saline and methylcellulose both reduced bacterial counts to a significant level. Overall, this study demonstrated that saline as a carrier was most effective and should be routinely used.


[Comparative assessment of the clastogenic potential of various industrial enterprises].
The paper comparatively assesses the level and qualitative spectrum of chromosomal aberrations (CA) in 192 workers engaged in 3 industries (cake and by-product, aluminum, and mining concentration processes). The maximum and minimum rates (6.43(+)-0.32% and 3.81(+)-0.46%) of CA have been observed in those engaged in cake and by-product and mining concentration processes, respectively. The combined influence of chemical and radiation factors are a cause of the higher rate of CA. Gender- and age-specific features do not effect on the level of structural CA. Smoking is a factor of their slight modification as there are no significant differences in the frequencies of aberrations between smokers and non-smokers in any professional group. There is an indirect relationship between the frequency of CA and the length of service, which may be different under the conditions of various industries.


Noninvasive assessment of coronary anatomy and myocardial perfusion: going toward an integrated imaging approach.
Many noninvasive imaging techniques are available for the evaluation of patients with known or suspected chronic coronary artery disease. Among these, computed tomography-based techniques allow the quantification of coronary atherosclerotic calcium and noninvasive imaging of coronary arteries, whereas nuclear cardiology is the most widely used noninvasive approach for the assessment of myocardial perfusion. The available single-photon emission computed tomography flow agents are characterized by a cardiac uptake proportional to myocardial blood flow. In addition, different positron emission tomography tracers may be used for the quantitative measurement of myocardial blood flow and coronary flow reserve. Extensive research is currently being performed in the development of noninvasive coronary angiography and myocardial perfusion imaging using cardiac magnetic resonance. Finally, new multimodality imaging systems have been recently developed, bringing together anatomical and functional information. This review sought to provide a description of the relative merits of noninvasive imaging techniques in the assessment of coronary anatomy and myocardial perfusion in patients with known or suspected coronary artery disease.


Roles for the Rad27 Flap Endonuclease in Mitochondrial Mutagenesis and Double-Strand Break Repair in Saccharomyces cerevisiae.
The structure-specific nuclease, Rad27p/FEN1, plays a crucial role in DNA repair and replication mechanisms in the nucleus. Genetic assays using the rad27-∆ mutant have shown altered rates of DNA recombination, microsatellite instability, and point mutation in mitochondria. In this study, we examined the role of Rad27p in mitochondrial mutagenesis and double-strand break (DSB) repair in Saccharomyces cerevisiae Our findings show that Rad27p is essential for efficient mitochondrial DSB repair by a pathway that generates deletions at a region flanked by direct repeat sequences. Mutant analysis suggests that both exonuclease and endonuclease activities of Rad27p are required for its role in mitochondrial DSB repair. In addition, we found that the nuclease activities of Rad27p are required for the prevention of mitochondrial DNA (mtDNA) point mutations, and in the generation of spontaneous mtDNA rearrangements. Overall, our findings underscore the importance of Rad27p in the maintenance of mtDNA, and demonstrate that it participates in multiple DNA repair pathways in mitochondria, unlinked to nuclear phenotypes.


Health outcome after total knee replacement in the very elderly.
Between 1992 and 1994 we performed a prospective study of the effect of total knee replacement (TKR) on the health status of 119 patients over the age of 80 years who had had a primary unilateral TKR. The Nottingham Health Profile was used to assess this before and at three and 12 months after operation. We found a significant improvement in the scores for pain, emotional reaction, sleep and physical mobility at three months. After 12 months, the scores for pain and sleep were well maintained. The other factors had deteriorated slightly but remained better than before operation. Our findings show that TKR leads to a significant improvement in the general health status of the very elderly.


