Correlation of Aurora-A expression with the effect of chemoradiation therapy on esophageal squamous cell carcinoma.
Chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC). However, because some patients respond well to CRT and others do not, it is important to be able to predict response to CRT before beginning treatment by using markers. Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions in centrosome maturation and chromosome segregation. In this study, we investigated the relationship between the expression of Aurora-A and the response to CRT in patients with ESCC. We immunohistochemically investigated the expression of Aurora-A in biopsy specimens of untreated primary tumors of 78 patients with ESCC and determined the relationship between Aurora-A levels and patient responses to CRT, which consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. Tumors were judged as Aurora-A positive when more than 10% of the cancer cells displayed a distinct positive nuclear anti-Aurora-A immunoreaction by immunohistochemical evaluation. The tumors of 46 of 78 patients (58.9%) displayed positive expression of Aurora-A. In terms of clinical response the percentage of patients showing complete response (CR), incomplete response/stable disease of primary lesion (IR/SD), and progressive disease (PD) was 19.2, 69.2, and 11.5%, respectively. In terms of histological response the tumor grade of the 41 patients who underwent surgery was as follows: grade 1, 48.8%; grade 2, 29.2%; grade 3, 22.0%. CRT was effective for patients who had Aurora-A (+) tumors (clinically: P = 0.0003, histologically: P = 0.036). Our results suggest that Aurora-A expression in biopsy specimens of primary tumors is associated with CRT efficacy in patients with ESCC. Assessment of Aurora-A expression in biopsy specimens maybe useful for regarding the potential utility of CRT therapy for patients with ESCC before treatment.


Silicone-induced foreign body reaction and lymphadenopathy after temporomandibular joint arthroplasty.
Eight patients with previously placed silicone temporomandibular joint (TMJ) implants were operated on again. Excised tissues from in and around the joint were histologically evaluated. In one case, a parotid lymph node was also examined. All specimens revealed fragmented, amorphous, refractile, but nonbirefringent, irregularly spherical foreign material consistent with fragmented silicone. Granulomatous inflammation and multinucleated giant cells were associated with the silicone material. These findings demonstrated that silicone may not be a totally inert material and that its biomechanical properties are not ideal for use in the TMJ.


Aberrant synaptophysin expression in classic Hodgkin lymphoma.
Synaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has not yet been described. However, we experienced an index case of classic Hodgkin lymphoma with synaptophysin expression. This experience prompted us to investigate synaptophysin expression in classic Hodgkin lymphoma. Immunohistochemical staining of synaptophysin was performed in 59 diagnosed cases of classic Hodgkin lymphoma, 10 anaplastic large cell lymphomas, 16 diffuse large B-cell lymphomas, and 5 extranodal marginal zone lymphoma of the mucosa-associated tissue. Synaptophysin-positive cases were stained for both chromogranin and CD56a. Of 59 classic Hodgkin lymphoma cases, 11 (19%) were positive for synaptophysin. None of the anaplastic large cell lymphomas expressed synaptophysin. Synaptophysin showed weak but specific expression in the cytoplasm of the Hodgkin lymphoma tumor cells. Other background inflammatory cells (such as macrophages, B-, and T-lymphocytes) were all negative for synaptophysin expression. Chromogranin and CD56a were not expressed in the synaptophysin-positive classic Hodgkin lymphomas. Synaptophysin is an integral glycoprotein present in presynaptic vesicles of neurons and neuroendocrine cells. It is a diagnostic marker for neuroendocrine tumors. Aberrant synaptophysin expression has been reported in non-neuroendocrine tumors but not in lymphoma or leukemia. To the best of our knowledge, synaptophysin positivity has only been reported in a single case of precursor T-lymphoblastic leukemia/lymphoma to date. Our study showed that aberrant synaptophysin expression in classic Hodgkin lymphoma is an unexpectedly frequent finding. The mechanism underlying, and prognostic significance of, such aberrant expression is unclear. Thus, in a small biopsy, aberrant synaptophysin expression could be a diagnostic pitfall and should be carefully avoided.


Microbleeds after Stent-assisted Coil Embolization of Unruptured Intracranial Aneurysms: Incidence, Risk Factors and the Role of Thromboelastography.
To analyze the incidence and risk factors of microbleeds lesions and to use thromboelastography (TEG) to evaluate the relationship between perioperative platelet function and microbleed events in patients with unruptured intracranial aneurysms (UIAs) undergoing Stent-Assisted Coil (SAC) embolization. We retrospectively enrolled 261 patients with UIAs undergoing SAC embolization between November 2017 and October 2019. All patients received unanimous antiplatelet protocol (aspirin 300 mg and clopidogrel 300 mg). Platelet function was evaluated by TEG, and magnetic resonance susceptibility-weighted imaging (SWI) was performed for microbleeds detection before and after surgery. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for microbleeds following embolization. Microbleed lesions were identified in 122 of 261 patients (46.7%). Most of the microbleeds were asymptomatic, except for 22 patients complaining slight headaches, and 3 patients who developed cerebral hemorrhage after discharge. Among the clinical characters, female, previous intracerebral hemorrhage (ICH) history and TEG parameters variation (higher reaction time (R) and lower maximum amplitude of adenosine diphosphate (MAADP)) were associated with microbleeds occurrence. Subsequent multivariate analysis indicated that gender, hemorrhage history, R, and MAADP were still independent risk factors of microbleeds. The R-value (>7.6 min) and MAADP (<29.2 mm) were predictive values, yielding areas under the receiver operating curve (ROC) of 0.76 (95% CI 0.70 to 0.82) and 0.89 (95% CI 0.86 to 0.93), respectively. The incidence of microbleeds may be high in UIA patients treated with SAC and dual antiplatelet therapy. Lesions occurred more frequently in female patients and patients with ICH history. Among the TEG parameters, the R-value and MAADP were predictors for microbleed events.


Effect of Middle-Ear Pathology on High-Frequency Ear Canal Reflectance Measurements in the Frequency and Time Domains.
The effects of middle-ear pathology on wideband acoustic immittance and reflectance at frequencies above 6-8 kHz have not been documented, nor has the effect of such pathologies on the time-domain reflectance. We describe an approach that utilizes sound frequencies as high as 20 kHz and quantifies reflectance in both the frequency and time domains. Experiments were performed with fresh normal human temporal bones before and after simulating various middle-ear pathologies, including malleus fixation, stapes fixation, and disarticulation. In addition to experimental data, computational modeling was used to obtain fitted parameter values of middle-ear elements that vary systematically due to the simulated pathologies and thus may have diagnostic implications. Our results demonstrate that the time-domain reflectance, which requires acoustic measurements at high frequencies, varies with middle-ear condition. Furthermore, the extended bandwidth frequency-domain reflectance data was used to estimate parameters in a simple model of the ear canal and middle ear that separates three major conductive pathologies from each other and from the normal state.


Antigonadal activity of the melatonin analogs 2-iodomelatonin and 2-chloromelatonin in the juvenile Djungarian hamster, Phodopus sungorus campbelli.
The antigonadal effects of daily (20 micrograms, s.c.) injection of melatonin and two analogs, 2-iodomelatonin and 2-chloromelatonin, were compared in juvenile Djungarian hamsters housed under long photoperiod (L:D 16:8). Melatonin, 2-iodomelatonin, and 2-chloromelatonin injected 3 h before lights off for 16 days (17-34 days of age) significantly inhibited testis growth compared to vehicle-injected hamsters. In addition, melatonin and both analogs significantly reduced body weight gain. These 2-substituted analogs appear to be melatonin agonists with a potency in vivo similar to the parent compound, melatonin.


Post-mortem MRI of the foetal spine and spinal cord.
To compare the findings of post-mortem magnetic resonance imaging (MRI) of the foetal spine with autopsy with a view to using post-mortem MRI as an alternative or adjunct to autopsy, particularly in foetal and neonatal cases. The brains and spines of 41 foetuses, with a gestational age range of 14-41 weeks, underwent post-mortem MRI before autopsy. Post-mortem MRI of the brain consisted of T2-weighted sequences in three orthogonal planes and MRI of the spine consisted of T2-weighted sequence in the sagittal and axial planes in all cases and coronal planes in selected cases. Thirty of 41 (78%) foetal spines were found to be normal at autopsy and on post-mortem MRI. Eleven of 41 (22%) foetal spines were abnormal: eight foetuses had myelomeningocoeles and Chiari 2 deformities, one foetus had limited dorsal myeloschisis, one foetus had caudal regression syndrome, and one had diastematomyelia. The post-mortem MRI findings concurred with the autopsy findings in 10/11 of the abnormal cases, the disagreement being the case of diastematomyelia that was shown on post-mortem MRI but was not diagnosed at autopsy. In this series, post-mortem MRI findings agreed with the autopsy findings in 40/41(98%) cases and in one case the post-mortem MRI demonstrated an abnormality not demonstrated at autopsy.


The association of comorbidity with Parkinson's disease-related hospitalizations.
Unplanned hospital admissions associated with Parkinson's disease could be partly attributable to comorbidities. We studied nationwide claims databases and registries. Persons with newly diagnosed Parkinson's disease were identified based on the first Parkinson's disease-related reimbursement claim by a medical specialist. Comorbidities were classified based on the Charlson Comorbidity Index. We studied hospitalization admissions because of falls, psychiatric diseases, pneumonia and urinary tract infections, PD-related hospitalizations-not otherwise specified. The association between comorbidities and time-to-hospitalization was estimated using Cox proportional hazard modelling. To better understand pathways leading to hospitalizations, we performed multiple analyses on causes for hospitalizations. We identified 18 586 people with newly diagnosed Parkinson's disease. The hazard of hospitalization was increased in persons with peptic ulcer disease (HR 2.20, p = 0.009), chronic obstructive pulmonary disease (HR 1.61, p < 0.001), stroke (HR 1.37, p = 0.002) and peripheral vascular disease (HR 1.31, p = 0.02). In the secondary analyses, the hazard of PD-related hospitalizations-not otherwise specified (HR 3.24, p = 0.02) and pneumonia-related hospitalization (HR 2.90, p = 0.03) was increased for those with comorbid peptic ulcer disease. The hazard of fall-related hospitalization (HR 1.57, p = 0.003) and pneumonia-related hospitalization (HR 2.91, p < 0.001) was increased in persons with chronic obstructive pulmonary disease. The hazard of pneumonia-related hospitalization was increased in those with stroke (HR 1.54, p = 0.03) or peripheral vascular disease (HR 1.60, p = 0.02). The population attributable risk of comorbidity was 8.4%. Several comorbidities increase the risk of Parkinson's disease related-hospitalization indicating a need for intervention strategies targeting these comorbid disorders.


