Optimal use of nitrogen to suppress the high pressure nervous syndrome.
Five subjects were compressed to 1000 ft (31 ATA) for 2 h breathing 3.2 ATA nitrogen, 0.5 ATA oxygen, and the remainder helium. The compression took 33 min with a 10-s stage at 50 ft (2.5 ATA), 1 MIN AT 320 FT (10.7 ATA), and 2 min at 700 ft (22 ATA). Hypothetically, this 1:10 ratio for nitrogen-helium partial pressures should induce neither nitrogen narcosis nor the High Pressure Nervous Syndrome (HPNS). Tests, therefore, were made during the experiment of postural tremor, spontaneous electroencephalogram, psychomotor and intellectual activities, and subjective sensations. One diver worked underwater for 40 min on a simulated engineering assembly while breathing with a closed-circuit breathing apparatus and wearing a battery-heated suit in water at 56 degrees F. Decompression was in 4 d using 0.8 ATA oxygen and helium. The performance tests indicated no narcosis and little or no signs of HPNS. No tremor or EEG changes were seen. The "wet" diver reported sensations of mild euphoria but the other four reported no difficulties. No nausea or dizziness of HPNS was reported. It is concluded that use of a ratio of 1:10::N2:He is effective in the control of narcosis and HPNS during rapid compression to 1000 ft (31 ATA).


Flow cytometric-based isolation of nucleated erythroid cells during maturation: an approach to cell surface antigen studies.
Nucleated red blood cells (NRBCs) are involved in normal physiologic processes, as well as in several malignancies. They are usually counted manually under the microscope. However, blood sample manipulation may be a source of variability and manual counting is imprecise, time-consuming, and subjective. To improve identification of CD45-negative cells, we used a flow cytometry technique that avoids the addition of lysing reagents and stains viable cell nuclei. We applied this method for counting and isolating NRBC subpopulations in whole blood samples, using DNA/RNA viable staining to discriminate nonnucleated erythroid cells and debris. NRBC counts gave 197.95 cells per mm(3) in mobilized peripheral blood samples (1.00%, n = 20), 3897.59 cells per mm(3) in leukapheresis products (3.08%, n = 20), and 765.21 cells per mm(3) in cord blood samples (6.09%, n = 20). Normal bone marrow counts were 5449.42 cells per mm(3) (11.76%, n = 20). Scatter profiles showed three distinct populations, from early to late-stage erythroblasts, consisting of erythroblasts, orthochromatic erythroblasts, and ejected nuclei, as confirmed by Wright-Giemsa staining. In addition, flow cytometry immunophenotyping showed that glycophorin A was expressed dimly on NRBCs during maturation. These findings point to the feasibility of live NRBCs studies, which offer great potential for a wide range of disciplines.


Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease.
Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.


The barriers and enablers to achieving adequate calcium intake in young adults: a qualitative study using focus groups.
Despite the established benefits of calcium consumption, many young Australians are not meeting the recommendations for calcium intake. This is concerning because an adequate calcium consumption is important throughout young adulthood to reach peak bone mass and for the prevention of osteoporosis. Therefore, the present study aimed to explore the barriers and enablers to consuming calcium-rich foods with young adults. Using a semi-structured question guide, five focus group discussions were conducted with 39 participants [mean (SD) age 22.5 (1.8) years]. Participants were mostly females (n = 29) and enrolled in tertiary education (n = 31). A deductive approach was used to group common ideas into themes. The findings from the focus groups were analysed using the COM-B framework, which examines the interactions between three key components (i.e. capability, opportunity and motivation). On examining the young adults' capability to consume a diet adequate in calcium, it was found that young adults had limited knowledge of sources, prevention of disease and recommended amounts. Some participants voiced physical barriers to consumption (lactose intolerance). Opportunity was reported as a physical (availability of calcium-rich foods), financial and social opportunity. Some participants reported motivation to include dairy as a result of the habit becoming engrained during their childhood under parental influence (automatic motivation), whereas others reflected on a lack of awareness relating to inadequacy and health consequences (reflective motivation). Although social media was seen to be an acceptable mode of intervention, concerns were raised about the source and credibility of the information. The findings may inform the development of future interventions targeting eating habits of young adults.


The influence of autonomy on personal support workers' job satisfaction, capacity to care, and intention to stay.
Using survey data collected in Ontario, Canada, we explore the impacts of autonomy on community-based Personal Support Workers' intrinsic job satisfaction, capacity to care for and about clients, and intention to continue working in home care. Autonomy was measured as "freedom to decide how to do your job" and "working on your own." Findings show that freedom to do your job and working on your own are both positively associated with job satisfaction and capacity to care, and indirectly increase intention to stay through their relationships with job satisfaction and capacity to care. We suggest that policies should allow personal support workers to make decisions about how to do their job within the care plans provided, to facilitate retention of this highly needed workforce.


Weight management strategies in Middle-Aged Women (MAW): Development and validation of a questionnaire based on the Oxford Food and Activity Behaviors Taxonomy (OxFAB-MAW) in a Portuguese sample.
The Oxford Food and Activity Behaviors (OxFAB) taxonomy systematize the cognitive-behavioral strategies adopted by individuals who are attempting to manage their weight. The present study aimed to (1) develop a questionnaire based on the OxFAB taxonomy, specifically adapted for middle-aged women-the OxFAB-MAW-stage of life and sex, which present a high incidence of obesity, (2) assess the psychometric properties of this tool, and (3) evaluate the discriminative power of the OxFAB-MAW (normal weight vs. obesity). Overall, 1,367 Portuguese middle-aged women between 45 and 65 years (M = 52.3, SD = 5.15) filled in a sociodemographic, health, and menopause-related questionnaire, as well as the OxFAB-MAW. Confirmatory factor analysis demonstrated an acceptable model fit (comparative fit index = 0.928, Tucker-Lewis index = 0.913, root mean square error of approximation = 0.072, and standardized root mean square residual = 0.054). Five domains with one item were grouped into other domains, and the Weight Management Aids domain was also removed. The OxFAB-MAW showed factorial, convergent, discriminant, and external validity, as well as composite reliability. The OxFAB-MAW questionnaire is a valid, reliable, and theory-driven tool for assessing weight management strategies in middle-aged women, being able to discriminate between clinical and non-clinical groups (normal weight vs. obesity) in several domains. This instrument can be used to gather valid and reliable data, useful in both research and clinical settings (especially focused on structuring interventions and preventive obesity programs within this specific life cycle stage).


Adherence to uroepithelial cells of Providencia stuartii isolated from the catheterized urinary tract.
The long-term catheterized urinary tract appears to offer a niche for Providencia stuartii, otherwise an unusual clinical isolate. P. stuartii, the most frequent and persistent isolate from the urine of 51 long-term catheterized patients, was recovered from 761 of 1230 (62%) weekly urine specimens. To test the hypothesis that prevalence of this species may be due to adherence properties of the organism, 20 selected strains from 14 patients at two nursing homes, representing six distinct serotypes and harbouring combinations of nine different plasmid species, were tested for adherence to uroepithelial cells (UEC). Optimal conditions were determined for differentiating strains on the basis of in vitro adherence to UEC. These strains, grown in nutrient broth, were incubated with UEC isolated from the urine of a healthy adult female (10(8) bacteria per 10(5) cells). Washed UEC, retained on 8 micron pore diameter filters, were transferred to slides, fixed and stained; bacteria were counted on each of 40 cells. Fourteen of the 20 strains were defined as adherent to UEC by comparison of mean adherent bacteria and percentage of uroepithelial cells with more than 10 bacteria. Adherence was compared to that of a P-fimbriated strain of Escherichia coli. It was not inhibited by 50 mM-mannose. We conclude that the majority of P. stuartii isolates are adherent to UEC in vitro and suggest that this may play a role in the persistence of this organism in the catheterized urinary tract.


[The characteristics of the protein and lipid metabolic indices of poultry farmers with extrinsic allergic alveolitis].
The content of albumins, globulin fractions and cholesterol was studied in blood serum of poultry breeders with exogenic allergic alveolitis (EAA) having different service terms. Breeders suffering from EAA with service term of 1-20 years show a decrease in the albumin content and an increase in globulin fractions and cholesterol in blood which may indicate liver disturbances and hypercholesterolemia.


Dandelion (Taraxacum officinale) and Agrimony (Agrimonia eupatoria) as Indicators of Geogenic Contamination of Flysch Soils in Eastern Slovakia.
Contents of potentially toxic elements Fe, Mn, Cr, Ni, Co, V, Cu, and Mo were determined in common dandelion (Taraxacum officinale) and agrimony (Agrimonia eupatoria) to show their usefulness as bioindicators of geogenic soil pollution. Both plants were collected on geochemically anomalous soils developed on flysch sedimentary rocks (Paleogene) of Eastern Slovakia, which also are composed of weathered detritus of some ultramafic rocks. Generally, contents of the investigated association of potentially toxic elements are highly increased in these "serpentine"-like soils. Elevated concentrations were detected in both shoots and roots of the plants. The highest values, which exceed world average values for plants, were observed for Ni content. They ranged from 1.7 to 16.3 mg kg(-1) in dandelion and from 1.6 to 22.6 mg kg(-1) in agrimony. Essential elements, such as Mo, Cu, and Mn, were the most concentrated in plants, whereas Co, V, and Cr were the least concentrated. Although the bioindication value of the common dandelion for anthropogenic soil pollution is well known, it is not mentioned for agrimony in literature, and no data exist to indicate the geogenic pollution for both plants. Dandelion and agrimony are widely used as herbal drugs; therefore, our intention also was to point out another fact, namely, possible high uptake of potentially toxic elements by herbal plants growing on similar soils.


