Implementation of Home Hospitalization and Early Discharge as an Integrated Care Service: A Ten Years Pragmatic Assessment.
Home Hospitalization has proven efficacy, but its effectiveness and potential as an Integrated Care Service in a real world setting deserves to be explored. To evaluate implementation and 10 years follow-up of Home Hospitalization and Early Discharge as an Integrated Care Service in an urban healthcare district in Barcelona. Prospective study with pragmatic assessment. Patients: Surgical and medical acute and exacerbated chronic patients requiring admission into a highly specialized hospital, from 2006 to 2015. Intervention: Home-based individualized care plan, administered as a hospital-based outreach service, aiming at substituting hospitalization and implementing a transitional care strategy for optimal discharge. Main measurements: Emergency Department, readmissions and mortality. Patients' and professionals' perspectives, technologies and costs were evaluated. 4,165 admissions (71 ± 15 yrs; Charlson Index 4 ± 3). In-hospital stay was 1 (0-3) days and the length of home-based stay was 6 (5-7) days. The 30-day readmission rate was 11% and mortality was 2%. Patients, careers and health professionals expressed high levels of satisfaction (98%). At the start, the service was reimbursed at a flat rate of 918€ per patient discharged, significantly lower than conventional hospitalization (2,879€) but still allowing the hospital to keep a balanced budget. At present, there is no difference in the payment schemes for both types of services. The service freed an average of 6 in-hospital days per patient. The program showed health value generation, as well as potential for synergies with community-based Integrated Care Services.


Alpha 1-adrenergic receptor-mediated downregulation of angiotensin II receptors in neuronal cultures.
Previous evidence has suggested that brain catecholamine levels are important in the regulation of central angiotensin II receptors. In the present study, the effects of norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine) on angiotensin II receptor regulation in neuronal cultures from rat hypothalamus and brainstem have been examined. Both catecholamines elicit significant decreases in [125I]angiotensin II-specific binding to neuronal cultures prepared from normotensive rats, effects that are dose dependent and that are maximal within 4-8 h of preincubation. Saturation and Scatchard analyses revealed that the norepinephrine-induced decrease in the binding is due to a decrease in the number of angiotensin II receptors in neuronal cultures, with little effect on the receptor affinity. Norepinephrine has no significant actions on [125I]angiotensin II binding in cultures prepared from spontaneously hypertensive rats. The downregulation of angiotensin II receptors by norepinephrine or dopamine is blocked by alpha 1-adrenergic and not by other adrenergic antagonists, a result suggesting that this effect is initiated at the cell surface involving alpha 1-adrenergic receptors. This is further supported by our data indicating a parallel downregulation of specific alpha 1-adrenergic receptors elicited by norepinephrine. In summary, these results show that norepinephrine and dopamine are able to alter the regulation of neuronal angiotensin II receptors by acting at alpha 1-adrenergic receptors, which is a novel finding.


Self-directed learning and medical rehabilitation: a comparison.
A comparison is made between medical rehabilitation and continuing medical education (CME). It is hypothesized that such a comparison can help physicians who have little formal training in educational methodology to become more efficient and effective in carrying out their own self-directed learning. This hypothesis is based on the premise that the decision-making processes are similar for managing the medical rehabilitation of a patient and for carrying out self-directed CME.


The clinical management of fibromyalgia.
Fibromyalgia is characterized by chronic diffuse muscular aches, fatigue and poor sleep; it affects nearly three million individuals in the United States alone, predominantly younger women. The diagnosis of fibromyalgia requires adherence to the American College of Rheumatology criteria and the exclusion of secondary causes and systemic diseases. Treatment with sleep cycle regulators, NSAIDs, and light aerobic exercise is usually helpful. Patients must be reminded that fibromyalgia is often a chronic condition, but can be successfully treated.


Effects of dantrolene and D2O on K+-stimulated respiration of skeletal muscle.
We have examined the effects of dantrolene and D2O on the K+-stimulated respiration in frog skeletal muscle. The threshold for K+ stimulation was around 10 mM extracellular potassium concentration ([K+]o). A further marked increase in respiration to levels about ten times the resting level was noted when [K+]o was between 15 and 20 mM. The increase was sustained for hours when [K+]o was less than 20 mM; however, with higher concentrations the stimulation consisted of an initial burst followed by a decline. Dantrolene shifted the relationship between [K+]o and peak increase in respiration toward higher [K+]o by about 10 mM; in addition it nearly completely blocked the sustained component of the increase. D2O, nearly abolished the K+-induced respiration. Neither agent shifted the relationship between [K+]o and membrane potential nor abolished the stimulation of respiration caused by caffeine. Dantrolene did not block the stimulation of Na+ efflux caused by 15 mM K+. The results with these agents are consistent with the proposal that K+-stimulated respiration is due to Ca2+ release into the cytoplasm. In addition, they provide evidence that the stimulated rate of Ca2+ release into the cytoplasm can remain at a persistently high level for hours provided [K+]o does not exceed 20 mM. We calculated that the level of this constant Ca2+ release is about 3.4 X 10(16) ions/(s.cm3).


Biomechanical Comparison of 3 Novel Repair Techniques for Radial Tears of the Medial Meniscus: The 2-Tunnel Transtibial Technique, a "Hybrid" Horizontal and Vertical Mattress Suture Configuration, and a Combined "Hybrid Tunnel" Technique.
Historically, radial meniscal tears were treated with partial or near-total meniscectomy, which usually resulted in poor outcomes. Radial meniscal tears function similar to a total meniscectomy and are challenging to treat. Repair of radial meniscal tears should be performed to prevent joint deterioration and the need for salvage procedures in the future. The purpose was to compare 3 repair techniques for radial tears of the medial meniscus: the 2-tunnel, hybrid, and hybrid tunnel techniques. It was hypothesized that there would be no differences among the 3 groups in regard to gapping and ultimate failure strength. Controlled laboratory study. Thirty human male cadaver knees (10 matched pairs, n = 20; 10 unpaired, n = 10) were used to compare the 2-tunnel, hybrid, and hybrid tunnel repairs. A complete radial tear was made at the midbody of the medial meniscus. Repairs were performed according to the described techniques. Specimens were potted and mounted on a universal material testing machine where each specimen was cyclically loaded for 1000 cycles before experiencing a pull to failure. Gap distances at the tear site, ultimate failure load, and failure location were measured and recorded. After 1000 cycles of cyclic loading, there were no significant differences in displacement among the 2-tunnel repair (3.0 ± 1.7 mm), hybrid repair (3.0 ± 0.9 mm), and hybrid tunnel repair (2.3 ± 1.0 mm; P = .4042). On pull-to-failure testing, there were also no significant differences in ultimate failure strength among the 2-tunnel repair (259 ± 103 N), hybrid repair (349 ± 149 N), and hybrid tunnel repair (365 ± 146 N; P = .26). However, the addition of vertical mattress sutures to act as a "rip stop" significantly reduced the likelihood of the sutures pulling through the meniscus during pull-to-failure testing for the hybrid and hybrid tunnel repairs (4 of 16, 25%) as compared with the 2-tunnel repair (7 of 9, 78%; P = .017). The results showed equivalent biomechanical testing with regard to gap distance and pull-to-failure strength among the 3 repairs. The addition of the vertical mattress sutures to act as a rip stop was effective in preventing meniscal cutout through the meniscus. Effective healing of radial meniscal tears after repair is paramount to prevent joint deterioration and symptom development. Each tested repair showed a biomechanically equivalent and stable construct to use to repair radial meniscal tears. The authors recommend that rip stop vertical mattress sutures be used, especially in poor-quality meniscal tissue, to prevent suture cutout.


Coronary blood flow changes following activation of adrenergic receptors in the conscious dog.
The role of coronary vascular adrenergic receptors in changing coronary flow was studied in dogs instrumented to measure left circumflex artery blood flow (CBF), mean coronary artery blood pressure (CBP), and heart rate (HR). Norepinephrine (NE), isoproterenol (IP), and phenylephrine (PH) were injected into the left circumflex artery before and after selective intracoronary alpha- and beta 1- or combined beta 1- and beta 2-receptor blockade. NE, IP, and PH did not alter CBP (112 +/- 6 mmHg). In addition, IP and PH did not affect HR (103 +/- 4 beats/min). NE increased HR to 150 +/- 6 beats/min, which was eliminated by blocking beta 1-receptors with atenolol and by removing the left stellate ganglion. IP increased CBF from 65 +/- 9 to 115 +/- 16 ml/min (mediated by both beta 1- and beta 2-receptors). PH caused an alpha-receptor-mediated coronary vasoconstriction (42 +/- 5 ml/min), which was potentiated by beta 1- and beta 2-receptor blockade. NE caused a biphasic flow response. CBF initially increased to 117 +/- 14 ml/min (mediated predominantly by beta 1-receptors) followed by a prolonged decrease to 54 +/- 7 ml/min (mediated by alpha-receptors). Removing the left stellate ganglion did not affect the CBF response to NE. These data indicate that PH directly stimulates coronary alpha-receptors and IP stimulates myocardial beta 1- and coronary beta 2-receptors. NE also stimulates myocardial cells causing a reflex that increases HR and indirectly increases CBF. The vasoconstriction to NE and PH was not evident after pentobarbital anesthesia, whereas the coronary vasodilation and increase in HR to NE was still present.


