Real-time electrochemical monitoring of adenosine triphosphate in the picomolar to micromolar range using graphene-modified electrodes.
We report on a competitive electrochemical detection system that is free of wash steps and enables the real-time monitoring of adenosine triphosphate (ATP) in a quantitative manner over a five-log concentration range. The system utilizes a recognition surface based on ATP aptamer (ATPA) capture probes prebound to electroactive flavin adenine dinucleotide (FAD) molecules, and a signaling surface utilizing graphene (Gr) and gold nanoparticle (AuNP) modified carbon paste electrode (Gr-AuNP-CPE) that is optimized to enhance electron-transfer kinetics and signal sensitivity. Binding of ATP to ATPA at the recognition surface causes the release of an equivalent concentration of FAD that can be quantitatively monitored in real time at the signaling surface, thereby enabling a wide linear working range (1.14 × 10(-10) to 3.0 × 10(-5) M), a low detection limit (2.01 × 10(-11) M using graphene and AuNP modified glassy carbon), and fast target binding kinetics (steady-state signal within 12 min at detection limit). Unlike assays based on capture probe-immobilized electrodes, this double-surface competitive assay offers the ability to speed up target binding kinetics by increasing the capture probe concentration, with no limitations due to intermolecular Coulombic interactions and nonspecific binding. We utilize the real-time monitoring capability to compute kinetic parameters for target binding and to make quantitative distinctions on degree of base-pair mismatch through monitoring target binding kinetics over a wide concentration range. On the basis of the simplicity of the assay chemistry and the quantitative detection of ATP within fruit and serum media, as demonstrated by comparison of ATP levels against those determined using a standard high-performance liquid chromatography (HPLC)-UV absorbance method, we envision a versatile detection platform for applications requiring real-time monitoring over a wide target concentration range.


Placebo Effects on the Neurologic Pain Signature: A Meta-analysis of Individual Participant Functional Magnetic Resonance Imaging Data.
Placebo effects reduce pain and contribute to clinical analgesia, but after decades of research, it remains unclear whether placebo treatments mainly affect nociceptive processes or other processes associated with pain evaluation. We conducted a systematic, participant-level meta-analysis to test the effect of placebo treatments on pain-associated functional neuroimaging responses in the neurologic pain signature (NPS), a multivariate brain pattern tracking nociceptive pain. Medline (PubMed) was searched from inception to May 2015; the search was augmented with results from previous meta-analyses and expert recommendations. Eligible studies were original investigations that were published in English in peer-reviewed journals and that involved functional neuroimaging of the human brain with evoked pain delivered under stimulus intensity-matched placebo and control conditions. The authors of all eligible studies were contacted and asked to provide single-participant data. Data were collected between December 2015 and November 2017 following the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. Results were summarized across participants and studies in a random-effects model. The main, a priori outcome was NPS response; pain reports were assessed as a secondary outcome. We obtained data from 20 of 28 identified eligible studies, resulting in a total sample size of 603 healthy individuals. The NPS responses to painful stimulation compared with baseline conditions were positive in 575 participants (95.4%), with a very large effect size (g = 2.30 [95% CI, 1.92 to 2.69]), confirming its sensitivity to nociceptive pain in this sample. Placebo treatments showed significant behavioral outcomes on pain ratings in 17 of 20 studies (85%) and in the combined sample (g = -0.66 [95% CI, -0.80 to -0.53]). However, placebo effects on the NPS response were significant in only 3 of 20 studies (15%) and were very small in the combined sample (g = -0.08 [95% CI, -0.15 to -0.01]). Similarly, analyses restricted to studies with low risk of bias (g = -0.07 [95% CI, -0.15 to 0.00]) indicated very small effects, and analyses of just placebo responders (g = -0.22 [95% CI, -0.34 to -0.11]) indicated small effects, as well. Placebo treatments have moderate analgesic effects on pain reports. The very small effects on NPS, a validated measure that tracks levels of nociceptive pain, indicate that placebo treatments affect pain via brain mechanisms largely independent of effects on bottom-up nociceptive processing.


Postoperative abdominal CT findings in patients submitted to Roux-en-y gastric bypass without ring.
To evaluate by CT scan in patients undergoing laparoscopic Roux-en-Y gastric bypass without a ring for treatment of morbid obesity that looked for medical assistance after the operation. We studied 40 CT exams from patients attended at the radiology service with the intention to clarify abdominal complains. The patients were in post-bariatric surgical follow-up and were operated in the same hospital. We excluded patients who had undergone bariatric surgery by other surgical techniques, operated by another surgical team and the ones who did not agree with the administration of oral or intravenous iodinated contrast media and exceeding the weight limit of the examination table. The patients were aged from 23 to 70 years, 11 male and 29 female. There were no extra-abdominal changes, and 30 of the 40 patients had CT findings within normal limits. The presence of stenosis at the gastrojejunal anastomosis was found in one patient, internal hernias occurred in five, anastomotic leak in one and the presence of abscess occurred in three of patients. Total abdominal CT failed to inform the cause of the symptoms in 87.5% of patients seeking medical re-evaluation for symptoms of post-operative bariatric surgery.


External quality assurance in nongynecologic cytology: The Australasian experience.
The Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program has operated an external quality assurance program in nongynecologic cytopathology since 1993. Glass slide preparations of a wide range of nongynecologic cases were circulated to approximately 200 cytopathology laboratories in 16 countries. General nongynecologic cytology cases were manufactured from residual specimens after routine diagnosis. Fine-needle aspiration (FNA) cases were made by sampling fresh tissue and making direct specimens. The majority of cases consisted of both air-dried and fixed preparations. Results returned to laboratories included illustrated case discussions highlighting diagnostic features, key differential diagnoses, and useful adjunctive tests. The current study reviewed >22,000 results for 123 nongynecologic cases. Cases found to cause the most diagnostic difficulties included serous effusion cases with metastatic carcinoma in a dispersed pattern, well-differentiated carcinoma, and cellular reactive cases; urine specimens with sparse malignant cells; reactive pneumocytes in a bronchoalveolar lavage; breast FNA cases with papillary lesions; gestational specimens; and fibroadenoma. FNA specimens from the lung and thyroid, particularly papillary thyroid carcinoma, generally were well reported. The use of multiple preparations of the same specimen has allowed interlaboratory comparison, and the quality assurance program has played an educational role as well as informing the laboratory accreditation process. Cancer Cytopathol 2017;125:349-361. © 2017 American Cancer Society.


Theory of diffraction of vortex beams from 2D orthogonal periodic structures and Talbot self-healing under vortex beam illumination.
This work presents a detailed analytic approach to the diffraction of vortex beams from 2D orthogonal periodic structures. Using the presented formulation, the diffraction of vortex beams from 2D sinusoidal and Ronchi gratings is investigated. For these gratings, the Talbot self-healing effect under vortex beam illumination is examined. In the illumination of a 2D grating with a vortex beam, we refer the Talbot self-healing effect to the filling of the null area of the incident beam under propagation. We show that, for an incident vortex beam having odd value of topological charge, the generated Talbot self-images over the self-healing area are a 2D array of optical vortices, in which each of the individual self-images gets the form of an optical vortex with a topological charge of l=1 regardless of the topological charge of the incident beam. Both the Talbot self-healing effect and generation of the 2D array of optical vortices occur optimally between a definite interval of propagation distance. Using an intuitive approach based on the interference of the diffracted orders of the grating, we determine the self-healing interval. We show that a 2D array of optical vortices can be generated directly in the interference of eight copies of a vortex beam having proper lateral shifts and relative tilts. Easy tuning and energy preservation are two main advantages that the interference-based method has over the above-mentioned diffraction-based method for generating a 2D array of optical vortices. However, setup and implementation of the diffraction-based method are very simple. We believe that both the diffraction-based and interference-based methods for creating vortex beam arrays might find applications in optical tweezers, micromanipulations, and microfluidics.


FBP21's C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase.
Based on our recent finding that FBP21 regulates human Brr2 helicase activity involved in the activation of the spliceosomal B-complex, we investigated the structural and dynamic contribution of FBP21 to the interaction. By using NMR spectroscopy, we could show that the 50 C-terminal residues of FBP21 (FBP21326-376), which are sufficient to fully form the interaction with the C-terminal Sec63 unit of Brr2 (Brr2C-Sec63), adopt a random-coil conformation in their unbound state. Upon interaction with Brr2C-Sec63, 42 residues of FBP21326-376 cover the large binding site on Brr2C-Sec63 in an extended conformation. Short charged motifs are steering complex formation, still allowing the bound state to retain dynamics. Based on fragment docking in combination with experimental restraints, we present models of the complex structure. The FBP21326-376/Brr2C-Sec63 interaction thus presents an example of an intrinsically disordered protein/ordered-protein interaction in which a large binding site provides high specificity and, in combination with conformational disorder, displays a relatively high affinity.