A Novel Patient Engagement Platform Using Accessible Text Messages and Calls (Epharmix): Feasibility Study.
Patient noncompliance with therapy, treatments, and appointments represents a significant barrier to improving health care delivery and reducing the cost of care. One method to improve therapeutic adherence is to improve feedback loops in getting clinically acute events and issues to the relevant clinical providers as necessary (ranging from detecting hypoglycemic events for patients with diabetes to notifying the provider when patients are out of medications). Patients often don't know which information should prompt a call to their physician and proactive checks by the clinics themselves can be very resource intensive. We hypothesized that a two-way SMS system combined with a platform web service for providers would enable both high patient engagement but also the ability to detect relevant clinical alerts. The objectives of this study are to develop a feasible two-way automated SMS/phone call + web service platform for patient-provider communication, and then study the feasibility and acceptability of the Epharmix platform. First, we report utilization rates over the course of the first 18 months of operation including total identified clinically significant events, and second, review results of patient user-satisfaction surveys for interventions for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. To test this question, we developed a web service + SMS/phone infrastructure ("Epharmix"). Utilization results were measured based on the total number of text messages or calls sent and received, with percentage engagement defined as a patient responding to a text message at least once in a given week, including the number of clinically significant alerts generated. User satisfaction surveys were sent once per month over the 18 months to measure satisfaction with the system, frequency and degree of communication. Descriptive statistics were used to describe the above information. In total, 28,386 text messages and 24,017 calls were sent to 929 patients over 9 months. Patients responded to 80% to 90% of messages allowing the system to detect 1164 clinically significant events. Patients reported increased satisfaction and communication with their provider. Epharmix increased the number of patient-provider interactions to over 10 on average in any given month for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. Engaging high-risk patients remains a difficult process that may be improved through novel, digital health interventions. The Epharmix platform enables increased patient engagement with very low risk to improve clinical outcomes. We demonstrated that engagement among high-risk populations is possible when health care comes conveniently to where they are.


Inhibition of cellular fatty acid synthase impairs replication of budded virions of Autographa californica multiple nucleopolyhedrovirus in Spodoptera frugiperda cells.
Fatty acid synthase (FASN) catalyzes the synthesis of palmitate, which is required for formation of complex fatty acids and phospholipids that are involved in energy production, membrane remodeling and modification of host and viral proteins. Presently, the roles of cellular fatty acid synthesis pathway in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection is not clear. In this study, we found that the transcripts level of fasn was significantly up-regulated at the early stage of AcMNPV infection. Treatment of AcMNPV-infected Spodoptera frugiperda Sf9 cells with C75, a specific inhibitor of FASN, did not affect the internalization of budded virions into cells, but dramatically reduced the infectious AcMNPV production. Further analysis revealed that the presence of C75 significantly decreased the expression level for two reporter genes, beta-galactosidase and beta-glucuronidase, that were separately directed by the early and late promoter of AcMNPV. Similarly, Western blot analysis showed that, in C75-treated cells, the expression of viral gp64 was delayed and decreased. Additionally, treatment with C75 also resulted in a significant reduction in the accumulation of viral genomic DNA. Together, these results demonstrate that the fatty acid synthesis pathway is required for efficient replication of AcMNPV, but it might not be necessary for AcMNPV entry into insect cells.


Insight into Kinetics and Mechanisms of AOT Vesicle Adsorption on Silica in Unfavorable Conditions.
The structure of adsorbed surfactant layers at the equilibrium state has already been investigated using various experimental techniques. However, the comprehension of the formation of structural intermediates in nonequilibrium states and the resulting adsorption kinetics still remain a challenging task. The temporal characterization of these intermediate structures provides further understanding of the layer structure at equilibrium and of the main interactions involved in the adsorption process. In this article, we studied the adsorption kinetics of AOT vesicles on silica at different pHs at ambient temperature. The AOT vesicles were formed in a brine solution. Quartz crystal microbalance with dissipation monitoring (QCM-D) was used to obtain information on the kinetics of surfactant adsorption and on the structure of the adsorbed layer at the equilibrium state. Additionally, neutron reflectivity experiments were performed to provide a detailed description of the mean surfactant concentration profile normal to the surface at equilibrium. Results suggest that vesicles in the bulk influence the adsorption mechanisms. In acidic conditions, after a time-dependent structural rearrangement step, followed by the rupture of initially adsorbed vesicles, the formation of a bilayer was observed. At an intermediate and basic pH, in spite of the electrostatic repulsion between the negatively charged surfactants and silica, results demonstrated the existence of an adsorbed layer composed of AOT vesicles. Vesicles are more or less closely packed depending on the pH of the solution. Results show a non-negligible influence of NaCl addition at pH values where adsorption is initially inhibited. Vesicle adsorption at the intermediate and basic pH is probably due to the combination of attractive van der Waals interactions promoted in high ionic strength systems and the formation of hydrogen bonds. Interpretation of adsorption kinetics gave insight into adsorption mechanisms in an electrostatic repulsion environment.


Effectiveness and sustainability of the ViSC Social Competence Program to prevent cyberbullying and cyber-victimization: Class and individual level moderators.
We investigated whether the general anti-bullying program ViSC sustainably prevents cyberbullying and cyber-victimization. A longitudinal randomized control group design was used to examine (i) program effectiveness immediately after a 1 year implementation phase and (ii) sustainable program effects 6 months later taking several moderators on the class level (class climate and ethnic diversity) and on the individual level (gender, age, internet usage, traditional bullying/victimization) into account. Effectiveness (e.g., the change between waves 2 and 1) was examined in 2,042 students (47.6% girls), aged 11.7 years (SD = 0.88) enrolled in 18 schools and 103 classes. Sustainability (e.g., the change between waves 3 and 2) was examined in a sub-sample of 6 schools and 35 classes comprising 659 students. The self-assessment multiple-item scales showed longitudinal and multiple group invariance. Factor scores were extracted to compute difference scores for effectiveness (Posttest minus Pretest) and sustainability (Follow-up test minus Posttest) for cyberbullying and cyber-victimization. Multilevel Modeling was applied to examine (i) the effectiveness and (ii) the sustainability of the ViSC intervention controlling for several individual and class level variables. Controlling for covariates, it was demonstrated that the ViSC program is effective in preventing cyberbullying and cyber-victimization and that the effects are sustainable after 6 months. The consequences for cyberbullying prevention are discussed.


Readmission Patterns Over 90-Day Episodes of Care Among Medicare Fee-for-Service Beneficiaries Discharged to Post-acute Care.
Examine readmission patterns over 90-day episodes of care in persons discharged from hospitals to post-acute settings. Retrospective cohort study. Acute care hospitals. Medicare fee-for-service enrollees (N = 686,877) discharged from hospitals to post-acute care in 2013-2014. The cohort included beneficiaries >65 years of age hospitalized for stroke, joint replacement, or hip fracture and who survived for 90 days following discharge. 90-day unplanned readmissions. The cohort included 127,680 individuals with stroke, 442,195 undergoing joint replacement, and 117,002 with hip fracture. Thirty-day readmission rates ranged from 3.1% for knee replacement patients discharged to home health agencies (HHAs) to 14.4% for hemorrhagic stroke patients discharged to skilled nursing facilities (SNFs). Ninety-day readmission rates ranged from 5.0% for knee replacement patients discharged to HHAs to 26.1% for hemorrhagic stroke patients discharged to SNFs. Differences in readmission rates decreased between stroke subconditions (hemorrhagic and ischemic) and increased between joint replacement subconditions (knee, elective hip, and nonelective hip) from 30 to 90 days across all initial post-acute discharge settings. We observed clear patterns in readmissions over 90-day episodes of care across post-acute discharge settings and subconditions. Our findings suggest that patients with hemorrhagic stroke may be more vulnerable than those with ischemic over the first 30 days after hospital discharge. For patients receiving nonelective joint replacements, readmission prevention efforts should start immediately after discharge and continue, or even increase, over the 90-day episode of care.


Refill-Exchange Procedure of the Port Delivery System With Ranibizumab: Overview and Clinical Trial Experience.
To describe the Port Delivery System with ranibizumab refill-exchange procedure. Procedure based on the clinical trial program in patients with retinal diseases. The refill-exchange procedure is performed under topical anesthesia and strict aseptic conditions. Supplemental task lighting and magnification are recommended throughout the procedure. Ranibizumab is aseptically transferred from the vial with the filter needle and air is removed from the syringe. The filter needle is then replaced with the refill needle; any remaining air is removed from the syringe and the plunger is advanced to the 0.1-mL mark. Targeting the implant septum center, the refill needle is inserted perpendicularly to the globe until the soft stop contacts the conjunctiva (perpendicular orientation and conjunctival contact are maintained throughout the procedure); a cotton-tipped applicator is recommended for globe stabilization. The entire syringe contents are slowly injected over 5-10 seconds while existing solution fills the fluid collection reservoir. Once completed, the needle is carefully withdrawn while maintaining perpendicularity. The procedure can be successfully performed in rare, specific cases, including subconjunctival thickening or fibrous capsule formation, fluid-filled bleb formation, and corneal patch grafts. The procedure is straightforward but distinct from intravitreal injections and requires adherence to standardized techniques. With appropriate preparation, the procedure can be performed in specific cases. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:257-265.].