Immunofluorescent identification of melanocytes in murine hair follicles.
Immunocytochemical identification of skin cells are difficult due to numerous endogenous autofluorescent components within the cell and the environment. This is particularly evident in hair follicles. This paper reports on a serendipitous modification to an existing method which results in a drastically reduced background fluorescence. Immediately after antigen retrieval, sections exposed to 0.3% hydrogen peroxide in methanol for 30 min at room temperature exhibited low background fluorescence, increased antigenicity and revealed quantifiable numbers of melanocytes. This method is applicable to both human and mouse melanocytes particularly in the hair follicle.


Comprehensive Survey of ChIP-Seq Datasets to Identify Candidate Iron Homeostasis Genes Regulated by Chromatin Modifications.
Vital biochemical reactions including photosynthesis to respiration require iron, which should be tightly regulated. Although increasing evidence reveals the importance of epigenetic regulation in gene expression and signaling, the role of histone modifications and chromatin remodeling in plant iron homeostasis is not well understood. In this study, we surveyed publicly available ChIP-seq datasets of Arabidopsis wild-type and mutants defective in key enzymes of histone modification and chromatin remodeling and compared the deposition of epigenetic marks on loci of genes involved in iron regulation. Based on the analysis, we compiled a comprehensive list of iron homeostasis genes with differential enrichment of various histone modifications. This report will provide a resource for future studies to investigate epigenetic regulatory mechanisms of iron homeostasis in plants.


Comparison of a new tumour marker, CA 19-9, with alpha-fetoprotein and carcinoembryonic antigen in patients with upper gastrointestinal diseases.
Serum CA 19-9 antigen concentrations were measured in 246 patients with benign and histologically confirmed malignant gastrointestinal diseases. The CA 19-9 concentration was above the upper limit of the normal range (0-37 U/ml) in 76% of patients with pancreatic carcinoma, 73% of patients with cholangiocarcinoma, 42% of patients with gastric carcinoma, and 22% of patients with hepatoma. High CA 19-9 concentrations were found mainly in patients with a metastasised cancer, whereas 71% of patients with a localised carcinoma had normal CA 19-9 concentrations. All of the patients with benign gastric diseases had normal CA 19-9 values. Moderately increased concentrations were found in 15-36% of the patients with benign pancreatic, liver, and biliary tract diseases. alpha-fetoprotein was a better marker for hepatomas than CA 19-9. CA 19-9 was better than carcinoembryonic antigen in differentiating malignant from benign diseases. The results indicate that the CA 19-9 assay is not completely specific for cancer but serves as a valuable adjunct, especially in the diagnosis of pancreatic carcinoma.


Translocation 10;18 in a patient with juvenile neuronal ceroid-lipofuscinosis (Batten disease).
We report the first observation of a chromosome abnormality in a patient with typical juvenile ceroid-lipofuscinosis (NCL), who was found to have an apparently balanced translocation between chromosomes 10 and 18 [t(10;18)(q22.1;q21.1)]. Since juvenile NCL was previously mapped to 16p12, this report raises the possibility of heterogeneity in this form of NCL.


Sensitivity to hierarchical relations among affordances in the assembly of asymmetric tools.
Research on affordances typically has focused on the identification and perception of a single affordance. However, in daily life, multiple affordances are available. We investigated potential hierarchical relations among affordances of tools in two experiments. In Experiment 1, participants assembled a tool consisting of an L-shaped object and attached masses so as to perform a particular behavior on a target object-tipping over or sliding it-located at a particular distance from the participant. In Experiment 2, participants performed the same task with additional precision constraints on the tool use task. In both experiments, participants selected longer objects when target objects were farther away and added more mass to tools to be used for tipping than for sliding. The results were compatible with the hypothesis that participants were simultaneously sensitive to affordances for tool assembly (as revealed in their actualization of affordances in tool assembly) and, prospectively, to affordances for tool use (as revealed in relations between assembled tools and the nature of tasks for which they were assembled).


Which surgical decisions should patients participate in and how? Reflections on women's recollections of discussions about variants of hysterectomy.
Current guidance about informed consent suggests patients ought to know about the procedures involved in any treatments they agree to undergo, and have a right to be involved in decisions about their care. However, it is not clear how this guidance is and should be applied to decisions between variant surgical procedures such as abdominal or vaginal hysterectomy. We sent structured questionnaires about information provision and decision-making to 157 women who were scheduled for hysterectomy in north-east Scotland. A purposive sub-sample of 20 women was interviewed in depth post-operatively. 104 women (66%) responded to the questionnaires. 75% reported being told at outpatient clinics what kind of hysterectomy they would have, but fewer than half had been told about the advantages and disadvantages of different kinds. Between 26% and 65% of women thought they had been given too little information about various issues pertaining to different types of hysterectomy. The interview accounts suggested that gynaecologists offered women little opportunity to influence the selection of a surgical procedure. Women did not express a desire for a greater say in this selection, but appreciated being told, or would have liked to know, why particular procedures were recommended for them. There may be circumstances in which it is important for surgeons to tell patients about options they have ruled out in their particular cases. Decisions between alternative surgical procedures are often highly contingent on the dispositions and skills of individual surgeons. They raise practical and ethical issues that have been neglected in recent discussions about patient involvement in decision-making. As policy makers continue to emphasise the importance of choice and patients become increasingly aware of the existence of variant procedures, these issues need careful consideration.


Age-related evolution in color appearance of endometriosis.
Endometriosis presents a large variety of color manifestations, most nonblack, and many easily missed unless meticulous inspection is used to identify small or nonhemorrhagic lesions. An evolution in appearance with age may occur, with resultant spurious effects on conclusions regarding the natural history of the disease. This study confirms and expands the concept of nonhemorrhagic appearances presented by Jansen and Russell.


Protective effects of CG-4203, a novel stable prostacyclin analog, in traumatic shock.
We studied the effects of CG-4203, a novel stable prostacyclin analog, in a severe model of traumatic shock in rats. Traumatic shock was produced by Noble Collip drum trauma and was characterized by marked hypotension, a 4- to 5-fold increase in plasma cathepsin D and myocardial depressant factor activities, and survival time of 95 +/- 15 minutes. Treatment with CG-4203 (100 ng/kg/min) significantly prolonged survival time to 194 +/- 20 min (p less than 0.002). Traumatized rats treated with CG-4203 exhibited significantly lower plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05). Furthermore, the plasma accumulation of myocardial depressant factor (MDF) activity was also significantly blunted in traumatized CG-4203 treated rats when compared with traumatized rats receiving only the vehicle (p less than 0.01). Our results suggest that a combination of membrane stabilizing and anti-proteolytic effects and inhibition of platelet aggregation may mediate the protective effects of CG-4203 in traumatic shock.


Age-dependent decrease in the hepatic uptake and biliary excretion of ouabain in rats.
The biliary excretion of i.v. injected ouabain was examined in male and female Wistar-derived rats in relation to age. The hepatic uptake velocity for ouabain was also determined in isolated hepatocyte preparations obtained from male rats of various ages. Biliary recovery values of ouabain (percent of the dose) were fairly comparable for young male and female rats (3-4 month old). Recovery progressively decreased with age, the first 10-min recoveries at 24 months being about one-third those of respective young values in both sexes. A significant linear relation was demonstrated between the first 10-min recovery (Y, percent of the dose) and rat age (X, month), yielding the relations of Y = 17.75-0.43X for males and Y = 18.99-0.43X for females respectively. Similarly, the initial uptake velocity (Y, nmol/mg/min) for ouabain decreased in a linear fashion with age (X, month), yielding a significant negative correlation (Y = 0.704-0.0021X, r = -0.839, P less than 0.005, N = 21) at an ouabain concentration of 8 microM. Kinetic studies using non-linear regression analysis revealed a significantly lower Vmax value (0.533 +/- 0.041 nmol/mg/min) in old (24-29 months) rats compared to the young (4-4.5 months) value (1.193 +/- 0.105 nmol per mg/min, P less than 0.05), while the affinity constant (Km, microM) did not differ significantly between young and old animals (203.12 +/- 25.42 microM in young rats vs 283.68 +/- 28.90 microM in old rats, mean +/- SE, 0.05 less than P less than 0.1). The results of the present study suggest that the age-dependent decrease in the biliary recovery of i.v. injected ouabain in rats can be largely explained by the decrease with age in the hepatic uptake of ouabain. Furthermore, the results provide further support for our previous thesis that the decrease in the lateral mobility of hepatocyte plasma membrane proteins, as revealed by the fluorescence recovery after photobleaching technique, may play a significant role in the age-dependent decrease in the physiological function(s) of the hepatocyte plasma membrane, such as the hepatobiliary transport of ouabain.