Neuroprotection by Cocktails of Dietary Antioxidants under Conditions of Nerve Growth Factor Deprivation.
Dietary antioxidants may be useful in counteracting the chronic inflammatory status in neurodegenerative diseases by reducing oxidative stress due to accumulation of reactive oxygen species (ROS). In this study, we newly described the efficacy of a number of dietary antioxidants (polyphenols, carotenoids, thiolic compounds, and oligoelements) on viability of neuronal PC12 cells following Nerve Growth Factor (NGF) deprivation, a model of age-related decrease of neurotrophic support that triggers neuronal loss. Neuroprotection by antioxidants during NGF deprivation for 24 h was largely dependent on their concentrations: all dietary antioxidants were able to efficiently support cell viability by reducing ROS levels and restoring mitochondrial function, while preserving the neuronal morphology. Moreover, ROS reduction and neuroprotection during NGF withdrawal were also achieved with defined cocktails of 3-6 different antioxidants at concentrations 5-60 times lower than those used in single treatments, suggesting that their antioxidant activity was preserved also at very low concentrations. Overall, these data indicate the beneficial effects of antioxidants against oxidative stress induced by decreased NGF availability and suggest that defined cocktails of dietary factors at low concentrations might be a suitable strategy to reduce oxidative damage in neurodegenerative diseases, while limiting possible side effects.


A Meta-Analysis Linking Parent-to-Child Aggression and Dating Abuse During Adolescence and Young Adulthood.
Relationship continuity and social learning theories provide support for parent-to-child aggression as one potential explanatory factor for dating abuse (DA); however, empirical results are mixed across studies as to the strength of this association. This meta-analysis sought to estimate the overall size of this effect among adolescent and young adult samples and investigate potential moderating factors including sample and measurement variables. Records were identified using a computerized search of databases with several keywords. Peer-reviewed journal articles and dissertations were included if they measured both parent-to-child aggression and DA perpetration and/or victimization among adolescents (aged 12-18) or young adults (aged 18-29). Sixty-six records met inclusion criteria, yielding 370 unique effect sizes for the relation between parent-to-child aggression and DA across 94 unique samples. As hypothesized, there was a small-to-medium effect size between parent-to-child aggression and subsequent DA during both adolescence and young adulthood. The strength of these findings was consistent across DA outcome (perpetration and victimization) and both physical and psychological forms, youth and parent gender, and youth age. Stronger associations were found when the gender of the parental aggressor was undefined compared to either a defined paternal or maternal aggressor. Records using the Conflict Tactics Scale to measure both parent-to-child aggression and DA yielded stronger associations compared to sources that used different measures, but single informant versus multiple informants did not yield any differences.


Interferometric distributed optical-fiber sensor.
An interferometric technique is described for detecting and locating perturbations along an optical fiber. This distributed sensor, based on a modified fiber-ring interferometer, has a position-dependent response to time-varying disturbances such as strain or temperature. These disturbances cause a phase shift that is detected and converted to spatial information. The sensor consists of two parts, namely, a reflecting-fiber-ring interferometer and a differentiating-ring interferometer. The reflecting ring consists of a fiber ring with one port of the coupler connected to a reflector. Consequently the output port of the reflecting-ring interferometer is the same as the input port. Because it is an inherent zero-path-imbalanced system, a short-coherence-length source such as a light-emitting diode can be used. Any time-varying perturbation on the fiber in the ring results in a detector signal proportional to the product of the rate-of-phase change caused by the perturbation and the distance of the perturbation relative to the center of the fiber ring. The second part of the system, a differentiating-ring interferometer, consists of the same fiber-ring interferometer modified only slightly. The output of this part of the sensor is proportional only to the rate of phase change as a result of the unknown perturbation and contains no distance information. By dividing the output of the reflecting-ring interferometer by the output of the differentiating-ring interferometer, we determine disturbance location. Results obtained with a 155-m distributed fiber sensor are discussed.


Patterns of HIV testing at a London teaching hospital between 2004 and 2007.
To observe trends in testing for HIV between 2004 and 2007 in a London hospital and to observe the seroprevalence of HIV within subgroups. Tests were grouped according to source and reason for testing; 58,720 tests were considered (HIV-1 seroprevalence = 0.9%). The majority (75.4%) of tests were performed as part of routine and opt-out protocols including antenatal and genitourinary screening. Among people specifically seeking HIV testing, the HIV seroprevalence was 3.5%. Medical specialties performed fewer tests but a high HIV seroprevalence was observed, including infectious disease (seroprevalence 4.4%) and other medical specialties (seroprevalence 3.4%). A small number of specialties performed few HIV tests. HIV testing was cost-effective in virtually all settings. This study suggests that more HIV tests could be performed, for example, in acute medicine, and training might increase the number of tests offered in some settings. The most effective way of increasing testing appears to be opt-out testing.


A survey of food problems experienced by Toronto street youth.
A brief survey was undertaken to assess the nature and severity of food scarcity experienced by a sample of 88 street youth in downtown Toronto, and to identify markers of vulnerability to food scarcity. Almost half of the youth reported experiencing involuntary hunger or food deprivation during the previous 30 days. Youth who were literally homeless (i.e., on the street or "squatting" in abandoned buildings) and those relying primarily on street-based activities for income appeared particularly vulnerable to food deprivation. Although limited in scope, the findings raise questions about the nutritional well-being of street youth and highlight the need for more effective interventions to address problems of poverty, hunger, and homelessness among Canadian youth.


Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.
In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).


The selective effect of the image of a hand on visuotactile interactions as assessed by performance on the crossmodal congruency task.
Seeing one's own body (either directly or indirectly) can influence visuotactile crossmodal interactions. Previously, it has been shown that even viewing a simple line drawing of a hand can also modulate such crossmodal interactions, as if viewing the picture of a hand somehow primes the representation of one's own hand. However, factors other than the sight of a symbolic picture of a hand may have modulated the crossmodal interactions reported in previous research. In the present study, we examined the crossmodal modulatory effects of viewing five different visual images (photograph of a hand, line drawing of a hand, line drawing of a car, an U-shape, and an ellipse) on tactile performance. Participants made speeded discrimination responses regarding the location of brief vibrotactile targets presented to either the tip or base of their left index finger, while trying to ignore visual distractors presented to either the left or right of central fixation. We compared the visuotactile congruency effects elicited when the five different visual images were presented superimposed over the visual distractors. Participants' tactile discrimination performance was modulated to a significantly greater extent by viewing the photograph of a hand than when viewing the outline drawing of a hand. No such crossmodal congruency effects were reported in any of the other conditions. These results therefore suggest that visuotactile interactions are specifically modulated by the image of the hand rather than just by any simple orientation cues that may be provided by the image of a hand.


Carotid intima-media thickness and arterial stiffness as early markers of atherosclerosis in pediatric celiac disease.
The association between pediatric celiac disease (CD) and atherosclerosis is unknown. Our aim was to investigate whether pediatric CD patients have an increased risk of atherosclerosis. We evaluated the premature atherosclerosis by pulse wave velocity (PWV) and carotid intima-media thickness (cIMT). A total of 37 CD patients (20 girls, mean age 13±3.3 years) and 36 healthy age and sex matched controls were enrolled. Mean duration of CD was 47.1±32.3 months and 40.5% of patients had positive tissue transglutaminase antibody (tTg) IgA. Total cholesterol level was lower in CD (p=0.026) and cIMT was lower in tTg IgA antibody negative CD (p=0.030). cIMT was significantly correlated with tTg IgA antibody positivity (r=0.336; p=0.042). Adherence to strict gluten-free diet is associated with decreased cIMT, suggesting that gluten withdrawal seems to have a beneficial effect on premature atherosclerosis.


Pharmacological characterization of GABAA receptors in taurine-fed mice.
Taurine is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. Chronic supplementation of taurine in drinking water to mice increases brain excitability mainly through alterations in the inhibitory GABAergic system. These changes include elevated expression level of glutamic acid decarboxylase (GAD) and increased levels of GABA. Additionally we reported that GABAA receptors were down regulated with chronic administration of taurine. Here, we investigated pharmacologically the functional significance of decreased / or change in subunit composition of the GABAA receptors by determining the threshold for picrotoxin-induced seizures. Picrotoxin, an antagonist of GABAA receptors that blocks the channels while in the open state, binds within the pore of the channel between the beta2 and beta3 subunits. These are the same subunits to which GABA and presumably taurine binds. Two-month-old male FVB/NJ mice were subcutaneously injected with picrotoxin (5 mg kg-1) and observed for a) latency until seizures began, b) duration of seizures, and c) frequency of seizures. For taurine treatment, mice were either fed taurine in drinking water (0.05%) or injected (43 mg/kg) 15 min prior to picrotoxin injection. We found that taurine-fed mice are resistant to picrotoxin-induced seizures when compared to age-matched controls, as measured by increased latency to seizure, decreased occurrence of seizures and reduced mortality rate. In the picrotoxin-treated animals, latency and duration were significantly shorter than in taurine-treated animas. Injection of taurine 15 min before picrotoxin significantly delayed seizure onset, as did chronic administration of taurine in the diet. Further, taurine treatment significantly increased survival rates compared to the picrotoxin-treated mice. We suggest that the elevated threshold for picrotoxin-induced seizures in taurine-fed mice is due to the reduced binding sites available for picrotoxin binding due to the reduced expression of the beta subunits of the GABAA receptor. The delayed effects of picrotoxin after acute taurine injection may indicate that the two molecules are competing for the same binding site on the GABAA receptor. Thus, taurine-fed mice have a functional alteration in the GABAergic system. These include: increased GAD expression, increased GABA levels, and changes in subunit composition of the GABAA receptors. Such a finding is relevant in conditions where agonists of GABAA receptors, such as anesthetics, are administered.