Antigenic and immunogenic phage displayed mimotopes as substitute antigens: applications and limitations.
The most exciting potential of phage displayed peptide libraries is to obtain small peptide molecules that mimic an antigen, at least with respect to a particular epitope. In addition to their interest as research tools, such mimotopes could in principle be useful as diagnostic tools or for eliciting antibodies to a predefined epitope. However, the reduction of the phage insert sequence to a short peptide that can compete with the antigenic and in particular with the immunogenic properties of the natural antigen faces considerable difficulties. This review assesses critically the antigenicity of phage displayed peptides as free peptides and in different molecular environments. The difficulties to use mimotopes to induce antibodies that bind to the natural antigen (crossreactive immunogenicity) and the considerable discrepancy between antigenicity and immunogenicity of phage-derived peptides are discussed. Peptides selected with antibodies from phage displayed random peptide libraries have raised considerable expectations as low molecular weight substitutes of the natural antigen. This review will focus on the results of phage displayed random peptide libraries screened with antibodies specific for proteins, carbohydrates and nucleic acids and critically examine how the above expectations have been met.


Hemodynamic patterns for symptomatic presentations of severe aortic stenosis.
The aim of this study was to investigate intracardiac hemodynamic idiosyncrasies responsible for various presentations of severe aortic stenosis (AS). Syncope, dyspnea, and chest pain are well-established indications for aortic valve replacement in patients with severe AS. Patients' survival is limited once they develop symptoms from AS, and survival depends on what type of symptoms a patient develops. We hypothesized that there would be a relationship between the type of AS symptoms and intracardiac hemodynamics as well as AS severity. We analyzed 498 patients (men: 58.4%, 66 ± 12 years of age) with severe AS and normal left ventricular ejection fraction from 2003 to 2009 who had comprehensive echocardiography examination for AS. The study population was divided into 4 groups based on presenting symptom(s) (341 in group I, asymptomatic; 15 in group II, syncope; 110 in group III, dyspnea; 32 in group IV, chest pain). Echocardiographic measurements for cardiac structure, function, and intracardiac hemodynamic parameters were compared among these 4 groups. Mean aortic valve pressure gradient and aortic valve area were 57.1 ± 15.2 mm Hg and 0.74 ± 0.19 cm(2), respectively. AS severity based on mean gradient and aortic valve area was similar among 4 groups. Compared with the asymptomatic group, symptomatic patients were older and had lower cardiac output, and higher E/e' ratio while having a similar aortic valve area and gradient. Group II (syncope) displayed smaller LV dimension, stroke volume, cardiac output, left atrial volume index, and E/e' ratio. Conversely, group III (dyspnea) was found to have the worst diastolic function with largest left atrial volume index and highest E/e' ratio. Among patients with severe AS, their symptoms are often linked to specific hemodynamic patterns associated with AS: smaller left ventricular cavity and reduced output for syncope versus more advanced diastolic dysfunction for dyspnea. Hence, comprehensive intracardiac hemodynamics including diastolic function and stroke volume need to be evaluated in addition to aortic valve area and pressure gradient for assessment of AS.


An information processing model for schizophrenia.
A disorder of information processing must be present for a person to receive the diagnosis of schizophrenia, and is present when schizophrenic symptoms occur along with other diseases. We created a model for this disorder that resolves some paradoxic findings and suggests directions for future study. Basically, schizophrenics have a deficiency in information processing that can be characterized as conscious, serial, and limited in channel capacity. In contrast, those processes that seem automatic, unconscious, parallel, and almost unlimited in capacity seem to be normal or supernormal.


Transitions experienced by older survivors of critical care.
The transition from hospital to home is complicated for older adults who experience a serious or life-threatening illness. The specific aims of this prospective, observational cohort study were to determine the number of older adults who experience a change in their functional ability and residence after an intensive care unit (ICU) stay and to explore risk factors for functional decline and new institutionalization at hospital discharge. We found high rates of unrecognized preexisting cognitive impairment, delirium, complications, functional decline, and new institutionalization in this sample (N = 43). A number of variables were associated with functional decline or new institutionalization, including narcotic agent use (p = 0.03), ICU complications (p = 0.05), comorbidities (p = 0.01), depression (p = 0.05), and severity of illness (p = 0.05). We identified device self-removal, admission type, and ICU delirium as also potentially associated with these outcomes (p ≤ 0.25). There are a number of important and potentially modifiable factors that influence an older adult's ability to recover after a critical illness.


Distance and plasmon wavelength dependent fluorescence of molecules bound to silica-coated gold nanorods.
Plasmonic nanoparticles can strongly interact with adjacent fluorophores, resulting in plasmon-enhanced fluorescence or fluorescence quenching. This dipolar coupling is dependent upon nanoparticle composition, distance between the fluorophore and the plasmonic surface, the transition dipole orientation, and the degree of spectral overlap between the fluorophore's absorbance/emission and the surface plasmon band of the nanoparticles. In this work, we examine the distance and plasmon wavelength dependent fluorescence of an infrared dye ("IRDye") bound to silica-coated gold nanorods. Nanorods with plasmon band maxima ranging from 530 to 850 nm are synthesized and then coated with mesoporous silica shells 11-26 nm thick. IRDye is covalently attached to the nanoparticle surface via a click reaction. Steady-state fluorescence measurements demonstrate plasmon wavelength and silica shell thickness dependent fluorescence emission. Maximum fluorescence intensity, with approximately 10-fold enhancement, is observed with 17 nm shells when the nanorod plasmon maximum is resonant with IRDye absorption. Time-resolved photoluminescence reveals multiexponential decay and a sharp reduction in fluorescence lifetime with decreasing silica shell thickness and when the plasmon maximum is closer to IRDye absorption/emission. Control experiments are carried out to confirm that the observed changes in fluorescence are due to plasmonic interactions, is simply surface attachment. There is no change in fluorescence intensity or lifetime when IRDye is bound to mesoporous silica nanoparticles. In addition, IRDye loading is limited to maintain a distance between dye molecules on the surface to more than 9 nm, well above the Förster radius. This assures minimal dye-dye interactions on the surface of the nanoparticles.


Convective lyapunov exponents and propagation of correlations
We conjecture that in one-dimensional spatially extended systems the propagation velocity of correlations coincides with a zero of the convective Lyapunov spectrum. This conjecture is successfully tested in three different contexts: (i) a Hamiltonian system (a Fermi-Pasta-Ulam chain of oscillators); (ii) a general model for spatiotemporal chaos (the complex Ginzburg-Landau equation); (iii) experimental data taken from a CO2 laser with delayed feedback. In the last case, the convective Lyapunov exponent is determined directly from the experimental data.


Adenoid cystic carcinoma of external auditory canal: A rare disease.
External auditory canal, like other epithelialized surfaces is predisposed to malignancies such as Squamous cell carcinomas (SCC), melanomas and adenocarcinomas. In this background, malignancies like adenoid cystic carcinoma (ACC) are a rare occurrence and need to be thoroughly evaluated both locally and for distant extension. The malignancy needs to be addressed with an aggressive approach surgically with adequate marginal clearance. The role of radiation is debatable considering the outcomes in the limited data. Here we present the case of a 35-year-old female who came in with otalgia and otorrhea associated with a mass in the external auditory canal. After biopsy and imaging, a diagnosis of adenoid cystic carcinoma was made and the patient was managed accordingly.


Identification and Characterization of CD8+ CD27+ CXCR3- T Cell Dysregulation and Progression-Associated Biomarkers in Systemic Lupus Erythematosus.
Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4+ T cells and loss of immune tolerance. However, the involvement of CD8+ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8+ CD27+ CXCR3- T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8+ CD27+ CXCR3- T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8+ CD27+ CXCR3- T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.


Material properties of mouse cervical tissue in normal gestation.
An appropriately timed cervical remodeling process is critical for a healthy delivery, yet little is known about the material property changes of the cervix in pregnancy because obtaining human tissue samples is difficult. Rodent models offer advantages including accurately timed pregnant tissues and genetically altered models. Determining the material properties of the mouse cervix, however, is challenging because of its small size and complex geometry. The aim of this study is to quantify cervical material property changes in a normal mouse pregnancy using a microstructurally-inspired porous fiber composite model. We mechanically test intact, whole, gestation-timed mouse cervix by pulling apart tensioned sutures through its inner canal. To interpret our mechanical testing results, we conduct an inverse finite element analysis, taking into account the combined loading state of the thick-walled cylindrical tissue. We fit the material model to previous osmotic swelling data and load-deformation data from this study using a nonlinear optimization scheme, and validate the model by predicting a separate set of deformation data. Overall, the proposed porous fiber composite model captures the mechanical behavior of the mouse cervix in large deformation. The evolution of cervical material parameters indicates that in a normal mouse pregnancy, the cervix begins to soften between day 6 and day 12 of a 19-day gestation period. The material parameter associated with the collagen fiber stiffness decreases from 3.4MPa at gestation day 6 to 9.7e-4MPa at gestation day 18, while the ground substance stiffness decreases from 2.6e-1MPa to 7.0e-4MPa. Accelerated cervical remodeling can lead to extremely premature births. Little is known, however, about the material property changes of the cervix in pregnancy because pregnant human tissue samples are limited. Rodent models overcome this limitation and provide access to gestation-timed samples. Measuring the material property changes of the mouse cervix in pregnancy is challenging due to its small size and complex geometry. Here, we establish a combined experimental and modeling framework. We use this framework to determine the cervical material property changes throughout a normal mouse pregnancy. We present our experimental methods for mechanically testing whole, intact cervical tissue samples. We fit a porous fiber composite material model to the mechanical data and show that the mouse cervix begins to soften between day 6 and day 12 of a 19-day gestation period.