[Characteristics of therapy of acute myocardial infarction in diabetes].
Therapy of acute myocardial infarction (STEMI and NSTEMI) in diabetics does not principally differ from that of non-diabetic patients. Due to the higher mortality in diabetics reperfusion measures, such as direct percutaneous coronary intervention (PCI), should be rapidly performed. An intensive drug treatment with thrombocyte aggregation inhibitors, angiotensin-converting enzyme (ACE) inhibitors and beta-receptor blocking agents must be carried out according to the current guidelines. An important factor is the high risk of renal failure due to the contrast dye administered during PCI in the presence of pre-existing diabetic kidney damage which should be limited to 100 ml if possible. Direct PCI should be limited to the infarcted vessel. After stabilization a comprehensive strategy to cure coronary artery disease, whether with PCI or coronary artery bypass graft (CABG) should be finalized. If severe coronary 3-vessel disease is present, CABG should be favored in diabetic patients. After surviving an acute myocardial infarction differentiated metabolic monitoring is mandatory.


Prognostic Implications of Non-Invasive Vascular Function Tests in High-Risk Atherosclerosis Patients.
The aim of this study was to assess the role of clinically available vascular function tests as predictors of cardiovascular events and decline in kidney function. One hundred and fourteen patients who had at least 2 cardiovascular risk factors were recruited for vascular function assessment including ankle-brachial blood pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and flow-mediated vasodilatation (%FMD). During a median period of 51 months, 35 patients reached the primary endpoint (29 cardiovascular events and 6 cardiac deaths), and 30 patients reached the secondary endpoint (decline in kidney function: defined as a 5% per year decline of estimated glomerular filtration rate). In sequential Cox models, a model on the basis of the Framingham risk score, hemoglobin, and high-sensitivity C-reactive protein (chi-squared, 16.6) was improved by the ABI (chi-squared: 21.5; P=0.047). The baPWV (hazard ratio: 1.42 per 1 SD increase; P=0.025) and the CAVI (hazard ratio: 1.52 per 1 SD increase; P=0.040) were associated with the secondary endpoint. The %FMD was only slightly associated with the primary and secondary endpoints. Both ABI and baPWV are significantly associated with future cardiovascular events in high-risk patients with cardiovascular disease. The predictive capabilities of these parameters are greater than that of other parameters in this cohort.


Graft versus host disease: findings on plain abdominal radiography.
The plain abdominal radiographs of 31 patients who had undergone bone marrow transplantation were reviewed retrospectively to determine the radiological abnormalities caused by intestinal graft versus host disease. Abnormal radiological signs were observed in 95% of patients with acute graft versus host disease but none were sufficiently characteristic to differentiate between patients with and without acute intestinal graft versus host disease.


The varicella-zoster virus immediate-early 63 protein affects chromatin-controlled gene transcription in a cell-type dependent manner.
Varicella Zoster Virus Immediate Early 63 protein (IE63) has been shown to be essential for VZV replication, and critical for latency establishment. The activity of the protein as a transcriptional regulator is not fully clear yet. Using transient transfection assays, IE63 has been shown to repress viral and cellular promoters containing typical TATA boxes by interacting with general transcription factors. In this paper, IE63 regulation properties on endogenous gene expression were evaluated using an oligonucleotide-based micro-array approach. We found that IE63 modulates the transcription of only a few genes in HeLa cells including genes implicated in transcription or immunity. Furthermore, we showed that this effect is mediated by a modification of RNA POL II binding on the promoters tested and that IE63 phosphorylation was essential for these effects. In MeWo cells, the number of genes whose transcription was modified by IE63 was somewhat higher, including genes implicated in signal transduction, transcription, immunity, and heat-shock signalling. While IE63 did not modify the basal expression of several NF-kappaB dependent genes such as IL-8, ICAM-1, and IkappaBalpha, it modulates transcription of these genes upon TNFalpha induction. This effect was obviously correlated with the amount of p65 binding to the promoter of these genes and with histone H3 acetylation and HDAC-3 removal. While IE63 only affected transcription of a small number of cellular genes, it interfered with the TNF-inducibility of several NF-kappaB dependent genes by the accelerated resynthesis of the inhibitor IkappaBalpha.


An exploratory study of the concerns of mature access to nursing students and the coping strategies used to manage these adverse experiences.
The inter-connections between educational, family and social spheres of life are integral to the experiences and outcomes of mature student participation in education. This relationship highlights the need to understand the educational experience in the context of the life of the mature student. Mature nursing students have been shown to experience many difficulties during their course. These problems include childcare, relationship and financial difficulties. What is not well documented are the problems and coping strategies of future nursing students who are undertaking Access to Nursing courses and whether these mirror those found in mature nursing students. This small scale exploratory study investigated the course-related problems and coping strategies of mature students undertaking an access to nursing in a Further Education College. This study is one part of a larger programme of research investigating mature students in nursing. In-depth interviews were conducted on mature students and data were analysed using content analysis methods. Content analysis revealed particular concerns regarding the obstacles faced by mature nursing students. In particular the findings suggested that financial difficulties and re-entry into tertiary education were the prominent concerns for these individuals. The coping mechanisms identified to overcome these problems included; support networks, prioritizing and organising, and positive expectations and attitudes for the future. Understanding how students cope with their difficulties will provide the building block for future intervention strategies designed to minimise problems and increase retention rates. Further longitudinal research is required on the long term and cumulative nature of stress and coping in this group from access to post-qualification.


Three-dimensional structure of the shell plate assembly of the chiton Tonicella marmorea and its biomechanical consequences.
This study investigates the three-dimensional structure of the eight plate exoskeletal (shell) assembly of the chiton Tonicella marmorea. X-ray micro-computed tomography and 3D printing elucidate the mechanism of conformational change from a passive (slightly curved, attached to surface) to a defensive (rolled, detached from surface) state of the plate assembly. The passive and defensive conformations exhibited differences in longitudinal curvature index (0.43 vs. 0.70), average plate-to-plate overlap (∼62% vs. ∼48%), cross-sectional overlap heterogeneity (60-82.5% vs. 0-90%, fourth plate), and plate-to-plate separation distance (100% increase in normalized separation distance between plates 4 and 5), respectively. The plate-to-plate interconnections consist of two rigid plates joined by a compliant, actuating muscle, analogous to a geometrically structured shear lap joint. This work provides an understanding of how T. marmorea achieves the balance between mobility and protection. In the passive state, the morphometry of the plates and plate-to-plate interconnections results in an approximately continuous curvature and constant armor thickness, resulting in limited mobility but maximum protection. In the defensive state, the underlying soft tissues gain protection and the chiton gains mobility through tidal flow, but regions of vulnerability open dorsally, due to the increase in plate-to-plate separation and decrease in plate-to-plate overlap. Lastly, experiments using optical and scanning electron microscopy, mercury porosimetry, and Fourier-transform infrared spectroscopy explore the microstructure and spatial distribution of the six layers within the intermediate plates, the role of multilayering in resisting predatory attacks, and the detection of chitin as a major component of the intra-plate organic matrix and girdle.


A suggested terminology for populations of coccidia (Eimeriorina), particularly of the genus Eimeria (Protozoa: Apicomplexa).
A short list of terms has been compiled which provides for the discussion of variation of coccidia of the genus Eimeria at infrasubspecific levels. Based upon this list, guidelines are given for the designation of strains and lines.


Seed priming with plant growth-promoting bacteria (PGPB) improves growth and water stress tolerance of Secale montanum.
Abiotic and biotic stresses are major global threats to food security in the 21st century. Application of plant growth-promoting bacteria (PGPB) in rangeland plants is the only possible alternative that supports plant growth and development to combat environmental stress and successfully restoring rangelands. PGPBs were also found to be a potential substitute for chemical fertilizers and pesticides. The challenge is to determine which biofertilizers can be used for Secale montanum in normal and under water stress conditions. We sought to determine the benefits of PGPB for S. montanum under water stress conditions in terms of seedling growth traits, growth indicators, and nutrient uptake in the research greenhouse. Therefore, a completely randomized factorial design was conducted with two treatments of PGPB inoculation, including the control (no PGPB inoculation), PGPBs Bacillus cereus, Pseudomonas aeruginosa, Azospirillum lipoferm, and Azotobacter chroococcum, and water stress in the research greenhouse. Overall, the results of the current study showed that water stress greatly reduced the above-ground fresh weight of above-ground plant parts and the nitrogen and potassium content of S. montanum. The present study confirms the positive effects of PGPB on fresh and dry weights of above- and below-ground parts and seedling, vigor index, quality index, and nitrogen and potassium content of S. montanum, except for below-ground parts length, compared with the controls, which shows that PGPB usually improves some indicators of plant growth and development. We suggest that restoration of S. montanum seed inoculation with PGPB should be supported in degraded rangelands and marginal drylands in low rainfall years, which may cause water scarcity and consequently water stress in arid and semi-arid regions.


Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.
Two plasmid-encoded dihydrofolate reductase (DHFR) isoforms, DfrA1 and DfrA5, that give rise to high levels of resistance in Gram-negative bacteria were structurally and biochemically characterized to reveal the mechanism of TMP resistance and to support phylogenic groupings for drug development against antibiotic resistant pathogens. Preliminary screening of novel antifolates revealed related chemotypes that showed high levels of inhibitory potency against Escherichia coli chromosomal DHFR (EcDHFR), DfrA1, and DfrA5. Kinetics and biophysical analysis, coupled with crystal structures of trimethoprim bound to EcDHFR, DfrA1 and DfrA5, and two propargyl-linked antifolates (PLA) complexed with EcDHFR, DfrA1 and DfrA5, were determined to define structural features of the substrate binding pocket and guide synthesis of pan-DHFR inhibitors.