Can the cardiovascular family history reported by our patients be trusted? The Norwegian Stroke in the Young Study.
Family history (FH) is used as a marker for inherited risk. Using FH for this purpose requires the FH to reflect true disease in the family. The aim was to analyse the concordance between young and middle-aged ischaemic stroke patients' reported FH of cardiovascular disease (CVD) with their parents' own reports. Ischaemic stroke patients aged 15-60 years and their eligible parents were interviewed using a standardized questionnaire. Information of own CVD and FH of CVD was registered. Concordance between patients and parents was tested by kappa statistics, sensitivity, specificity, predictive values and likelihood ratios. Regression analyses were performed to identify patient characteristics associated with non-concordance of replies. There was no difference in response rate between fathers and mothers (P = 0.355). Both parents responded in 57 cases. Concordance between patient and parent reports was good, with kappa values ranging from 0.57 to 0.7. The patient-reported FH yielded positive predictive values of 75% or above and negative predictive values of 90% or higher. The positive likelihood ratios (LR+) were 10 or higher and negative likelihood ratios (LR-) were generally 0.5 or lower. Interpretation regarding peripheral arterial disease was limited due to low parental prevalence. Higher age was associated with impaired concordance between patient and parent reports (odds ratio 1.05; 95% confidence interval 1.01-1.09; P = 0.020). The FH provided by young and middle-aged stroke patients is in good concordance with parental reports. FH is an adequate proxy to assess inherited risk of CVD in young stroke patients.


Obesity-Altered Adipose Stem Cells Promote ER⁺ Breast Cancer Metastasis through Estrogen Independent Pathways.
Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These cells are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER⁺) breast cancer (BC) tumor growth and metastasis. In this study, we evaluate the effect of obASCs on ER⁺BC outside of the ERα signaling axis using breast cancer models with constitutively active ERα resulting from clinically relevant mutations (Y537S and D538G). We found that while obASCs promote tumor growth and proliferation, it occurs mostly through abrogated estrogen signaling when BC has constitutive ER activity. However, obASCs have a similar promotion of metastasis irrespective of ER status, demonstrating that obASC promotion of metastasis may not be completely estrogen dependent. We found that obASCs upregulate two genes in both ER wild type (WT) and ER mutant (MUT) BC: SERPINE1 and ABCB1. This study demonstrates that obASCs promote metastasis in ER WT and MUT xenografts and an ER MUT patient derived xenograft (PDX) model. However, obASCs promote tumor growth only in ER WT xenografts.


The effect of penicillin therapy on cognitive outcomes in neurosyphilis: a systematic review of the literature.
Neurosyphilis commonly presents with cognitive impairment, and penicillin remains the treatment of choice. However, despite a rapid increase in syphilis incidence, the effect of penicillin on long-term cognitive outcomes has not previously been evaluated. We therefore aimed to assess the effect of penicillin on cognitive function in neurosyphilis. We performed a systematic review of all studies of neurosyphilis, where cognitive function was assessed objectively both before and after penicillin therapy for at least one patient. Where Mini-Mental State Examination (MMSE) scores were taken, we performed a paired-samples t test to assess the change in cognitive function and aimed to correlate this with change in serological titers. Nine studies met inclusion criteria. The one cohort study reported a nonsignificant overall improvement in MMSE, while amalgamation of case reports produced a significant improvement (P=.02) in MMSE after treatment. However, follow-up duration was inadequate, and data were insufficient to correlate changes in cognitive function with serological markers. Despite evidence of short-term improvement, there are insufficient data to support the long-term benefit of penicillin therapy on cognitive function in neurosyphilis.


Comment on "Tequila, a neurotrypsin ortholog, regulates long-term memory formation in Drosophila".
Didelot et al. (Reports, 11 August 2006, p. 851) claimed that Drosophila Tequila (Teq) and human neurotrypsin are orthologs and concluded that deficient long-term memory after Teq inactivation indicates that neurotrypsin plays its essential role for human cognitive functions through a similar mechanism. Our analyses suggest that Teq and neurotrypsin are not orthologous, leading us to question their equivalent roles in higher brain function.


Measurements of spectral emission and absorption of a high pressure xenon arc in the stationary and the flashed modes.
Concurrently with emission measurements of a high pressure xenon arc in the spectral range 3000 A to 2 micro, its absorption in the ir was measured by a technique based on modulating the less intense radiation of a carbon arc used as background source. The emission measurements were repeated with a rapid scanning spectrometer while flashing the xenon arc for 0.1 see at 10 kW, which is five times the normal power input. The arc showed excellent stability and reproducibility both in the stationary and the flashed modes. The intensity increase of the continuum was proportional to the increase of power input during the flash. A simple expression was derived connecting the spectral radiance of the continuum directly with the temperature and pressure of the arc. The temperature profile of the xenon arc was obtained using this expression and also by applying the Planck-Kirchhoff method to the Abel inverted emission and absorption of an ir xenon line. Both approaches show fair agreement at the arc center. The wavelength dependence of the correction factor for departures from hydrogenic behavior of the xenon continuum was derived from the measured spectral radiances and compared with theoretical calculations.


Backbone circularization of Bacillus subtilis family 11 xylanase increases its thermostability and its resistance against aggregation.
The activity of proteins is dictated by their three-dimensional structure, the native state, and is influenced by their ability to remain in or return to the folded native state under physiological conditions. Backbone circularization is thought to increase protein stability by decreasing the conformational entropy in the unfolded state. A positive effect of circularization on stability has been shown for several proteins. Here, we report the development of a cloning standard that facilitates implementing the SICLOPPS technology to circularize proteins of interest using split inteins. To exemplify the usage of the cloning standard we constructed two circularization vectors based on the Npu DnaE and gp41-1 split inteins, respectively. We use these vectors to overexpress in Escherichia coli circular forms of the Bacillus subtilis enzyme family 11 xylanase that differ in the identity and number of additional amino acids used for circularization (exteins). We found that the variant circularized with only one additional serine has increased thermostability of 7 °C compared to native xylanase. The variant circularized with six additional amino acids has only a mild increase in thermostability compared to the corresponding exteins-bearing linear xylanase, but is less stable than native xylanase. However, this circular xylanase retains more than 50% of its activity after heat shock at elevated temperatures, while native xylanase and the corresponding exteins-bearing linear xylanase are largely inactivated. We correlate this residual activity to the fewer protein aggregates found in the test tubes of circular xylanase after heat shock, suggesting that circularization protects the protein from aggregation under these conditions. Taken together, these data indicate that backbone circularization has a positive effect on xylanase and can lead to increased thermostability, provided the appropriate exteins are selected. We believe that our cloning standard and circularization vectors will facilitate testing the effects of circularization on other proteins.


Evolution of a mesoporous bioactive glass scaffold implanted in rat femur evaluated by (45)Ca labeling, tracing, and histological analysis.
Mesoporous bioactive glass (MBG) as a biodegradable scaffold with a nanostructure has attracted significant attention. However, the in vivo evolution of MBG, which includes in situ degradation, the local effect induced by degradation, and the disposition of degradation products, remains unclear. In this study, we performed in situ labeling and synthesis of an MBG scaffold for the first time using (45)CaCl2. The obtained (45)Ca-MBG scaffolds possessed a mesoporous-macroporous cross-linked structure. These (45)Ca-MBG scaffolds were implanted in critical-sized rat femur defects (3 × 3 mm) for 1 day and for 1, 4, 8, and 12 weeks and analyzed by isotopic quantitative tracing. The results illustrated that the MBG scaffolds gradually degraded over time and persisted at a local level of approximately 9.63% at week 12. This finding suggests that only a very small amount of MBG-released calcium ions may have been transformed into calcium components of the new bone matrix. The research also confirmed that the active ingredients derived from the degradation of MBG scaffolds could actively regulate the mRNA expression levels of osteoblast-related genes in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and promote bone regeneration in vivo. Moreover, through isotopic tracing of the entire body, (45)Ca, which disappeared in situ after implantation, could be detected in the heart, lungs, spleen, kidneys, intestines, and brain via the blood and was mainly accumulated in distal bone tissue, including the radius and cranium. However, (45)Ca radioactivity in the body tissues significantly decreased or disappeared after 12 weeks. Systemic toxicological studies on MBG scaffolds demonstrated the degradation products that spread to major organs did not cause abnormal histopathological changes. The above discoveries comprehensively address crucial issues regarding the application of MBG in vivo, and these findings provide a scientific basis for introducing a material with mesoporous structure into clinical applications.


Adult nutrient intake as a risk factor for Parkinson's disease.
This population-based case-control study evaluated nutrient intake as a risk factor for Parkinson's disease (PD) among people aged > or =50 years in metropolitan Detroit. Cases (n = 126) were diagnosed between 1991 and 1995 and neurologist-confirmed. Controls (n = 432) were frequency-matched for sex, age (+/-5 years) and race. Using a standardized food frequency questionnaire, subjects reported the foods they ate within the past year. Estimating the association between PD and risk of being in the highest versus the lowest intake quartile, there were elevated odds ratios for total fat (OR 1.94, 95% confidence interval [CI] : 1.05-3.58), cholesterol (OR 2.11, 95% CI: 1.14-3.90), lutein (OR 2.52, 95% CI: 1.32-4.84) and iron (OR 1.88, 95% CI: 1.05-3.38). These results suggest an association of PD with high intake of total fat, saturated fats, cholesterol, lutein and iron.