Developing national obesity policy in middle-income countries: a case study from North Africa.
The prevalence of overweight and obesity is a rapidly growing threat to public health in both Morocco and Tunisia, where it is reaching similar proportions to high-income countries. Despite this, a national strategy for obesity does not exist in either country. The aim of this study was to explore the views of key stakeholders towards a range of policies to prevent obesity, and thus guide policy makers in their decision making on a national level. Using Multicriteria Mapping, data were gathered from 82 stakeholders (from 33 categories in Morocco and 36 in Tunisia) who appraised 12 obesity policy options by reference to criteria of their own choosing. The feasibility of policies in practical or political terms and their cost were perceived as more important than how effective they would be in reducing obesity. There was most consensus and preference for options targeting individuals through health education, compared with options that aimed at changing the environment, i.e. modifying food supply and demand (providing healthier menus/changing food composition/food sold in schools); controlling information (advertising controls/mandatory labelling) or improving access to physical activity. In Tunisia, there was almost universal consensus that at least some environmental-level options are required, but in Morocco, participants highlighted the need to raise awareness within the population and policy makers that obesity is a public health problem, accompanied by improving literacy before such measures would be accepted. Whilst there is broad interest in a range of policy options, those measures targeting behaviour change through education were most valued. The different socioeconomic, political and cultural contexts of countries need to be accounted for when prioritizing obesity policy. Obesity was not recognized as a major public health priority; therefore, convincing policy makers about the need to prioritize action to prevent obesity, particularly in Morocco, will be a crucial first step.


The P-3 and EST loci in the honeybee Apis mellifera.
Data for Apis mellifera indicate that the P-3 proteins and one esterase enzyme are controlled by two genes, P-3 and Est, with two alleles each. The frequency of the P-3 alleles is different in the two subspecies (adansonii and ligustica), that for P-3(F) in Italian bees being 46.9% and in African 0.5%. The frequency of Est(F) is 2.8% in both populations. The Est locus has two codominant alleles and the locus P-3 has two incompletely dominant alleles; the heterozygote P-3( S)/P-3(F) shows only an intermediate band. The two loci are not genetically linked.


Synthetic Peptide dendrimers block the development and expression of experimental allergic encephalomyelitis.
Multiple Ag peptides (MAPs) containing eight proteolipid protein (PLP)(139-151) peptides arranged around a dendrimeric branched lysine core were used to influence the expression and development of relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. The PLP(139-151) MAPs were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP(139-151) monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP(72-84) MAP (a dendrimeric octamer composed of the 72-84 peptide) and PLP(178-191) MAP (a dendrimeric octamer composed of the PLP(178-191) peptide) had no treatment effect on PLP(139-151)-induced EAE. PLP(139-151) MAP treatment initiated after clinical signs of paralysis also altered the subsequent course of EAE; it limited developing signs of paralysis and effectively limited the severity and number of disease relapses in MAP-treated mice over a 60-day observation period. PLP(139-151) MAP therapy initiated before disease onset acts to limit the numbers of Th17 and IFN-gamma-producing cells that enter into the CNS. However, Foxp3(+) cells entered the CNS in numbers equivalent for nontreated and PLP(139-151) MAP-treated animals. The net effect of PLP(139-151) MAP treatment dramatically increases the ratio of Foxp3(+) cells to Th17 and IFN-gamma-producing cells in the CNS of PLP(139-151) MAP-treated animals.


Topography of simian virus 40 A protein-DNA complexes: arrangement of protein bound to the origin of replication.
DNA binding regions I, II, and III at the origin of replication have different arrangements of A protein (T antigen) recognition pentanucleotides. The A protein also protects each region from DNase in distinctly different patterns. Footprint and fragment assays led to the following conclusions: (i) in some cases a single recognition pentanucleotide is sufficient to direct the binding and accurate alignment of A protein on DNA; (ii) the A protein binds within isolated region I or II in a sequential process leading to multiple overlapping areas of DNase protection within each region; and (iii) the 23-base pair span of recognition sequences in region II allows binding and protection of a longer length of DNA than the 23-base pair span in region I. We propose a model of protein binding that addresses the problem of variations in the arrangement of pentanucleotides in regions I and II and explains the observed DNase protection patterns. The central feature of the model requires each protomer of A protein to bind to a pentanucleotide in a unique direction. The resulting orientation of protein would protect more DNA at the 5' end of the 5'-GAGGC-3' recognition sequence than at the 3' end. The arrangement of multiple protomers at the origin of simian virus 40 replication is discussed.