Redox Potential of the Oxygen-Evolving Complex in the Electron Transfer Cascade of Photosystem II.
In photosystem II (PSII), water oxidation occurs in the Mn4CaO5 cluster with the release of electrons via the redox-active tyrosine (TyrZ) to the reaction-center chlorophylls (PD1/PD2). Using a quantum mechanical/molecular mechanical approach, we report the redox potentials (Em) of these cofactors in the PSII protein environment. The Em values suggest that the Mn4CaO5 cluster, TyrZ, and PD1/PD2 form a downhill electron transfer pathway. Em for the first oxidation step, Em(S0/S1), is uniquely low (730 mV) and is ∼100 mV lower than that for the second oxidation step, Em(S1/S2) (830 mV) only when the O4 site of the Mn4CaO5 cluster is protonated in S0. The O4-water chain, which directly forms a low-barrier H-bond with the Mn4CaO5 cluster and mediates proton-coupled electron transfer in the S0 to S1 transition, explains why the second lowest oxidation state, S1, is the most stable and S0 is converted to S1 even in the dark.


Variation in fruit size and susceptibility to seed predation among and within populations of the cocklebur, Xanthium strumarium L.
Burr size is the major factor affecting variation in the intensity of predation by two species of insect on the seeds of the cocklebur, Xanthium strumarium. Mean burr size varied among 10 adjacent local populations studied over three years, as did intensity of seed predation. Seed predation was more intense in populations with low mean burr length and declined linearly with increasing burr length under field and experimental conditions. Seed predation thus is a selective factor influencing the evolution of both burr size and correlated protective characteristics such as burr spine length and wall thickness. As in some other plants, morphological rather than chemical features appear to pose the major barrier to attack by host-specific seed predators. The advantage of more highly developed tissues protecting seeds may occur at the expense of total seed production.


Cortical stimulation mapping in a patient with foreign accent syndrome: case report.
Foreign accent syndrome is a rare language output disorder characterized by changes in various speech features leading to a perceived foreign accent. There are few cases reported in the literature. Due to the rarity of this condition, information regarding the functional neuroanatomy of FAS is lacking. We present the case of a 60-year-old woman with a left anterior parietal lobe breast carcinoma metastasis who developed foreign accent syndrome (FAS). This patient presented to the emergency room with right upper extremity weakness, facial weakness, and altered speech. Neurological examination revealed the patient's speech to be dysarthric and accented, but otherwise appropriate. Brain magnetic resonance (MR) imaging demonstrated a 3cm x 3cm x 3cm lesion in the left anterior parietal lobe. The patient underwent craniotomy for resection of the mass. Intra-operative cortical stimulation mapping demonstrated the lesion to be confined to somatosensory cortex and gross total resection was performed. There were no new neurological deficits post-operatively. To our knowledge, this is a unique case of FAS due to breast carcinoma metastasis. Additionally, this is the first documented case of electrocortical function stimulation mapping of language and Rolandic cortex in a patient with FAS.


A new species of Amusurgus (Usgmona) Furukawa from China (Orthoptera: Gryllidae: Trigonidiinae).
Amusurgus (Usgmona) excavatus Liu, Shi et Zhou, sp. nov. (China, Fujian) is described and illustrated with the male genitalia. Photos of habitus and ecological habitat are also included.


Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR.
LmrR is a multidrug binding transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical transcriptional repressors. Here, we found that the transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the repressor on the genomic DNA via nonspecific DNA adsorption.


Differences in the prevention and incidence of maternal venous thromboembolism according to the type of institution in Japan in 2018: A sub-analysis of national questionnaire surveillance.
To clarify the relation between institutions capacity to manage venous thromboembolism (VTE) and its incidence in pregnant women throughout Japan. Among the 2299 institutions that received the surveillance questionnaire, 666 (29.0%) responded, after which data from 295 961 women who gave birth at those institutions in 2018 were analyzed. Incidences and characteristics of antepartum and postpartum VTE in perinatal medical centers (PMCs), general hospital with obstetric facilities (GHs), and maternal clinic with beds (MCs) were then determined. The frequencies at which routine antepartum and postpartum thromboprophylaxis for high-risk women and routine transport to the more advanced medical institutions upon antepartum and postpartum pulmonary thromboembolism (PE) onset were performed differed significantly according to types of institution (PMCs: 92.4%, 96.2%, 23.8%, and 21.2%; GHs: 76.5%, 80.6%, 58.8%, and 54.1%; MCs: 29.2%, 41.7%, 96.5%, and 96.2%, respectively). Among the 295 961 women analyzed, 243 (0.082%) developed VTE. Incidences of antepartum VTE differed significantly according to institution types (PMCs: 106.4, GHs: 51.6, and MCs: 11.6 per 100 000 women). PMCs and GHs had significantly higher incidences of postpartum VTE compared to MCs (43.3 and 26.6 vs. 10.7 per 100 000 women, respectively), although PMCs and GHs had similar incidences. Among the four women (1.4%) who died due to VTE, three and one developed a PE in a PMC and MC, respectively. PMCs had higher incidences of VTE despite their more frequent performance of thromboprophylaxis. Several pregnant women with higher risk of VTE transported to PMCs.


Scientific and clinical aspects of radiotherapy in the relief of bone pain.
Radiotherapy is highly effective in relieving metastatic bone pain. The mechanism of action remains unclear, and tumour shrinkage may be relatively unimportant in producing analgesia. Various techniques of localized external beam therapy are in use with no consistent advantage seen for either high doses or multiple fractions. For scattered painful metastases, wide-field hemibody irradiation or the systemic administration of radioisotopes are effective but may be associated with greater toxicity than localized irradiation.


[Short-term versus long-term antimicrobial prophylaxis in abdominal surgery: a multicenter open randomized comparative trial].
To evaluate the outcome of short-term antimicrobial prophylaxis versus long-term in surgical site infection (SSI). 731 patients undergoing abdominal operation from 15 hospitals were randomly divided into 2 groups. 358 patients were enrolled in the short-term group (24 h), and 373 patients in the long-term group (72 h). There was no difference between the 2 groups with regard to age, sex, and types operation. Netilmicin was used alone or in combination with metronidazole. The rates of SSI in the short-term and long-term groups were 0.84% and 2.68% (P > 0.05), respectively. The results demonstrated that the short-term antimicrobial agents prophylaxis is effective in the prevention of post-operative SSI. The long-term one act does not better than the short-term in terms of rationality and pharmacoeconomics.


Maternal educational practices and mental health disorders of school-age children.
To investigate the association between emotional and behavioral difficulties in schoolchildren and maternal educational practices. Participants and Setting: 631 mother-child pairs were evaluated in a poor urban district in Recife, northeastern Brazil. Cross-sectional study carried out between 2013 and 2014. It integrates a prospective cohort study designed to investigate the consequences of intimate partner violence that occurred during pregnancy, postpartum, and seven years after birth for the physical and mental health of women and their children. Maternal educational practices were assessed using the Parent-Child Conflict Tactics Scale (CTSPC - mother-child version) and the child's behavioral and emotional disorders through the Strengths and Difficulties Questionnaire (SDQ) mother-version. The association was estimated through crude and adjusted prevalence ratios, using Poisson regression considering the 95% confidence interval. The prevalence of violent maternal educational practices was 91.8% (572/631) being 89.7% (566/631) of psychological aggression and 75.6% of physical aggression, subdivided into corporal punishment (73.5%), physical maltreatment (35.8%) and severe physical maltreatment (1.7%). Corporal punishment (Adjusted PR 1.5; CI 95%: 1.1-2.1; p = 0.010) and severe physical maltreatment (Adjusted PR 1.9; CI 95%: 1.3-2.8; p = 0.002) were associated with emotional and behavioral difficulties in schoolchildren. The high prevalence of violent maternal educational practices, especially corporal punishment and severe physical maltreatment is associated with emotional and behavioral disorders in children. Therefore, it is necessary to interventions that promote parental support and effective use of non-violent discipline in conducting the educational process to establish healthier family relationships and to prevent/mitigate the impact of emotional and behavioral problems in children.


The presbyopic add. I. Magnitude and distribution in a historical context.
The presbyopic addition or 'add' is the (binocular) spherical positive power supplement superimposed on any distance refractive correction to counter near vision difficulties associated with the physiological age-related loss of accommodation and consequent recession of the near point: its necessity is first encountered in middle age. The continuous (linear) ascending trend in near lens power versus increasing age advocated since the seventeenth century is at odds with the twentieth-century clinical observation that there is a deceleration in add requirement beyond an individual's mid-fifties. It is shown here that this difference is reconciled--in broadly qualitative terms if not in magnitude-when typical clinical near addition data are superimposed on the accepted distance hypermetropic refractive base recorded from early middle age onwards: a continuous rising function is produced spanning most of the three decades beyond 40 years of age. This result is considered in the context of the age markings found on certain eighteenth-century antique near vision glasses and the recommendations attached to the self-selection of ready-made reading glasses in the late twentieth century.


Kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data.
The identification of differentially expressed genes (DEGs) from transcriptomic datasets is a major avenue of research across diverse disciplines. However, current bioinformatic tools do not support covariance matrices in DEG modeling. Here, we introduce kimma (Kinship In Mixed Model Analysis), an open-source R package for flexible linear mixed effects modeling including covariates, weights, random effects, covariance matrices, and fit metrics. In simulated datasets, kimma detects DEGs with similar specificity, sensitivity, and computational time as limma unpaired and dream paired models. Unlike other software, kimma supports covariance matrices as well as fit metrics like Akaike information criterion (AIC). Utilizing genetic kinship covariance, kimma revealed that kinship impacts model fit and DEG detection in a related cohort. Thus, kimma equals or outcompetes current DEG pipelines in sensitivity, computational time, and model complexity. Kimma is freely available on GitHub https://github.com/BIGslu/kimma with an instructional vignette at https://bigslu.github.io/kimma_vignette/kimma_vignette.html.