Intestinal Behçet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis?
Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor α antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision.


Is the secure base phenomenon evident here, there, and anywhere? A cross-cultural study of child behavior and experts' definitions.
The evolutionary rationale offered by Bowlby implies that secure base relationships are common in child-caregiver dyads and thus, child secure behavior observable across diverse social contexts and cultures. This study offers a test of the universality hypothesis. Trained observers in nine countries used the Attachment Q-set to describe the organization of children's behavior in naturalistic settings. Children (N = 547) were 10-72 months old. Child development experts (N = 81) from all countries provided definitions of optimal child secure base use. Findings indicate that children from all countries use their mother as a secure base. Children's organization of secure base behavior was modestly related to each other both within and across countries. Experts' descriptions of the optimally attached child were highly similar across cultures.


Sources of organic nitrogen at the serpentinite-hosted Lost City hydrothermal field.
The reaction of ultramafic rocks with water during serpentinization at moderate temperatures results in alkaline fluids with high concentrations of reduced chemical compounds such as hydrogen and methane. Such environments provide unique habitats for microbial communities capable of utilizing these reduced compounds in present-day and, possibly, early Earth environments. However, these systems present challenges to microbial communities as well, particularly due to high fluid pH and possibly the availability of essential nutrients such as nitrogen. Here we investigate the source and cycling of organic nitrogen at an oceanic serpentinizing environment, the Lost City hydrothermal field (30°N, Mid-Atlantic Ridge). Total hydrolizable amino acid (THAA) concentrations in the fluids range from 736 to 2300 nm and constitute a large fraction of the dissolved organic carbon (2.5-15.1%). The amino acid distributions, and the relative concentrations of these compounds across the hydrothermal field, indicate they most likely derived from chemolithoautotrophic production. Previous studies have identified the presence of numerous nitrogen fixation genes in the fluids and the chimneys. Organic nitrogen in actively venting chimneys has δ(15) N values as low as 0.1‰ which is compatible with biological nitrogen fixation. Total hydrolizable amino acids in the chimneys are enriched in (13) C by 2-7‰ compared to bulk organic matter. The distribution and absolute δ(13) C(THAA) values are compatible with a chemolithoautotrophic source, an attribution also supported by molar organic C/N ratios in most active chimneys (4.1-5.5) which are similar to those expected for microbial communities. In total, these data indicate nitrogen is readily available to microbial communities at Lost City.


Dissemination and replication of MCMV after supraciliary inoculation in immunosuppressed BALB/c mice.
To study replication and dissemination of murine cytomegalovirus (MCMV) in immunosuppressed (IS) and non-IS BALB/c mice after ocular inoculation via the supraciliary route. BALB/c mice were immunosuppressed by injections of methylprednisolone, and MCMV was injected via the supraciliary route. Ocular and nonocular tissues from both IS and non-IS mice were studied by plaque assay of tissue homogenates. The frequency of virus-positive leukocytes was determined by PCR. In the inoculated eye, virus replication was significantly higher in both the anterior segment and the posterior segment of IS mice. Virus spread to extraocular sites in both IS and non-IS mice; however, significantly higher titers of virus were recovered from the salivary glands and lungs of IS mice than from non-IS mice, and clearance of virus from these sites was delayed in IS mice. Virus spread from the injected eye via leukocytes, and PCR amplification revealed that the frequency of virus-infected leukocytes was approximately 200-fold higher in IS mice. The results of these studies suggest that immunosuppression significantly enhances virus replication in the inoculated eye, salivary glands, and lungs, leads to a higher frequency of virus-positive leukocytes, and delays clearance of virus from ocular and nonocular tissues. These results also suggest that retinitis in the injected eye of IS mice correlates with significantly higher titers of virus in the posterior segment.


Nickel-catalyzed dimerization of pyrrolidinoindoline scaffolds: systematic access to chimonanthines, folicanthines and (+)-WIN 64821.
While metal-promoted activation of tertiary alkyl halides often causes elimination and hydrodehalogenation, we have developed a nickel-catalyzed reductive dimerization that allows the generation of a potently reactive tertiary radical equivalent to form a very congested C(sp(3))-C(sp(3)) bond even below room temperature. The catalytic protocol is applicable to the dimerization of several pyrrolidinoindoline scaffolds through an appropriate choice of catalyst to accommodate different substrate reactivities with functional group compatibilities. The efficiency of the nickel-catalyzed protocol was successfully demonstrated through a systematic total synthesis of chimonanthines, folicanthines and (+)-WIN 64821.


Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients.
Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).


Primary and secondary dimer interfaces of the fibroblast growth factor receptor 3 transmembrane domain: characterization via multiscale molecular dynamics simulations.
Receptor tyrosine kinases are single-pass membrane proteins that form dimers within the membrane. The interactions of their transmembrane domains (TMDs) play a key role in dimerization and signaling. Fibroblast growth factor receptor 3 (FGFR3) is of interest as a G380R mutation in its TMD is the underlying cause of ~99% of the cases of achondroplasia, the most common form of human dwarfism. The structural consequences of this mutation remain uncertain: the mutation shifts the position of the TMD relative to the lipid bilayer but does not alter the association free energy. We have combined coarse-grained and all-atom molecular dynamics simulations to study the dimerization of wild-type, heterodimer, and mutant FGFR3 TMDs. The simulations reveal that the helices pack together in the dimer to form a flexible interface. The primary packing mode is mediated by a Gx3G motif. There is also a secondary dimer interface that is more highly populated in heterodimer and mutant configurations that may feature in the molecular mechanism of pathology. Both coarse-grained and atomistic simulations reveal a significant shift of the G380R mutant dimer TMD relative to the bilayer to allow interactions of the arginine side chain with lipid headgroup phosphates.


The cooking task: making a meal of executive functions.
Current standardized neuropsychological tests may fail to accurately capture real-world executive deficits. We developed a computer-based Cooking Task (CT) assessment of executive functions and trialed the measure with a normative group before use with a head-injured population. Forty-six participants completed the computerized CT and subtests from standardized neuropsychological tasks, including the Tower and Sorting Tests of executive function from the Delis-Kaplan Executive Function System (D-KEFS) and the Cambridge prospective memory test (CAMPROMPT), in order to examine whether standardized executive function tasks, predicted performance on measurement indices from the CT. Findings showed that verbal comprehension, rule detection and prospective memory contributed to measures of prospective planning accuracy and strategy implementation of the CT. Results also showed that functions necessary for cooking efficacy differ as an effect of task demands (difficulty levels). Performance on rule detection, strategy implementation and flexible thinking executive function measures contributed to accuracy on the CT. These findings raise questions about the functions captured by present standardized tasks particularly at varying levels of difficulty and during dual-task performance. Our preliminary findings also indicate that CT measures can effectively distinguish between executive function and Full Scale IQ abilities. Results of the present study indicate that the CT shows promise as an ecologically valid measure of executive function for future use with a head-injured population and indexes selective executive function's captured by standardized tests.


Case-control study of lung cancer during 1994-1997 in the birth cohort in Tasmania, Australia, with an excess of female cases during 1983-1992.
In Tasmania, Australia, lung cancer incidence for 25-44-year-old women has reached that of 25-44-year-old men despite less smoking by the women. We investigated whether this could be due to greater female-than-male relative risk for smoking. This was a case-control study of lung cancer in the 1939-1964 birth cohort. In person (n = 100) or by proxy, 158 of the 160 cases arising during 1994-1997 were interviewed. Controls were a representative sample of the cohort (response 82.8%). Detailed measurements of tobacco smoking were made by questionnaire, and using the results of 17 machine tests of cigarette "tar" yields. The male smokers had greater accumulated exposure to smoking and, in reversal of the previously reported excess of female cases in this cohort, most (99/160) of the 1994-1997 cases were men. Nevertheless, the proportions attributable to smoking were similar: 0.86 (0.76-0.97) of male cases, and 0.87 (0.74-0.99) of female cases. Calculated relative to male never-smokers, the estimated relative risks were similar for male and female smokers, particularly with exposure measured by cumulative tar yield of all cigarettes smoked. We found no compelling evidence of greater susceptibility to lung cancer for female smokers.


Abnormal mitochondrial structure in human unfertilized oocytes and arrested embryos.
To clarify the relationship between mitochondria and embryo development, we collected human unfertilized oocytes, early embryos, and arrested embryos. Unfertilized oocytes and poor-quality embryos were collected, and the ultrastructure of mitochondria was determined by transmission electron micrography. Four criteria for determining the mitochondrial state were mitochondrial morphology, cristae shape, location, and number of mitochondria. In mature oocytes, mitochondria were rounded with arched cristae and a dense matrix and were distributed evenly in the ooplasm. In pronuclear zygotes, the size and shape of mitochondria were similar to those in mature oocytes; however, mitochondria appeared to migrate and concentrate around pronuclei. In this study, 67% of examined unfertilized oocytes had fewer mitochondria in the cytoplasm. A decreased number of mitochondria located near the nucleus was also demonstrated in 60% of arrested embryos. Fewer differentiated cristae were determined in all three arrested blastocyst stages of embryos. The relative expressions of oxidative phosphorylation genes in oocytes and embryos were also determined. These data imply that inadequate redistribution of mitochondria, unsuccessful mitochondrial differentiation, or decreased mitochondrial transcription may result in poor oocyte fertilization and compromised embryo development.