Cyanoacrylate as a microbial sealant: examining the evidence.
This article examines the evidence base for the use of microbial sealant as a skin preparation prior to surgery. Firstly, using the steps of evidence-based practice the use of cyanoacrylate as a microbial sealant was explored. Next the evidence regarding the use of cyanoacrylate based microbial sealant was sought and then critically appraised. Having found evidence to support its use to be lacking in rigour and quality, an argument is made for the omission of cyanoacrylate-based microbial sealants as part of current preoperative preparation.


Physicochemical basis for the rapid time-action of LysB28ProB29-insulin: dissociation of a protein-ligand complex.
The rate-limiting step for the absorption of insulin solutions after subcutaneous injection is considered to be the dissociation of self-associated hexamers to monomers. To accelerate this absorption process, insulin analogues have been designed that possess full biological activity and yet have greatly diminished tendencies to self-associate. Sedimentation velocity and static light scattering results show that the presence of zinc and phenolic ligands (m-cresol and/or phenol) cause one such insulin analogue, LysB28ProB29-human insulin (LysPro), to associate into a hexameric complex. Most importantly, this ligand-bound hexamer retains its rapid-acting pharmacokinetics and pharmacodynamics. The dissociation of the stabilized hexameric analogue has been studied in vitro using static light scattering as well as in vivo using a female pig pharmacodynamic model. Retention of rapid time-action is hypothesized to be due to altered subunit packing within the hexamer. Evidence for modified monomer-monomer interactions has been observed in the X-ray crystal structure of a zinc LysPro hexamer (Ciszak E et al., 1995, Structure 3:615-622). The solution state behavior of LysPro, reported here, has been interpreted with respect to the crystal structure results. In addition, the phenolic ligand binding differences between LysPro and insulin have been compared using isothermal titrating calorimetry and visible absorption spectroscopy of cobalt-containing hexamers. These studies establish that rapid-acting insulin analogues of this type can be stabilized in solution via the formation of hexamer complexes with altered dissociation properties.


Vitamin K status in spaceflight and ground-based models of spaceflight.
Bone loss is a well-documented change during and after long-duration spaceflight. Many types of countermeasures to bone loss have been proposed, including vitamin K supplementation. The objective of this series of studies was to measure change in vitamin K status in response to microgravity under a variety of spaceflight and spaceflight analog (model) conditions, including long-duration spaceflight studies (n = 15), three bed rest studies (n = 15, 49, and 24), and a 14-day saturation dive (n = 6). In crew members who flew 2-6 months on the International Space Station, in-flight and postflight plasma phylloquinone concentrations were unchanged from the preflight mean. Consistent with this finding, urinary γ-carboxyglutamic acid (GLA), a measure of vitamin K-dependent protein turnover, did not change in response to flight. Serum undercarboxylated osteocalcin (%ucOC), a measure of vitamin K function, was generally unchanged in response to flight. Spaceflight findings were corroborated by findings of no changes in phylloquinone, urinary GLA, or %ucOC during or after bed rest in three separate bed rest studies (21-90 days in duration) or after a 14-day saturation dive. The data presented here do not support either a need for vitamin K supplementation during spaceflight or the suggestion of using vitamin K as a bone loss countermeasure in spaceflight.


