A novel wheat alpha-amylase gene (alpha-Amy3).
A genomic clone of a wheat alpha-amylase gene (lambdaAmy3/33) was identified, on the basis of hybridisation properties, as different from alpha-Amy1 and alpha-Amy2 genes which had been characterised previously. The nucleotide sequence revealed that this gene has the normal sequence motifs of an active gene and an open reading frame interrupted by two introns. The protein sequence encoded by this open reading frame is recognisably similar to that of alpha-amylase from the alpha-Amy1 and alpha-Amy2 genes and there is high sequence homology in all three proteins at the putative active sites and Ca++ binding region. In addition, the introns are at positions equivalent to the position of introns in the alpha-Amy1 and alpha-Amy2 genes. However, the sequence was less similar to alpha-Amy1 and alpha-Amy2 than these are to each other. Southern blot analysis showed that the lambdaAmy3/33 DNA is one of a small multigene family carried on a different chromosome (group 5) from either the alpha-Amy1 or alpha-Amy2 genes. A further difference from the alpha-Amy1 and alpha-Amy2 genese was the pattern of expression. lambdaAmy3/33 was expreseed only in immature grains and, unlike the alpha-Amy1 and alpha-Amy2 genes, not at all in germinating aleurones. These data suggested therefore that this gene represents a third type of alpha-amylase gene, not described before, which shares a common evolutionary ancestor with the alpha-Amy1 and alpha-Amy2 genes.


Attenuation of homeostatic sleep response and rest-activity circadian rhythm in vitamin D deficient mice.
The link between vitamin D deficiency (VDD) and sleep disturbances has long been suggested. However, the direct causality between VDD, sleep disturbances, and circadian rhythm remains unclear. We aimed to characterize sleep-wake behavior and circadian rhythms in an animal model of VDD. VDD was induced by feeding vitamin D-deficient chow, and we analyzed sleep and circadian rhythm parameters. During light period, VDD mice exhibited reduced wake with more frequent wake bouts and increased NREM sleep time. However, during dark period, the wake EEG power spectrum peaked at theta band frequency, and slow-wave energy was suppressed in mice with VDD. Rest-activity analyses revealed increased circadian period, lower wheel counts, and more frequent and short activity bouts during VDD. Combining sleep and circadian data, we found significantly suppressed activities during the hours with a wake duration shorter than 30 minutes. Moreover, mice in VDD state exhibited a negative correlation between wake theta power and hourly wheel-running counts during dark period. Our data point to a direct link between VDD and disturbances in sleep and rest-activity circadian rhythm, featuring frequent wake bouts during the sleeping phase, reduced sleep pressure build-up in dark period, and reduced activity levels due to increased susceptibility to sleepiness.


Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients.
The aim of this work was to evaluate the neutrophil activation state in chronic kidney disease (CKD) patients under hemodialysis, and its linkage with resistance to recombinant human erythropoietin (rhEPO) therapy. We studied 63 CKD patients under hemodialysis and rhEPO treatment (32 responders and 31 non-responders to rhEPO therapy). In 20 of the CKD patients (10 responders and 10 non-responders to rhEPO therapy), blood samples were also collected immediately after dialysis. Twenty-six healthy volunteers were included in a control group. Hemoglobin levels, total and differential leukocyte counts, and circulating levels of C-reactive protein (CRP), elastase and lactoferrin were measured in all patients and controls. Compared with controls, CKD patients presented with significantly higher CRP, neutrophil and elastase levels. When we compared the 2 groups of patients, we found that non-responders presented statistically significantly higher elastase plasma levels. A positive significant correlation was found between elastase levels and weekly rhEPO dose and CRP serum levels. After the hemodialysis procedure, a statistically significant rise in elastase, lactoferrin and, elastase/neutrophil and lactoferrin/neutrophil ratios were found. Our data show that CKD patients under hemodialysis present higher elastase levels (particularly in non-responding patients), which could be related to the rise in neutrophils, and to be part of the enhanced inflammatory process found in these patients.


Cloning and characterization of a gene of Streptomyces griseus that increases production of extracellular enzymes in several species of Streptomyces.
A 7.2 kb Bg/II restriction fragment, which increases the production of several extracellular enzymes, including alkaline phosphatase, amylase, protease, lipase and beta-galactosidase, was cloned in Streptomyces lividans from the DNA of S. griseus ATCC 10137. This gene (named saf) showed a positive gene dosage effect on production of extracellular enzymes. When the saf gene was introduced into cells in high copy numbers it delayed the formation of pigments and spores in S. lividans and also retarded actinorhodin production in Streptomyces coelicolor. The saf gene hybridized with specific bands in the DNA of several Streptomyces strains tested. A 1 kb fragment containing the saf gene was sequenced and contains an open reading frame (ORF) of 306 nucleotides which encodes a polypeptide of Mr 10,500. This ORF is contained within a fragment of 432 bp which retained activity in Streptomyces. A fragment with promoter activity is present upstream of the saf reading frame. The predicted Saf polypeptide has a strong positive charge, and does not show a typical amino acid composition for a membrane protein, and contains a DNA-binding domain similar to those found in several regulatory proteins.