Extracting state transition dynamics from multiple spike trains using hidden Markov models with correlated poisson distribution.
Neural activity is nonstationary and varies across time. Hidden Markov models (HMMs) have been used to track the state transition among quasi-stationary discrete neural states. Within this context, an independent Poisson model has been used for the output distribution of HMMs; hence, the model is incapable of tracking the change in correlation without modulating the firing rate. To achieve this, we applied a multivariate Poisson distribution with correlation terms for the output distribution of HMMs. We formulated a variational Bayes (VB) inference for the model. The VB could automatically determine the appropriate number of hidden states and correlation types while avoiding the overlearning problem. We developed an efficient algorithm for computing posteriors using the recursive relationship of a multivariate Poisson distribution. We demonstrated the performance of our method on synthetic data and real spike trains recorded from a songbird.


In vitro evaluation of different methods of handling human liposuction aspirate and their effect on adipocytes and adipose derived stem cells.
Nowadays, fat tissue transplantation is widely used in regenerative and reconstructive surgery. However, a shared method of lipoaspirate handling for ensuring a good quality fat transplant has not yet been established. The study was to identify a method to recover from the lipoaspirate samples the highest number of human viable adipose tissue-derived stem cells (hADSCs) included in stromal vascular fraction (SVF) cells and of adipocytes suitable for transplantation, avoiding an extreme handling. We compared the lipoaspirate spontaneous stratification (10-20-30 min) with the centrifugation technique at different speeds (90-400-1500 × g). After each procedure, lipoaspirate was separated into top oily lipid layer, liquid fraction, "middle layer", and bottom layer. We assessed the number of both adipocytes in the middle layer and SVF cells in all layers. The histology of middle layer and the surface phenotype of SVF cells by stemness markers (CD105+, CD90+, CD45-) was analyzed as well. The results showed a normal architecture in all conditions except for samples centrifuged at 1500 × g. In both methods, the flow cytometry analysis showed that greater number of ADSCs was in middle layer; in the fluid portion and in bottom layer was not revealed significant expression levels of stemness markers. Our findings indicate that spontaneous stratification at 20 min and centrifugation at 400 × g are efficient approaches to obtain highly viable ADSCs cells and adipocytes, ensuring a good thickness of lipoaspirate for autologous fat transfer. Since an important aspect of surgery practice consists of gain time, the 400 × g centrifugation could be the recommended method when the necessary instrumentation is available.


The polyomaviruses WUPyV and KIPyV: a retrospective quantitative analysis in patients undergoing hematopoietic stem cell transplantation.
The polyomaviruses WUPyV and KIPyV have been detected in various sample types including feces indicating pathogenicity in the gastrointestinal (GI) system. However, quantitative viral load data from other simultaneously collected sample types are missing. As a consequence, primary replication in the GI system cannot be differentiated from swallowed virus from the respiratory tract. Here we present a retrospective quantitative longitudinal analysis in simultaneously harvested specimens from different organ sites of patients undergoing hematopoietic stem cell transplantation (HSCT). This allows the definition of sample types where deoxyribonucleic acid (DNA) detection can be expected and, as a consequence, the identification of their primary replication site. Viral DNA loads from 37 patients undergoing HSCT were quantified in respiratory tract secretions (RTS), stool and urine samples as well as in leukocytes (n = 449). Leukocyte-associated virus could not be found. WUPyV was found in feces, RTS and urine samples of an infant, while KIPyV was repeatedly detected in RTS and stool samples of 4 adult patients.RTS and stool samples were matched to determine the viral load difference showing a mean difference of 2.3 log copies/ml (p < 0.001). The data collected in this study suggest that virus detection in the GI tract results from swallowed virus from the respiratory tract (RT). We conclude that shedding from the RT should be ruled out before viral DNA detection in the feces can be correlated to GI symptoms.


Spectroscopic analysis of the trinuclear cluster in the Fet3 protein from yeast, a multinuclear copper oxidase.
The Fet3 protein (Fet3p) is a multinuclear copper oxidase essential for high-affinity iron uptake in yeast. Fet3p contains one type 1, one type 2, and a strongly antiferromagnetically coupled binuclear Cu(II)-Cu(II) type 3 copper. The type 2 and type 3 sites constitute a structurally distinct trinuclear cluster at which dioxygen is reduced to water. In Fet3p, as in ceruloplasmin, Fe(II) is oxidized to Fe(III) at the type 1 copper; this is the ferroxidase reaction that is fundamental to the physiologic function of these two enzymes. Using site-directed mutagenesis, we have generated type 1-depleted (T1D), type 2-depleted (T2D), and T1D/T2D mutants. None were active in the essential ferroxidase reaction catalyzed by Fet3p. However, the spectroscopic signatures of the remaining Cu(II) sites in any one of the three mutants were indistinguishable from those exhibited by the wild type. Although the native protein and the T1D mutant were isolated in the completely oxidized Cu(II) form, the T2D and T1D/T2D mutants were found to be completely reduced. This result is consistent with the essential role of the type 2 copper in dioxygen turnover, and with the suggestions that cuprous ion is the valence state of intracellular copper. Although stable to dioxygen, the Cu(I) sites in both proteins were readily oxidized by hydrogen peroxide. The double mutant was extensively analyzed by X-ray absorption spectroscopy. Edge and near-edge features clearly distinguished the oxidized from the reduced form of the binuclear cluster. EXAFS was strongly consistent with the expected coordination of each type 3 copper by three histidine imidazoles. Also, copper scattering was observed in the oxidized cluster along with scattering from a ligand corresponding to a bridging oxygen. The data derived from the reduced cluster indicated that the bridge was absent in this redox state. In the reduced form of the double mutant, an N/O ligand was apparent that was not seen in the reduced form of the T1D protein. This ligand in T1D/T2D could be either the remaining type 2 copper imidazole ligand (from His416) or a water molecule that could be stabilized at the type 3 cluster by H-bonding to this side chain. If present in the native protein, this H(2)O could provide acid catalysis of dioxygen reduction at the reduced trinuclear center.


A Bayesian model of acquisition and clearance of bacterial colonization incorporating within-host variation.
Bacterial populations that colonize a host can play important roles in host health, including serving as a reservoir that transmits to other hosts and from which invasive strains emerge, thus emphasizing the importance of understanding rates of acquisition and clearance of colonizing populations. Studies of colonization dynamics have been based on assessment of whether serial samples represent a single population or distinct colonization events. With the use of whole genome sequencing to determine genetic distance between isolates, a common solution to estimate acquisition and clearance rates has been to assume a fixed genetic distance threshold below which isolates are considered to represent the same strain. However, this approach is often inadequate to account for the diversity of the underlying within-host evolving population, the time intervals between consecutive measurements, and the uncertainty in the estimated acquisition and clearance rates. Here, we present a fully Bayesian model that provides probabilities of whether two strains should be considered the same, allowing us to determine bacterial clearance and acquisition from genomes sampled over time. Our method explicitly models the within-host variation using population genetic simulation, and the inference is done using a combination of Approximate Bayesian Computation (ABC) and Markov Chain Monte Carlo (MCMC). We validate the method with multiple carefully conducted simulations and demonstrate its use in practice by analyzing a collection of methicillin resistant Staphylococcus aureus (MRSA) isolates from a large recently completed longitudinal clinical study. An R-code implementation of the method is freely available at: https://github.com/mjarvenpaa/bacterial-colonization-model.


Initial Experience with Aortic Valve Replacement via a Minimally Invasive Approach: A Comparison of Stented, Stentless and Sutureless Valves.
BACKGROUND This study aimed to compare the short-term outcomes of MIS-AVR among 3 different types of biological heart valves. MATERIAL AND METHODS Complete data were obtained from 79 patients who underwent MIS-AVR between January 2010 and June 2015. Patients were divided into 3 groups: 27 patients (group A) received Medtronic 3f® (Medtronic Inc., Fridley, MN, USA), 36 patients (group B) received DokimosPlus® (LabCor Laboratórios Ltda., Belo Horizonte, Brazil) and 16 patients (group C) received Perceval® (Sorin Biomedica Cardio S.r.l., Saluggia VC, Italy) valves. Operative and postoperative parameters such as duration of operation, bypass time, duration of ventilation, morbidity, and mortality were statistically analyzed using the Kruskal-Wallis test. Hemodynamic assessment with transthoracic echocardiography was performed before discharge. RESULTS The EuroSCORE II ranged between 0.67 and 6.94 with no significant difference between the groups. The median operative time was 166 min (range 90-230 min) in total, with significantly shorter times in group C (120 min [range 90-200]). The median total ventilation time was significantly lower in group C and significantly higher in group A. Hemodynamic evaluation demonstrated a mean maximal velocity (vmax) over the aortic valve of 2.3 m/s (range 0.9-4.3 m/s) with average mean and peak pressure gradient values of 10 mmHg (range 3-24 mmHg) and 20 mmHg (range 5-42 mmHg), respectively. Group A showed the highest values for vmax (H>5.99). No significant difference was found regarding duration of hospitalization. Mortality was 3%. CONCLUSIONS In conclusion, all 3 valves showed good perioperative results, satisfying hemodynamic performance, and low complication rates.