Use of phoA fusions to study the topology of the Escherichia coli inner membrane protein leader peptidase.
A topology of the Escherichia coli leader peptidase has been previously proposed on the basis of proteolytic studies. Here, a collection of alkaline phosphatase fusions to leader peptidase is described. Fusions to the periplasmic domain of this protein exhibit high alkaline phosphatase activity, while fusions to the cytoplasmic domain exhibit low activity. Elements within the cytoplasmic domain are necessary to stably anchor alkaline phosphatase in the cytoplasm. The amino-terminal hydrophobic segment of leader peptidase acts as a weak export signal for alkaline phosphatase. However, when this segment is preceded by four lysines, it acts as a highly efficient export signal. The coherence of in vitro studies with alkaline phosphatase fusion analysis of the topology of leader peptidase further indicates the utility of this genetic approach to membrane protein structure and insertion.


Association of frontal and maxillary bone fractures and concomitant craniocerebral injuries in patients presenting with head trauma.
Maxillofacial fractures and craniocerebral injuries are common in patients with head trauma. These are injuries with high mortality and morbidity. Therefore, patients with head trauma should be evaluated early with a multidisciplinary approach. The association between frontal and maxillary bone fractures and concurrent craniocerebral injuries were investigated in patients presenting with head trauma in this study. The data of the patients were analyzed retrospectively. Age and gender distributions were evaluated in frontal and maxillary fractures. Concomitant craniocerebral injuries were investigated. Craniocerebral injuries were grouped as pneumocephalus, extra-axial, intra-axial injuries and brain edema. Craniocerebral injuries in frontal and maxillary fractures were compared statistically. Frontal bone and maxillary bone fractures were detected in 24% and 95% of the patients. Coexistence of pneumocephalus and intra-axial injuries in frontal bone fracture was statistically significant. The association of frontal posterior wall fractures with pneumocephalus and parenchymal contusion was found to be statistically significant. In addition, the association of craniocerebral injuries were evaluated and statistically significant ones were determined. The presence of maxillofacial fractures in patients presenting with head trauma increases mortality and morbidity. Craniocerebral injuries can be life-threatening and delay the treatment of facial fractures. Upper facial bone fractures are significantly more common in craniocerebral injuries.


Flagellum couples cell shape to motility in Trypanosoma brucei.
In the unicellular parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, complex swimming behavior is driven by a flagellum laterally attached to the long and slender cell body. Using microfluidic assays, we demonstrated that T. brucei can penetrate through an orifice smaller than its maximum diameter. Efficient motility and penetration depend on active flagellar beating. To understand how active beating of the flagellum affects the cell body, we genetically engineered T. brucei to produce anucleate cytoplasts (zoids and minis) with different flagellar attachment configurations and different swimming behaviors. We used cryo-electron tomography (cryo-ET) to visualize zoids and minis vitrified in different motility states. We showed that flagellar wave patterns reflective of their motility states are coupled to cytoskeleton deformation. Based on these observations, we propose a mechanism for how flagellum beating can deform the cell body via a flexible connection between the flagellar axoneme and the cell body. This mechanism may be critical for T. brucei to disseminate in its host through size-limiting barriers.


The Importance of Salt-Enhanced Electrostatic Repulsion in Colloidal Crystal Engineering with DNA.
Realizing functional colloidal single crystals requires precise control over nanoparticles in three dimensions across multiple size regimes. In this regard, colloidal crystallization with programmable atom equivalents (PAEs) composed of DNA-modified nanoparticles allows one to program in a sequence-specific manner crystal symmetry, lattice parameter, and, in certain cases, crystal habit. Here, we explore how salt and the electrostatic properties of DNA regulate the attachment kinetics between PAEs. Counterintuitively, simulations and theory show that at high salt concentrations (1 M NaCl), the energy barrier for crystal growth increases by over an order of magnitude compared to low concentration (0.3 M), resulting in a transition from interface-limited to diffusion-limited crystal growth at larger crystal sizes. Remarkably, at elevated salt concentrations, well-formed rhombic dodecahedron-shaped microcrystals up to 21 μm in size grow, whereas at low salt concentration, the crystal size typically does not exceed 2 μm. Simulations show an increased barrier to hybridization between complementary PAEs at elevated salt concentrations. Therefore, although one might intuitively conclude that higher salt concentration would lead to less electrostatic repulsion and faster PAE-to-PAE hybridization kinetics, the opposite is the case, especially at larger inter-PAE distances. These observations provide important insight into how solution ionic strength can be used to control the attachment kinetics of nanoparticles coated with charged polymeric materials in general and DNA in particular.


Immunohistochemical detection of GLUT-1 can discriminate between reactive mesothelium and malignant mesothelioma.
The separation of benign reactive mesothelium (RM) from malignant mesothelial proliferation can be a major challenge. A number of markers have been proposed, including epithelial membrane antigen, p53 protein, and P-glycoprotein. To date, however, no immunohistochemical marker that allows unequivocal discrimination of RM from malignant pleural mesothelioma (MPM) has been available. A family of glucose transporter isoforms (GLUT), of which GLUT-1 is a member, facilitate the entry of glucose into cells. GLUT-1 is largely undetectable by immunohistochemistry in normal epithelial tissues and benign tumors, but is expressed in a variety of malignancies. Thus, the expression of GLUT-1 appears to be a potential marker of malignant transformation. Recently, in fact, some studies have shown that GLUT-1 expression is useful for distinguishing benign from malignant lesions. The purpose of the present study was to evaluate the diagnostic utility of GLUT-1 expression for diagnostic differentiation between RM and MPM. Immunohistochemical staining for GLUT-1 was performed in 40 cases of RM, 48 cases of MPM, and 58 cases of lung carcinoma. Immunohistochemical GLUT-1 expression was seen in 40 of 40 (100%) MPMs, and in all cases the expression was demonstrated by linear plasma membrane staining, sometimes with cytoplasmic staining in addition. GLUT-1 expression was also observed in 56 out of 58 (96.5%) lung carcinomas. On the other hand, no RM cases were positive for GLUT-1. GLUT-1 is a sensitive and specific immunohistochemical marker enabling differential diagnosis of RM from MPM, whereas it cannot discriminate MPM from lung carcinoma.


Gender-Related Factors for Depressive Symptoms in Turkish Adolescents.
Currently more adolescents suffer from mental health problems than compared to the past. This study was designed to extend the knowledge of depressive symptoms in adolescence and to determine the gender-related factors associated with it. The study sample consisted of (N = 487) adolescents. The Children's Depression Inventory (CDI), Multidimensional Scale of Perceived Social Support (MSPSS), Strengths and Difficulties Questionnaire (SDQ-S), and UCLA loneliness scale (UCLA-LS) were completed by the participants. Among the study population, 26.6% (n = 130) scored ≥ 19 on the CDI, which was the cut-off point. UCLA-LS, hyperactivity and conduct problems, and peer problems subscale scores of SDQ-S were found significantly higher in males (p < .05). Emotional symptoms, pro-social behavior subscale scores of SDQ-S, and a family member, a friend subscale scores of MSPSS were found significantly higher in females (p < .05). For males, loneliness and hyperactivity and conduct problems, while for females, emotional symptoms and loneliness (p < .05) were predictive variables. Pro-social behavior and perceived family member support were protective variables for females scoring high enough to be diagnosed with depression (p < .05). We suggest further studies to confirm these results as well as establishing strategies for better detection of depressive symptoms when working on adolescents.


Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys.
Twenty young male Cebus apella monkeys were infected with CA1 Trypanosoma cruzi strain and reinfected with CA1 or Tulahuen T. cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CA1 strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were performed with the virulent Tulahuén strain or high doses of CA1 strain. Clinical, electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic chronic myocarditis. All monkeys survived and no mortality was observed.


Treating pain in primary care: Optimizing an integrated psychological intervention based on perspectives of psychologists, primary care providers, and patients.
Although behavioral health treatment can improve distress and pain functioning for patients with chronic pain, few who are referred by their primary care physician will see a behavioral health specialist. Given the benefits of integrating behavioral health into primary care, this may be an avenue for delivering a psychological intervention for chronic pain. The purpose of this study was to optimize a psychological intervention for patients with chronic pain to be delivered in primary care, utilizing the perspectives of providers and patients. Psychologists (n = 9), primary care providers (n = 9), and patients with chronic pain (n = 9) participated in separate focus groups. Participants reviewed the proposed 4-session intervention, provided feedback prompted by a set of open-ended questions, and completed a survey. Statements from focus groups were transcribed and coded into 2 thematic categories: (a) content of the intervention and (b) logistics and design. Participants believed that offering a brief, behavioral intervention for chronic pain in a primary care clinic was feasible and useful. All providers (100%) agreed or strongly agreed that they would refer a patient to this intervention, and 100% of patients agreed or strongly agreed that they would participate. Feedback solicited from the focus groups led to alterations to the treatment manual, such as adding a fifth session, using different psychological strategies, and logistical changes in delivery (i.e., meeting biweekly and intervisit contacts). The modified version of this intervention will be evaluated with a pilot randomized controlled clinical trial. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Lymphoid hyperplasia of the colon and its association with underlying allergic airway diseases.
The purpose of this study was to determine the prevalence of lymphoid hyperplasia in the lower gastrointestinal tract and its role in patients undergoing colonoscopic examinations, particularly focusing on any allergic predisposition. A database search performed at the Department of Gastroenterology at Onomichi Municipal Hospital identified seven patients with lymphoid hyperplasia in the large intestine (i.e., cecum, colon, and/or rectum). Data regarding the endoscopic, biological, and pathological examinations performed and the allergic histories for each patient were retrospectively reviewed from the clinical records. Median age of the patients (four males, three females) was 50 years. Lymphoid hyperplasia was seen in the cecum (n = 5), ascending colon (n = 2), and transverse colon (n = 1). Six patients (85.7%) had one of the allergic airway diseases: allergic rhinoconjunctivitis for pollen (n = 3), bronchial asthma (n = 1), infantile asthma (n = 1), or allergic bronchitis (n = 1). Drug allergy (n = 3) and urticaria (n = 2) were also found. All seven patients had one or more allergic diseases; however, none had a history of food allergy. Blood tests for allergens revealed that six patients (85.7%) had positive reactions to inherent allergens, whereas only one patient had a positive reaction to food allergens. Our results indicate that lymphoid hyperplasia in the large intestine may be associated with allergic airway diseases rather than with food allergies; thus, its presence may be useful to detect patients with underlying airway hyperreactivity.