Membrane traffic during embryonic development: epithelial formation, cell fate decisions and differentiation.
The analysis of membrane trafficking has in the past mainly dealt with single cells in culture. Recent studies of membrane trafficking in Drosophila focus on how cells are organized in tissues and form epithelia during embryogenesis. During these processes, the specific involvement of distinct biosynthetic and endocytic routes is starting to be understood. Once organized in epithelia, cells communicate with each other to make cell fate decisions through morphogen gradients and lateral inhibition. Endocytosis seems to play unexpected roles in shaping morphogen gradients and in biasing lateral inhibition events. Once committed to a developmental program, cells differentiate. In the case of neurons, trafficking through the biosynthetic and endocytic pathways may give the necessary speed of response and versatility to axons that navigate through a changing environment during pathfinding.


Daily use of the physio dialysis system: long-term experience.
Hypovolaemia has been implicated as a major causal factor of morbidity during haemodialysis (HD). In order to avoid the appearance of destabilising hypovolaemia a biofeedback control system for intra-HD blood volume (BV) change modelling has been developed (Hemocontrol, Hospal Italy). It is based on an adaptive controller incorporated into a HD machine (Integra, Hospal Italy). The Hemocontrol biofeedback system (HBS) monitors BV contraction during HD with an optical device; furthermore, HBS modulates BV contraction rates (by adjusting the ultrafiltration rate--UFR) and the refilling rate (by adjusting dialysate conductivity--DC) in order to obtain the desired pre-determined BV trajectories. Nineteen patients prone to hypotension (7 males, 12 females, mean age 64.5 +/- 3.0 SEM years, on maintenance HD for 80.5 +/- 13.2 months) volunteered for the prospective study which aimed to compare the efficacy and safety of bicarbonate HD treatmentequipped with HBS, as a whole (HBS),with the gold standard, bicarbonate treatment, equipped with a constant UFR and DC (BD). The study included one period of 6 months of BD always preceding a follow-up period of HBS treatment ranging from 14 to 30 months (mean 24.0 +/- 1.6). The overall occurrence of symptomatic hypotension and muscle cramps was significantly less in HBS treatment. Self-evaluation of intra- and inter-HD symptoms (the worst score was o and the best one 10) did reveal a statistically significant difference, as far as post-HD fatigue is concerned (6.2 +/- 0.2 in HBS vs. 4.3 +/- 0.1 in BD treatment, p < 0.0001). No difference between the two treatments was observed when comparing pre- and post-HD lying blood pressure, heart rate, body weights and body weight changes. HBS is an effective treatment. Hypovolaemia-associated morbidity occurs less in BD treatment than HBS. Furthermore, HBS is a safe treatment in the medium-term because these results are achieved without potentially harmful changes in blood pressure, body weight and serum sodium concentration.


Junction-Controlled Topological Polymerization.
Methodology that enables the controlled synthesis of linear and branched polymers from an identical monomer will be a novel pathway for polymer synthesis and processing. Herein we first describe the control of one or both of the C(3)-C(3') and C(6)-C(6') coupling reactions of carbazolyl. In a second approach, an identical monomer containing two carbazolyls is polymerized using chemical and electrochemical oxidizers, leading to topologically controllable growth of linear polymers in weak oxidizer or of cross-linked polymer chains in strong oxidizer, with satisfactory long chain propagation of step growth polymerization (Mn =6.0×104 g mol-1 , Mw /Mn =2.3). This very simple polymerization with cheap reagents and low levels of waste has provided a flexible pathway for synthesis and processing of polymers.


Evaluation of xeroradiographic image quality.
A theory of edge enhancement has been developed to describe xeroradiographic images of linear step objects. The theory is shown to give an accurate description of the relationship between edge enhancement, subject contrast, radiation exposure, selenium charging potential and developer bias potential. An optimal transmitted x-ray exposure exists which gives the maximum edge enhancement. For low contrast structures, this same optimal exposure was found to yield the most acceptable images as judged subjectively. This finding has led to the successful application of automatic exposure termination in mammographic examinations using xeroradiography.