A murine model of latex allergy-induced airway hyperreactivity.
Sensitization to latex proteins can cause immediate IgE mast cell-mediated reactions. Health care workers have been found to be particularly at risk because of high exposure. Latex allergy can be produced in mice as demonstrated by IgE and eosinophil responses. Thus the mouse is a potential animal model for studying this disease, but the airway response to latex sensitization in mice has not been evaluated previously. In the present study, we immunized BALB/c mice intranasally with nonammoniated latex proteins. Animals were anesthetized, and lung mechanics were evaluated plethysmographically. Changes in pulmonary conductance (GL) and compliance (Cdyn) were measured in response to a nonspecific challenge with methacholine or to a direct challenge with intravenous latex antigen. Latex sensitization resulted in elevated levels of IgE and latex-specific IgG1 as well as interstitial infiltrates consistent with an allergic response. The methacholine dose-response ED50 for GL was 116.4 microg for the control mice and fell significantly to 20.9 microg for latex-sensitized mice. The ED50 calculated for Cdyn was also significantly lower after latex sensitization. The GL in latex-sensitized mice challenged with latex antigen fell significantly from a prechallenge value of 1.87 +/- 0.41 (S.E.) to 0. 198 +/- 0.03 ml x s-1 x cmH2O after latex antigen challenge. The results indicate that latex-sensitized mice did exhibit increased airway reactivity in the methacholine challenge test. The latex allergic response in mice is unique in that direct challenge with latex antigen itself also resulted in a significant airway response.


Generation of oxidants in the near-UV photooxidation of human lens alpha-crystallin.
In this study we report on the generation of superoxide anion (O2-) and hydrogen peroxide in the near-UV irradiation of human lens alpha-crystallin by monochromatic light at 300 nm. Photolysis of human lens alpha-crystallin at 300 nm, at irradiances similar to those encountered in sunlight causes an alteration of protein tertiary structure, a loss of tryptophan fluorescence and increase of nontryptophan fluorescence. The nontryptophan fluorescence is likely to be due to the photooxidation of tryptophan to N-formylkynurenine (N-FK or related species), which is a good photodynamic sensitizer, has significant absorption at 300 nm, and can thus react via its triplet state with O2 to generate 1O2 or with reducing substrates (amino acids of the protein) to generate free radicals. The latter, in the presence of O2 can lead to the generation of O2- and H2O2. These species have been directly assayed in this study in photolyzed solutions of fetal, young and old human lens alpha-crystallin. The addition of superoxide dismutase (SOD) to the protein solution prior to photolysis increased the amount of H2O2 generated by 3- to 4-fold. This observation not only provides definitive evidence for the photogeneration of O2-, but also indicates that only a fraction of this species is transformed into H2O2 in the absence of SOD. Significant amounts of O2- and H2O2 were formed by 340 nm irradiation of old human lens alpha-crystallin, in which the basal level of N-FK is high. The role of 1O2 in these photoreactions has been studied by investigating the quenching effect of azide and the enhancing effects of D2O on the rate of loss of tryptophan fluorescence yield and the effect of azide on the rate of H2O2 generation.


Negative pressure and muscle activity during discrete sips from high resistance straws.
The purpose of the current investigation was to explore how intra-oral negative pressure and submental muscle activity vary across sips from straws varying in internal diameter and across conditions of low versus high effort. Healthy adults took discrete sips from four straws varying in internal diameter. Sips were performed under normal and high effort conditions. Submental surface electromyography (sEMG) and negative intra-oral pressure were recorded during sips. Significant main effects of straw condition were observed for negative intra-oral pressure. A non-significant trend for increased muscle activity associated with smaller straw diameter was also observed. Significant main effects of effort condition were observed for both submental sEMG and negative intra-oral pressure. The findings are interpreted as supporting the clinical hypothesis that high resistance drinking straws varying in diameter may offer systematic overload to the oral musculature. The findings also support encouraging maximum effort to achieve even further overload.


Complex life cycles and density dependence: assessing the contribution of egg mortality to amphibian declines.
In the last decade there has been increasing evidence of amphibian declines from relatively pristine areas. Some declines are hypothesized to be the result of egg mortality caused by factors such as elevated solar UV-B irradiation, chemical pollutants, pathogenic fungi, and climate change. However, the population-level consequences of egg mortality have not been examined explicitly, and may be complicated by density dependence in intervening life-history stages. Here we develop a demographic model for two amphibians with contrasting life-history strategies, Bufo boreas and Ambystoma macrodactylum. We then use the complementary approaches of elasticity and limitation to examine the relationships among stage-specific survival rates, larval-stage density dependence and amphibian population dynamics. Elasticity analyses showed that for a range of density dependence scenarios both species were more sensitive to changes in post-embryonic survival parameters, particularly juvenile survival, than to egg survival, suggesting that mortality of later stages may play an important role in driving declines. Limitation analyses revealed that larval density dependence can dramatically alter the consequences of early mortality, reducing or even reversing the expected population-level effects of egg mortality. Thus, greater focus on later life stages and density dependence is called for to accurately assess how stressors are likely to affect amphibian populations of conservation concern.


The peptidyl-prolyl isomerase Pin1 determines parathyroid hormone mRNA levels and stability in rat models of secondary hyperparathyroidism.
Secondary hyperparathyroidism is a major complication of chronic kidney disease (CKD). In experimental models of secondary hyperparathyroidism induced by hypocalcemia or CKD, parathyroid hormone (PTH) mRNA levels increase due to increased PTH mRNA stability. K-homology splicing regulator protein (KSRP) decreases the stability of PTH mRNA upon binding a cis-acting element in the PTH mRNA 3' UTR region. As the peptidyl-prolyl isomerase (PPIase) Pin1 has recently been shown to regulate the turnover of multiple cytokine mRNAs, we investigated the role of Pin1 in regulating PTH mRNA stability in rat parathyroids and transfected cells. The data generated were consistent with Pin1 being a PTH mRNA destabilizing protein. Initial analysis indicated that Pin1 activity was decreased in parathyroid protein extracts from both hypocalcemic and CKD rats and that pharmacologic inhibition of Pin1 increased PTH mRNA levels posttranscriptionally in rat parathyroid and in transfected cells. Pin1 mediated its effects via interaction with KSRP, which led to KSRP dephosphorylation and activation. In the rat parathyroid, Pin1 inhibition decreased KSRP-PTH mRNA interactions, increasing PTH mRNA levels. Furthermore, Pin1-/- mice displayed increased serum PTH and PTH mRNA levels, suggesting that Pin1 determines basal PTH expression in vivo. These results demonstrate that Pin1 is a key mediator of PTH mRNA stability and indicate a role for Pin1 in the pathogenesis of secondary hyperparathyroidism in individuals with CKD.


Prevalence of resistence to activated protein C (APC-resistance) in blood donors in Kosovo.
One of the most frequent hereditary causes of thrombophilia is, without a doubt, resistance to Activated Protein C (APC-resistance), which is a consequence of point mutation in gene coding for coagulation Factor V (Factor V Leiden) in 90-95% of cases. The aim of this paper was to determine prevalence of APC-resistance in a group of healthy blood donors. The size of the group is quite representative of Kosovo Albanians. A total of 944 blood donors were examined (537 males and 407 females), for whom APC-resistance was determined by functional methods of coagulation using the kit ACTICLOT(R) Protein C Resistance. Method is based on the test of APTT determined twice: first in the presence and second in the absence of activated Protein C (APC). The ratio of these two values constitutes is called Activated Protein C- Sensitivity Ratio (APC-SR). From 944 examined donors, pathologic values of APC-SR (1,3-1,9) were found in 32 persons (3,4% of the total number). The distribution among sexes was 3,35% (18/537) in male and 3,43% (14/407) in female subjects. The mean values of APC-SR (1,64 in male and 1,71 in female subjects) were not significantly different (P = 0,22). Based on these results, we conclude that the prevalence of APC resistance in Albanian population of Kosovo is within the lower limit of prevalence in general population in different countries of European countries, which, according to some authors ranges is from 3 to 7%.


Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study.
A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. To increase the specificity of screening for lethal PCa at an early stage. We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.


Iatrogeny: why patients come to harm.
latrogeny remains a constant challenge to all members of the health team who must be made aware from the onset of their roles and responsibility to their patients with particular reference to patients' rights and well-being. Physicians, as the acknowledged leaders of the health team, have the greatest role in this respect; their training and involvement in supervising and monitoring members of their health teams must reflect an acknowledgement of this responsibility. The protection of the legacy associated with the medical profession for ethical behaviour and acting in the patient's best interest remains a challenge which must be addressed in the face of changing societal dynamics where rights and responsibilities are in a constant state of evolution. Medical schools must be at the forefront of responding to these challenges and reflect this by constant review of their training programmes.