Morphologic and functional association of retinal layers beneath the epiretinal membrane with spectral-domain optical coherence tomography in eyes without photoreceptor abnormality.
To access the differential thickening of retinal layers in the epiretinal membrane (ERM) and to determine their correlation with visual acuity. Prospective and comparative case series of 22 patients, each of whom has one unilateral ERM eye and one normal eye. The eyes with abnormal photoreceptor layer by OCT images were excluded. Spectral-domain optical coherence tomography (SD-OCT) images were generated with Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The thicknesses were obtained by a volume scan program using manual segmentation of the total retina, inner retina, inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) in the fovea (1.0 mm diameter) and the parafovea (3.0 mm diameter). The thickness and the proportion of each retinal layer and their relationship with visual acuity were analyzed. All retinal layers of ERM eyes were thicker than the patients' normal eyes (P < 0.05). In the fovea, the levels of thickness difference of inner retina (240.38%) and INL (266.26%) were significantly higher than total retina (126.7%). Visual acuity was not correlated with the retinal thickness in both ERM eyes and normal eyes (P > 0.05). However, significant correlations between visual acuity difference with retinal thickness difference were found in the total retina (rho = 0.450, P = 0.046) and the inner retina (rho = 0.602, P = 0.005) of the fovea, as well as in the inner retina (rho = 0.468, P = 0.037) and the INL (rho = 0.466, P = 0.039) of the parafovea. When we convert each retinal thickness into a proportion, in the foveal area, the percentages of thickness of the inner retina and the INL of ERM eye were significantly higher than that of the normal eye (P < 0.05), whereas that of the ONL was significantly lower (P < 0.05). In the parafoveal area, the percentage of thickness of the inner retina of the ERM eye was significantly higher than that of the normal eye (P < 0.05), whereas that of ONL was significantly lower (P < 0.05). Idiopathic ERM affects the volume of all retinal layers. Inner retina had the most variability of thickness and is strongly associated with visual acuity changes in the case of intact photoreceptor layer.


[One-stage radical eradication and wedged vertebral osteotomy through a purely posterior procedure in treating thoracic and lumbar spine tuberculosis associated with kyphosis or scoliokyphosis demormity].
To investigate the feasibility, clinical indications and significance of one-stage radical eradication, wedged vertebral osteotomy and instrumentation in the treatment of tuberculosis of thoracic and lumbar spine associated with kyphosis or scoliokyphosis through a purely posterior procedure. Sixteen cases with tuberculosis of thoracic and lumbar spine associated with kyphosis or scoliokyphosis were treated by one-stage radical eradication, wedged vertebral osteotomy and instrumentation fixation through posterior procedure. All patients included 12 males and 4 females, and the average age was 37.1 years (from 17 to 53 years). The preoperative average Cobb angle of kyphosis was 78.3 degrees (range from 54 degrees to 138 degrees ). There were 2 cases associated with scoliosis (the Cobb angle of scoliosis was 31 degrees and 24 degrees), and 1 case with lateral transition. Spinal cord compression were found in 7 cases. According to the Frankel's classification, 2 cases belonged to C degree, and 5 cases to D degree. There were 2 cases with caudal equina or nerve root lesions. The average blood loss during the operation was 1100 ml (range from 450 to 2200 ml), and the average operation time was 265 min (range from 215 to 325 min). The postoperative results were satisfactory, 14 cases were excellent and 2 cases were good. Obvious improvement was obtained in 9 cases with neurological dysfunction. The postoperative average Cobb' angle was 28.5 degrees (range from 0 degrees to 67 degrees), and the corrective rate was 63.6%. The followed-up was ranged from 14 to 52 months with an average of 26.3 months. There were no major complications related to the fixations, loss of correction and the fusion were achieved in all patients. One-stage radical eradication, wedged vertebral osteotomy and instrumentation is a feasible and an effective procedure in the treatment of spinal tuberculosis associated with kyphosis or scoliokyphosis. Compared with combined anterior and posterior procedure, the surgical technique may decrease injuries and has better result.


Prophylaxis with trimethoprim-sulfamethoxazole in abdominal, pelvic, and prostatic surgery.
The literature on use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in abdominal, pelvic, and prostatic surgery is meager. There is some evidence that TMP-SMZ may be effective prophylactically in biliary surgery (in patients with functioning gall bladders). Further study is needed to clarify the mixed results seen in prostatic and pelvic surgery. An evaluation was made of the effectiveness of TMP-SMZ in the prevention of endomyometritis following cesarean section in 206 women who were comparable in terms of risk factors. Among patients given a placebo, a total of 44 infections (42%) occurred, whereas among those given TMP-SMZ prophylaxis, 22 infections (22%) occurred, a statistically significant difference (P = .037, chi 2). The rate of endomyometritis among placebo recipients was 33%, as contrasted with one of 19% in those given TMP-SMZ (P = .02, chi 2). Prophylactic treatment resulted in lower rates of endomyometritis in both high- and low-risk women, but the results reached statistical significance only among high-risk patients. In essence, prophylaxis changed high-risk patients into low-risk patients.