Quality of life in paediatric inflammatory bowel disease measured by a generic and a disease-specific questionnaire.
This study assessed the impact of inflammatory bowel disease (IBD) on the health-related quality of life (HRQoL) of children and adolescents, using both a generic and a disease-specific instrument. Three questionnaires were sent to all patients (8-18 y old) from the database of two large secondary/tertiary hospitals in the western part of The Netherlands. In total, 83 (66%) children responded, 18 were between 8 and 12 y old and the remaining 65 were older. HRQoL was measured using a generic instrument, the TNO-AZL Children's Quality of Life questionnaire (TACQOL), assessing seven domains, and the Impact-II (NL), a disease-specific instrument assessing six domains. Disease activity was measured by a five-item symptom card. Compared with scores from a large reference population (n= 1810), younger children with IBD had a comparable HRQoL (measured by the TACQOL) on six domains, and better cognitive functioning, although they did not have severely active disease. Adolescent patients with IBD had a significantly impaired HRQoL on four domains (body complaints, motor functioning, autonomy and negative emotions). The Impact-II discriminated well between patients with varying disease activity states on all domains. Adolescents with IBD have a severely affected HRQoL. Impairment on motor functioning and autonomy is a threat to gaining independence from caregivers, and a high occurrence of negative emotions places patients at risk for depressive and behavioural disorders. The Impact-II is recommended for clinical use because of its high discriminative validity.


Immune cells as messengers from the CNS to the periphery: the role of the meningeal lymphatic system in immune cell migration from the CNS.
In recent decades there has been a large focus on understanding the mechanisms of peripheral immune cell infiltration into the central nervous system (CNS) in neuroinflammatory diseases. This intense research led to several immunomodulatory therapies to attempt to regulate immune cell infiltration at the blood brain barrier (BBB), the choroid plexus (ChP) epithelium, and the glial barrier. The fate of these infiltrating immune cells depends on both the neuroinflammatory environment and their type-specific interactions with innate cells of the CNS. Although the fate of the majority of tissue infiltrating immune cells is death, a percentage of these cells could become tissue resident immune cells. Additionally, key populations of immune cells can possess the ability to "drain" out of the CNS and act as messengers reporting signals from the CNS toward peripheral lymphatics. Recent data supports that the meningeal lymphatic system is involved not just in fluid homeostatic functions in the CNS but also in facilitating immune cell migration, most notably dendritic cell migration from the CNS to the meningeal borders and to the draining cervical lymph nodes. Similar to the peripheral sites, draining immune cells from the CNS during neuroinflammation have the potential to coordinate immunity in the lymph nodes and thus influence disease. Here in this review, we will evaluate evidence of immune cell drainage from the brain via the meningeal lymphatics and establish the importance of this in animal models and humans. We will discuss how targeting immune cells at sites like the meningeal lymphatics could provide a new mechanism to better provide treatment for a variety of neurological conditions.


CuH-Catalyzed Atropoenantioselective Reduction of Bringmann's Lactones via Dynamic Kinetic Resolution.
A CuH-catalyzed atropoenantioselective reduction of Bringmann's lactones via dynamic kinetic resolution has been disclosed. This protocol features a broad substrate scope and good functional group tolerance and allows the rapid assembly of various valuable axially chiral biaryls in good to high yields (up to 92% yield) with high to excellent enantioselectivities (up to 96% ee). Moreover, this report represents a rare example that a carbonyl group of esters is reduced under homogeneous asymmetric CuH catalysis.


Food and nutrition security in the Philippines during the COVID-19 pandemic.
Objective: The COVID-19 pandemic placed the Philippines' food and nutrition issues front and center. In this paper, we discuss the response of its government in addressing food and nutrition security at the beginning of the COVID-19 pandemic and describe its implications on nutritional status. We also cite initiatives that address food accessibility and availability in the communities. Lastly, we explore the importance of nutrition security dimension in food security. Methods: We analyze food and nutrition security issues in the Philippines during the COVID-19 pandemic through online reports and news articles. Results: The distribution of food and financial assistance in the country was extensive, albeit insufficient, considering the prolonged lockdown restrictions. Constantly changing community quarantine guidelines have affected the movement of food supply, delivery of health services, and household economic security. Nutrition programs, such as vitamin A supplementation, feeding for children, and micronutrient supplementation for pregnant women, had lower coverage rates, and by the latter half of 2020, the country had reached its highest recorded hunger rate. Cases of both undernutrition and overnutrition are predicted to rise because of dietary imbalances and a variety of factors. Conversely, community members and some local government units took it upon themselves to improve the food situation in their areas. The provision of food packs containing fresh fruits and vegetables was lauded, as it exemplified a conscious effort to deal with nutrition security. Conclusion: Efforts to address food security have always focused on increasing accessibility, availability, and affordability, often neglecting the nutritional components of foods. Strategies that incorporate nutrition security into food security are much needed in the country, especially during emergencies like the COVID-19 pandemic.


Stress-induced modulation of nociceptive responses in the rat anterior cingulate cortex.
In the limbic system, the anterior cingulate cortex (ACCX) is one of the key areas involved in the close association between pain and emotion. However, neuronal changes in ACCX nociceptive responses after stress conditioning have not yet been quantitatively investigated. We investigated the modulation of nociceptive responses in the ACCX neurons following restraint stress in rats. The present study demonstrated that stress-conditioning enhanced excitatory nociceptive responses in the ACCX following tail stimuli in the mid-term (7 days). Short-term (3 days) and long-term (21 days) of stress conditioning did not affect these responses significantly. Nociceptive responses evoked by other sites of the body (nose, back and four paws) stimulation were not changed by stress-conditioning, indicating that neural information from the tail is important for emotional system modulation. It is suggested that the emotional/affective part of the pain sensation is strongly modified by stress through neuroplasticity in the ACCX.