De-escalation of P2Y12 Inhibitor Use After Percutaneous Coronary Intervention and Acute Coronary Syndromes.
De-escalation from potent platelet P2Y12 inhibitors to clopidogrel is common. Despite having a clinical rationale, non-bleeding-related de-escalation when a lateral change between potent agents is an option may put patients at increased ischemic risk. We set out to define the scope of P2Y12 inhibitor de-escalation in a large clinical registry and evaluate the potential impact of non-bleeding-related de-escalation on clinical outcomes. : A retrospective cohort study was performed on consecutive patients in the Cardiovascular Percutaneous Intervention Trial (CAPITAL) registry to identify those who underwent a switch in therapy within 1 year of percutaneous coronary intervention. The de-escalations were categorized as bleeding-related or non-bleeding-related. The primary outcome was major adverse cardiovascular events, a composite of death, myocardial infarction, and stroke. Secondary outcomes included individual components of major adverse cardiovascular events and a safety endpoint of thrombolysis in myocardial infarction bleeding. Of 1854 patients, 209 (11.3%) underwent de-escalation: 24.9% of cases were bleeding-related, 37.8% were non-bleeding-related, and 37.3% were for unknown reasons. All patients with non-bleeding-related de-escalation were switched from ticagrelor to clopidogrel. The primary outcome occurred in 14 (6.7%) patients, of which 50% underwent non-bleeding-related de-escalation (P = 0.430). Among those with non-bleeding-related de-escalation, 7.6% were hospitalized for myocardial infarction, compared to 1.9% and 3.8% among those with a bleeding-related and unknown rationale, respectively (P = 0.293). De-escalation, particularly non-bleeding-related de-escalation, of P2Y12 inhibitors is common. A substantial proportion of such de-escalation may be avoidable. Given the potential risk of ischemic complications, strategies should be considered to encourage both the upfront use of potent P2Y12 inhibitors and alternative strategies to de-escalation.


Vaccination in the Elderly and IBD.
Significant gaps in knowledge and utilization of vaccinations exist among practitioners providing care for patients with IBD. This review is intended to update the reader on best practices for vaccination within the IBD population with a specific focus on the elderly. Advances in IBD therapeutics have recently increased the number of immunosuppressive therapies available to practitioners. Differences in mechanisms of action of these medications have led to differential implications pertaining to vaccination strategies. Additionally, new vaccines, including the recombinant zoster vaccine, have recently become available for the use in the IBD population. Given the prominent role the IBD provider plays in the management of patients with IBD, a clear understanding of best practices is essential. This review provides a framework for the integration of optimal vaccination strategies for practitioners caring for adult and elderly patients with IBD.


Estrogen receptor beta and matrix metalloproteinase 1 are coexpressed in uterine endometrium and endometriotic lesions of patients with endometriosis.
To evaluate the local matrix metalloproteinase 1 (MMP-1), estrogen receptor (ER) alpha, and ERbeta protein expression in eutopic and dystopic tissue from patients with endometriosis and to compare the endometrial expression pattern in women with and without endometriosis. Immunohistochemical analysis of MMP-1, ERalpha, and ERbeta in paired samples of uterine and endometriotic endometrium from cycling women with endometriosis and in endometrial tissue from 37 healthy women. Research laboratory at a medical school. Thirty-seven matched samples from endometriotic and corresponding endometrial biopsies obtained during the proliferative and secretory phase. Thirty-seven endometrial biopsies obtained from healthy women during comparable cycle phases. Sampling of endometrial and endometriotic tissue. Matrix metalloproteinase 1, ERalpha, and ERbeta protein expression in paraffin-embedded tissue biopsies was measured by IHC. In patients with endometriosis, epithelial and stromal cells from endometriotic lesions both express significantly higher levels of MMP-1 and lower levels of ERalpha than corresponding cells in uterine endometrium. Endometriotic epithelium also expresses higher levels of ERbeta than of ERalpha. In both endometrial glands and corresponding endometriotic epithelium, the distribution of MMP-1 is correlated with ERbeta. No significant differences in endometrial ERalpha, ERbeta, or MMP-1 expression could, however, be detected when patients with endometriosis and healthy controls were compared. We have shown that MMP-1 and ERbeta are coexpressed and up-regulated in endometriotic lesions, whereas local ERalpha expression is down-regulated. The altered ERbeta/ERalpha ratio in endometriotic glands suggests that estrogenic effects on MMP-1 are primarily mediated via ERbeta, and the local control of MMP-1 in eutopic endometrium is not different from that observed in healthy cycling women.


[Training for Roma health advocacy: a case study of Torreblanca, Seville].
The objective of this study is to build advocacy capacity among a group of gipsy Roma neighbours living in contexts of risk of social exclusion. A Community Based Participatory Action Research design was used, in which 4 members of the community participated in the process of collecting evidence by photo-voice, analysing it using the ReACT method and disseminating the results. A total of 96 pieces of evidence were collected and analysed for qualitative data analysis. These were categorised according to (a) the type of unhealthy conditions and (b) the area of the neighbourhood where they were located. The subsequent thematic grouping made it possible to identify the causes: (a) the abandonment of public services; (b) discrimination; and (c) the lack of Roma presence in community spaces. The consequences identified were (a) mental and physical health problems and (b) the normalisation of undignified living conditions. The plan was designed to advocate for the presence of Roma in community spaces. Our study highlighted the relevance of the photo-voice to transcend the biomedical perspective and develop advocacy actions based on the knowledge created by the community. Future research should look more deeply into the impact of health advocacy on reducing inequalities and consider the importance of involving researchers, public health professionals and the community in addressing it.


Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series.
The management of "aggressive" and "highly-active" relapsing-remitting multiple sclerosis remains problematic. Although a number of highly efficacious agents are currently available, the optimal timing of their use and the balancing between efficacy and immediate and long-term consequences are still a matter of conjecture. We describe the clinical, radiological and immunological profile of three multiple sclerosis patients with persistent clinical and radiological disease activity under fingolimod treatment. After fingolimod cessation patients demonstrated severe disease exacerbation and were successfully treated with alemtuzumab. All patients experienced significant improvement after the administration of alemtuzumab and achieved no evidence of disease activity status that persisted after a median of 19 months of follow-up (range: 17-25 months). Confirmed disability improvement was achieved in all cases. Quantitative MRI data demonstrated a reduction of the T2 lesion load in 2 out of 3 patients and complete abrogation of inflammatory activity in all patients after the administration of alemtuzumab. Α patient presented a previously unreported, persistent lymphocytosis after alemtuzumab administration, that was not associated with infectious, lymphoproliferative or autoimmune diseases and had no apparent clinical implications. Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod.


Pathogenic variants of the GNAS gene introduce an abnormal amino acid sequence in the β6 strand/α5 helix of Gsα, causing pseudohypoparathyroidism type 1A and pseudopseudohypoparathyroidism in two unrelated Japanese families.
Pseudohypoparathyroidism 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by loss-of-function variants of GNAS, which encodes Gsα. We present two unrelated Japanese families with PHP1A and PPHP harboring unreported pathogenic variants of GNAS (c.1141delG, p.Asp381Thrfs*23 and c.1117delC, p.Arg373Alafs*31). These variants introduce abnormal amino acids in the β6 strand/α5 helix of Gsα, which interact with G protein coupling receptor (GPCR). We conclude that these variants alter the association of Gsα with GPCR and cause PHP1A or PPHP.


Cost Effectiveness of Universal Screening for Hepatitis C Virus Infection in the Era of Direct-Acting, Pangenotypic Treatment Regimens.
Most persons infected with hepatitis C virus (HCV) in the United States were born from 1945 through 1965; testing is recommended for this cohort. However, HCV incidence is increasing among younger persons in many parts of the country and treatment is recommended for all adults with HCV infection. We aimed to estimate the cost effectiveness of universal 1-time screening for HCV infection in all adults living in the United States and to determine the prevalence of HCV antibody above which HCV testing is cost effective. We developed a Markov state transition model to estimate the effects of universal 1-time screening of adults 18 years or older in the United States, compared with the current guideline-based strategy of screening adults born from 1945 through 1965. We compared potential outcomes of 1-time universal screening of adults or birth cohort screening followed by antiviral treatment of those with HCV infection vs no screening. We measured effectiveness with quality-adjusted life-years (QALY), and costs with 2017 US dollars. Based on our model, universal 1-time screening of US residents with a general population prevalence of HCV antibody greater than 0.07% cost less than $50,000/QALY compared with a strategy of no screening. Compared with 1-time birth cohort screening, universal 1-time screening and treatment cost $11,378/QALY gained. Universal screening was cost effective compared with birth cohort screening when the prevalence of HCV antibody positivity was greater than 0.07% among adults not in the cohort born from 1945 through 1965. Using a Markov state transition model, we found a strategy of universal 1-time screening for chronic HCV infection to be cost effective compared with either no screening or birth cohort-based screening alone.


The Association between Tear Film Thickness as Measured with OCT and Symptoms and Signs of Dry Eye Disease: A Pooled Analysis of 6 Clinical Trials.
To determine the association between tear film thickness (TFT) as measured with ultra-high resolution optical coherence tomography (UHR-OCT) and signs and symptoms of dry eye disease (DED). A total of 450 eyes from 225 patients with DED from six different randomized clinical trials were included in this pooled analysis. In all subjects, TFT was measured with a custom-built UHR-OCT system. Symptoms of DED were quantified using a standardized Ocular Surface Disease Index (OSD)I questionnaire and clinical signs including tear film break up time (TFBUT) and Schirmer I test were assessed. Associations of the average TFT with OSDI, TFBUT, and Schirmer I test were calculated using a linear regression analysis. The average TFT of the included sample (mean age, 45.0 ± 13.3 years; 65% female) was 4.2 ± 0.5 µm and the OSDI 36.2 ± 10.4. A significant negative correlation was found between TFT and OSDI (r = -0.36 to -0.31; p < 0.001). Tear break up time and Schirmer I test were not correlated with OSDI. Significant albeit weak correlations were found between TFT and TFBUT (r = 0.17 to 0.25; p < 0.01) as well as Schirmer I (r = 0.36 to 0.37; p < 0.001). Subgroup analysis revealed that the correlation was stronger in the subjects with abnormal Schirmer I (<15 mm; r = 0.50 to 0.54; p < 0.001). The present study demonstrates an objective measurement of TFT using a novel OCT approach for DED that correlates with symptoms and signs of DED. Our data are consistent with the idea that TFT represents the aqueous-deficient component of DED.