Characterization of melanoma cell membrane tumor-associated antigens using xenoserum, alloserum, and autoserum: I. immunofluorescence.
Xenoantiserum, alloantiserum, and autoantiserum prepared against human melanoma cells from cell lines maintained in tissue culture were evaluated by indirect immunofluorescence (ind IF) for their content of antibodies reactive with melanoma cell membrane tumor-associated antigens (TAA). Following absorptions which removed all detectable anti-human species, anti-RBC, and anti-HLA antigen activity, the antisera were tested against a panel of human cell lines. Three apparently distinct melanoma-associated cell membrane antigens were detected. The first of these was present on all human cells maintained in tissue culture including cells of both malignant and nonmalignant origin. The second antigen was expressed on all cells of malignant origin and also by fetal fibroblasts. The third antigen was detectable only on melanoma cells and was expressed by a majority of the melanomas tested. No evidence was obtained to suggest the presence of melanoma TAA unique to a single melanoma cell line. Marked differences were observed in the antigenic profile detected by the three antisera.


Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED2 score.
Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12-66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.


Cell-autonomous alterations in dendritic arbor morphology and connectivity induced by overexpression of MeCP2 in Xenopus central neurons in vivo.
Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Mutations in the MeCP2 gene have been linked to Rett syndrome, a severe X-linked progressive neurodevelopmental disorder, and one of the most common causes of mental retardation in females. MeCP2 duplication and triplication have also been found to affect brain development, indicating that both loss of function and gain in MeCP2 dosage lead to similar neurological phenotypes. Here, we used the Xenopus laevis visual system as an in vivo model to examine the consequence of increased MeCP2 expression during the morphological maturation of individual central neurons in an otherwise intact brain. Single-cell overexpression of wild-type human MeCP2 was combined with time-lapse confocal microscopy imaging to study dynamic mechanisms by which MeCP2 influences tectal neuron dendritic arborization. Analysis of neurons co-expressing DsRed2 demonstrates that MeCP2 overexpression specifically interfered with dendritic elaboration, decreasing the rates of branch addition and elimination over a 48 hour observation period. Moreover, dynamic analysis of neurons co-expressing wt-hMeCP2 and PSD95-GFP revealed that even though neurons expressing wt-hMeCP2 possessed significantly fewer dendrites and simpler morphologies than control neurons at the same developmental stage, postsynaptic site density in wt-hMeCP2-expressing neurons was similar to controls and increased at a rate higher than controls. Together, our in vivo studies support an early, cell-autonomous role for MeCP2 during the morphological differentiation of neurons and indicate that perturbations in MeCP2 gene dosage result in deficits in dendritic arborization that can be compensated, at least in part, by synaptic connectivity changes.


Hole injection dynamics from two structurally related Ru-bipyridine complexes into NiO(x) is determined by the substitution pattern of the ligands.
The dyes bis[2,2′-bipyridine][4,4′-dicarboxy-2,2′-bipyridine]ruthenium(II) dihexafluorophosphate, [Ru(bpy)2dcb](PF6)2 (Ru1), and tris[4,4′-bis(ethylcarboxy)-2,2′-bipyridine]ruthenium(II) dihexafluorophosphate, [Ru(dceb)3](PF6)2 (Ru2), attached to NiOx nanoparticle films were investigated using transient absorption and luminescence spectroscopy. In acetonitrile solution the dyes reveal very similar physical and chemical properties, i.e. both dyes exhibit comparable ground state and long-lived, broad excited state absorption. However, when immobilized onto a NiOx surface the photophysical properties of the two dyes differ significantly. For Ru1 luminescence is observed, which decays within 18 ns and ultrafast transient absorption measurements do not show qualitative differences from the photophysics of Ru1 in solution. In contrast to this the luminescence of photoexcited Ru2 on NiOx is efficiently quenched and the ultrafast transient absorption spectra reveal the formation of oxidized nickel centres overlaid by the absorption of the reduced dye Ru2 with a characteristic time-constant of 18 ps. These findings are attributed to the different localization of the initially photoexcited state in Ru1 and Ru2. Due to the inductive effect (−I) of the carboxylic groups, the lowest energy excited state in Ru1 is localized on the dicarboxy-bipyridine ligand, which is bound to the NiOx surface. In Ru2, on the other hand, the initially populated excited state is localized on the ester-substituted ligands, which are not bound to the semiconductor surface. Hence, the excess charge density that is abstracted from the Ru-ion in the metal-to-ligand charge-transfer transition is shifted away from the NiOx surface, which ultimately facilitates hole transfer into the semiconductor.


Urbanity as a determinant of exposure to grass pollen in Helsinki Metropolitan area, Finland.
Little is known about the levels of exposure to grass pollen in urban environments. We assessed the spatio-temporal variation of grass pollen concentrations and the role of urbanity as a determinant of grass pollen exposure in the Helsinki Metropolitan area. We monitored grass pollen concentrations in 2013 at 16 sites during the peak pollen season by using rotorod-type samplers at the breathing height. The sites were in the cities of Helsinki and Espoo, Finland, and formed city-specific lines that represented urban-rural gradient. The monitoring sites were both visually and based on land use data ranked as high to low (graded 1 to 8) pollen area. The lowest grass pollen concentrations were observed in the most urban sites compared to the least urban sites (mean 3.6 vs. 6.8 grains/m3 in Helsinki; P<0.0001, and 5.2 vs. 87.5 grains/m3 in Espoo; P<0.0001). Significant differences were observed between concentrations measured in morning periods compared to afternoon periods (4.9 vs. 5.4 in Helsinki, P = 0.0186, and 21.8 vs. 67.1 in Espoo, P = 0.0004). The mean pollen concentration increased with decreasing urbanity both in Helsinki (0.59 grains/m3 per urbanity rank, 95% CI 0.25-0.93) and Espoo (8.42, 6.23-10.61). Pollen concentrations were highest in the afternoons and they were related to the ambient temperature. Urbanity was a strong and significant determinant of pollen exposure in two Finnish cities. Pollen exposure can periodically reach such high levels even in the most urban environments that can cause allergic reactions among individuals with allergies.


Cinacalcet reduces vascular and soft tissue calcification in secondary hyperparathyroidism (SHPT) in hemodialysis patients.
Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis (HD) can be challenging. Conventional treatments can lead to hypercalcemia and hyperphosphatemia, both of which are associated with vascular and soft tissue calcification and increased risk of cardiovascular disease. We report the effect of treatment with the Type II calcimimetic cinacalcet on vascular calcification in a HD patient with SHPT. A 40-year-old male with a 24-year history of kidney failure secondary to mesangial proliferative glomerulonephritis, commenced HD in October 2004 following chronic graft dysfunction. The patient was admitted to hospital with renal insufficiency and metabolic abnormalities. An anatomopathological study showed calcium (Ca) deposits in the alveolar septa, bronchial wall and pulmonary arterioles. Parathyroid methoxy isobutyl isonitrile (MIBI) scintigraphy revealed multiglandular parathyroid disease and an ectopic gland behind the sternal notch. Serum intact parathyroid hormone (iPTH) was repeatedly found to be > or = 2,500 pg/ml, and was accompanied by significant abnormalities in phosphorus (P) and Ca metabolism which were difficult to control. The patient was initially treated with sevelamer, low dose calcium carbonate, a low P and reduced protein diet and high doses of intravenous erythropoietin. In addition, he received HD with a high efficiency membrane for 4.5 hours, 4-times weekly. Treatment with cinacalcet was initiated at 30 mg/day and adjusted to achieve National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for iPTH, P, Ca and Ca-P product. One year following cinacalcet treatment, a chest x-ray showed a moderate reduction in Ca deposits, a bone X-ray showed a significant reduction in vascular calcifications, and parathyroid MIBI scintigraphy showed a disappearance of ectopic focus and minimal remains of glands. Significant reductions in calcemia were controlled by concomitant modifications to oral Ca supplementation, Ca concentration in the dialysis liquid, and administration of paricalcitriol. In the second year of treatment, iPTH was maintained within the target range, with moderate rises in P and stabilization of serum Ca. An echocardiogram showed an improvement in left ventricular hypertrophy. Chest and hand X-rays showed a progressive reduction in calcifications. Radiology showed an improvement in bone morphology, with reduced trabeculation and better cortical definition in the phalanx bones. In conclusion, the changes in iPTH, P and Ca associated with cinacalcet treatment were accompanied by reduced vascular and soft tissue calcification in this patient. There were no cardiovascular events and the patient experienced a marked improvement in quality of life.