Mn-doped zinc sulphide nanocrystals for immunofluorescent labeling of epidermal growth factor receptors on cells and clinical tumor tissues.
The field of molecular detection and targeted imaging has evolved considerably with the introduction of fluorescent semiconductor nanocrystals. Manganese-doped zinc sulphide nanocrystals (ZnS:Mn NCs), which are widely used in electroluminescent displays, have been explored for the first time for direct immunofluorescent (IF) labeling of clinical tumor tissues. ZnS:Mn NCs developed through a facile wet chemistry route were capped using amino acid cysteine, conjugated to streptavidin and thereafter coupled to biotinylated epidermal growth factor receptor (EGFR) antibody utilizing the streptavidin-biotin linkage. The overall conjugation yielded stable EGFR antibody conjugated ZnS:Mn NCs (EGFR ZnS:Mn NCs) with a hydrodynamic diameter of 65 ± 15 nm, and having an intense orange-red fluorescence emission at 598 nm. Specific labeling of EGF receptors on EGFR(+ve) A431 cells in a co-culture with EGFR(-ve) NIH3T3 cells was demonstrated using these nanoprobes. The primary antibody conjugated fluorescent NCs could also clearly delineate EGFR over-expressing cells on clinical tumor tissues processed by formalin fixation as well as cryopreservation with a specificity of 86% and accuracy of 88%, in comparison to immunohistochemistry. Tumor tissues labeled with EGFR ZnS:Mn NCs showed good fluorescence emission when imaged after storage even at 15 months. Thus, ZnS nanobioconjugates with dopant-dependent and stable fluorescence emission show promise as an efficient, target-specific fluorophore that would enable long term IF labeling of any antigen of interest on clinical tissues.


Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster.
Octreotide is a somatostatin analogue binding on two receptor subtypes. In previous trials Octreotide showed inhibitory effects on tumour growth and liver metastasis in experimental pancreatic cancer. Thus we evaluated whether the new somatostatin analogue SOM-230 binding on 4 receptor subtypes has superior effects on carcinogenesis in pancreatic carcinoma. About 120 Syrian hamsters were randomised into six groups (n = 20): Gr.1: Aqua/Aqua, Gr.2: BOP/Aqua, Gr.3: Aqua/Octreotide, Gr.4: BOP/Octreotide, Gr.5: Aqua/SOM-230, Gr.6: BOP/SOM-230. Tumour groups 2,4,6 subcutaneously received 10 mg/kg body weight N-nitrosobis-2-oxopropylamin (BOP) weekly for 10 weeks, healthy control Gr.1,3,5 were given aqua. In the 17th week therapy started with Octreotide and SOM-230 for 16 weeks, after 32 weeks animals were sacrificed. Pancreas and liver were histopathologically analysed. Hepatic lipidperoxidation was determined by activities of antioxidative enzymes gluthation-peroxidase (GSH-Px) and superoxiddismutase (SOD) as well as concentration of thiobarbituric-acid reactive substances (TBARS). Incidence of liver metastases was 88.2% in Gr.2 (BOP/Aqua), it was decreased in Gr.4 (BOP/Octreo: 40%) and Gr.6 (BOP/SOM-230: 50%) (P < 0.05). Mean number/animal and mean-2-dimensional size of liver metastases did not differ between tumour groups. Comparing GSH-Px-activity in intrametastatic and extrametastatic hepatic tissue revealed a significant increase extrametastatically in Gr.2 (BOP/Aqua) and Gr.6 (BOP/SOM-230). SOD-activity in liver metastases was decreased in Gr.2 (1,801) (P < 0.05) versus Gr.4 (8,304) and Gr.6 (7,038). Intrametastatic TBARS concentration was increased in Gr.2 compared to Gr.4 (BOP/Octreotid) and Gr.6 (BOP/SOM-230) (P < 0.05). Octreotide and SOM-230 equally reduced liver metastasis in ductal pancreatic adenocarcinoma probably by a reduction of lipidperoxidation.