Screening for Hypertension in Children and Adolescents: Methodology and Current Practice Recommendations.
Hypertension (HTN) requires urgent, uniform, and consistent attention across all frontiers of pediatric health care not only because of established links between the onset of HTN during one's youth and its sustenance throughout adulthood but also because of the sequelae associated with the disease's trajectory, such as cardiovascular disease, end organ damage, and decreased quality of life. Although national guidelines for the diagnosis and management of pediatric HTN have been available for nearly 40 years, knowledge and recognition of the problem by clinicians remain poor due to a host of influencing factors. The purpose of this article is to explicate key issues contributing to the inaccurate measurement of blood pressure and misclassification of HTN among children and to present strategies to address these issues.


[Study advances in regulation effect of Tripterygium wilfordii and its extracts on innate immune system in rheumatoid arthritis cases].
Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.


Simultaneous Determination of Three Furanocoumarins by UPLC/MS/MS: Application to Pharmacokinetic Study of Angelica dahurica Radix after Oral Administration to Normal and Experimental Colitis-Induced Rats.
In traditional oriental medicine, Angelica dahurica Radix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg), blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (Tmax) of imperatorin and isoimperatorin was significantly delayed (p < 0.05). Lower peak plasma concentrations (Cmax) and longer mean residence times for all furanocoumarins were also observed (p < 0.05) compared with normal rats. There was no significant difference in the area under the plasma concentration-time curve or elimination half-lives. Thus, the delayed Tmax and decreased Cmax, with no influence on the elimination half-life, could be colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention.


Schooling of migrant children in China: Perspectives of school teachers.
The impact of family migration on children's schooling has been the focus of much investigation in western countries. However, there are limited data on such impact in China, despite a large number of rural-to-urban migrants. In-depth interviews were conducted among 20 school teachers in Beijing. Findings reveal that barriers for migrant children to attend public schools include extra financial charge and stigmatization resulting from their migratory status. The schools serving solely migrant children were perceived as having poor teaching facilities and lacking adequately trained teachers. Migrant parents were generally perceived as having limited involvement in their children's schooling. Findings suggest that national policy related to the schooling of migrant children should be improved and support from family and society should be emphasized.


Survival rates of anterior composites in managing tooth wear: systematic review.
The use of composite restorations for patients with tooth wear is considered as a more conservative treatment option. The aim of this study was to systematically review the literature investigating the survival rates of anterior composite restorations when used in managing tooth wear in patients. PubMed and MEDLINE (Ovid) databases were screened for studies from 1995 to 2015. Cross-referencing was used to further identify articles. Article selection and data extraction were performed in duplication. Languages were restricted to English. A quality appraisal of included studies was carried out using the Strength of Recommendation Taxonomy system. Six hundred and sixty-six articles were initially identified from which eight articles were full-text reviewed. Six articles involving five studies were selected for inclusion. Three studies were prospective and two retrospective. Included studies involved placement of 772 direct and indirect anterior composite restorations in 100 patients with follow-up periods between 5 months and 10 years. The survival rates of anterior composites were >90% and 50% at 2.5 and 5 years, respectively. Posterior occlusion was re-established in 91% of patients within 18 months. Meta-analysis could not be performed due to the heterogeneity of included studies. The systematic review's overall strength of recommendation was graded B. There is evidence to support the use of anterior composite restorations at an increased vertical dimension of occlusion in the short/medium-term management of tooth wear. Long-term reporting of outcomes remains limited. Further research is needed with standardised study design, detailed reporting of outcomes and long-term review.


Experimental epiphysial distraction producing and correcting angular deformities.
Angular deformities of the distal radius of 15 sheep were induced by asymmetrical epiphysial distraction. Eleven sheep were between 10 and 20 weeks old; four were older than 24 weeks. Gradual distraction on the medial side of the limb caused partial separation of the epiphysis from the metaphysis, resulting in a valgus deformity. The distraction device was removed three to six weeks after insertion. Spontaneous correction of angulation with growth occurred in the younger sheep; but when the induced valgus angle exceeded 20 degrees correction was poor. In two sheep further distraction was applied on the lateral side and this produced complete correction. Premature closure of epiphyses did not occur after distraction and longitudinal growth of the bone remained normal. In the older sheep asymmetrical distraction succeeded in inducing angulation in only one case, and correction was poor.


Transverse wave propagation in photonic crystal based on holographic polymer-dispersed liquid crystal.
This study investigates the transversely propagating waves in a body-centered tetragonal photonic crystal based on a holographic polymer-dispersed liquid crystal film. Rotating the film reveals three different transverse propagating waves. Degeneracy of optical Bloch waves from reciprocal lattice vectors explains their symmetrical distribution.