Psychosocial factors and pre-abortion psychological health: The significance of stigma.
Most research in mental health and abortion has examined factors associated with post-abortion psychological health. However, research that follows women from before to after their abortion consistently finds that depressive, anxiety, and stress symptoms are highest just before an abortion compared to any time afterwards. This finding suggests that studies investigating psychosocial factors related to pre-abortion mental health are warranted. The current study uses data from 353 women seeking abortions at three community reproductive health clinics to examine predictors of pre-abortion psychological health. Drawing from three perspectives in the abortion and mental health literature, common risks, stress and coping, and sociocultural context, we conducted multivariable analyses to examine the contribution of important factors on depressive, anxiety, and stress symptoms just before an abortion, including sociodemographics, abortion characteristics, childhood adversities, recent adversities with an intimate partner, relationship context, future pregnancy desires, and perceived abortion stigma. Childhood and partner adversities, including reproductive coercion, were associated with negative mental health symptoms, as was perceived abortion stigma. Before perceived abortion stigma was entered into the model, 18.6%, 20.7%, and 16.8% of the variance in depressive, anxiety, and stress symptoms respectively, was explained. Perceived abortion stigma explained an additional 13.2%, 9.7%, and 10.7% of the variance in depressive, anxiety, and stress symptoms pre-abortion. This study, one of the first to focus on pre-abortion mental health as an outcome, suggests that addressing stigma among women seeking abortions may significantly lower their psychological distress.


Theoretical investigations of the dissociation of charged protein complexes in the gas phase.
A series of calculations, varying from simple electrostatic to more detailed semi-empirical based molecular dynamics ones, were carried out on charged gas phase ions of the cytochrome c(') dimer. The energetics of differing charge states, charge partitionings, and charge configurations were examined in both the low and high charge regimes. As well, preliminary free energy calculations of dissociation barriers are presented. It is shown that one must always consider distributions of charge configurations, once protein relaxation effects are taken into account, and that no single configuration dominates. All these results also indicate that in the high charge limit, the dissociation of protein complex ions is governed by electrostatic repulsion from the net charges, the consequences of which are enumerated and discussed. There are two main trends deriving from this, namely that charges will move so as to approximately maintain constant surface charge density, and that the lowest barrier to dissociation is the one that produces fragment ions with equal charges. In particular, it is shown that the charge-to-mass ratio of a fragment ion is not the key physical parameter in predicting dissociation products. In fact, from the perspective of the division of total charge, many dissociation pathways reported to be "asymmetric" in the literature should be more properly labelled as "symmetric" or "near-symmetric". The Coulomb repulsion model assumes that the timescale for charge transfer is faster than that for protein structural changes, which in turn is faster than that for complex dissociation.


Physical association of pyrimidine dimer DNA glycosylase and apurinic/apyrimidinic DNA endonuclease essential for repair of ultraviolet-damaged DNA.
T4 endonuclease V [endodeoxyribonuclease (pyrimidine dimer), EC 126.96.36.199)], which is involved in repair of UV-damaged DNA, has been purified to apparent physical homogeneity. Incubation of UV-irradiated poly(dA).poly(dT) with the purified enzyme preparations resulted in production of alkali-labile apyrimidinic sites, followed by formation of nicks in the polymer. The activity to produce alkali-labile sites was optimal in a relatively broad pH range (pH 6.0-8.5), whereas the activity to form nicks had a narrow optimum near pH 6.5. By performing a limited reaction with T4 endonuclease V at pH 8.5, irradiated polymer was converted to an intermediate form that carried a large number of alkali-labile sites but only a few nicks. The intermediate was used as substrate for the assay of apurinic/apyrimidinic DNA endonuclease activity [endodeoxyribonuclease (apurinic or apyrimidinic, EC 184.108.40.206]. The two activities, a pyrimidine dimer DNA glycosylase and an apurinic/apyrimidinic DNA endonuclease, were copurified and found in enzyme preparations that contained only a 16,000-dalton polypeptide. An enzyme fraction from cells infected with bacteriophage T4v1, a mutant that is sensitive to UV radiation, was defective in both glycosylase and endonuclease activities. Moreover, occurrence of an amber mutation in the denV gene caused a simultaneous loss of the two activities, and suppression of the mutation rendered both activities partially active. These results strongly suggested that a DNA glycosylase specific for pyrimidine dimers and an apurinic/apyrimidinic DNA endonuclease reside in a single polypeptide chain coded by the denV gene of bacteriophage T4. Because the two activities exhibited different thermosensitivity, it was further suggested that conformation of the active sites for these activities may be different.


Effect of re-use of a disposable micro-polisher on the surface of a microhybrid resin composite.
To evaluate the surface roughness of Esthet-X resin-based composite with the multi-use of a one-step disposable diamond micro polisher PoGo with profilometer and scanning electron microscope (SEM). 35 discs were obtained by condensing Esthet-X in an 8x2 mm plexiglass mold covered with a Mylar strip. The specimens were polymerized 40 seconds on both sides. Five Mylar strips' surfaces were used as a control. Six groups of five discs were formed by reusing the same PoGo disc 1, 2, 3, 4, 5 and 6 times. The surfaces of the 30 discs were ground wet with a 1200 grit silicon carbide paper and then polished 30 seconds with PoGo. The surface roughness was measured with Surtronic 4. One representative sample of each group was selected to visualize the surfaces morphology by SEM. The results were statistically evaluated by one-way ANOVA (P< 0.01). There were no statistical differences with the Mylar-created surfaces and one, two and three times' use of PoGo. Furthermore, reusing PoGo one to four times was not found to affect the surface roughness (P> 0.01). There were no differences with four and five re-uses of PoGo while using the same disc six times exhibited more roughness than single use and Mylar strip (P< 0.01). The SEM and the profilometer revealed similar results.


In vitro evaluation of sunscreens: an update for the clinicians.
Topical sunscreens contain molecules or molecular complexes that can absorb, reflect, or scatter UV photons. Evaluation of the efficacy of sunscreen products has been made through the Sun Protection Factor (SPF), a mean of quantitatively assessing in vivo the degree of protection offered by sunscreen products against solar radiation. In vivo evaluation of SPF has several drawbacks. First of all, this evaluation method is expensive in terms of money and time. Moreover, it raises several ethical issues concerning the potential damage to skin volunteers. Several in vitro techniques have been developed, but at present there is no broadly accepted method. In this paper, we will discuss some of the recent advances concerning the in vitro evaluation of sunscreens which would be acceptable for replacing in vivo assays.


Full-length de novo viral quasispecies assembly through variation graph construction.
Viruses populate their hosts as a viral quasispecies: a collection of genetically related mutant strains. Viral quasispecies assembly is the reconstruction of strain-specific haplotypes from read data, and predicting their relative abundances within the mix of strains is an important step for various treatment-related reasons. Reference genome independent ('de novo') approaches have yielded benefits over reference-guided approaches, because reference-induced biases can become overwhelming when dealing with divergent strains. While being very accurate, extant de novo methods only yield rather short contigs. The remaining challenge is to reconstruct full-length haplotypes together with their abundances from such contigs. We present Virus-VG as a de novo approach to viral haplotype reconstruction from preassembled contigs. Our method constructs a variation graph from the short input contigs without making use of a reference genome. Then, to obtain paths through the variation graph that reflect the original haplotypes, we solve a minimization problem that yields a selection of maximal-length paths that is, optimal in terms of being compatible with the read coverages computed for the nodes of the variation graph. We output the resulting selection of maximal length paths as the haplotypes, together with their abundances. Benchmarking experiments on challenging simulated and real datasets show significant improvements in assembly contiguity compared to the input contigs, while preserving low error rates compared to the state-of-the-art viral quasispecies assemblers. Virus-VG is freely available at https://bitbucket.org/jbaaijens/virus-vg. Supplementary data are available at Bioinformatics online.


[A bioluminescent method of determining the degree of intoxication in peritonitis].
A method for estimating the severity of the clinical condition and of the body intoxication in peritonitis patients is suggested. High sensitivity of the method permits classifying the patients into 4 groups in accordance with the severity of their condition: mild, moderate, severe, and extremely grave. This method is also applicable for the assessment of the efficacy of detoxification measures, such as abdominal cavity sanitization during surgery, lymph drainage. The method is simple and the time of analysis is 1 min.


Transcriptome sequencing and analysis of the fast growing shoots of moso bamboo (Phyllostachys edulis).
The moso bamboo, a large woody bamboo with the highest ecological, economic, and cultural value of all bamboos, has one of the highest growth speeds in the world. Genetic research into moso bamboo has been scarce, partly because of the lack of previous genomic resources. In the present study, for the first time, we performed de novo transcriptome sequencing and mapped to the moso bamboo genomic resources (reference genome and genes) to produce a comprehensive dataset for the fast growing shoots of moso bamboo. The fast growing shoots mixed with six different heights and culms after leaf expansion of moso bamboo transcriptome were sequenced using the Illumina HiSeq™ 2000 sequencing platform, respectively. More than 80 million reads including 65,045,670 and 68,431,884 clean reads were produced in the two libraries. More than 81% of the reads were matched to the reference genome, and nearly 50% of the reads were matched to the reference genes. The genes with log 2 ratio > 2 or < -2 (P<0.001) were characterized as the most differentially expressed genes. 6,076 up-regulated and 4,613 down-regulated genes were classified into functional categories. Candidate genes which mainly involved transcript factors, plant hormones, cell cycle regulation, cell wall metabolism and cell morphogenesis genes were further analyzed and they may form a network that regulates the fast growth of moso bamboo shoots. Firstly, our data provides the most comprehensive transcriptomic resource for moso bamboo to date. Candidate genes have been identified and they are potentially involved in the growth and development of moso bamboo. The results give a better insight into the mechanisms of moso bamboo shoots rapid growth and provide gene resources for improving plant growth.


Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass.
High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients). However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Prospective and cross-over study. Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim) were assessed. Thirteen (46.4%) patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation). Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6%) non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01). Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05). We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD.


Pleasure and addiction.
What is the role and value of pleasure in addiction? Foddy and Savulescu (1) have claimed that substance use is just pleasure-oriented behavior. They describe addiction as "strong appetites toward pleasure" and argue that addicts suffer in significant part because of strong social and moral disapproval of lives dominated by pleasure seeking. But such lives, they claim, can be autonomous and rational. The view they offer is largely in line with the choice model and opposed to a disease model of addiction. Foddy and Savulescu are sceptical of self-reports that emphasize the ill effects of addiction such as loss of family and possessions, or that claim an absence of pleasure after tolerance sets in. Such reports they think are shaped by social stigma which makes available a limited set of socially approved addiction narratives. We will not question the claim that a life devoted to pleasure can be autonomously chosen. Nor do we question the claim that the social stigma attached to the use of certain drugs increases the harm suffered by the user. However our interviews with addicts (as philosophers rather than health professionals or peers) reveal a genuinely ambivalent and complex relationship between addiction, value, and pleasure. Our subjects did not shy away from discussing pleasure and its role in use. But though they usually valued the pleasurable properties of substances, and this played that did not mean that they valued an addictive life. Our interviews distinguished changing attitudes towards drug related pleasures across the course of substance use, including diminishing pleasure from use over time and increasing resentment at the effects of substance use on other valued activities. In this paper we consider the implications of what drug users say about pleasure and value over the course of addiction for models of addiction.


Trastuzumab Blocks the Receiver Function of HER2 Leading to the Population Shifts of HER2-Containing Homodimers and Heterodimers.
HER2, a member of the Erythroblastosis Protein B/Human Epidermal Growth Factor Receptor (ErbB/HER) family of receptor tyrosine kinase, is overexpressed in 20~30% of human breast cancers. Trastuzumab, a HER2-targeted therapeutic monoclonal antibody, was developed to interfere with the homodimerization of HER2 in HER2-overexpressing breast cancer cells, which attenuates HER2-mediated signaling. Trastuzumab binds to the domain IV of the HER2 extracellular domain and does not directly block the dimerization interface of HER2-HER2 molecules. The three-dimensional structures of the tyrosine kinase domains of ErbB/HER family receptors show asymmetrical packing of the two monomers with distinct conformations. One monomer functions as an activator, whereas the other acts as a receiver. Once activated, the receiver monomer phosphorylates the activator or other proteins. Interestingly, in our previous work, we found that the binding of trastuzumab induced phosphorylation of HER2 with the phosphorylation pattern of HER2 that is different from that mediated by epidermal growth factor (EGF) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Binding of trastuzumab to HER2 promoted an allosteric effect of HER2, in both tyrosine kinase domain and ectodomain of HER2 although details of allosteric regulation were missing. In this study, we utilized molecular dynamics (MD) simulations to model the allosteric consequences of trastuzumab binding to HER2 homodimers and heterodimers, along with the apo forms as controls. We focused on the conformational changes of HER2 in its monomeric and dimeric forms. The data indicated the apparent dual role of trastuzumab as an antagonist and an agonist. The molecular details of the simulation provide an atomic level description and molecular insight into the action of HER2-targeted antibody therapeutics.


Phosphorus-31 nuclear magnetic resonance studies of the conformation of an adenosine 5'-triphosphate analogue at the active site of (Na+ + K+)-ATPase from kidney medulla.
It has previously been shown that there are two sites for divalent metals at the active site of kidney (Na+ + K+)-ATPase, one bound directly to the enzyme and one coordinated to the ATP substrate [Grisham, C. (1981) J. Inorg. Biochem. 14, 45; O'Connor, S., & Grisham, C. (1980) FEBS Lett. 118, 303]. The conformation of the metal-nucleotide complex has been studied by using beta, gamma-bidentate Co-(NH3)4ATP, a substitution-inert analogue of MgATP. Kinetic studies show that Co(NH3)4ATP is a competitive inhibitor with respect to MnATP for the (Na+ + K+)-ATPase. The Ki values under both high- and low-affinity conditions (Ki = 10 microM and Ki = 1.6 mM, respectively) are similar to the Km values for MnATP under the same conditions (2.88 microM and 0.902 mM). From the paramagnetic effect of Mn2+ bound to the ATPase on the longitudinal relaxation rates of the phosphorus nuclei of Co(NH3)4ATP at the substrate site (at 40.5 and 145.75 MHz), Mn-P distances to all three phosphates are determined. The distances are consistent with the formation of a second sphere coordination complex on the enzyme between Mn2+ and the phosphates of Co(NH3)4ATP. In this respect, kidney (Na+ + K+)-ATPase appears to be similar to pyruvate kinase [Sloan, D., & Mildvan, A. (1976) J. Biol. Chem. 251, 2412] and phosphoribosylpyrophosphate synthetase [Granot, J., Gibson, K., Switzer, R., & Mildvan, A. (1980) J. Biol. Chem. 255, 10931]. Roles for both of the active site divalent cations are discussed.


Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties.
The role of cell surface glycoproteins in determining in vivo blood-borne arrest and survival characteristics of murine melanoma sublines of low (B16-F1) or high (B16-F10) potential to form experimental lung metastases after injection i.v. was assessed after inhibiting tumor cell protein glycosylation with tunicamycin. Incubation of B16-F1 or B16-F10 cells with 0.5 micrograms (or above) tunicamycin per ml for 12 to 36 hr inhibited significantly lung tumor colony formation. Examination of B16 cells in the presence of 0.5 micrograms drug per ml indicated that complex oligosaccharide synthesis was inhibited greater than 90%, while protein synthesis remained at about 50% of the control levels. Tunicamycin induced morphological changes in B16-F1 and B16-F10 cells such as cellular rounding. Cell growth was also inhibited by tunicamycin. These effects were reversible, and B16 cells recovered their normal morphologies and growth rates within 24 hr after removal of the drug. Exposed cell surface protein analyzed by lactoperoxidase-catalyzed 125I iodination-sodium dodecyl sulfate-polyacrylamide gel electrophoresis-autoradiography showed few changes after tunicamycin treatment; however, sialogalactoproteins (detected by the binding of 125I-labeled R. communis agglutinin I to polyacrylamide gels containing desialized B16 cell surface components) were reduced dramatically by the drug. The adhesive properties of untreated and tunicamycin-treated B16 cells were assessed by the binding of 51Cr-labeled B16 cells to endothelial cell monolayers. Tunicamycin-treated B16-F1 and B16-F10 cells adhered at lower rates to endothelial cells such that after 24 to 36 hr of drug (0.5 micrograms/ml) treatment adhesion was almost completely blocked, suggesting that tunicamycin-induced cell surface glycoprotein changes in B16 melanoma cells may interfere with tumor cell-host cell interactions that lead to arrest and survival of blood-borne malignant cells.


Colour associations in children and adults.
A growing body of research has investigated how we associate colours and social traits. Specifically, studies have explored the links between red and perceptions of qualities like attractiveness and anger. Although less is known about other colours, the prevailing framework suggests that the specific context plays a significant role in determining how a particular colour might affect our perceptions of a person or item. Importantly, this factor has yet to be considered for children's colour associations, where researchers focused on links between colours and emotions, rather than social traits. Here, we consider whether context-specific colour associations are demonstrated by 5- to 10-year-old children and compare these associations with adult data collected on the same task. We asked participants to rank order sets of six identical images (e.g., a boy completing a test), which varied only in the colour of a single item (his T-shirt). Each question was tailored to the image set to address a specific context, for example, "Which boy do you think looks the most likely to cheat on a test?" Our findings revealed several colour associations shared by children, and many of these were also present in adults, although some had strengthened or weakened by this stage of life. Taken together, our results demonstrate the presence of both stable and changing context-specific colour associations during development, revealing a new area of study for further exploration.