Cystic fibrosis of the pancreas: involvement of MUC6 mucin in obstruction of pancreatic ducts.
Cystic fibrosis (CF) is characterized by pancreatic destruction following the gradual obstruction of small pancreatic ducts, from the mid-trimester of gestation onwards. To date, the material causing the obstruction has not been identified. The MUC6 mucin cDNA was isolated from human stomach and has been shown to be expressed in a number of other tissues in the gastrointestinal tract, including the gall bladder and parts of the ileum and colon. We have examined the expression of MUC6 mucin in the human pancreas, both during development and postnatally, by mRNA in situ hybridization and immunocytochemistry. In this report we establish that MUC6 transcripts are abundant in pancreatic epithelial cells and show a very similar pattern of expression in the epithelium lining small ducts and centroacinar cells to that shown by the cystic fibrosis transmembrane conductance regulator gene (CFTR). In addition, material obstructing the pancreatic ducts of CF pancreas was shown to contain MUC6 mucin. We have identified MUC6 mucin as a significant constituent of the material obstructing the small pancreatic ducts in CF.


Carbon dioxide supersaturation in the surface waters of lakes.
Data on the partial pressure of carbon dioxide (CO(2)) in the surface waters from a large number of lakes (1835) with a worldwide distribution show that only a small proportion of the 4665 samples analyzed (less than 10 percent) were within +/-20 percent of equilibrium with the atmosphere and that most samples (87 percent) were supersaturated. The mean partial pressure of CO(2) averaged 1036 microatmospheres, about three times the value in the overlying atmosphere, indicating that lakes are sources rather than sinks of atmospheric CO(2). On a global scale, the potential efflux of CO(2) from lakes (about 0.14 x 10(15) grams of carbon per year) is about half as large as riverine transport of organic plus inorganic carbon to the ocean. Lakes are a small but potentially important conduit for carbon from terrestrial sources to the atmospheric sink.


Modeling Semantic Encoding in a Common Neural Representational Space.
Encoding models for mapping voxelwise semantic tuning are typically estimated separately for each individual, limiting their generalizability. In the current report, we develop a method for estimating semantic encoding models that generalize across individuals. Functional MRI was used to measure brain responses while participants freely viewed a naturalistic audiovisual movie. Word embeddings capturing agent-, action-, object-, and scene-related semantic content were assigned to each imaging volume based on an annotation of the film. We constructed both conventional within-subject semantic encoding models and between-subject models where the model was trained on a subset of participants and validated on a left-out participant. Between-subject models were trained using cortical surface-based anatomical normalization or surface-based whole-cortex hyperalignment. We used hyperalignment to project group data into an individual's unique anatomical space via a common representational space, thus leveraging a larger volume of data for out-of-sample prediction while preserving the individual's fine-grained functional-anatomical idiosyncrasies. Our findings demonstrate that anatomical normalization degrades the spatial specificity of between-subject encoding models relative to within-subject models. Hyperalignment, on the other hand, recovers the spatial specificity of semantic tuning lost during anatomical normalization, and yields model performance exceeding that of within-subject models.


Office diagnosis of lower extremity venous insufficiency and treatment with the use of nonprescription support hose.
A two-part crossover study assessed the efficacy of nonprescription support pantyhose by evaluating the relative performance of sheer- versus firm-support types in 30 women with lower extremity complaints. In this clinical trial, 23 women wore nonprescription firm-support pantyhose and seven wore sheer-support pantyhose during the initial 4-week treatment period. Next, treatment was discontinued for 2 weeks, after which a 4-week crossover trial was started. During the crossover, the 23 women who had worn the firm-support hose during the initial trial wore the sheer-support hose, and the seven who had worn the sheer-support hose switched to wearing the firm-support hose. The 2-week washout period did not prove sufficient to allow measured values to return to baseline, thus invalidating the crossover comparisons between the sheer- and firm-support pantyhose. However, the direct comparison of results showed that patients generally experienced an improvement in venous circulation by using either firm- or sheer-support hose as evaluated by venous index measurements and a corresponding decrease in subjective complaints. One year after this study was completed, the patients were recalled. Of the 25 who were seen at this follow-up, 91% continued to use support hose, either when they had symptoms or on a regular daily basis. Venous circulation, as evaluated by noninvasive Doppler ultrasound and photoplethysmography, remained improved.


Workplace health promotion and stakeholder positions: a Finnish case study.
Modern workplace health promotion (WHP) requires collaboration, partnerships, and alliances with both internal and external stakeholders. However, the identification of the key stakeholders as well as the systematic mapping of their views has barely been covered in the existing research literature. This article describes the stakeholders and stakeholder positions in WHP in Finland. In this study, the stakeholders were classified as internal, interface, and external stakeholders. Furthermore, based on the authors' research, stakeholders and their positions were represented on a stakeholder map as well as by the power-interest matrix of the stakeholders. The governmental authorities play a key role in driving the strategic change toward WHP by preparing the required legislation and regulatory measures. However, both active employers and active employees can through their own work accelerate the development of new WHP services. Close collaboration between employers and employees is required at the individual workplaces. Some stakeholders, such as pension funds and occupational health services (OHS) providers, can act as important driving forces and support the strategic implementation of WHP in the workplaces. However, alone they have only limited opportunities to organize the WHP activities. Understanding the various stakeholders and the systematic mapping of their positions is essential for the successful planning and implementation of WHP activities.


Early warning signs for saddle-escape transitions in complex networks.
Many real world systems are at risk of undergoing critical transitions, leading to sudden qualitative and sometimes irreversible regime shifts. The development of early warning signals is recognized as a major challenge. Recent progress builds on a mathematical framework in which a real-world system is described by a low-dimensional equation system with a small number of key variables, where the critical transition often corresponds to a bifurcation. Here we show that in high-dimensional systems, containing many variables, we frequently encounter an additional non-bifurcative saddle-type mechanism leading to critical transitions. This generic class of transitions has been missed in the search for early-warnings up to now. In fact, the saddle-type mechanism also applies to low-dimensional systems with saddle-dynamics. Near a saddle a system moves slowly and the state may be perceived as stable over substantial time periods. We develop an early warning sign for the saddle-type transition. We illustrate our results in two network models and epidemiological data. This work thus establishes a connection from critical transitions to networks and an early warning sign for a new type of critical transition. In complex models and big data we anticipate that saddle-transitions will be encountered frequently in the future.


Perinatal sadness among Shuar women: support for an evolutionary theory of psychic pain.
Psychiatry faces an internal contradiction in that it regards mild sadness and low mood as normal emotions, yet when these emotions are directed toward a new infant, it regards them as abnormal. We apply parental investment theory, a widely used framework from evolutionary biology, to maternal perinatal emotions, arguing that negative emotions directed toward a new infant could serve an important evolved function. If so, then under some definitions of psychiatric disorder, these emotions are not disorders. We investigate the applicability of parental investment theory to maternal postpartum emotions among Shuar mothers. Shuar mothers' conceptions of perinatal sadness closely match predictions of parental investment theory.


Chemogenomic library design strategies for precision oncology, applied to phenotypic profiling of glioblastoma patient cells.
Designing a targeted screening library of bioactive small molecules is a challenging task since most compounds modulate their effects through multiple protein targets with varying degrees of potency and selectivity. We implemented analytic procedures for designing anticancer compound libraries adjusted for library size, cellular activity, chemical diversity and availability, and target selectivity. The resulting compound collections cover a wide range of protein targets and biological pathways implicated in various cancers, making them widely applicable to precision oncology. We characterized the compound and target spaces of the virtual libraries, in comparison with a minimal screening library of 1,211 compounds for targeting 1,386 anticancer proteins. In a pilot screening study, we identified patient-specific vulnerabilities by imaging glioma stem cells from patients with glioblastoma (GBM), using a physical library of 789 compounds that cover 1,320 of the anticancer targets. The cell survival profiling revealed highly heterogeneous phenotypic responses across the patients and GBM subtypes.


The importance of social support for women with elevated anxiety undergoing care for gynecologic malignancies.
The aim of this study was to screen for depression and anxiety and to assess well-being among women diagnosed with gynecologic malignancies, identify factors associated with elevated depressive or anxiety symptoms, and further characterize the needs of those with elevated anxiety or depressive symptoms. Women presenting for gynecologic cancer at an academic center during the course of 10 months were offered screening for depressive and anxiety symptoms. Patients were screened with the Primary Care Evaluation of Mental Disorders' Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7. The Functional Assessment of Cancer Therapy-General assessed well-being. Demographics, psychiatric history, and components about the cancer and treatment were collected. Those who screened positive with scores of 10 or higher on the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 were offered a meeting with the study psychiatrist for further evaluation both with the Structured Clinical Interview for Diagnosis as well as with an interview to discuss their experiences and to assess their desired needs. When family and social well-being was added to the logistic regression model, higher family and social well-being was the strongest factor associated with lower amounts of anxiety (odds ratio, 0.10; P = 0.001 for a cutoff of 10; odds ratio, 0.21; P = 0.012 for a cutoff of 8). Less than 30% who screened positive met with the study psychiatrist and were not receiving optimal treatment. Given that low family and social well-being and elevated anxiety symptoms were so highly correlated, those with anxiety symptoms would most benefit from social interventions. However, this study also found that patients with elevated depressive or anxiety symptoms were difficult to engage with a psychiatric provider. We need partnership between psychiatry and gynecology oncology to identify those with elevated depressive and anxiety symptoms and develop better ways to provide psychosocial supports.