Effect of sitagliptin on expression of skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α and irisin in a rat model of type 2 diabetes mellitus.
To evaluate the effect of sitagliptin on skeletal muscle expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), irisin, and phosphoadenylated adenylate activated protein kinase (p-AMPK) in a rat model of type 2 diabetes mellitus (T2DM). A high-fat diet/streptozotocin T2DM rat model was established. Rats were divided into T2DM, low-dose sitagliptin (ST1), high-dose sitagliptin (ST2), and normal control groups (NC). PGC-1α, irisin, and p-AMPK protein levels in skeletal muscle were measured by western blot, and PCG-1α and Fndc5 mRNA levels were assessed by reverse transcription-polymerase chain reaction. Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment-insulin resistance (HOMA-IR), and tumor necrosis factor-α (TNF-α) were significantly up-regulated in the T2DM compared with the other groups, and FPG, FIns, total cholesterol, triglycerides, TNF-α, and HOMA-IR were significantly down-regulated in the ST2 compared with the ST1 group. PGC-1α, irisin, and p-AMPK expression levels decreased successively in the ST2, ST1, and DM groups compared with the NC, and were all significantly up-regulated in the ST2 compared with the ST1 group. Down-regulation of PGC-1α and irisin in skeletal muscle may be involved in T2DM. Sitagliptin can dose-dependently up-regulate PCG-1α and irisin, potentially improving insulin resistance and glycolipid metabolism and inhibiting inflammation.


Outcome of combined Ahmed glaucoma valve implant and penetrating keratoplasty in refractory congenital glaucoma with corneal opacity.
To investigate surgical outcomes following simultaneous Ahmed glaucoma valve implant and penetrating keratoplasty (PKP) in the management of refractory congenital glaucoma with corneal opacity. A retrospective review was undertaken of pediatric patients who underwent simultaneous Ahmed glaucoma valve implant and PKP at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, between January 1994 and September 1999. Twenty eyes of 17 patients were included in the study. Cumulative probabilities of success by Kaplan-Meier analysis showed 85%, 44%, and 33% IOP control and 85%, 43%, and 17% graft success at 2, 24, and 48 months. The most common cause of glaucoma failure that required subsequent surgery was subconjunctival scarring, which resulted in loss of long-term IOP control. Main graft-related complications included failure (13/20) and graft ulceration (6/20), and in 4/6 ulcerated grafts, Streptococcus pneumoniae was cultured positively. Subsequent surgery was the only significant clinical factor associated with poor outcome of glaucoma. However, low graft survival rate was significantly associated with delinquency of follow-ups, corneal ulcer, subsequent surgery, and postoperative complications. The long-term success of simultaneous Ahmed glaucoma valve implant and PKP in refractory congenital glaucoma associated with corneal opacity is low, and the complication rate is high.


Quality-of-life assessment in osteoporosis: health-status and preference-based measures.
Health-status and preference-based approaches to assessing health-related quality of life (HR-QOL) in osteoporosis are reviewed. Osteoporosis-targeted health-status instruments [i.e. Osteoporosis Quality-of-Life Questionnaire (OQLQ), Osteoporosis Assessment Questionnaire (OPAQ), Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO), Osteoporosis-Targeted Quality-of-Life Questionnaire (OPTQoL), Osteoporosis Functional Disability Questionnaire (OFDQ), Quality-of-Life Questionnaire in Osteoporosis (QUALIOST)], which have been utilised to document the adverse impact of osteoporosis on HR-QOL in diverse clinical and epidemiological studies, are described first. Preference-based approaches to osteoporosis health-outcome measurement are then considered in both clinical and health policy settings. In the clinical setting, direct preference assessments [i.e. visual analogue scale (VAS), time tradeoff (TTO), standard gamble (SG)] using either experienced or described health outcomes have consistently shown significantly lower values for osteoporosis-related health states relative to usual or ideal health. In the health-policy context, preference-classification systems [i.e. EuroQoL (EQ-5D), Health Utilities Index (HUI)] for valuing health in economic studies are reviewed. At present, there is little evidence to guide the choice of one system over another for assessing the cost effectiveness of osteoporosis interventions; however, use of a consistent set of health-state values is essential. Further research is needed to characterise associations between osteoporosis-targeted health-status instruments and preference-based health-outcome measures. In addition, the longitudinal impact of osteoporosis and related fractures on HR-QOL must be documented.


Effect of Uniconazole and Gibberellin on the Flowering of Pharbitis nil.
The role of endogenous gibberellin (GA) in the flowering of the short-day plant, Pharbitis nil, was investigated by using uniconazole, which is a specific inhibitor of GA biosynthesis. Both the endogenous GA level and flowering response decreased with increasing concentration of uniconazole applied via the roots. The strongest inhibition of flowering was observed when uniconazole was applied one day before a 15-h dark treatment. The inhibition by uniconazole was overcome by an application of GAs to the plumules, the order of effectiveness of the endogenous GAs in P. nil being GA1 ≧GA20>GA19≧GA44>GA53»GAH. This is the first report of the correlation between the endogenous GA level and flowering response in P. nil. It was found that endogenous GAs were required for the flowering of P. nil during or just after the dark period.