Digital Analysis of the Dimensional Change Of an Irreversible Hydrocolloid Impression Material (Alginate) with Varying Storage Times.
The aim of this study was to digitally measure the dimensional changes in an irreversible hydrocolloid impression material (alginate) resulting from varying storage times under optimal storage conditions. A single type V dental stone control cast was used to make 25 alginate impressions using perforated stock trays. The impressions were randomly assigned into five groups of five samples each (n=5 per group) with varying storage times: Group 1, poured at 15 minutes; Group 2, poured at one hour; Group 3, poured at 24 hours (one day); Group 4, poured at 72 hours (three days); Group 5, poured at 168 hours (seven days). All impressions were stored in sealed Ziploc® plastic bags with a wet paper towel (100% relative humidity) at room temperature and stored according to the assigned group storage times. All impressions were poured in type V dental stone according to the manufacturer's instructions. The casts were scanned with a digital 3D desktop scanner and saved as electronic stereolithography (.stl) files. Each .stl file of the scanned casts were superimposed on the .stl file of the control cast using Geomagic® Control X™ software. Three preselected fixed comparison measuring points (CMP) on each cast were compared to the control cast. Point one (CMP1) was on the midfacial surface of central incisor. Point two (CMP2) and point three (CMP3) were on the mesiobuccal proximal marginal ridge areas of third molars. The discrepancies between the files at each point were analysed with colour maps, and quantified (Table 1). The tolerance was set at ±10μm. CMP scores were analysed using one-way analysis of variance (ANOVA) and Kruskal-Wallis (K-W) non-parametric H tests. Average gap distances across groups ranged from 0.04mm (seven-day group) to 0.06mm (one hour and 24-hour groups). Colour maps indicated increased dimensional change with increased storage time up to one day. After three days, shrinkage up to 139μm was measured. ANOVA results for CMP1 (F[4,20] = 1.65, p = 0.020) and CMP3 (F[4,20] = 0.44, p = -0.78) were not statistically significant. Similarly, K-W results for CMP2 were not significant (χ2= 3.62, p = 0.46). Under optimal storage conditions, there were no significant dimensional changes in casts poured from alginate up to seven days.


Remodeling of the cervix and parturition in mice lacking the progesterone receptor B isoform.
Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition.


The Nuts and Bolts of SARS-CoV-2 Spike Receptor-Binding Domain Heterologous Expression.
COVID-19 is a highly infectious disease caused by a newly emerged coronavirus (SARS-CoV-2) that has rapidly progressed into a pandemic. This unprecedent emergency has stressed the significance of developing effective therapeutics to fight the current and future outbreaks. The receptor-binding domain (RBD) of the SARS-CoV-2 surface Spike protein is the main target for vaccines and represents a helpful "tool" to produce neutralizing antibodies or diagnostic kits. In this work, we provide a detailed characterization of the native RBD produced in three major model systems: Escherichia coli, insect and HEK-293 cells. Circular dichroism, gel filtration chromatography and thermal denaturation experiments indicated that recombinant SARS-CoV-2 RBD proteins are stable and correctly folded. In addition, their functionality and receptor-binding ability were further evaluated through ELISA, flow cytometry assays and bio-layer interferometry.


[Inheritance of grain esterase genes in rye populations (Secale cereale L.)].
Genetic analysis of four tow straw rye populations has been carried out basing on the trait electrophoretic spectrum of grain esterase isozymes. Expression of seven independent Est genes has been shown. Three of them are clustered and their intrapopulation polymorphism exceeds two alleles. Comparative analysis of the frequences of different genes in parental populations and in F2 with literature data about localization of Est genes makes it possible to carry out chromosomal localization of the genes identified according to the fact of presence or absence of linking with the genes of rye self-incompatibility.


Patient and family perceptions of the provision of medicines as part of virtual outpatient consultations for children during COVID-19 pandemic.
To evaluate (1) views and perceptions of patients/parents/carers and healthcare professionals on the medicines optimisation (MO) process following virtual outpatient clinic (VOC) during the COVID-19 pandemic and (2) the processes introduced at this time, identifying areas for improvements and suggest potential solutions. A mixed-methods service evaluation using qualitative and quantitative methods of the MO pathway in children aged 0-18 years following VOC across three specialist children's units.Semi-structured interviews were conducted over the telephone with the participants exploring their experiences and categorised into themes.Process mapping sessions with the multidisciplinary team identified areas for improvement and an ease impact framework developed for potential solutions.Outcome measures included: (1) themes from interviews, (2) patients satisfaction rates, (3) process maps and (4) development of a simplified future process. One hundred and twenty-five patients' families were contacted: 71 families consented to participate and their views were categorised into four main themes: (1) patient experience, (2) communication, (3) need for virtual video consultations for patient education by hospital pharmacists and (4) need for electronic processes to send prescriptions to local pharmacies.Median patient satisfaction rate was 96% (range 67%-100%). The convenience of receiving medications directly to patient's homes; access to medicines information helplines and education provided by pharmacists were regarded as valuable. Communication between care providers, development of virtual video consultations by hospital pharmacists and electronic transfer of some prescriptions directly to community pharmacies were identified as areas of improvement. Participants appreciated the pharmacy processes adopted during the pandemic, however, challenges and recommendations for improvement in delivering MO VOC were identified. As digital innovations evolve within the NHS, future research should focus on integrated care and improved communication between care providers with selected medications prescribed directly to community pharmacies using electronic prescription service, with clinical screening and education provided by hospital pharmacists.


International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.
Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.


Sea-ATI unravels novel vocabularies of plant active cistrome.
The cistrome consists of all cis-acting regulatory elements recognized by transcription factors (TFs). However, only a portion of the cistrome is active for TF binding in a specific tissue. Resolving the active cistrome in plants remains challenging. In this study, we report the assay sequential extraction assisted-active TF identification (sea-ATI), a low-input method that profiles the DNA sequences recognized by TFs in a target tissue. We applied sea-ATI to seven plant tissues to survey their active cistrome and generated 41 motif models, including 15 new models that represent previously unidentified cis-regulatory vocabularies. ATAC-seq and RNA-seq analyses confirmed the functionality of the cis-elements from the new models, in that they are actively bound in vivo, located near the transcription start site, and influence chromatin accessibility and transcription. Furthermore, comparing dimeric WRKY CREs between sea-ATI and DAP-seq libraries revealed that thermodynamics and genetic drifts cooperatively shaped their evolution. Notably, sea-ATI can identify not only positive but also negative regulatory cis-elements, thereby providing unique insights into the functional non-coding genome of plants.


A new look at screening and diagnosing diabetes mellitus.
Diabetes is underdiagnosed. About one third of people with diabetes do not know they have it, and the average lag between onset and diagnosis is 7 yr. This report reconsiders the criteria for diagnosing diabetes and recommends screening criteria to make case finding easier for clinicians and patients. R.M.B. invited experts in the area of diagnosis, monitoring, and management of diabetes to form a panel to review the literature and develop consensus regarding the screening and diagnosis of diabetes with particular reference to the use of hemoglobin A1c (HbA1c). Participants met in open session and by E-mail thereafter. Metrika, Inc. sponsored the meeting. A literature search was performed using standard search engines. The panel heard each member's discussion of the issues, reviewing evidence prior to drafting conclusions. Principal conclusions were agreed on, and then specific cut points were discussed in an iterative consensus process. The main factors in support of using HbA1c as a screening and diagnostic test include: 1) HbA1c does not require patients to be fasting; 2) HbA1c reflects longer-term glycemia than does plasma glucose; 3) HbA1c laboratory methods are now well standardized and reliable; and 4) errors caused by nonglycemic factors affecting HbA1c such as hemoglobinopathies are infrequent and can be minimized by confirming the diagnosis of diabetes with a plasma glucose (PG)-specific test. Specific recommendations include: 1) screening standards should be established that prompt further testing and closer follow-up, including fasting PG of 100 mg/dl or greater, random PG of 130 mg/dl or greater, or HbA1c greater than 6.0%; 2) HbA1c of 6.5-6.9% or greater, confirmed by a PG-specific test (fasting plasma glucose or oral glucose tolerance test), should establish the diagnosis of diabetes; and 3) HbA1c of 7% or greater, confirmed by another HbA1c- or a PG-specific test (fasting plasma glucose or oral glucose tolerance test) should establish the diagnosis of diabetes. The recommendations are offered for consideration of the clinical community and interested associations and societies.


Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-ILb-perinatal-extraocular.
Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes. and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.


Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents.
Calprotectin is a marker of inflammation and zonulin is a marker of intestinal permeability. Diets with lower carbohydrate content and higher contents of fat, fiber and protein, e.g., Okinawan-based diet, are considered to reduce inflammation and intestinal permeability. The aim of the present study was to evaluate calprotectin and zonulin levels in serum and feces after intervention with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2 diabetes, mean age 57.5±8.2 years, BMI 29.9±4.1 kg/m2, were served the diet during 12 weeks, and were followed for another 16 weeks. Anthropometric and metabolic parameters were registered. Fasting levels of calprotectin and zonulin in serum and feces, and hormones in plasma, were measured by Luminex or ELISA before study start and after 12 and 28 weeks. Calprotectin in serum tended to be increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28 weeks (P=0.014). In contrast to baseline, there was a correlation between calprotectin and zonulin in serum and feces after dietary intervention (P=0.025 vs. P=0.079). Energy percentage of protein in breakfast correlated with serum calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059). Calprotectin in serum tended to be elevated, and zonulin in serum and feces are elevated after introduction of an Okinawan-based Nordic diet. These biomarkers correlate with energy percentage of protein.