Efficient CRISPR/Cas9-based genome editing in carrot cells.
The first report presenting successful and efficient carrot genome editing using CRISPR/Cas9 system. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome editing tool that has been widely adopted in model organisms recently, but has not been used in carrot-a model species for in vitro culture studies and an important health-promoting crop grown worldwide. In this study, for the first time, we report application of the CRISPR/Cas9 system for efficient targeted mutagenesis of the carrot genome. Multiplexing CRISPR/Cas9 vectors expressing two single-guide RNA (gRNAs) targeting the carrot flavanone-3-hydroxylase (F3H) gene were tested for blockage of the anthocyanin biosynthesis in a model purple-colored callus using Agrobacterium-mediated genetic transformation. This approach allowed fast and visual comparison of three codon-optimized Cas9 genes and revealed that the most efficient one in generating F3H mutants was the Arabidopsis codon-optimized AteCas9 gene with up to 90% efficiency. Knockout of F3H gene resulted in the discoloration of calli, validating the functional role of this gene in the anthocyanin biosynthesis in carrot as well as providing a visual marker for screening successfully edited events. Most resulting mutations were small Indels, but long chromosome fragment deletions of 116-119 nt were also generated with simultaneous cleavage mediated by two gRNAs. The results demonstrate successful site-directed mutagenesis in carrot with CRISPR/Cas9 and the usefulness of a model callus culture to validate genome editing systems. Given that the carrot genome has been sequenced recently, our timely study sheds light on the promising application of genome editing tools for boosting basic and translational research in this important vegetable crop.


Dysconnection topography in schizophrenia revealed with state-space analysis of EEG.
The dysconnection hypothesis has been proposed to account for pathophysiological mechanisms underlying schizophrenia. Widespread structural changes suggesting abnormal connectivity in schizophrenia have been imaged. A functional counterpart of the structural maps would be the EEG synchronization maps. However, due to the limits of currently used bivariate methods, functional correlates of dysconnection are limited to the isolated measurements of synchronization between preselected pairs of EEG signals. To reveal a whole-head synchronization topography in schizophrenia, we applied a new method of multivariate synchronization analysis called S-estimator to the resting dense-array (128 channels) EEG obtained from 14 patients and 14 controls. This method determines synchronization from the embedding dimension in a state-space domain based on the theoretical consequence of the cooperative behavior of simultaneous time series-the shrinking of the state-space embedding dimension. The S-estimator imaging revealed a specific synchronization landscape in schizophrenia patients. Its main features included bilaterally increased synchronization over temporal brain regions and decreased synchronization over the postcentral/parietal region neighboring the midline. The synchronization topography was stable over the course of several months and correlated with the severity of schizophrenia symptoms. In particular, direct correlations linked positive, negative, and general psychopathological symptoms to the hyper-synchronized temporal clusters over both hemispheres. Along with these correlations, general psychopathological symptoms inversely correlated within the hypo-synchronized postcentral midline region. While being similar to the structural maps of cortical changes in schizophrenia, the S-maps go beyond the topography limits, demonstrating a novel aspect of the abnormalities of functional cooperation: namely, regionally reduced or enhanced connectivity. The new method of multivariate synchronization significantly boosts the potential of EEG as an imaging technique compatible with other imaging modalities. Its application to schizophrenia research shows that schizophrenia can be explained within the concept of neural dysconnection across and within large-scale brain networks.


Ultrastructural features of contact lens-induced deep corneal neovascularization and associated stromal leukocytes.
Deep stromal vascularization was observed in corneas of four cynomolgus monkeys after extended monocular hydrogel contact lens wear. Keratocytes and extravascular leukocytes, including macrophages, lymphocytes, and in one case, neutrophils, were associated with the vessels in three monkeys. Vessel regression was observed in some animals, but not when lens wear was continuous. In one animal, neutrophil infiltration of the stroma associated with gross epithelial edema was observed. Involution of neutrophils by apoptosis and phagocytosis of pyknotic cells by macrophages was noted. The present study describes the ultrastructural features of deep corneal vascularization developed during extended contact lens wear and illustrates an association between leukocytes and new vessels.


Ag@Au nanoprism-metal organic framework-based paper for extending the glucose sensing range in human serum and urine.
In this work, we present a Ag@Au nanoprism-metal-organic framework-paper based glucose sensor for rapid, sensitive, single-use and quantitative glucose determination in human serum. To achieve painless measurement of glucose with a non-invasive detection methodology, this biosensor was further tested in human urine. In this approach, a new hybrid-Ag@Au nanoprism loaded in close proximity to micrometer sized coordination polymers as phosphorescent luminophores significantly enhanced the emission intensity due to metal-enhanced phosphorescence and worked as reaction sites to support more dissolved oxygen. Reports of enhanced phosphorescence intensity are relatively rare, especially at room temperature. The true enhancement factor of Ag@Au-phosphorescent metal-organic frameworks on paper was deduced to be 110-fold, making it a better optical type glucose meter. The results demonstrate the validity of the intensity enhancement effect of the excitation of the overlap of the emission band of a luminophore with the surface plasmon resonance band of Ag@Au nanoprisms. Ag@Au nanoprisms were used not only to improve the detection limit of glucose sensing but also to extend the glucose sensing range by enhancing the oxygen oxidation efficiency. The oxidation of glucose as glucose oxidase is accompanied by oxygen consumption, which increases the intensity of the phosphorescence emission. The turn-on type paper-based biosensor exhibits a rapid response (0.5 s), a low detection limit (0.038 mM), and a wide linear range (30 mM to 0.05 mM), as well as good anti-interference, long-term longevity and reproducibility. Finally, the biosensor was successfully applied to the determination of glucose in human serum and urine.


Water consumption in the production of ethanol and petroleum gasoline.
We assessed current water consumption during liquid fuel production, evaluating major steps of fuel lifecycle for five fuel pathways: bioethanol from corn, bioethanol from cellulosic feedstocks, gasoline from U.S. conventional crude obtained from onshore wells, gasoline from Saudi Arabian crude, and gasoline from Canadian oil sands. Our analysis revealed that the amount of irrigation water used to grow biofuel feedstocks varies significantly from one region to another and that water consumption for biofuel production varies with processing technology. In oil exploration and production, water consumption depends on the source and location of crude, the recovery technology, and the amount of produced water re-injected for oil recovery. Our results also indicate that crop irrigation is the most important factor determining water consumption in the production of corn ethanol. Nearly 70% of U.S. corn used for ethanol is produced in regions where 10-17 liters of water are consumed to produce one liter of ethanol. Ethanol production plants are less water intensive and there is a downward trend in water consumption. Water requirements for switchgrass ethanol production vary from 1.9 to 9.8 liters for each liter of ethanol produced. We found that water is consumed at a rate of 2.8-6.6 liters for each liter of gasoline produced for more than 90% of crude oil obtained from conventional onshore sources in the U.S. and more than half of crude oil imported from Saudi Arabia. For more than 55% of crude oil from Canadian oil sands, about 5.2 liters of water are consumed for each liter of gasoline produced. Our analysis highlighted the vital importance of water management during the feedstock production and conversion stage of the fuel lifecycle.


Diabetes mellitus: incidence, prevalence, survivorship, and causes of death in Rochester, Minnesota, 1945-1970.
The incidence and prevalence of diabetes mellitus in residents of Rochester, Minnesota, for 25 years (1945 to 1970) were determined from available medical records. The over-all incidence rate for diabetes is 133 new cases per 100,000 population per year (age-adjusted to 1970 U.S. white population). The rate increased with age for both men and women and was higher among men over 30 years of age. The average annual incidence rates per five-year period for juvenile-onset diabetes mellitus were low and variable and showed little change. Polyuria, polydipsia, glycosuria, lean habitus, loss of weight, and high levels of fasting hyperglycemia at initial diagnosis occurred more frequently in younger than in older patients. The peak incidence in 1960 through 1964 and the decrease in the following five years may be a reflection of the introduction of the AutoAnalyzer method for blood glucose in 1958. The average annual incidence rates for 1955 through 1959 and 1965 through 1969 were essentially the same. The over-all prevalence for diabetes mellitus is 1.6 per cent, with a higher rate among men than among women over 40 years of age; among school children the rate is 0.1 per cent. Survivorship in the diabetic population is lower than that in the general population. The leading cause of death was coronary heart disease, the death rate from it being higher than for the general population.


Endobronchial ultrasound-transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: variability of results and perspectives.
The remarkable value of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of non-small cell lung cancer (NSCLC) is recognized worldwide. Reports from different centers however show considerable variation of EBUS-TBNA performance in terms of diagnostic yield, sensitivity and negative predictive value (NPV). Interpretation of EBUS-TBNA diagnostic efficacy requires clarifying whether the technique is used for purely diagnostic purpose or mediastinal staging, recognizing that different study groups may be inherently heterogeneous and that numerous factors may impact on the procedure outcomes. Review of these factors indicates that the prevalence of N2/N3 disease, the thoroughness of mediastinal sampling and >3 needle passes per target lymph node (LN) [in the absence of rapid on-site evaluation (ROSE)] influence the procedure outcomes, while many details in the sample preparation technique are unlikely to impact on the results and should be left to the proceduralists' preference. Generalized use of a standardized database for prospective collection of relevant EBUS-TBNA data would allow reporting institutional results by sub-groups of N2/N3 disease prevalence and thoroughness of staging, and would help establishing quality standards for the procedure.