A 3D Analysis of Dendritic Solidification and Mosaicity in Ni-Based Single Crystal Superalloys.
Ni-based single crystal superalloys contain microstructural regions that are separated by low-angle grain boundaries. This gives rise to the phenomenon of mosaicity. In the literature, this type of defect has been associated with the deformation of dendrites during Bridgman solidification. The present study introduces a novel serial sectioning method that allows to rationalize mosaicity on the basis of spatial dendrite growth. Optical wide-field micrographs were taken from a series of cross sections and evaluated using quantitative image analysis. This allowed to explore the growth directions of close to 2500 dendrites in a large specimen volume of approximately 450 mm3. The application of tomography in combination with the rotation vector base-line electron back-scatter diffraction method allowed to analyze how small angular differences evolve in the early stages of solidification. It was found that the microstructure consists of dendrites with individual growth directions that deviate up to ≈4° from the average growth direction of all dendrites. Generally, individual dendrite growth directions coincide with crystallographic <001> directions. The quantitative evaluation of the rich data sets obtained with the present method aims at contributing to a better understanding of elementary processes that govern competitive dendrite growth and crystal mosaicity.


Ankle Joint Bone Density Distribution Correlates with Overall 3-Dimensional Foot and Ankle Alignment.
Altered stress distribution in the lower limb may impact bone mineral density (BMD) in the ankle bones. The purpose of the present study was to evaluate the spatial distribution of BMD with use of weight-bearing cone-beam computed tomography (WBCT). Our hypothesis was that BMD distribution would be even in normal hindfeet, increased medially in varus hindfeet, and increased laterally in valgus hindfeet. In this study, 27 normally aligned hindfeet were retrospectively compared with 27 valgus and 27 varus-aligned hindfeet. Age (p = 0.967), body mass index (p = 0.669), sex (p = 0.820), and side (p = 0.708) were similar in the 3 groups. Hindfoot alignment was quantified on the basis of WBCT data sets with use of multiple measurements. BMD was calculated with use of the mean Hounsfield unit (HU) value as a surrogate. The HU medial-to-lateral ratio (HUR), calculated from tibial and talar medial and lateral half-volumes, was the primary outcome of the study. The 3 groups significantly differed (p < 0.001) in terms of tibial HUR (median, 0.91 [interquartile range (IQR), 0.75 to 0.98] in valgus hindfeet, 1 [IQR, 0.94 to 1.05] in normal hindfeet, and 1.04 [IQR, 0.99 to 1.1] in varus hindfeet) and talar HUR (0.74 [IQR, 0.50 to 0.80] in valgus hindfeet, 0.82 [IQR, 0.76 to 0.87] in normal hindfeet, and 0.92 [IQR, 0.86 to 1.05] in varus hindfeet). Linear regression showed that all hindfoot measurements significantly correlated with tibial and talar HUR (p < 0.001 for all). The mean HU values for normally-aligned hindfeet were 495.2 ± 110 (medial tibia), 495.6 ± 108.1 (lateral tibia), 368.9 ± 80.3 (medial talus), 448.2 ± 90.6 (lateral talus), and 686.7 ± 120.4 (fibula). The mean HU value for each compartment was not significantly different across groups. Hindfoot alignment and medial-to-lateral BMD distribution were correlated. In varus hindfeet, an increased HU medial-to-lateral ratio was consistent with a greater medial bone density in the tibia and talus as compared with the lateral parts of these bones. In valgus hindfeet, a decreased ratio suggested greater bone density in the lateral as compared with the medial parts of both the tibia and the talus. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


5-fluorouracil and cardiotoxicity: a review.
Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.


Efficient Oxidation of 5-Hydroxymethylfurfural Using a Flavoprotein Oxidase from the Honeybee Apis mellifera.
The chemical 5-hydroxymethylfurfural (HMF) can be derived from lignocellulose and is an interesting bio-based platform chemical as it has the potential to be transformed into numerous valuable building blocks such as the polymer-precursor 2,5-diformylfuran (DFF). To date, only a few oxidases acting on HMF are known and by sampling atypical species, we discovered a novel flavin-dependent oxidoreductase from the honeybee Apis mellifera (beeHMFO). The enzyme can perform the chemoselective oxidation of HMF to DFF but can also readily accept other aromatic alcohols as substrates. The function of the enzyme may well be the antimicrobial generation of hydrogen peroxide using HMF, which is very abundant in honey. The discovery of this insect-derived flavoprotein oxidase holds promising potential in the synthesis of renewable products and demonstrates that insects can be an interesting source of novel biocatalysts.


A case of bilateral microsporidial keratitis from Bangladesh--infection by an insect parasite from the genus Nosema.
An HIV-negative patient from Bangladesh with bilateral keratitis was found to be infected with a microsporidian parasite belonging to the genus Nosema. Significantly, the patient had bathed in a rural pond 7 days prior to the development of ocular symptoms. Nosema parasites are common insect parasites and the source of this microsporidial infection was possibly from mosquito larvae developing in the pond in which the patient bathed. The reduced temperature of the human eye and its immune status may have allowed a poikilothermic insect parasite to establish infection in the cornea of a homeothermic human host. This case highlights the opportunistic potential of insect microsporidial parasites to infect immunocompetent humans as well as those who are immunodeficient.


Initial inhomogeneity-induced crazy-clock behavior in the iodate-arsenous acid reaction in a buffered medium under stirred batch conditions.
It is unambiguously demonstrated that in the case of an autocatalytic reaction, initial inhomogeneities induced by the imperfectly mixed part of the overall volume may result in a serious irreproducibility of the individual kinetic runs. A statistically meaningful number of repetitions, however, gives rise to a reproducible cumulative probability distribution curve often referred to as a support of the stochastic feature. The iodate-arsenous acid reaction being autocatalytic with respect to both iodide and hydrogen ions displays clock behavior. However, the time lag necessary for the appearance of iodine, even in buffered solution, varies in an apparently random manner. Careful analysis of the variation of the different parameters like stirring rate, overall volume, geometry of the reactor and the way of mixing the reactants led us to conclude that the fate of the individual samples is determined at the initial stage when the reacting system is per se inhomogeneous. The place, the size of the so-called ignition volume, where the reacting system is imperfectly stirred, as well as the residence time spent there by the imperfectly mixed reactants all seem to depend on external factors.


Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women.
Current literature examining associations between vitamin D and chronic disease generally use a single assessment of 25-hydroxyvitamin D [25(OH)D], assuming the 25(OH)D concentration of an individual is consistent over time. We investigated the intraindividual variability between two measures of plasma 25(OH)D concentrations collected approximately five years apart (1997-2000 to 2002-2005) in 672 postmenopausal women participating in the Women's Health Initiative. Plasma 25(OH)D was assessed using the DiaSorin LIAISON® chemiluminescence immunoassay. The within-pair coefficient of variation (CV) was 4.9% using blinded quality control samples. Mean and SDs of 25(OH)D at the two time points were compared using a paired t test. An intraindividual CV and intraclass correlation coefficient (ICC) were used to assess intraindividual variability. A Spearman correlation coefficient (r) assessed the strength of the association between the two measures, and concordance in vitamin D status at two time points was compared. Mean 25(OH)D concentrations (nmol/L) significantly increased over time from 60.0 (SD = 22.2) to 67.8 (SD = 22.2; P < 0.05). The CV was 24.6%, the ICC [95% confidence interval (CI)] was 0.59 (0.54-0.64), and the Spearman r was 0.61 (95% CI = 0.56-0.66). Greater concordance over five years was observed in participants with sufficient compared with deficient or inadequate baseline 25(OH)D concentrations (weighted kappa = 0.39). Reliability measures were moderately influenced by season of blood draw and vitamin D supplement use. There is moderate intraindividual variation in 25(OH)D concentrations over approximately five years. These data support the use of a one-time measure of blood 25(OH)D in prospective studies with ≤ five years of follow-up.


Osmostress-induced apoptosis in Xenopus oocytes: role of stress protein kinases, calpains and Smac/DIABLO.
Hyperosmotic shock induces cytochrome c release and caspase-3 activation in Xenopus oocytes, but the regulators and signaling pathways involved are not well characterized. Here we show that hyperosmotic shock induces rapid calpain activation and high levels of Smac/DIABLO release from the mitochondria before significant amounts of cytochrome c are released to promote caspase-3 activation. Calpain inhibitors or EGTA microinjection delays osmostress-induced apoptosis, and blockage of Smac/DIABLO with antibodies markedly reduces cytochrome c release and caspase-3 activation. Hyperosmotic shock also activates the p38 and JNK signaling pathways very quickly. Simultaneous inhibition of both p38 and JNK pathways reduces osmostress-induced apoptosis, while sustained activation of these kinases accelerates the release of cytochrome c and caspase-3 activation. Therefore, at least four different pathways early induced by osmostress converge on the mitochondria to trigger apoptosis. Deciphering the mechanisms of hyperosmotic shock-induced apoptosis gives insight for potential treatments of human diseases that are caused by perturbations in fluid osmolarity.


Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients.
Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (Cmin) of abiraterone. Patients with a plasma Cmin below the target of 8.4 ng/mL may benefit from treatment optimization by dose increase or concomitant intake with food. This study aims to investigate the cost-effectiveness of monitoring abiraterone Cmin in patients with mCRPC. A Markov model was built with health states progression-free survival, progressed disease, and death. The benefits of monitoring abiraterone Cmin followed by a dose increase or food intervention were modeled via a difference in the percentage of patients achieving adequate Cmin taking a healthcare payer perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainties and their impac to the incremental cost-effectiveness ratio (ICER). Monitoring abiraterone followed by a dose increase resulted in 0.149 incremental quality-adjusted life-years (QALYs) with €22 145 incremental costs and an ICER of €177 821/QALY. The food intervention assumed equal effects and estimated incremental costs of €7599, resulting in an ICER of €61 019/QALY. The likelihoods of therapeutic drug monitoring (TDM) with a dose increase or food intervention being cost-effective were 8.04%and 81.9%, respectively. Monitoring abiraterone followed by a dose increase is not cost-effective in patients with mCRPC from a healthcare payer perspective. Monitoring in combination with a food intervention is likely to be cost-effective. This cost-effectiveness assessment may assist decision making in future integration of abiraterone TDM followed by a food intervention into standard abiraterone acetate treatment practices of mCRPC patients.


Intracellular and extracellular forces drive primary cilia movement.
Primary cilia are ubiquitous, microtubule-based organelles that play diverse roles in sensory transduction in many eukaryotic cells. They interrogate the cellular environment through chemosensing, osmosensing, and mechanosensing using receptors and ion channels in the ciliary membrane. Little is known about the mechanical and structural properties of the cilium and how these properties contribute to ciliary perception. We probed the mechanical responses of primary cilia from kidney epithelial cells [Madin-Darby canine kidney-II (MDCK-II)], which sense fluid flow in renal ducts. We found that, on manipulation with an optical trap, cilia deflect by bending along their length and pivoting around an effective hinge located below the basal body. The calculated bending rigidity indicates weak microtubule doublet coupling. Primary cilia of MDCK cells lack interdoublet dynein motors. Nevertheless, we found that the organelles display active motility. 3D tracking showed correlated fluctuations of the cilium and basal body. These angular movements seemed random but were dependent on ATP and cytoplasmic myosin-II in the cell cortex. We conclude that force generation by the actin cytoskeleton surrounding the basal body results in active ciliary movement. We speculate that actin-driven ciliary movement might tune and calibrate ciliary sensory functions.


Results of a peer review process: the distribution of codes by examining dentists in the Republic of Ireland 2006-2007.
The Health Service Executive (HSE) appointed 20 examining dentists in April 2006 under contract for one year as part of a probity assurance initiative by peer review in the Dental Treatment Services Scheme (DTSS) in the Republic of Ireland. The aim of the study was to analyse the distribution of codes assigned to the reports drawn up by the examining dentists. At the end of the year's contract, each examining dentist forwarded an end of contract report of their activity, including the distribution of codes issued, to the HSE. These were correlated into a national summary of examining dentist activity, from which the data used in the study was extracted. A total of 11 different codes were used, varying from an indication of agreement between the examining dentist and the contracting dentist (code A) to a significant disagreement (code D). The vast majority (94.5%) of reports on the clinical examination of patients, drawn up by examining dentists, were in broad agreement with the treatment or estimate of the responsible contracting dentists. A total of 622 contracting dentists received such reports. The small minority of reports (4.8%) where there was a significant disagreement related to a small number of dentists (47 dentists). The study provides evidence that most contracting dentists were not a probity risk. The author suggests that any future probity assurance initiative should focus on areas of high risk rather than random selection of patients/contracting dentists. An enhanced advisory role for the examining dentist is recommended.


Semantic reasoning with XML-based biomedical information models.
The Extensible Markup Language (XML) is increasingly being used for biomedical data exchange. The parallel growth in the use of ontologies in biomedicine presents opportunities for combining the two technologies to leverage the semantic reasoning services provided by ontology-based tools. There are currently no standardized approaches for taking XML-encoded biomedical information models and representing and reasoning with them using ontologies. To address this shortcoming, we have developed a workflow and a suite of tools for transforming XML-based information models into domain ontologies encoded using OWL. In this study, we applied semantics reasoning methods to these ontologies to automatically generate domain-level inferences. We successfully used these methods to develop semantic reasoning methods for information models in the HIV and radiological image domains.


Neuroradiologic Pearls for Neuro-oncology.
This article reviews key principles in the identification of tumors of the central nervous system (CNS) using standard and advanced imaging modalities. This article highlights the pitfalls and pearls of the imaging evaluation of patients with cancer at time of diagnosis and during cancer therapy and discusses the challenges of the imaging evaluation of treatment-related toxicities. Treatment of CNS tumors with surgery, chemotherapy, or radiation alters the imaging appearance of the tumor and can be associated with a variety of treatment-related toxicities. The clinician must be familiar with how to assess response to treatment and how to differentiate tumor progression from treatment-related effects. Management and follow-up of neuro-oncology patients is optimized by a comprehensive radiologic approach to CNS tumors and recognition of the challenges in the assessment of response to treatments.


Use of phenotyping and genotyping to verify transmission of Escherichia coli O157:H7 from dairy farms.
A total of 80 human infections by Escherichia coli O157:H7 were documented in Finland in 1997 and 1998. Most were sporadic and their sources undetermined. Five cases not associated with one another, one of which led to secondary transmission within a family, could be traced to five different dairy farms. These five case patients (age range 2-17 years, median age 3 years) were hospitalised with bloody diarrhoea; two of them developed haemolytic uraemic syndrome. All nine human isolates obtained were sorbitol negative, carried the verocytotoxin 2 and eae genes, and produced verocytotoxin and enterohaemolysin. The phage and pulsed-field gel electrophoresis types of the human and bovine isolates from the corresponding farms were indistinguishable. The cattle (20-70 animals per farm) were monitored for up to 2 years after the human cases. The proportion of cattle excreting the type that caused the human infections varied from 3.2 to 66.7% when sampled soon after the human cases, and from 0.0 to 5.3% about a year or so later. On most of the farms, the animals excreted the pathogen intermittently. On one farm, Escherichia coli O157 isolates with other characteristics were also occasionally isolated. Although the infections were traced back to the farms, it could not be established whether the source was unpasteurised milk or direct or indirect contact with cattle. The results of this study emphasise the need for special recommendations for children visiting or living on a farm to prevent these infections.


A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP) buprenorphine treatment for African Americans.
Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans. Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors. Participants assigned to OP received, on average, 3.67 (SD=1.30)h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68)h of counseling per active week (less than the anticipated 9h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05). Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.


Coxiella burnetii Infection in Cats.
Q fever is a zoonotic disease caused by Coxiella burnetii, with farm ruminants being considered the main sources of infection for humans. However, there have been several cases of the disease in people that have been related to domestic cats as well. Cats can become infected through various routes, including ingestion of raw milk, hunting and consuming infected rodents and birds, consumption of contaminated pet food, inhalation of contaminated aerosols and dust, and bites from hematophagous arthropods. Infected cats typically do not show symptoms, but pregnant queens may experience abortion or give birth to weak kittens. Accurate diagnosis using serological and molecular methods is crucial in detecting infected cats, allowing for prompt action with appropriate treatments and preventive measures. Breeders, cattery personnel, veterinarians, and owners should be informed about the risks of C. burnetii infections associated with cats experiencing reproductive disorders.


Elevated plasma concentrations of atrial and brain natriuretic peptide in type 1 diabetic subjects.
The intravenous infusion of atrial (ANP) and brain (BNP) natriuretic peptides have been shown to increase urinary albumin excretion in type 1 diabetes. To measure plasma ANP and BNP concentrations in patients with type 1 diabetes and to examine the parameters associated with elevated plasma concentrations. Methods We measured plasma ANP and BNP concentrations, UAER, HbA1C systolic blood pressure, and left ventricular mass index. Plasma ANP and BNP were also measured in non-diabetic control subjects for comparison. Using multivariate regression analysis plasma ANP correlated positively with HbA1C (1.9 + 0.47, p = 0.0002), UAER (0.37 + 0.05, p = 0.00001), SBP (1.26 + 0.5, p = 0.01) and LVMI (00.46 + 0.25, p = 0.07). BNP was positively related with LVMI (0.95 + 0.4, p = 0.02), and UAER (0.56 + 0.08, p = 0.001). Plasma concentrations of ANP and BNP are elevated in some patients with type 1 diabetes. Plasma ANP concentrations are closely related to UAER and elevated plasma concentrations are associated with poor glycaemic control and systemic hypertension. Plasma BNP concentration is related to LVMI.