[Angiographic assessment of functionally insignificant left main coronary artery stenoses: reliability compared to intracoronary pressure measurement].
Left main coronary artery disease (LMCA) is still a widely accepted indication for coronary artery bypass surgery. Intermediate LMCA disease, however, often cannot be evaluated reliably on the basis of clinical and angiographic information alone. The deferral of surgical revascularization based on fractional flow reserve (FFR) measurements has been shown to be safe and feasible when taking an FFR value of (3) 0.75 as cutoff. This study was performed to compare the accuracy of visual angiographic assessment of intermediate LMCA stenoses by experienced interventional cardiologists with functional assessment by FFR in a patient population with excellent long-term outcome after deferral of surgery on the basis of FFR measurements. 24 of 51 consecutive patients with intermediate LMCA disease were deferred from surgery based on an FFR value of > or = 0.75. Each angiogram was retrospectively reviewed independently by three experienced interventional cardiologists. Reviewers were blinded to initial FFR results, clinical data, and clinical outcome and asked to classify each lesion as SIGNIFICANT (FFR < 0.75), NOT SIGNIFICANT (FFR > or = 0.75), or UNSURE if the observer was unable to make a decision based on the angiogram. Mean follow-up was 29 +/- 13.6 months. No death or myocardial infarction was observed, event-free survival was 69 %. When taking the "unsure" classifications into consideration the individual reviewers achieved correct lesion classification with respect to FFR results on average in 58 % to 82 % of cases. Interobserver variability resulted in only 46 % of cases in concordant lesion classification (3 agreements or 2 agreements and 1 "unsure" evaluation). The number of concordant agreements between the individual pairs of reviewers did not exceed the rate of coincidental agreements that could be expected to result from simple guessing (mean KAPPA coefficient 0.04). More than 50 % of patients with excellent long-term outcome after deferral of surgery would potentially have undergone operative revascularization if consensual decision making had been solely based on angiographic lesion assessment. The functional significance of intermediate or equivocal LMCA lesions should not be based on visual assessment alone, even when performed by experienced interventional cardiologists.


Direct incorporation of a ferric ion in the porphyrinogen core: tetrakis(cyclohexyl)iron porphyrinogen anion with different conformers and its reaction with iodine.
Et(4)N[L' 'Fe(III)].3DCM (1) is directly synthesized by adding ferric chloride into a solution of a lithium salt of tetrakis(cyclohexyl)porphyrinogen (L' '). [L' '](4-) is a good chelating ligand for both Fe(III) and Fe(II) ions. It is an avid proton scavenger but not a reducing agent. 1 showed a magnetic moment (mu(eff)) of 4.3 micro(B) in the solid, which changed to 6.0 micro(B) in solution. This change in spin state is common for all iron porphrinogens. 1 showed polymorphism, and with pyridine in the lattice, it changed to Et(4)N[L' 'Fe(III)].DCM(0.5)Py(1.5) (2), possessing two different conformers. Calculation of these conformers at the density functional theory level showed the relative energies of all d orbital changes in three conformers, highlighting the influence of the disposition of a peripheral ligand. Iodine oxidation of 1 yielded [L' '(DeltaDelta)Fe(II)I][I(3).I(2)(+).I(3)(-)] (3) with the introduction of two C(alpha)-C(alpha) bonds with concomitant reduction of Fe(III) to Fe(II). Its mu(eff) (5.4 mu(B)) in the solid changed to 4.8 micro(B) in solution, suggesting a high spin state (S = 2) for Fe(II).


Artificial neural network comparison of expert and novice problem-solving strategies.
The successful strategies of second-year medical students were electronically captured from computer-based simulations in immunology and infectious disease and were used to train artificial neural networks for the rapid classification of subsequent students' and experts' strategies on these problems. Such networks could categorize problem solutions of other students as successful or nonsuccessful > 85% of the time. These neural networks, however, performed poorly (as low as 13%) when classifying experienced immunologists' or internists' successful performances, suggesting an ability to distinguish between novice and expert strategies. The neural networks also identified a group of students who framed the infectious disease problems correctly, but had difficulty discriminating between differential diagnoses.