General practitioners versus other physicians in the quality of primary care: a cross-sectional study in Guangdong Province, China.
The primary care in China can be provided by general practitioners (GPs) and other physicians (non-GPs). However, China's general practice system has never been really established. Chinese patients tend to consider the quality of primary care provided by GPs much lower than that of non-GPs. Besides, many GPs presently prefer leaving their own positions and seeking better development in big hospitals, which has made the already weak GP system weaker. Yet, few studies have specially compared the quality of primary care provided by Chinese GPs and other physicians and no studies have explored the independent predictors of Chinese GPs' intentions to stay on their current job. In this study, we aimed to compare the quality of primary care offered by GPs with non-GPs and to explore the independent predictors of GPs' future work intentions. This cross-sectional study applied multi-stage random cluster sampling methodology. The data were collected from November 2013 to September 2014 in Guangdong Province. In total, 401 effective questionnaires were selected from the physicians. Quality of primary care was assessed using the Primary Care Assessment Tool (PCAT) Provider Part, representing six primary care domains: ongoing care, coordination (i.e., referrals and information systems), comprehensiveness (i.e., service available and service provided), family-centeredness, community orientation and cultural competence. Of 401 participating physicians, 163 (40.6 %) were GPs. The total PCAT score was 26.32 ± 2.24 which was the sum score of the six domains and represent the quality of primary care. GPs achieved significantly different total scores and scores on three individual scales: comprehensiveness: service available, comprehensiveness: service provided and community orientation. Multiple linear regressions revealed GPs had a higher total score and scores for comprehensiveness: service provided and community orientation after adjusting for sociodemographic characteristics. In addition, GPs were more likely to intend to stay in their current job in the coming year, and this was associated with their educational level. Our findings showed that GPs reported higher quality of primary care than other physicians, and were more inclined to stay in their current job. With more comprehensive care and community orientation provided by GPs, residents could reach basic medical cares and needn't to crowd into larger hospitals.


Evaluation of the MicroFoss system for the detection of Listeria species in environmental samples.
The MicroFoss system was evaluated for its ability to detect Listeria species in environmental samples. The sensitivity and specificity of the MicroFoss were determined in relation to a standard culture method for Listeria detection. The sensitivities of both the MicroFoss and standard culture methods were similar (88.4%-MicroFoss, 90.7%-Culture) based on the total number of positive results obtained by both methods. The MicroFoss system detected Listeria spp. in 12 samples, which were not detected by culture, and the culture method detected Listeria spp. in 15 samples, which were not detected by the MicroFoss method. This was likely due to uneven distribution of low levels of Listeria organisms in the split sponge samples used to assess the performance of these test methods. The specificity value determined for the MicroFoss system was 92.7%. The majority of microbes causing false positive results in the MicroFoss system were Bacillus species, which were readily distinguishable from Listeria species by a simple Gram stain and morphological features. Listeria monocytogenes (89.4%-MicroFoss, 88.0%-Culture) and Listeria innocua (8.8%-MicroFoss, 7.7%-Culture) were the most common isolates of Listeria detected by the two test methods, with L. monocytogenes being the most predominant isolate detected. The highly comparable results and rapid nature of the MicroFoss system demonstrate its effectiveness as a detection system for species of Listeria in environmental samples. The fact that the sensitivity of the MicroFoss system was similar to that of the culture method and the Listeria results were obtained within 48 h of testing, support the use of the MicroFoss as an alternative rapid method for screening large numbers of environmental samples for Listeria spp.


Inappropriate Implantable Cardioverter-Defibrillation Detection of Ventricular Fibrillation Induced by Transcutaneous Electrical Nerve Stimulation.
We describe 2 cases of electromagnetic interference (EMI) with a transcutaneous electrical nerve stimulation (TENS) device in patients with implantable cardioverter-defibrillators (ICDs). Both patients were using DR-HO'S® pain therapy system for chronic back pain (VGH Solutions Inc., Markham, ON, Canada). In both cases, EMI was inappropriately labeled as ventricular fibrillation. In the first case, the noise detected was of a short duration and did not fulfill the discriminator criteria to deliver ICD therapy. In the second case, inappropriate anti-tachycardia pacing and shocks resulting from EMI were delivered. Both patients were advised not to use TENS devices at home. Increased awareness of EMI resulting in inappropriate ICD therapies using these devices is needed.


N-(5-dimethylaminonaphthalene-1-sulfonyl)-3-aminobenzene boronic acid as an active-site-directed fluorescent probe of lipoprotein lipase.
Resonance energy transfer was used to monitor the interaction of an active-site-directed fluorescent inhibitor, N-(5-dimethylaminonaphthalene-1-sulfonyl)-3-aminobenzene boronic acid, and lipoprotein lipase (EC 184.108.40.206). The binding of this probe to the active site of lipoprotein lipase had an association constant, Ka, of 1.1 X 10(6) M-1, indicating a strong interaction. The binding was displaced competitively by benzene boronic acid. The method described provides a sensitive procedure to probe the active site of lipoprotein lipase.


Grb2 negatively regulates epidermal growth factor-induced phospholipase C-gamma1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-gamma1.
Phospholipase C-gamma1 (PLC-gamma1) plays pivotal roles in cellular growth and proliferation. Upon the stimulation of growth factors and hormones, PLC-gamma1 is rapidly phosphorylated at three known sites; Tyr771, Tyr783 and Tyr1254 and its enzymatic activity is up-regulated. In this study, we demonstrate for the first time that Grb2, an adaptor protein, specifically interacts with tyrosine-phosphorylated PLC-gamma1 at Tyr783. The association of Grb2 with PLC-gamma1 was induced by the treatment with epidermal growth factor (EGF). Replacement of Tyr783 with Phe completely blocked EGF-induced interaction of PLC-gamma1 with Grb2, indicating that tyrosine phosphorylation of PLC-gamma1 at Tyr783 is essential for the interaction with Grb2. Interestingly, the depletion of Grb2 from HEK-293 cells by RNA interference significantly enhanced increased EGF-induced PLC-gamma1 enzymatic activity and mobilization of the intracellular Ca2+, while it did not affect EGF-induced tyrosine phosphorylation of PLC-gamma1. Furthermore, overexpression of Grb2 inhibited PLC-gamma1 enzymatic activity. Taken together, these results suggest Grb2, in addition to its key function in signaling through Ras, may have a negatively regulatory role on EGF-induced PLC-gamma1 activation.


Evaluating variation in perioperative red blood cell transfusion for patients undergoing elective gastrointestinal cancer surgery.
Patients undergoing gastrointestinal cancer surgery often receive packed red blood cell transfusions. Understanding practice variation is critical to support efforts working toward responsible transfusion use. We measured the extent and importance of variation in perioperative packed red blood cell transfusion use across physicians and hospitals among gastrointestinal cancer surgery patients. We identified patients who underwent elective gastrointestinal cancer resection between 2007 and 2019 using linked administrative health data sets in Ontario, Canada. We used funnel plots to describe variation in transfusion use, adjusted for patient case mix. Hierarchical regression models quantified patient-level, between-physician, and between-hospital variation in transfusion use with R2 measures, variance partition coefficients, and median odds ratios. Of 59,964 included patients (median age 69 years; 43.2% female; 75.8% colorectal resections), 18.0% received perioperative packed red blood cell transfusions. Funnel plots showed variation in transfusion use among physicians and hospitals. Patient characteristics, such as age, comorbidity, and procedure type, combined to explain 12.8% of the variation. After adjusting for case mix, systematic between-physician and between-hospital differences were responsible for 2.8% and 2.1% of the variation, respectively. This translated to an approximately 30% difference in the odds of transfusion for 2 similar patients treated by distinct physicians (median odds ratio: 1.35, 95% confidence interval 1.30-1.40) and hospitals (median odds ratio: 1.30, 95% confidence interval 1.23-1.42). We observed comparable effects across procedure-type subgroups. Transfusion provision is highly driven by patient factors. Yet the impact of the treating physician and hospital on variation relative to other factors is important and reflects opportunities to target modifiable processes of care to standardize perioperative packed red blood cell transfusion practice.


Staged Carotid Artery Stenting for Prevention of Hyperperfusion-Induced Intracerebral Hemorrhage in Patients with Very High-Grade Carotid Stenosis and Poor Collateral Compensation.
Hyperperfusion-induced intracerebral hemorrhage (HICH) is a relatively rare but potentially devastating event after carotid artery stenting (CAS). Staged angioplasty (SAP), a 2-stage form of CAS, has been shown to be effective for preventing cerebral hyperperfusion syndrome. The aim of our retrospective single-center study was to investigate the safety and efficacy of SAP to prevent HICH in patients with very severe carotid stenosis (90%-99%) and poor collateral compensation. Between November 2011 and August 2018, 153 patients presented with severe symptomatic carotid artery stenosis ≥90%; 96 were scheduled to undergo regular CAS, and 57 were scheduled for SAP. High risk of HICH were identified based on severe stenosis degree (90%-99%) and poor collateral compensation, which were determined using digital subtraction angiography and qualitative computed tomography perfusion. Patients' clinical data, procedural details, and occurrence of HICH were compared between regular CAS and SAP groups. Of 57 patients scheduled for SAP, 3 were switched to regular CAS because of intraoperative dissection. The median interval between stages I and II was 8 days (IQR: 4-20 days). One patient who was switched to regular CAS experienced HICH. HICH occurred in 1 patient (1.75%; 1/57) in the SAP group and 12 patients (12.5%; 12/96) in the regular CAS group (odds ratio 0.117, 95% confidence interval 0.014-0.990, P = 0.049). Multivariate analysis showed that SAP was negatively related to cerebral hyperperfusion syndrome (odds ratio 0.117; 95% confidence interval 0.014-0.990; P = 0.049). SAP is an effective treatment for avoiding HICH in patients with carotid preocclusive stenosis (90%-99%) and poor collateral compensation.


LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma.
Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan-Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62-87%] versus 60% [95% CI: 32-80%], p = 0.062) and EFS (74% [95% CI: 58-85%] versus 43% [95% CI: 15-69%], p = 0.070) and LI with OS (71% [95% CI: 57-81%] versus 56% [95% CI: 26-78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.


[Evaluation of lymphocyte cooperative interaction with neutrophils by the stimulation of lymphokine production in erysipelatous inflammation].
In erysipelatous inflammation lymphocytes were found to secrete lymphokine, both spontaneously and in response to in vitro stimulation with streptococcal allergen. The secreted lymphokine enhanced the oxygen-dependent metabolism of neutrophils. The lymphokine formation observed in this study depended on the clinical form of the disease. The character of the effect produced by lymphokine was determined by the initial state of target cells (macrophages).


The effect of hibernation on protein phosphatases from ground squirrel organs.
Protein phosphorylation has been identified as a reversible mechanism for the regulated suppression of metabolism and thermogenesis during mammalian hibernation. The effects of hibernation on the activity of serine/threonine and tyrosine protein phosphatases (PP1, PP2A, PP2C and PTPs) were assessed in five organs of Richardson's ground squirrel. Each phosphatase subfamily responded differently during torpor, and each showed organ-specific patterns of activity changes. The distribution of PP1 catalytic subunit (PP1c) isoforms (alpha, delta, gamma1) was assessed in five organs, and changes in the subcellular distribution of PP1 were observed during hibernation in liver and muscle. For example, in muscle, cytosolic PP1 content increased and myofibril-associated PP1 decreased during torpor. PP1c from ground squirrel liver was purified to homogeneity and characterized; temperature effects on PP1c maximal activity suggested that temperature had little or no effect on relative dephosphorylation potential at low temperatures. However, nucleotide inhibition of PP1c by ATP, ADP and AMP was much weaker at 5 degrees C compared with 37 degrees C assay temperatures. PP2A activity decreased in three organs (brown adipose, kidney, brain) during hibernation whereas PP2C activity was increased in liver and brain. PTPs were assessed using both a general substrate (ENDpYINASL) and a substrate (DADEpYLIPQQG) specific for PTPs containing the SH2-binding site; both revealed hibernation-associated changes in PTP activities. Changes in protein phosphatase activities suggest the relative importance of these modules in controlling metabolic function and cellular processes during mammalian hibernation.


ETS transcription factor ELK3 in human cancers: An emerging therapeutic target.
Cancer is a genetic and complex disorder, resulting from several events associated with onset, development, and metastasis. Tumor suppressors and oncogenes are among the main regulators of tumor progression, contributing to various cancer-related behaviors like cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis. Transcription factors (TFs) could act as tumor suppressors or oncogenes in cancer progression. E-twenty-six/E26 (ETS) family of TFs have a winged helix-turn-helix (HLH) motif, which interacted with specific DNA regions with high levels of purines and GGA core. ETS proteins act as transcriptional repressors or activators to modulate the expression of target genes. ETS transcription factor ELK3 (ELK3), as a type of ETS protein, was shown to enhance in various cancers, suggesting that it may have an oncogenic role. These studies indicated that ELK3 promoted invasion, migration, cell cycle, proliferation, and EMT, and suppressed cell apoptosis. In addition, these studies demonstrated that ELK3 could be a promising diagnostic and prognostic biomarker in human cancer. Moreover, accumulating data proved that ELK3 could be a novel chemoresistance mediator in human cancer. Here, we aimed to explore the overall change of ELK3 and its underlying molecular mechanism in human cancers. Moreover, we aimed to investigate the potential role of ELK3 as a prognostic and diagnostic biomarker as well as its capability as a chemoresistance mediator in cancer.


Idiopathic factor V inhibitor in a patient starting haemodialysis.
A 74-year-old Pacific Island man with end-stage renal failure planning to start haemodialysis presented with persistent bleeding after tunnelled dialysis catheter insertion. The laboratory findings revealed a prolonged activated partial thromboplastin time of 118 s, prothrombin ratio of 4.2, factor V activity of <2% and a factor V inhibitor of 40 Bethesda Units. No clear underlying aetiology was identified. The bleeding settled with conservative measures and the factor V inhibitor was successfully treated with oral cyclophosphamide for 6 weeks.


Two new Geranomyia Haliday (Diptera, Limoniidae) crane flies from Mount Jiulong in China, with an updated key to Chinese species.
The genus Geranomyia Haliday, 1833 is globally distributed, with 351 known species, of which 26 occur in China. Herein, an overview of the genus Geranomyia from Mount Jiulong, Zhejiang, China, is presented. Two new species are described and illustrated. Geranomyia jiulongensis sp. nov. and G. subablusa sp. nov. are distinguished from other Geranomyia species by the characters of the thorax and male genitalia. An updated key to the Geranomyia of China is presented.


Preoperative epoetin alfa in colorectal surgery: a randomized, controlled study.
Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs. A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded. A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group. Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions.


Techniques for monitoring bioavailable organic pollutants in sediment: Application of poly(methyl methacrylate) as a passive sampler.
A poly(methyl methacrylate) (PMMA) passive sampler was applied to harbor sediment to examine whether the substrate could be used as a tool to measure freely dissolved concentrations of contaminants. An ex situ method required at least 1 g of PMMA to detect freely dissolved polycyclic aromatic hydrocarbons (PAHs) in sediment with <100 ng/g dry weight. Two weeks were sufficient to reach equilibrium under 180 rpm for PAHs with a molar volume of <250 cm3/mol. For the in situ method, a deployment time of four months was sufficient to measure PAHs with a molar volume up to 250 cm3/mol in the sediment bed. The PMMA passive sampler could be used to measure the bioavailable fraction of PAHs in porewater, reflecting the complex properties of sediment with strong sorption such as black carbons.


[Impact of intensity-modulated radiotherapy on node irradiation for breast cancer].
Irradiation of node areas is still a complex challenge in external radiotherapy for breast cancer. Acceptable target coverage is always balanced by protection of organs at risk and patient morphology. Intensity-modulated radiotherapy increases the quality of dose distribution on the planning target volume, but modifies dramatically the irradiation coverage of critical structures in a different way compared to 3D treatment. In this paper we analyze this new technique in breast treatment with node regions, its expected gain and potential risks.


Effect of vehicle on pilocarpine-induced ocular hypotension.
The effect of 1.4% polyvinyl alcohol and castor oil vehicles on pilocarpine-induced hypotension was studied in 50 patients with open-angle glaucoma. Diurnal tension curves showed that the mean intraocular pressure was lower and the maximum diurnal variation smaller during the treatment with oily drops of 2% and 4% pilocarpine instilled 2-3 times daily than when 2% and 4% pilocarpine in polyvinyl alcohol was instilled 3-4 times daily. The differences were statistically significant. In long-term treatment no marked pilocarpine tolerance developed in cases treated with oily drops of pilocarpine. It is concluded that in the treatment of patients with open-angle glaucoma, the hypotensive effect of pilocarpine in an oily vehicle instilled 2-3 times daily is greater and more even than that of pilocarpine of corresponding strength in polyvinyl alcohol administered 3-4 times daily.


Poliovirus serotype 2 and coxsackievirus A promote the natural recombination of poliovirus.
Poliovirus (PV) is a member of the species Enterovirus C (EV-C), which may cause irreversible paralysis and death. So, for the purpose of analyzing the evolution of PV2 to help in eradicating PVs globally, a recombination analysis was performed to verify all viral genomes of EV-C, and we found 13 putative recombination events that produced PV1, 14 recombination events that can give rise to PV2, and 9 events that can lead to PV3. By analyzing our findings, we found that PV2 was involved in 25 of 36 PV recombination events, whereas coxsackievirus A (CVA) strains were involved in 12 of 36 PV recombination events, indicating that PV2 and CVAs play major roles in the natural recombination of PV. In addition, we found 11 of 36 breakpoint positions located in 2A region, which is the most active region of the recombination events.


From little things, big things grow: An exploratory analysis of the national cost of peripheral intravenous catheter insertion in Australian adult emergency care.
To estimate the total economic impact of peripheral intravenous catheter (PIVC) or cannula insertion and use in adult Australian EDs, including those cannulas that remain unused for therapeutic purposes. Searches on Australian government websites were conducted to find rates of insertion, complications and cost of cannula; following this, gaps in national data sets were filled with MEDLINE and PubMed searches to estimate the total cost of cannula use in Australian EDs. Once the data were collected, totals were combined to establish an estimated cost for the listed categories. The estimated cost of cannulation in Australia may be up to A$594 million per year, including the cost of insertion (equipment and staff), cost of complications such as Staphylococcus aureus bacteraemia and phlebitis, and patient-centred costs (lost patient productivity, infiltration, occlusion and dislodgement). Approximately A$305.9 million is attributed to unused cannulas and approximately 11 790 days of clinician time is spent annually inserting cannula that remains idle. The figures developed in the present study represent an important educational opportunity to encourage thoughtful consideration of all interventions, no matter how small. ED cannula insertion represents a large economic and health cost to Australia's health system, many of which remain unused. There are no national data sets that record complications associated with PIVCs and we highlight the urgent need for improved data.