Neo-humanism and COVID-19: Opportunities for a socially and environmentally sustainable world.
A series of crises, culminating with COVID-19, shows that going "Beyond GDP" is urgently necessary. Social and environmental degradation are consequences of emphasizing GDP as a measure of progress. This degradation created the conditions for the COVID-19 pandemic and limited the efficacy of counter-measures. Additionally, rich countries did not fare much better during the pandemic than poor ones. COVID-19 thrived on inequalities and lack of cooperation. In this article, we leverage on defensive growth theory to explain the relationships between these factors, and we put forward the idea of neo-humanism, a cultural movement grounded on evidence from quality-of-life studies. The movement proposes a new culture leading towards a socially and environmentally sustainable future. Specifically, neo-humanism suggests that prioritizing well-being by, for instance promoting social relations, would benefit the environment, and enable collective action to address public issues. This, in turn, would positively affect productivity and health - among other behavioral outcomes - and thereby instill a virtuous cycle. Such a society would have been better endowed to cope with COVID-19, and possibly even prevented the pandemic. Neo-humanism proposes a world in which the well-being of people comes before the well-being of markets, in which promoting cooperation and social relations represents the starting point for better lives, and a peaceful and respectful coexistence with other species on Earth.


Renewable pencil electrodes for highly sensitive stripping potentiometric measurements of DNA and RNA.
Renewable graphite pencil electrodes are demonstrated to be excellent materials for adsorptive stripping measurements of trace nucleic acids. While displaying an attractive stripping performance, comparable to that of conventional carbon paste electrodes, the pencil electrode offers a convenient (mechanical) renewal, with each stripping potentiogram recorded at a fresh surface. Various pencil lead materials and lengths have been examined and experimental variables of the pretreatment and measurement procedures have been explored and optimized. The extremely low detection limits (e.g., 3 micrograms l-1 tRNA with 10 min accumulation) are coupled to a good surface-to-surface reproducibility (RSD of 6.4% for 14 repetitive measurements of 1 mg l-1 ssDNA).


The role of patient preferences in nursing decision-making in evidence-based practice: excellent nurses' communication tools.
To develop an understanding of how nurses take account of patient preferences in nursing decision-making in evidence-based practice to provide individual tailored nursing care. Qualitative grounded theory. Semi-structured interviews were conducted with 27 nurses in four medium-sized hospitals in the Netherlands. Furthermore, seven nurses were observed during their shift. Constant comparative analysis underpinned by Strauss and Corbin's framework was used. Three communication tools of nurses were identified to discern and attend to patient preferences: (a) a click-making tool enables to build rapport instantly; (b) antennae monitor individual patient's needs; and (c) asking empathic questions to fine-tune to individual patient preferences. Participants emphasized that giving individual attention enhances the patient's experienced quality of life. Excellent nurses in evidence-based practice consciously spend time to discover patient preferences using the set of implicit and intuitive communication tools to attune their professional care. The use of these tools leads to individual tailored nursing care and appears to be part of the nurses' practical wisdom. Further studies on how nurses balance patient preferences in nursing decision-making in the evidence-based practice are recommended. The findings fill a gap in the literature on how nurses discover and balance all three aspects of the evidence-based practice in their decision-making: evidence derived from science, best practice, and patient preferences. Moreover, the use of this implicit knowledge in nursing deserves further research and attention in practice and education.


Assessment and management of right ventricular failure in left ventricular assist device patients.
Mechanical circulatory support devices, including ventricular assist devices (VADs) and the total artificial heart, have evolved to become accepted therapeutic options for patients with severe congestive heart failure. Continuous-flow left VADs are the most prevalent option for mechanical circulatory assistance and reliably provide years of support. However, problems related to acute and chronic right heart failure in patients with left VADs continue to cause important mortality and morbidity. This review discusses the assessment and management of right ventricular failure in left VAD patients. The goal is to summarize current knowledge and suggest new approaches to managing this problem.