Oxidant-antioxidant balance in patients with COPD.
The goal of this study was to evaluate the role of oxidant-antioxidant balance in the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female; mean age (yr) +/- SD: 62.4 +/- 9.3], 30 healthy smokers [27 male, 3 female; mean age (yr) +/- SD: 58.7 +/- 6.0], 71 patients with stable COPD [68 male, 3 female; mean age (yr) +/- SD: 63.5 +/- 7.9], and 31 patients with COPD exacerbation [30 male, 1 female; mean age (yr) +/- SD: 64.2 +/- 7.3]. In all study groups the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation (1048.2 +/- 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers (947.9 +/- 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity in healthy smokers and patients with stable COPD was higher than in healthy nonsmokers, the difference was not statistically significant. We found that healthy smokers and stable and exacerbated COPD patients had an impairment in oxidant-antioxidant balance. We suggested that new therapeutic interventions, which may repair the impaired oxidant-antioxidant balance in COPD, are needed to prevent the development of COPD.


3D Neuron Morphology Analysis.
We consider the problem of finding an accurate representation of neuron shapes, extracting sub-cellular features, and classifying neurons based on neuron shapes. In neuroscience research, the skeleton representation is often used as a compact and abstract representation of neuron shapes. However, existing methods are limited to getting and analyzing"curve"skeletons which can only be applied for tubular shapes. This paper presents a 3D neuron morphology analysis method for more general and complex neuron shapes. First, we introduce the concept of skeleton mesh to represent general neuron shapes and propose a novel method for computing mesh representations from 3D surface point clouds. A skeleton graph is then obtained from skeleton mesh and is used to extract sub-cellular features. Finally, an unsupervised learning method is used to embed the skeleton graph for neuron classification. Extensive experiment results are provided and demonstrate the robustness of our method to analyze neuron morphology.


The dimensional crossover of quantum transport properties in few-layered Bi2Se3 thin films.
Topological insulator bismuth selenide (Bi2Se3) thin films with a thickness of 6.0 quintuple layers (QL) to 23 QL are deposited using pulsed laser deposition (PLD). The arithmetical mean deviation of the roughness (R a) of these films is less than 0.5 nm, and the root square mean deviation of the roughness (R q) of these films is less than 0.6 nm. Two-dimensional localization and weak antilocalization are observed in the Bi2Se3 thin films approaching 6.0 nm, and the origin of weak localization should be a 2D electron gas resulting from the split bulk state. Localization introduced by electron-electron interaction (EEI) is revealed by the temperature dependence of the conductivity. The enhanced contribution of three-dimensional EEI and electron-phonon interaction in the electron dephasing process is found by increasing the thickness. Considering the advantage of stoichiometric transfer in PLD, it is believed that the high quality Bi2Se3 thin films might provide more paths for doping and multilayered devices.


Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.
S-phase kinase-associated protein 2 (Skp2) is a substrate-specific adaptor in Skp1-CUL1-ROC1-F-box E3 ubiquitin ligases and widely regarded as an oncogene. Therefore, Skp2 has remained as an active anticancer research topic since its discovery. Accordingly, the structure of Skp2 has been solved and numerous Skp2 inhibiting compounds have been identified. In this review, we would describe the structural features of Skp2, introduce the ubiquitination function of SCFSkp2, and summarize the diverse natural and synthetic Skp2 inhibiting compounds reported to date. The IC50 data of the Skp2 inhibitors or inhibiting compounds in various kinds of tumors at cellular levels implied that the cancer type, stage and pathological mechanisms should be taken into consideration when selecting Skp2-inhibiting compound for cancer treatment.


Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid.
Multicellular tumor spheroids (MTS) provide a closer in vitro correlate to in vivo malignancy than do conventional monolayer cultures; while simulating many parameters of in vivo growth, MTS systems provide those perquisites (i.e., experimental control, economy, expediency) associated with in vitro evaluation of preclinical therapeutic strategies. For these reasons, we exploited the proclivity of the highly metastatic human prostatic carcinoma subline I-LN-PC3-IA to spontaneously assume a spheroid morphology under routine culture conditions. I-LN spheroids demonstrate salient features described in other spheroid systems and exhibit histologic characteristics of human prostate carcinoma. Cells encompassed in the I-LN spheroid format demonstrated functional divergence from their monolayer counterparts with respect to immunoreactivity for prostatic acid phosphatase, positional dependence of prostate-restricted p40 antigen expression, and chemotherapeutic drug response. This new in vitro-in vivo transition model of human prostatic carcinoma should provide a valuable in vitro context to expediently evaluate in vivo correlates of oncolytic protocols on a malignancy that remains refractive to therapy.


[Chromosome synteny of the A genome of two evolutionary wheat lines].
In order to estimate synteny between A(t) and A polyploid wheat genomes belonging to different evolutionary lines (Timopheevi and Emmer), saturation of chromosome maps of Triticum timopheevii A(t) genome by molecular markers has been conducted. Totally, 179 EST-SSR and 48 genomic SSR-markers have been used with the following integration of 13 and 7 markers correspondingly into chromosome maps of A(t) genome. EST-SSR showed higher transferability and lower polymorphism than genomic SSR markers. The chromosome maps designed were compared to maps of homoeologous chromosome group of the T. aestivum A genome. No disturbances of colinearity, i.e., of the order of markers within the chromosome segments on which they had been previously mapped, were observed. According to the quantity assessment of markers amplifying in homoeologous chromosomes, the maximum divergence was detected in two groups (4A(t)/4A and 3A(t)/3A) among the seven chromosomes examined in the A(t) and A genomes. Comparison of molecular genetic mapping results with the published results of studying meiosis of F1 hybrids and the frequency of chromosomes substitution in introgressive T. aestivum x T. timopheevii lines suggest that individual chromosomes of the At and A genomes evolve differently. Translocations were shown to introduce the major impact on the divergence of 4A(t)/4A and 6A(t)/6A chromosomes, while mutations of the primary DNA structure, on the divergence of homoeologous group 3 chromosomes. The level of reorganization of other chromosomes during the evolution in the A(t) and A genomes was significantly lower.


African Orphan Crops Consortium (AOCC): status of developing genomic resources for African orphan crops.
The African Orphan Crops Consortium (AOCC) successfully initiated the ambitious genome sequencing project of 101 African orphan crops/trees with 6 genomes sequenced, 6 near completion, and 20 currently in progress. Addressing stunting, malnutrition, and hidden hunger through nutritious, economic, and resilient agri-food system is one of the major agricultural challenges of this century. As sub-Saharan Africa harbors a large portion of the severely malnourished population, the African Orphan Crops Consortium (AOCC) was established in 2011 with an aim to reduce stunting and malnutrition by providing nutritional security through improving locally adapted nutritious, but neglected, under-researched or orphan African food crops. Foods from these indigenous or naturalized crops and trees are rich in minerals, vitamins, and antioxidant, and are an integral part of the dietary portfolio and cultural, social, and economic milieu of African farmers. Through stakeholder consultations supported by the African Union, 101 African orphan and under-researched crop species were prioritized to mainstream into African agri-food systems. The AOCC, through a network of international-regional-public-private partnerships and collaborations, is generating genomic resources of three types, i.e., reference genome sequence, transcriptome sequence, and re-sequencing 100 accessions/species, using next-generation sequencing (NGS) technology. Furthermore, the University of California Davis African Plant Breeding Academy under the AOCC banner is training 150 lead African scientists to breed high yielding, nutritious, and climate-resilient (biotic and abiotic stress tolerant) crop varieties that meet African farmer and consumer needs. To date, one or more forms of sequence data have been produced for 60 crops. Reference genome sequences for six species have already been published, 6 are almost near completion, and 19 are in progress.


[The application of laparocentesis and peritoneal lavage and the analysis of hemo-peritoneal volume in the diagnosis of closed abdominal wound].
Laparocentesis and peritoneal lavage--are simple, quick and informative methods widely applied in surgical practice for diagnosis of closed injury of abdominal cavity organs. Modifications of these diagnostic methods, their combination with possibility of hemoperitoneum volume detection, occurring while the internal organs injury, the results of investigation interpretation permit to broaden their possibilities, peculiarly in the absence of other instrumental diagnostic facilities available.


Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo.
As multiple myeloma tumors universally dysregulate cyclin D genes we conducted high-throughput chemical library screens for compounds that induce suppression of cyclin D2 promoter transcription. The top-ranked compound was a natural triterpenoid, pristimerin. Strikingly, the early transcriptional response of cells treated with pristimerin closely resembles cellular responses elicited by proteosome inhibitors, with rapid induction of heat shock proteins, activating transcription factor 3 (ATF3), and CHOP. Enzymatic assays and immunoblotting confirm that pristimerin rapidly (< 90 minutes) and specifically inhibits chymotrypsin-like proteosome activity at low concentrations (< 100 nM) and causes accumulation of cellular ubiquitinated proteins. Notably, cytotoxic triterpenoids including pristimerin inhibit NF-kappaB activation via inhibition of IKK alpha or IKK beta, whereas proteosome inhibitors instead suppress NF-kappaB function by impairing degradation of ubiquitinated I kappaB. By inhibiting both IKK and the proteosome, pristimerin causes overt suppression of constitutive NF-kappaB activity in myeloma cells that may mediate its suppression of cyclin D. Multiple myeloma is exquisitely sensitive to proteosome or NF-kappaB pathway inhibition. Consistent with this, pristimerin is potently and selectively lethal to primary myeloma cells (IC(50) < 100 nM), inhibits xenografted plasmacytoma tumors in mice, and is synergistically cytotoxic with bortezomib--providing the rationale for pharmaceutical development of triterpenoid dual-function proteosome/NF-kappaB inhibitors as therapeutics for human multiple myeloma and related malignancies.