Advantages of magnetic resonance imaging (MRI) of the seminal vesicles and intra-abdominal vas deferens in patients with congenital absence of the vas deferens.
To show the flexibility in magnetic resonance imaging (MRI) of seminal vesicle (SV) and intra-abdominal segment of vas deferens for the patients with congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of vas deferens (CUAVD). Fourteen consecutive patients with CAVD had transrectal ultrasonography (TRUS) and further MRI evaluations. TRUS was performed using a 7.5-MHz transducer, and images of the SVs were obtained, calculated in the transaxial plane. MRI studies were performed with a 1.5-7 superconducting system, T1- and T2-weighted axial, coronal, and sagittal imaging of the pelvis was obtained. If the SVs were present, then their size was measured for the morphologic classification and diagnosis. All of the patients also received cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation testing. In a series of 12 men with CBAVD, only 4 were found to have bilateral SV agenesis using MRI. The remaining 8 men with unilateral hypoplasia still had SV remnants. MRI also detected the intra-abdominal segment of the vas deferens. Through our study of MRI, SV agenesis is not well associated with the presence of CFTR mutation in patients with CAVD. MRI provides a precise imaginal diagnosis of SV defect, which is superior to the TRUS examination for the patients with CAVD. Compared with the previous inaccurate examination method of TRUS, this study demonstrates that MRI can provide better images for the patients with CAVD for the clinical diagnosis of existing defects of internal seminal tract and internal organs.


Comprehensive model of wild-type and mutant HIV-1 reverse transciptases.
An enhanced version of COMBINE that uses both ligand-based and structure-based alignment of ligands has been used to build a comprehensive 3-D QSAR model of wild-type HIV-1 reverse transcriptase and drug-resistant mutants. The COMBINEr model focused on 7 different RT enzymes complexed with just two HIV-RT inhibitors, niverapine (NVP) and efavirenz (EFV); therefore, 14 inhibitor/enzyme complexes comprised the training set. An external test set of chiral 2-(alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones (DABOs) was used to test predictability. The COMBINEr model MC4, although developed using only two inhibitors, predicted the experimental activities of the test set with an acceptable average absolute error of prediction (0.89 pK (i)). Most notably, the model was able to correctly predict the right eudismic ratio for two R/S pairs of DABO derivatives. The enhanced COMBINEr approach was developed using only software freely available to academics.


A precisely timed asynchronous pattern of ON and OFF retinal ganglion cell activity during propagation of retinal waves.
Patterns of coordinated spontaneous activity have been proposed to guide circuit refinement in many parts of the developing nervous system. It is unclear, however, how such patterns, which are thought to indiscriminately synchronize nearby cells, could provide the cues necessary to segregate functionally distinct circuits within overlapping cell populations. Here, we report that glutamatergic retinal waves possess a substructure in the bursting of neighboring retinal ganglion cells with opposite light responses (ON or OFF). Within a wave, cells fire repetitive nonoverlapping bursts in a fixed order: ON before OFF. This pattern is absent from cholinergic waves, which precede glutamate-dependent activity, providing a developmental sequence of distinct activity-encoded cues. Asynchronous bursting of ON and OFF retinal ganglion cells depends on inhibition between these parallel pathways. Similar asynchronous activity patterns could arise throughout the nervous system, as inhibition matures and might help to separate connections of functionally distinct subnetworks.


Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis.
To follow two children with isolated glycerol kinase deficiency (GKD) with severe symptoms into adulthood. The patients were followed during approximately 20 y and interviewed about symptoms, diet and physical activity. Fasting provocations, bicycle ergometer tests, dietary registrations, enzyme and mutation analysis were performed by standard protocols. The activity of glycerol kinase (GK) in fibroblasts was <10% of reference. One case had a deletion of exon 17, the other a mutation in exon 7 of the GK gene (601 A-->G). Both mothers were heterozygotes. Two maternal male cousins in one of the families were hemizygotes without symptoms. Tests performed in childhood documented pronounced sensitivity to fasting and physical exercise, whereas such tests at 23 and 31 y of age were essentially normal but with pronounced ketonaemia. After puberty, the boys had no hypoglycaemic symptoms and now report no problems with their condition; thus, their phenotype has changed over time. The greater importance of glycerol as a gluconeogenetic substrate in children than in adults may explain the episodes in young patients with GKD, often elicited by catabolic stress. With meals at frequent intervals, access to glucose and avoidance of strenuous sports, the prognosis is good for a normal adult life of a young child with isolated GKD and symptoms of hypoglycaemia.


Serum complement sensitivity as a key factor in Lyme disease ecology.
The sensitivity of Borrelia burgdorferi sensu lato to animal sera was analyzed. Complement-mediated borreliacidal effects were observed with particular combinations of host serum and Borrelia genospecies. The species-specific pattern of viability and/or lysis is highly consistent with the pattern of reservoir competence of hosts for B. burgdorferi sensu lato, suggesting a key role of complement in the global ecology of Lyme borreliosis.


Resolving conflicts in public health protection and ecosystem service provision at designated bathing waters.
Understanding and quantifying the trade-off between the requirement for clean safe bathing water and beaches and their wider ecosystem services is central to the aims of the European Union (EU) Marine Strategy Framework Directive (MSFD), and vital for the sustainability and economic viability of designated bathing waters. Uncertainty surrounding the impacts of ensuing bathing water policy transitions, e.g. the EU revised Bathing Waters Directive (rBWD), puts new urgency on our need to understand the importance of natural beach assets for human recreation, wildlife habitat and for protection from flooding and erosion. However, managing coastal zones solely in terms of public health could have potentially negative consequences on a range of other social and cultural ecosystem services, e.g. recreation. Improving our knowledge of how bathing waters, surrounding beach environments and local economies might respond to shifts in management decisions is critical in order to inform reliable decision-making, and to evaluate future implications for human health. In this paper we explore the conflicts and trade-offs that emerge at public beach environments, and propose the development of an evaluative framework of viable alternatives in environmental management whereby bathing waters are managed for their greatest utility, driven by identifying the optimal ecosystem service provision at any particular site.


An effective strategy, applicable to Streptococcus salivarius and related bacteria, to enhance or confer electroporation competence.
Despite the large number of techniques available for transformation of bacteria, certain species and strains are still resistant to introduction of foreign DNA. Some oral streptococci are among the organisms that can be particularly difficult to transform. We performed a series of experiments that involved manipulation of growth and recovery media and cell wall weakening, in which the electroporation conditions, cell concentration, and type and concentration of the transforming plasmid were varied. The variables were optimized such that a previously untransformable Streptococcus salivarius strain, ATCC 25975, could be transformed reproducibly at a level of 10(5) transformants per microg of DNA. The technique was used to introduce a plasmid into other strains of S. salivarius, including a fresh isolate. Moreover, the same technique was applied successfully to a wide range of oral streptococci and other gram-positive bacteria.


Factors influencing owner satisfaction with companion-dog-training facilities.
The aim of this study was to survey people currently attending companion-dog-training facilities about their reasons for attending training, their expectations prior to training, their training experiences, and the factors contributing to their satisfaction with these experiences. The 178 participants indicated that they experienced few canine behavioral difficulties prior to attending training, with factors other than dog behavior influencing their decision to attend a particular facility. Features identified as important were characteristics of the instructors and the facility itself, opportunities for the dog caretaker (owner) to develop dog-training skills and knowledge, and specific canine behavior outcomes. Satisfaction was a multidimensional concept: satisfaction with the instructors and facility being dissociable from satisfaction with progress made by the dog and handler. Each of these represented different aspects of the training experience. Training facilities may need to address a wide range of issues to engage additional dog owners in training activities. Identification of these issues is an important first step in this process.


Additive activity between the trans-activation response RNA-binding protein, TRBP2, and cyclin T1 on HIV type 1 expression and viral production in murine cells.
Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR) occurs through the phosphorylation of the carboxy-terminal domain of the RNA polymerase II. The kinase complex, pTEFb, composed of cyclin T1 (CycT1) and CDK9, mediates this process. The trans-activation response (TAR) RNA-binding protein 2 (TRBP2) increases HIV-1 LTR expression through TAR and protein kinase R (PKR) binding, but not through interactions with the Tat-CycT1-CDK9 complex. TRBP2 and the Tat-CycT1-CDK9 complex have overlapping binding sites on TAR RNA. TRBP2 and CycT1 increased Tat trans-activation in NIH 3T3 cells with additive effects. Upon transfection of HIV-1 pLAI, pNL4-3, pMAL, and pAD molecular clones, reverse transcriptase (RT) activity and p24 concentration were decreased 200- to 900-fold in NIH 3T3 cells compared with HeLa cells in both cells and supernatants. In murine cells, cotransfection of the HIV clones with CycT1 or TRBP2 increased modestly the expression of RT activity in cell extracts. The analysis of Gag expression in murine cells transfected with CycT1 compared with human cells showed a 20-fold decrease in expression and a strong processing defect. The expression of both CycT1 and TRBP2 had a more than additive activity on RT function in cell extracts and on viral particle production in supernatant of murine cells. These results suggest an activity of CycT1 and TRBP2 at different steps in HIV-1 expression and indicate the requirement for another posttranscriptional factor in murine cells for full HIV replication.