Estimating Time-Varying PCB Exposures Using Person-Specific Predictions to Supplement Measured Values: A Comparison of Observed and Predicted Values in Two Cohorts of Norwegian Women.
Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reproduce empirical data. Here, we evaluated the capability of one such mechanistic model to reproduce measured PCB concentrations in individual Norwegian women. We also assessed individual life-course concentrations. Concentrations of four PCB congeners in pregnant (n = 310, sampled in 2007-2009) and postmenopausal (n = 244, 2005) women were compared with person-specific predictions obtained using CoZMoMAN, an emission-based environmental fate and human food-chain bioaccumulation model. Person-specific predictions were also made using statistical regression models including dietary and lifestyle variables and concentrations. CoZMoMAN accurately reproduced medians and ranges of measured concentrations in the two study groups. Furthermore, rank correlations between measurements and predictions from both CoZMoMAN and regression analyses were strong (Spearman's r > 0.67). Precision in quartile assignments from predictions was strong overall as evaluated by weighted Cohen's kappa (> 0.6). Simulations indicated large inter-individual differences in concentrations experienced in the past. The mechanistic model reproduced all measurements of PCB concentrations within a factor of 10, and subject ranking and quartile assignments were overall largely consistent, although they were weak within each study group. Contamination histories for individuals predicted by CoZMoMAN revealed variation between study subjects, particularly in the timing of peak concentrations. Mechanistic models can provide individual PCB exposure metrics that could serve as valuable supplements to measurements.


Nucleic acid-binding properties and subcellular localization of the 3a protein of brome mosaic bromovirus.
Brome mosaic bromovirus (BMV) 3a protein is required for cell-to-cell movement of the virus in host plants. The BMV 3a protein (B3a) was produced in Escherichia coli using an expression vector. Gel retardation analysis and UV cross-linking experiments demonstrated that B3a bound single-stranded RNA cooperatively without sequence specificity. Binding competition analysis showed that B3a bound to single-stranded nucleic acids more strongly than to double-stranded nucleic acids. Deletion mutagenesis located a nucleic acid-binding domain to amino acids 189-242. Western blot analysis of fractionated proteins of BMV-infected barley using monoclonal antibodies against B3a indicated that B3a may interact with membrane materials and form complexes in the cytoplasm. Immunogold labelling of thin sections of infected barley tissues revealed that B3a was associated with plasmodesmata and cytoplasmic inclusions.


Changes of the gastric endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma: an immunohistochemical quantitative study.
The regional distributions and relative frequencies of some gastric endocrine cells of C57BL/6 mice were studied by immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon and human pancreatic polypeptide (HPP) after subcutaneous implantation of murine lung carcinoma (3LL) cells. The experimental animals were divided into two groups, one is non-implanted sham and the other is 3LL-implanted group. Samples were collected from the two regions of stomach (fundus and pylorus) at 28 d after implantation of 3LL cells (1 x 10(5) cell/mouse). In this study, all the seven types of immunoreactive (IR) cells were identified except for HPP. Most of these IR cells in the gastric portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found occasionally. The regional distributions of gastric endocrine cells in the 3LL-implanted group were similar to those of non-implanted sham. However, significant decreases of some types of IR cells were detected in 3LL-implanted group compared to those of non-implanted sham. In addition, the IR cells showing degranulation were numerously detected in 3LL-implanted group. CGA-, serotonin- and somatostatin-IR cells in the fundus and pylorus regions, and gastrin-IR cells in the pylorus regions of 3LL-implanted groups significantly decreased compared to those of non-implanted sham. However, no changes on frequencies of CCK-8- and glucagon-IR cells were demonstrated between 3LL-implanted and non-implanted groups. Endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. Implantation of tumor cell mass (3LL) induced severe quantitative changes of gastric endocrine cell density, and the abnormality in density of gastric endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.


The Escherichia coli flagellar transcriptional activator flhD regulates cell division through induction of the acid response gene cadA.
FlhD is a positive regulator of cadA. A mutant with a transposon-mediated lacZ fusion to cadA exhibited a cell division phenotype similar to that of the flhD mutant and had FlhD-dependent beta-galactosidase activity. Under different growth conditions, the cell division rate correlated with the level of expression of cadA.