The impact of tear functions on visual outcome following keratoplasty in eyes with keratoconus.
To investigate the impact of preoperative and postoperative tear functions on visual outcome and the recovery of visual function following keratoplasty in eyes with keratoconus. Twenty-five eyes of 25 consecutive patients (5 females, 20 males, mean age: 34.3 ± 15.8 years (range: 19-70 years) with keratoconus who underwent either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK) were included in this prospective study. One patient who had a rejection episode during the follow-up period was excluded. All subjects underwent best corrected visual acuity (BCVA), corneal topography (refractive cylinder, surface regularity index: SRI and surface asymmetry index: SAI), Schirmer I test, tear film break-up time (BUT), corneal sensitivity, and fluorescein staining score measurements before as well as 1, 3, 6 and 12 months after keratoplasty. The relation between the tear functions and the duration until the achievement of maximum BCVA was also evaluated. Linear regression analysis was performed to study the statistical significance of the correlations and the time wise change of each examined parameter. SRI, SAI, and BCVA significantly improved after keratoplasty. The postoperative corneal sensitivity was still significantly low even at 12 months postoperatively. Postoperative BCVA at 3, 6 months and maximum BCVA showed a significant linear negative correlation with the preoperative BUT (3 months; r = -0.461, p = 0.036, 6 months; r = -0.494, p = 0.023, maximum BCVA; r = -0.473, p = 0.030). The duration until the achievement of maximum BCVA showed a significant negative correlation with the preoperative Schirmer test (r = -0.429, p = 0.036). BCVA at 1 and 3 months postoperatively showed significant linear negative correlations with BUT value at the respective periods (1 month; r = -0.665, p = 0.0036, 3 months; r = -0.580, p = 0.0059). Preoperative tear functions appeared to have an influence on postoperative BCVA and the duration of visual recovery in keratoconus patients undergoing keratoplasty. Postoperative tear film stability appears to play an important role for obtaining a better BCVA in the early postoperative period after keratoplasty.


Emerging Viruses in the Republic of Suriname: Retrospective and Prospective Study into Chikungunya Circulation and Suspicion of Human Hantavirus Infections, 2008-2012 and 2014.
Suriname is a country on the northeastern Atlantic coast of South America. It is unique in the sense that different ethnic cultures live together within the country, resulting in high levels of transport of both humans and products between the Asian, African, and European continents as well as the Caribbean. Travel is only one of the many factors present in Suriname contributing to the risk for the emergence or introduction of any infectious disease. Recently, circulation of both chikungunya virus (CHIKV) and hantavirus was reported in areas neighboring Suriname. Here we report a retrospective and prospective study into chikungunya and hantavirus circulation. A chikungunya and hantavirus retrospective serological study was conducted on samples submitted for dengue, leptospirosis, and/or influenza virus diagnostics between 2008 and 2012 to the Bureau of Public Health in Suriname. This was followed by a prospective CHIKV serological and molecular surveillance study until the detection of the first autochthonous CHIKV cases in Suriname in May and June of 2014. None of the tested samples showed the presence of CHIKV antibodies in the retrospective serological study. Prospective testing of CHIKV-suspected patients resulted in the detection of the first autochthonous CHIKV cases in Suriname in May, 2015. In one sample, we were able to isolate and sequence the virus. Retrospective testing for the presence of hantavirus antibodies showed a relative high response in both pan-hantavirus enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). However, neutralization tests did not yield any evidence for infection with either Seoul or Andes hantavirus. Here we report the presence of CHIKV in the republic of Suriname and the first serological indication of hantavirus infections in symptomatic patients.


The stereotype that girls lack talent: A worldwide investigation.
Recent research has shown that there exist gender stereotypes that portray men as more brilliant or inherently talented than women. We provide a large-scale multinational investigation of these stereotypes and their relationship with other gender gaps. Using a survey question asked to more than 500,000 students in 72 countries, we build a measure of the stereotypes associating talent with men and show that they are present in almost all studied countries. These stereotypes are stronger among high-achieving students and in more developed or more gender-egalitarian countries. Similar patterns are observed for gender gaps in competitiveness, self-confidence, and willingness to work in an ICT (Information and Communication Technology)-related occupation. Statistical analysis suggests that these three latter gender gaps could be related to stereotypes associating talent with men. We conclude that these stereotypes should be more systematically considered as a possible explanation for the glass ceiling.


Gastric siderosis: patterns and significance.
Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%) patients with pattern A, in all patients with pattern B (n = 4, 100%), and in none of patients with pattern C (n=3, 0%). Varying degrees of mucosal inflammation were noted in patients with pattern A cases, and 2 had evidence of active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis, only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal siderosis is relatively uncommon (3%) but is important to look for as it may lead to a diagnosis of hemochromatosis in some cases. Three patterns are recognized: A) a "nonspecific" stromal cell predominant pattern, which may be associated with gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B) extracellular coarse clumps of crystalline iron deposition associated with oral iron medications, mild gastritis, and reactive gastropathy type changes ("Iron-pill gastritis"); and C) gastric glandular siderosis, which may be associated with systemic iron overload/hemochromatosis.


[Instrumental correction of severe kyphosis in tuberculous spondylitis in young children (new technology)].
A new mode has been proposed to correct deformities in tuberculous spondylitis complicated by more than 50 degrees kyphotic deformity. The mode involves extended repair of the vertebral column, supplemented by the use of Luque-modified posterior multisupport hooked contractors. The mode ensures correction deformity to 47 degrees. The procedures of a surgical intervention are described.


Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML.
Sequestration in the bone marrow niche may allow leukemic stem cells to evade exposure to drugs. Because the CXCR4/SDF-1 axis is an important mechanism of leukemic stem cell interaction with marrow stroma, we tested whether plerixafor, an antagonist of CXCR4, may dislodge chronic myeloid leukemia (CML) cells from the niche, sensitizing them to tyrosine kinase inhibitors. We initially treated mice with retrovirally induced CML-like disease with imatinib plus plerixafor. Plerixafor mobilized CXCR4(+) cells, but no difference was observed in leukemia burden, possibly reflecting insufficient disease control by imatinib. In a second series of experiments, we tested the combination of plerixafor with dasatinib in the same as well as an attenuated CML model. Despite much improved leukemia control, plerixafor failed to reduce leukemia burden over dasatinib alone. In addition, mice receiving plerixafor had an increased incidence of neurologic symptoms in association with CNS infiltration by BCR-ABL-expressing cells. We conclude that plerixafor is ineffective in reducing leukemia burden in this model but promotes CNS infiltration. Beneficial effects of combining tyrosine kinase inhibitors with plerixafor may be observed in a situation of minimal residual disease, but caution is warranted when disease control is incomplete.


Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression--a prospective 5-year follow-up study.
In depression, non-remission, recurrence of depressive episodes after remission and conversion to bipolar disorder are crucial determinants of poor outcome. The present study aimed to determine the cumulative incidences and clinical predictors of these long-term outcomes after the first lifetime episode of depression. A total of 301 in- or out-patients aged 18-70 years with a validated diagnosis of a single depressive episode were assessed from 2005 to 2007. At 5 years of follow-up, 262 patients were reassessed by means of the life chart method and diagnostic interviews from 2011 to 2013. Cumulative incidences and the influence of clinical variables on the rates of remission, recurrence and conversion to bipolar disorder, respectively, were estimated by survival analysis techniques. Within 5 years, 83.3% obtained remission, 31.5% experienced recurrence of depression and 8.6% converted to bipolar disorder (6.3% within the first 2 years). Non-remission increased with younger age, co-morbid anxiety and suicidal ideations. Recurrence increased with severity and treatment resistance of the first depression, and conversion to bipolar disorder with treatment resistance, a family history of affective disorder and co-morbid alcohol or drug abuse. The identified clinical characteristics of the first lifetime episode of depression should guide patients and clinicians for long-term individualized tailored treatment.


Tumor necrosis factor α induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts.
The nonresolving character of synovial inflammation in rheumatoid arthritis (RA) is a conundrum. To identify the contribution of fibroblast-like synoviocytes (FLS) to the perpetuation of synovitis, we investigated the molecular mechanisms that govern the tumor necrosis factor α (TNFα)-driven inflammatory program in human FLS. FLS obtained from the synovial tissues of patients with RA or osteoarthritis were stimulated with TNFα and assayed for gene expression and cytokine production by real-time quantitative reverse transcription-polymerase chain reaction analysis and enzyme-linked immunosorbent assay. NF-κB signaling was evaluated by Western blotting. Histone acetylation, chromatin accessibility, and NF-κB p65 and RNA polymerase II (Pol II) occupancy at the interleukin-6 (IL-6) promoter were measured by chromatin immunoprecipitation and restriction enzyme accessibility assays. In FLS, TNFα induced prolonged transcription of messenger RNA (mRNA) for IL-6 and progressive accumulation of IL-6 protein over 4 days. Similarly, induction of mRNA for CXCL8/IL-8, CCL5/RANTES, matrix metalloproteinase 1 (MMP-1), and MMP-3 after TNFα stimulation was sustained for several days. This contrasted with the macrophage response to TNFα, which characteristically involved a transient increase in the expression of proinflammatory genes. In FLS, TNFα induced prolonged activation of NF-κB signaling and sustained transcriptional activity, as indicated by increased histone acetylation, chromatin accessibility, and p65 and Pol II occupancy at the IL-6 promoter. Furthermore, FLS expressed low levels of the feedback inhibitors A20-binding inhibitor of NF-κB activation 3 (ABIN-3), IL-1 receptor-associated kinase M (IRAK-M), suppressor of cytokine signaling 3 (SOCS-3), and activating transcription factor 3 (ATF-3), which terminate inflammatory responses in macrophages. TNFα signaling is not effectively terminated in FLS, which leads to an uncontrolled inflammatory response. The results suggest that prolonged and sustained inflammatory responses by FLS in response to synovial TNFα contribute to the persistence of synovial inflammation in RA.