The importance of evaluating primary midwifery care for improving the health of women and infants.
In most countries, maternal and newborn care is fragmented and focused on identification and treatment of pathology that affects only the minority of women and babies. Recently, a framework for quality maternal and newborn care was developed, which encourages a system-level shift to provide skilled care for all. This care includes preventive and supportive care that works to strengthen women's capabilities and focuses on promotion of normal reproductive processes while ensuring access to emergency treatment when needed. Midwifery care is pivotal in this framework, which contains several elements that resonate with the main dimensions of primary care. Primary health care is the first level of contact with the health system where most of the population's curative and preventive health needs can be fulfilled as close as possible to where people live and work. In this paper, we argue that midwifery as described in the framework requires the application of a primary care philosophy for all childbearing women and infants. Evaluation of the implementation of the framework should therefore include tools to monitor the performance of primary midwifery care.


Construction of polymeric delta-graph: a doubly fused tricyclic topology.
A doubly fused tricyclic polymer architecture, corresponding to a delta-graph, has been constructed effectively through metathesis polymer cyclization (MPC) of an 8-shaped dicyclic polymer precursor having two allyl groups placed at opposite positions of the two rings of the 8-shaped structure. The 8-shaped polymer precursor has been obtained through the covalent conversion of an electrostatic self-assembly (composed of two units of the linear poly(tetrahydrofuran)s, poly(THF)s, having pyrrolidinium salt end groups and having a pendant allyl group at the middle of the chain, carrying a tetrafunctional carboxylate counteranion) by the heating treatment under appropriate dilution to cause the ring-opening reaction of pyrrolidinium salt groups by carboxylate anions.


Volatile-mediated antagonism of soil bacterial communities against fungi.
Competition is a major type of interaction between fungi and bacteria in soil and is also an important factor in suppression of plant diseases caused by soil-borne fungal pathogens. There is increasing attention for the possible role of volatiles in competitive interactions between bacteria and fungi. However, knowledge on the actual role of bacterial volatiles in interactions with fungi within soil microbial communities is lacking. Here, we examined colonization of sterile agricultural soils by fungi and bacteria from non-sterile soil inoculums during exposure to volatiles emitted by soil-derived bacterial communities. We found that colonization of soil by fungi was negatively affected by exposure to volatiles emitted by bacterial communities whereas that of bacteria was barely changed. Furthermore, there were strong effects of bacterial community volatiles on the assembly of fungal soil colonizers. Identification of volatile composition produced by bacterial communities revealed several compounds with known fungistatic activity. Our results are the first to reveal a collective volatile-mediated antagonism of soil bacteria against fungi. Given the better exploration abilities of filamentous fungi in unsaturated soils, this may be an important strategy for bacteria to defend occupied nutrient patches against invading fungi. Another implication of our research is that bacterial volatiles in soil atmospheres can have a major contribution to soil fungistasis.


Performance on the CERAD neuropsychology battery of two samples of Japanese-American elders: norms for persons with and without dementia.
Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations.


Development of Machine Learning Model for Selecting the 1st Coil in the Treatment of Cerebral Aneurysms by Coil Embolization.
To achieve good treatment outcomes in coil embolization for cerebral aneurysms, it is important to select an appropriate 1st coil for each aneurysm since it serves as a frame to support the subsequent coils to be deployed. However, its selection as appropriate size and length from a wide variety of lineups is not easy, especially for inexperienced neurosurgeons. We developed a machine learning model (MLM) to predict the optimal size and length of the 1st coil by learning information on patients and aneurysms that were previously treated with coil embolization successfully. The accuracy rates of the MLM for the test data were 86.3% and 83.4% in the prediction of size and length, respectively. In addition, the accuracy rates for the 30 cases showed good prediction by the MLM when compared with two different skilled neurosurgeons. Although the accuracy rate of the well-experienced neurosurgeon is similar to MLM, the inexperienced neurosurgeon showed a worse rate and can benefit from the method.Clinical Relevance- The developed MLM has the potential to assist in the selection of the 1st coil for aneurysms. A technically and cost efficient supply chain in the treatment of aneurysms may also be achieved by MLM application.


Identification of proteins by combination of size-exclusion chromatography with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and comparison of some desalting procedures for both intact proteins and their tryptic digests.
Separation of a protein mixture by size-exclusion chromatography (SEC) was combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Identification of proteins in the collected fractions was performed both as intact proteins by MALDI-TOFMS and using peptide mass fingerprinting (PMF) after their digestion with trypsin. The presence of salts mostly disturbs the MALDI-TOFMS signal and, therefore, proper purification or desalting procedures must be employed. Four desalting procedures (desalting column packed with Sephadex G-100, on-target washing, centrifugal filter devices and ZipTip C(18)) for purification of fractions of proteins separated by SEC and their tryptic digests prior to determination of their exact molecular masses by MALDI-TOFMS were compared. In the case of intact proteins, the experiments showed that the best desalting procedures are the use of ZipTip C(18) pipette tips and Ultrafree CL centrifugal filter devices. The peptide digests can be purified by using ZipTip C(18) pipette tips or on-target washing when both of these procedures provide similar results. On-target washing can be used as a simple procedure to improve the mass spectra of salt-containing samples. Analyses of the droplets collected after the on-target washing show losses of sample and matrix caused by dissolution of these compounds during this procedure. Further, it was found that protein identification based on PMF is more sensitive than analyses of intact proteins and that multiple on-target washing is very advantageous for analyses of peptide mixtures with a high content of salts.


Structural and mechanistic determinants of a novel site for noncompetitive inhibition of GluN2D-containing NMDA receptors.
NMDA receptors are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in several neurological diseases. We have evaluated the mechanism of action of a class of novel subunit-selective NMDA receptor antagonists, typified by (E)-4-(6-methoxy-2-(3-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)-benzoic acid (QNZ46). We found that QNZ46 inhibits NMDA receptor function in a noncompetitive and voltage-independent manner by an unconventional mechanism that requires binding of glutamate to the GluN2 subunit, but not glycine binding to the GluN1 subunit. This dependency of antagonist association on glutamate binding to GluN2 renders these compounds nominally use-dependent, since inhibition will rely on synaptic release of glutamate. Evaluation of the structural determinants responsible for the subunit-selectivity of QNZ46 revealed that these compounds act at a new site that has not previously been described. Residues residing in the part of the agonist binding domain immediately adjacent to the transmembrane helices appear to control selectivity of QNZ46 for GluN2C- and GluN2D-containing receptors. These residues are well-positioned to sense glutamate binding to GluN2 and thus to mediate glutamate-dependent actions. This new class of noncompetitive antagonists could provide an opportunity for the development of pharmacological tools and therapeutic agents that target NMDA receptors at a new site and modulate function by a novel mechanism.


Segmented mirror alignment with far-field optimization in the presence of atmospheric turbulence.
The remote alignment of segmented mirror active optics with far-field optimization is reported. Farfield optimization eliminates the need for a wave-front sensor or gap sensors since it does not require any near-field measurements, but uses simple measures of the point-spread function as figures of merit. The simplex function minimization algorithm is used to configure iteratively the segmented mirror toalignment. We present results of computer simulations to demonstrate the application of far-field optimization to the segmented mirror alignment in the presence of atmospheric turbulence. The effects of static as well as dynamic Kolmogorov turbulence (turbulence phase screen drifting across the telescope aperture) are studied. We find that the segmented mirror alignment is fairly insensitive to the speed of drifting turbulence and aligns a segmented mirror active optical system with adequate correction bandwidth in a few seconds.


Uniportal video-assisted thoracoscopic right upper lobectomy and systemic mediastinal lymph nodes dissection.
Along with the progresses that have been made in techniques and instruments, uniportal video-assisted thoracoscopic surgery (VATS) became more and more popular. Here, we present the operation video of a 52-year-old female with early stage lung cancer in the right upper lobe (RUL), who underwent uniportal VATS right upper lobectomy and systemic mediastinal lymph nodes dissection performed by our team. The video demonstrated the Uniportal VATS techniques of hilar anatomy, bronchus and blood vessel separation, mediastinal lymph node areas exploration and en-bloc dissection. Once the vision angle is properly adapted, techniques and instruments are mastered, and the patients are well selected, uniportal VATS approach can be an alternative to the conventional VATS for early stage lung cancer.


A novel maskless approach towards aligned, density modulated and multi-junction ZnO nanowires for enhanced surface area and light trapping solar cells.
A maskless method of employing polymer growth inhibitor layers is used to modulate the conflicting parameters of density and alignment of multi-junction nanowires via large-scale low temperature chemical route. This low temperature chemical route is shown to synthesize multi-junction nanostructures without compromising the crystal quality at the interfaces. The final morphology of optimized multi-junctions nanowire arrays can be demonstrated on various substrates due to substrate independence and low temperature processing. Here, we also fabricated devices based on density modulated multi-junction nanowires tuned to infiltrate nanoparticles. The fabrication of hierarchically structured nanowire/nanoparticles composites presents an advantageous structure, one that allows nanoparticles to provide large surface areas for dye adsorption, whilst the nanowires can enhance the light harvesting, electron transport rate, and also the mechanical properties of the films. This work can be of great scientific and commercial interest since the technique employed is of low temperature (<90 degrees C) and economical for large-scale solution processing, much valued in today's flexible display and photovoltaic industries.