Analysis of salicylic acid based on the fluorescence enhancement of the As(III)-salicylic acid system.
A new, simple and sensitive spectrofluorimetric method for the determination of salicylic acid (lambda(ex)=315 nm, lambda(em) = 408 nm) using As(III) as a sensitizing reagent has been investigated by measuring the increase of fluorescence intensity of salicylic acid due to the complexation of As(III)-salicylic acid in presence of sodium dodecyl sulfate (SDS) 10(-3) M. Under optimum conditions, a significant relationship was obtained between the fluorescence intensity and salicylic acid concentration. A linear calibration curve was obtained in the range 13.8-13812 microg l(-1) with product-moment correlation coefficient (R) 0.99985 and detection limit 4.2 microg l(-1). The R.S.D. is 2.35% (n=5). The method was applied successfully to the determination of salicylic acid in human serum.


Case fatality rate with vena cava filters in hospitalized stable patients with cancer and pulmonary embolism.
In view of the high risk of pulmonary embolism in patients with cancer, we tested the hypothesis that stable patients with pulmonary embolism who have cancer might be a subset of patients who would show a lower case fatality rate with vena cava filters than without filters. Stable patients with pulmonary embolism and cancer at discharge from short-stay hospitals throughout the US from 1998-2009 were identified from the Nationwide Inpatient Sample. Patients with pulmonary embolism who had a diagnostic code for shock, ventilatory support, thrombolytic therapy, or pulmonary embolectomy were excluded because such patients have been shown to have lower case fatality rate with filters. In-hospital all-cause case fatality rate was lower with vena cava filters in stable patients with pulmonary embolism and solid malignant tumors providing they were aged >30 years, but there was variability according to type of tumor and age of patient. On average, case fatality rate among those >30 years with filters was 7070 of 69,350 (10.2%) (95% confidence interval, 10.0-10.4) versus 36,875 of 247,125 (14.9%) (95% confidence interval, 14.8-15.1) without filters (P <.0001) (relative risk 0.68). Among stable patients with hematological malignancies, case fatality rate, except in the elderly, was higher among those with vena cava filters than those without filters. Stable patients with pulmonary embolism and solid malignant tumors who are older than age 30 years appear to be a subset of patients with pulmonary embolism who would benefit from vena cava filters, but this needs to be tested prospectively.


Probable heat capacity signature of the supersolid transition.
Liquid 4He enters the superfluid state and flows without friction below 2.176 K. Thin liquid films adsorbed on solid substrates undergo the same transformation, although at a lower temperature. When the substrate is subjected to oscillatory motion a portion of the film, known as the superfluid fraction, decouples from the oscillation. A similar phenomenon has been observed in solid 4He, in which a fraction of the solid seems to decouple from the motion of the surrounding lattice. Although this observation has been replicated in various laboratories, no thermodynamic signature of the possible supersolid transition has been seen. Here we report the finding of a heat capacity peak that coincides with the onset of mass decoupling. This complementary experimental evidence supports the existence of a genuine transition between the normal solid and supersolid phases of 4He.


Bundling of myosin subfragment-1-decorated actin filaments.
We have reported previously that rabbit skeletal myosin subfragment-1 (S-1) assembles actin filaments into bundles. The rate of this reaction can be estimated roughly from the initial rate (Vo) of the accompanying turbidity increase ("super-opalescence") of the acto-S-1 solution. Vo is a function of the molar ratio (r) of S-1 to actin, with a peak at r = 1/6 to 1/7 and minimum around r = 1. In the present paper we report a different type of opalescence (we call it "hyper-opalescence") of acto-S-1 solutions, which also resulted from bundle formation. Adjacent filaments in the bundles had a distance of approximately 180 A. Hyper-opalescence occurred at r approximately equal to 1 when KCOOCH3 was used instead of KCl. By comparing the effects of ADP, epsilon-ADP, tropomyosin or ionic strength upon the super- and hyper-opalescence, we concluded that the two types of S-1-induced actin bundling had different molecular mechanisms. The hyper-opalescence type of bundling seemed to be induced by S-1, which was not complexed with actin in the manner of conventional rigor binding. The presence of the regulatory light chain did not affect hyper-opalescence (or super-opalescence), since there were no significant differences between papain S-1 and chymotryptic S-1 with respect to these phenomena.


Inhibition of human cytochrome P450 1A2 by flavones: a molecular modeling study.
Cytochrome P450 1A2 metabolizes a number of important drugs, procarcinogens, and endogenous compounds. Several flavones, a class of phytochemicals consumed in the human diet, have been shown to differentially inhibit human P450 1A2-mediated methoxyresorufin demethylase. A molecular model of this P450 was constructed in order to elucidate the molecular basis of the P450-flavone interaction. Flavone and its 3,5,7-trihydroxy and 3,5,7-trimethoxy derivatives were docked into the active site to assess their mode of binding. The site is hydrophobic and includes several residues that hydrogen bond with substituents on the flavone nucleus. The binding interactions of these flavones in the modeled active side are consistent with their relative inhibitory potentials, namely 3,5,7-trihydroxylflavone > flavone > 3,5,7-trimethoxylflavone, toward P450 1A2-mediated methoxyresorufin demethylation.


Investigation of proteins in living bacteria with in-cell NMR experiments.
In recent years NMR methods have been developed that enable the observation of proteins insideliving bacterial cells. Because of the sensitivity of the chemical shift to environmental changesthese in-cell NMR experiments can be used to study protein conformation, molecular interaction ordynamics in a protein's natural surrounding. Detection of proteins in the bacterial cytoplasmrelies on labeling of the protein of interest with NMR active isotopes. This review describes differentlabeling techniques based on either uniform (15)N or (13)Clabeling as well as amino acid specific labeling schemes. In addition potential applications of thesein-cell NMR experiments and their limitations are discussed.


The severity of late skin damage related to fraction size in women treated by radiotherapy after mastectomy.
A retrospective study has been undertaken to test the NSD formula as a predictor of isoeffective schedules in women treated after mastectomy by parasternal radiotherapy using fraction sizes of 2-3 Gy. Forty three women were identified who have been treated on the same orthovoltage unit 8-18 years previously and the severity of overall skin changes and telangiectasia were assessed by three observers using a 4-point categorical scale. At each level of skin damage, radiotherapy schedules delivered using fraction sizes of 250 R or 300 R were associated with lower TDF values than schedules using 225 R fraction. The difference between TDF factors for isoeffective regimes using small (225 R) and large (250 R and 300 R) fraction sizes is highly significant for both overall skin damage and telangiectasia (p = 0.004 by rank sum test). Care should be exercised when using current empirical formulae to calculate regimes isoeffective for late skin damage, even when modest changes in fraction size from 2 to 3 Gy are contemplated.


Spectrophotometric estimation of cobalt with ninhydrin.
A violet coloured complex was developed when cobalt metal reacts with ninhydrin at pH 8.2, using sodium acetate buffer solution. Absorbance of the complex was measured at 395 nm. Various factors, such as volume of the ligand used, solution pH, stability of the complex with time and interference of other metals, which effect the complex formation have been studied in detail. Present developed method can be used for the spectrophotometric estimation of cobalt with ninhydrin complex. The method is simple, selective and cheap for the determination of cobalt in very less time.


Evaluation of promoter strength in mouse and rat primary hepatocytes using adenovirus vectors.
Primary cultured hepatocytes are widely used in the studies of basic and clinical hepatology. Finding an efficient method for gene transfer into primary hepatocytes will be an important advance for these studies. In the present study, we evaluated the activity of an adenovirus vector including promoters for the Rous sarcoma virus (RSV), elongation factor 1alpha, and cytomegalovirus (CMV) as well as the beta-actin promoter/CMV enhancer (CA) using beta-galactosidase as a reporter gene. Although RSV and elongation factor 1alpha promoters had low transcriptional activity in hepatocytes, the CA and CMV promoters had high activity. The CA promoter was the most active, mediating 50.3- and 204.4-fold more activity than the RSV promoter in mouse and rat hepatocytes, respectively. Dose-response studies revealed that transgene activity can be controlled by as much as 1000-fold, by selection of the promoter and the number of infectious particles per cell. These findings should help in the construction of adenovirus vectors for expressing genes of interest in rodent primary cultured hepatocytes.


Phosphorylation of cysteine string protein on Serine 10 triggers 14-3-3 protein binding.
Cysteine string protein (CSP) is a neuronal chaperone that maintains normal neurotransmitter exocytosis and is essential for preventing presynaptic neurodegeneration. CSP is phosphorylated in vivo on a single residue, Ser10, and this phosphorylation regulates its cellular functions, although the molecular mechanisms involved are unclear. To identify novel phosphorylation-specific binding partners for CSP, we used a pull-down approach using synthetic peptides and recombinant proteins. A single protein band was observed to bind specifically to a Ser10-phosphorylated CSP peptide (residues 4-14) compared to a non-phosphorylated peptide. This band was identified as 14-3-3 protein of various isoforms using mass spectrometry and Western blotting. PKA phosphorylation of full-length CSP protein stimulated 14-3-3 binding, and this was abolished in a Ser10-Ala mutant CSP, confirming the binding site as phospho-Ser10. As both CSP and 14-3-3 proteins are implicated in neurotransmitter exocytosis and neurodegeneration, this novel phosphorylation-dependent interaction may help maintain the functional integrity of the synapse.


Arthroscopic treatment of septic arthritis in a patient with posterior stabilized total knee arthroplasty.
We report on a case of arthroscopic treatment of septic arthritis of the knee in a 73-year-old woman with a posterior stabilized knee endoprosthesis. Six months after arthroplasty of the right knee joint because of osteoarthritis, the patient experienced an erysipelas of the right lower leg after a cat bite. Although given intravenous antibiotic therapy, the patient developed septic arthritis of the right knee. Pasteurella multocida could be identified as the causative organism. The joint infection was classified as stage I according to Gächter. Via arthroscopic joint debridement, partial synovialectomy, the use of continuous irrigation-suction drains, and intravenous antibiotic therapy, the empyema could be cured without removal of the total endoprosthesis of the right knee.