[Investigation on invasion of preepiglottic space by supraglottic carcinoma].
This study, based on analysis of 100 whole-organ serial sections of the larynx, concluded that preepiglottic space invasion is involved in 60% of supraglottic carcinoma. The preepiglottic space is involved either by invasion through the adjacent structures of the epiglottis, or more frequently by destroying the epiglottic cartilage and the thyro-epiglottic ligament. The preepiglottic space is involved mainly by epiglottic and epiglottic-ventricular carcinomas, accounting for 95% of carcinomas which invade the space. The involvement of preepiglottic space by supraglottic carcinoma is intimately related to the morphologic features, marginal growth patterns, and T classification. Ulcerative carcinoma is the commonest, accounting for 65%. The incidence of the infiltrative carcinomas is the highest. With increase in T stage, the percentage of invasion of preepiglottic space is increased. We believe that the easy invasion of the preepiglottic space by the supraglottic carcinoma is due to the fact that the epiglottic and epiglttic-ventricular carcinomas which account for 83% of supraglottic carcinomas are located in front of the larynx. In addition, the carcinoma easily destroys the epiglottic, cartilage and enters the preepiglottic space because the embryonic barrier which exists below the glottis and the perichondrium of the epiglottic cartilage is quite fragile.


Powdery Mildew Outbreaks caused by Podosphaera macularis on Hop Cultivars Possessing the Resistance Gene R6 in the Pacific Northwestern United States.
Resistant cultivars of hop (Humulus lupulus) have been grown, with the aim of helping to manage powdery mildew in the Pacific Northwest since the first report of the disease in the field in 1997 (4). A major objective of many breeding programs is development of resistance to powdery mildew, and this has generally been achieved by single resistance genes (qualitative resistance). One such gene, R6 (3), has been utilized extensively in new cultivars and has prevented epidemics of the disease in those cultivars across the Pacific Northwestern United States for approximately 15 years. In 2011, a grower in Washington State reported outbreaks of powdery mildew on cv. Apollo, which is thought to possess powdery mildew resistance derived from R6. Fungicides and cultural control measures were applied, and the grower reported no substantial crop damage from the disease. During the winter of 2012, the same grower planted rhizomes of cv. Apollo in a greenhouse in the Yakima Valley of Washington State and later found the plants to be affected by powdery mildew. Affected leaves from plants of cvs. Apollo, Newport, and Nugget (all reported [3] or assumed to possess R6 based on pedigree) grown in the same greenhouse were later provided to the authors. Conidia obtained from each affected plants were transferred to plants of the highly susceptible cv. Symphony, which is not known to contain any resistance genes. After 10 to 14 days of incubation, resultant conidia from each cultivar above (total of three isolates) were transferred to greenhouse grown plants of cvs. Nugget and Symphony and incubated at 18°C. Within 7 days, all three isolates produced powdery mildew colonies characteristic of P. macularis (2) on both cultivars. Cleistothecia did not develop in any colonies. In addition, Nugget and Symphony plants were inoculated with a field population of P. macularis originating from cultivars lacking R6 in Oregon. These inoculations on Nugget did not develop powdery mildew whereas Symphony plants did. Non-inoculated controls remained free of powdery mildew. Results were identical in two additional experiments. The sequence of the mating type idiomorph, MAT1-1, was obtained to confirm identity of the pathogen as P. macularis as described previously (1). The sequences were identical among the three isolates obtained from the greenhouse in Washington and isolates of P. macularis obtained previously from Oregon and Washington. MAT1-2 idiomorph was not detected in the isolates collected. While R6-virulent strains have been detected previously in race characterization experiments, these strains have not caused widespread epidemics of powdery mildew. The increasing prevalence of virulent strains of P. macularis and outbreaks of powdery mildew on formerly resistant cultivars necessitates changes in breeding strategies and disease management efforts to minimize damage resulting from the disease. The distribution of virulent strains of the pathogen and susceptibility of formerly resistance cultivars to powdery mildew are currently under investigation. References: (1) B. Asalfet et al. Phytopathology 103:717, 2013. (2) R. Bélanger et al. The Powdery Mildews: a Comprehensive Treatise. APS Press, St. Paul, MN, 2002. (3) P. Darby. Brew Hist. 121:94, 2005. (4) C. Ocamb et al. Plant Dis. 83:1072, 1999.


Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation.
Modeling late-onset disorders such as Parkinson's disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC model of PD. In order to manipulate a factor that is involved in natural aging as well as in premature aging syndromes, we used telomere shortening as an age-inducing tool. We show that shortened telomeres result in age-associated as well as potentially disease-associated phenotypes in human pluripotent stem cell (hPSC)-derived midbrain dopamine (mDA) neurons. Our approach provides proof of concept for the further validation of telomere shortening as an induced-aging tool for late-onset-disease modeling.


Photoelectrochemical performance of BiOI/TiO2 nanotube arrays (TNAs) p-n heterojunction synthesized by SILAR-ultrasonication-assisted methods.
In order to extend the visible region activity of titania nanotube array (TNAs) films, the successive ionic layer adsorption and reaction (SILAR)-ultrasonication-assisted method has been used to prepare BiOI-modified TiO2 nanotube arrays (BiOI/TNAs). The band gap of BiOI/TNAs for all the variations reveals absorption in the visible absorption. The surface morphology of BiOI/TNAs is shown in the nanoplate, nanoflake and nanosheet forms with a vertical orientation perpendicular to TiO2. The crystalline structure of BiOI did not change the structure of the anatase TNAs, with the band gap energy of the BiOI/TNAs semiconductor in the visible region. The photocurrent density of the BiOI/TNAs extends to the visible-light range. BiOI/TNAs prepared with 1 mM Bi and 1 mM KI on TNAs 40 V 1 h, 50 V 30 min show the optimum photocurrent density. A tandem dye-sensitized solar cell (DSSC)-photoelectrochemical (PEC) was used for hydrogen production in salty water. BiOI/TNAs optimum was used as the photoanode of the PEC cell. The solar to hydrogen conversion efficiency (STH) of tandem DSSC-PEC reaches 1.34% in salty water.


Current challenges in population health intervention research.
Population health interventions (PHIs) are generally complex; their results depend on their interaction with the context of their implementation. Moreover, the distinction between intervention and context is arbitrary: we need rather to consider an 'interventional system', including both interventional and contextual components. Evaluation must go beyond effectiveness and must include two key research questions: a viability analysis, to verify that the intervention can be routinised in a real-life context; and a theory-based evaluation, to analyse mechanisms and to understand what produces effects among components and their interactions with each other and with the context. PHI research is a question not only of the object but also of perspectives. This means doing research differently, making use of interdisciplinarity and involving stakeholders. Such an approach may contribute to the development, transfer, implementation and scaling-up of innovative interventions.


Neurotoxicity of cytarabine (Ara-C) in dorsal root ganglion neurons originates from impediment of mtDNA synthesis and compromise of mitochondrial function.
Peripheral Nervous System (PNS) neurotoxicity caused by cancer drugs hinders attainment of chemotherapy goals. Due to leakiness of the blood nerve barrier, circulating chemotherapeutic drugs reach PNS neurons and adversely affect their function. Chemotherapeutic drugs are designed to target dividing cancer cells and mechanisms underlying their toxicity in postmitotic neurons remain to be fully clarified. The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons. For proof of mechanism study, we chose cytarabine (ara-C), an antimetabolite used in treatment of hematological cancers. Ara-C is a cytosine analog that terminates DNA synthesis. To investigate how ara-C affects postmitotic neurons, which replicate mitochondrial but not genomic DNA, we adapted a model of Dorsal Root Ganglion (DRG) neurons. We showed that DNA polymerase γ, which is responsible for mtDNA synthesis, is inhibited by ara-C and that sublethal ara-C exposure of DRG neurons leads to reduction in mtDNA content, ROS generation, oxidative mtDNA damage formation, compromised mitochondrial respiration and diminution of NADPH and GSH stores, as well as, activation of the DNA damage response. Hence, it is plausible that in ara-C exposed DRG neurons, ROS amplified by the high mitochondrial content shifts from physiologic to pathologic levels signaling stress to the nucleus. Combined, the findings suggest that ara-C neurotoxicity in DRG neurons originates in mitochondria and that continuous mtDNA synthesis and reliance on oxidative phosphorylation for energy needs sensitize the highly metabolic neurons to injury by mtDNA synthesis terminating cancer drugs.


[The role of Ca2+, entering the cell during reperfusion, in the mechanism of initiation and maintenance of reperfusion arrhythmias].
The role of calcium ions entering cells upon reperfusion of ischemic myocardium for reperfusion arrhythmias has been investigated on the model of isolated rat right ventricle perfused through coronary artery. Manipulation by concentration of calcium ions in the reperfusion solution demonstrates that calcium ions entering cells upon reperfusion do not play a major role in the initiation of reperfusion extrasystoles and tachycardias, but have a significant influence on the maintenance of tachycardias. Multielectrode mapping revealed a focal source as the mechanism underlying reperfusion arrhythmias at low concentration or in the absence of calcium ions in the reperfusion solution.