Endovascular Treatment of Cerebral Vein Thrombosis: Safety and Effectiveness in the Thrombectomy Era.
Cerebral venous thrombosis (CVT) is a rare cause of stroke that tends to affect young people. Endovascular treatment (EVT) has not yet shown to be beneficial in CVT and is therefore actually only indicated as rescue therapy in severe and refractory cases for medical treatment. Clinical, neuroimaging, procedural and follow-up data were evaluated in order to define the safety and efficacy of EVT in the management of CVT between January 2016 and December 2022. Safety was assessed on the basis of recording adverse events. Functional outcomes (NIHSS, mRS) and neuroimaging were recorded at onset, at discharge and at a 6-month follow-up. Efficacy was assessed evaluating the recanalization rate at the end of the procedure. Twenty-one patients (17 female, 4 male, range 16-84 years) with CVT underwent EVT. Overall morbidity and mortality were both at 4.7%. Median NIHSS at the onset and at the discharge were, respectively, 10 and 2. Successful recanalization was achieved in 21/23 procedures (91.3%). Imaging follow-up (FUP) showed stable recanalization in all but one patient with successful recanalization. In 18/21 patients, a good clinical independence (mRS 0-2) was recorded at 6 months. Our study adds evidence on the safety and efficacy of endovascular techniques in the treatment of CVT.


Venular endothelium-derived NO can affect paired arteriole: a computational model.
Venular endothelial cells can release nitric oxide (NO) in response to intraluminal flow both in isolated venules and in vivo. Experimental studies suggest that venular endothelium-released NO causes dilation of the adjacent paired arteriole. In the vascular wall, NO stimulates its target hemoprotein, soluble guanylate cyclase (sGC), which relaxes smooth muscle cells. In this study, a computational model of NO transport for an arteriole and venule pair was developed to determine the importance of the venular endothelium-released NO and its transport to the adjacent arteriole in the tissue. The model predicts that the tissue NO levels are affected within a wide range of parameters, including NO-red blood cell reaction rate and NO production rate in the arteriole and venule. The results predict that changes in the venular NO production affected not only venular endothelial and smooth muscle NO concentration but also endothelial and smooth muscle NO concentration in the adjacent arteriole. This suggests that the anatomy of microvascular tissue can permit the transport of NO from arteriolar to venular side, and vice versa, and may provide a mechanism for dilation of proximal arterioles by venules. These results will have significant implications for our understanding of tissue NO levels in both physiological and pathophysiological conditions.


Engineered disorder and light propagation in a planar photonic glass.
The interaction of light with matter strongly depends on the structure of the latter at wavelength scale. Ordered systems interact with light via collective modes, giving rise to diffraction. In contrast, completely disordered systems are dominated by Mie resonances of individual particles and random scattering. However, less clear is the transition regime in between these two extremes, where diffraction, Mie resonances and near-field interaction between individual scatterers interplay. Here, we probe this transitional regime by creating colloidal crystals with controlled disorder from two-dimensional self-assembly of bidisperse spheres. Choosing the particle size in a way that the small particles are transparent in the spectral region of interest enables us to probe in detail the effect of increasing positional disorder on the optical properties of the large spheres. With increasing disorder a transition from a collective optical response characterized by diffractive resonances to single particles scattering represented by Mie resonances occurs. In between these extremes, we identify an intermediate, hopping-like light transport regime mediated by resonant interactions between individual spheres. These results suggest that different levels of disorder, characterized not only by absence of long range order but also by differences in short-range correlation and interparticle distance, exist in colloidal glasses.


A new clinically relevant model for intracranial atherosclerosis in rats.
Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We developed a new rat model to study intracranial atherosclerosis. Twelve-week-old male Sprague-Dawley rats were divided into a control (on a maintain diet) and a high-cholesterol group (on a daily 1% cholesterol diet) for up to 6 weeks. During the first two weeks, NG-nitro-L-arginine methylester (L-NAME, 3 mg/mL) was added to the drinking water in the high-cholesterol group to induce intimal changes making the rats susceptible to atherosclerosis. Blood lipids, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL), were measured after 3 and 6 weeks. Histological sections of the brains, including internal carotid artery (ICA), middle cerebral artery (MCA), and basilar artery (BA), were prepared to study intracranial artery morphometry and intimal thickening. The levels of CD68, an inflammatory marker, within the vessel walls as determined by immunohistochemistry were also measured. The high-cholesterol diet increased the levels of classic blood markers of atherosclerosis, LDL, CHO, and TG as well as decreased HDL, which became progressively more intensive with time. Rats showed increased intimal thickening in the ICA, MCA, and BA. This protocol also increased the levels of CD68 immunoreactivity within the vessel walls. A rat model of intracranial atherosclerosis was effectively developed by high-cholesterol diet and L-NAME administration. This clinically relevant model would be beneficial for studying ICAS.


Cadmium-induced plant stress investigated by scanning electrochemical microscopy.
In vivo oxygen evolution above single stomata in Brassica juncea has been used to investigate, for the first time, the effect of Cd-induced stress as imaged by scanning electrochemical microscopy (SECM). SECM images showed a clear stomatal structure-a pore, whose aperture is modulated by two guard cells, serving as the conduit for the oxygen produced. Lower stomatal density and larger stoma size were found in plants treated with 0.2 mM CdCl2 compared with control plants. Either the introduction of Cd caused a slower cell replication in the plane of the epidermis, hence fewer stomata, and/or the number of open stomata was reduced when plants were under Cd-stress. Oxygen evolution above individual stomatal complexes in Cd-treated plants was lower than that from control plants, as determined from the electrochemical current above the middle of each stoma. All guard cells under illumination were swollen, indicating that the stomata were open in both control and treated plants. Thus, decreased oxygen evolution in response to Cd cannot be attributed to simple closing of the stomata, but to a lower photosynthetic yield. SECM provides an excellent tool for monitoring the effects of Cd on photosynthetic activity at the scale of individual stomata.


Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study.
To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692). Magnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease-burden covariates. Baseline normalized brain volume was predictive of disability worsening: Risk of 3-month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log-rank test: P = 0.0297). Moreover, on-study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P < 0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium-enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172 mm3 T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10 cm3). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both P < 0.0001). Baseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti-inflammatory treatment.


Ventral stabilization of thoracic kyphosis through bilateral intercostal thoracotomies using SOP (String of Pearls) plates contoured after a 3-dimensional print of the spine.
To describe a novel vertebral body stabilization and report its outcome in dogs with thoracic kyphosis and secondary myelopathy. Case series. Six pugs with thoracic kyphosis and secondary myelopathy. Medical records (2012-2017) of dogs with chronic progressive pelvic limb ataxia and ambulatory proprioceptive paraparesis due to thoracic kyphosis were reviewed. Dogs were evaluated via MRI and computed tomography. A 3-dimensional print of the kyphotic vertebral segment was used to precontour the SOP (String of Pearls) plates. Bilateral double, dorsal intercostal thoracotomies were performed to place precontoured SOP on the vertebral bodies. Long-term (6-16 months) clinical outcome was determined on the basis of neurological scoring (NS) and owner questionnaire. The only intraoperative complication consisted of a lung laceration due to preexisting adhesions. Postoperative complications included seroma formation (n = 2) and incidental radiographic evidence of screw breakage (n = 2). NS at presentation ranged between 2 and 4 and improved to 1 at long-term follow-up in all dogs but 1 (NS = 2). All owners felt that their dog had excellent quality of life at follow-up. In spite of the challenging local anatomy, all dogs undergoing vertebral stabilization with SOP placement experienced a good clinical outcome. Stabilization of vertebral bodies with precontoured SOP placed through bilateral thoracotomies may be considered as a treatment option for dogs with thoracic kyphosis and secondary myelopathy.


[Studies on the analysis of beta-blocking agents].
A method for the separation and identification of 13 beta-blockers using GC/MS and GC/NPD are described. The TFA and TMS derivatives were prepared by adding TFAA, MSTFA and MBTFA to the standard drugs. The mixture was heated at 65 degrees C for 20 min and chromatographed on FS capillary columns (HP-5). Preliminary results show that the derivatization with MSTFA is better than that with TFAA or MBTFA. There is not much difference between TFAA and MBTFA derivatization. The method is reliable, rapid and simple and may be used to screen these drugs and further applied to the analysis of biological fluids such as plasma and urine.


Sex hormone-binding globulin (SHBG) expression in ovarian carcinomas and its clinicopathological associations.
Sex hormone-binding globulin (SHBG) is known as a carrier protein. It is classically thought to be mainly synthesized in the liver and then secreted into the circulating system, where it binds to sex steroids with a high affinity and modulates the bio-availability of the hormones. Other organs known to produce SHBG include brain, uterus, testis, prostate, breast and ovary, and the local expressed SHBG may play an important role in tumor development. However, SHBG expression status and its clinicopathological significance in ovarian cancer cells are not reported yet. In our present study, we examined and found the variable SHBG expression in four ovarian cancer cell lines (OV-90, OVCAR-3, SKOV-3 and ES-2) by immunocytochemistry and Western blotting. We then extended our study to 248 ovarian carcinoma samples, which were collected at The Norwegian Radium Hospital, Oslo University Hospital with complete clinical information, and discovered that SHBG was variably expressed in these ovarian carcinomas. Higher level of SHBG expression was significantly associated with more aggressive histological subtype (p = 0.022), higher FIGO stage (p = 0.018) and higher histological grade (grade of differentiation, p = 0.020), although association between SHBG expression and OS/PFS was not observed. Our results demonstrate that ovarian cancer cells produce SHBG and higher SHBG expression in ovarian carcinoma is associated with unfavorable clinicopathological features.


A New Tetradentate Mixed Aza-Thioether Macrocycle and Its Complexation Behavior towards Fe(II), Ni(II) and Cu(II) Ions.
A new tetradentate mixed aza-thioether macrocyclic ligand 2,6-dithia[7](2,9)-1,10-phenanthrolinophane ([13]ane(phenN2)S2) was successfully synthesized. Reacting metal precursors [Fe(CH3CN)2(OTf)2], Ni(ClO4)2·6H2O, and Cu(ClO4)2·6H2O with one equivalent of [13]ane(phenN2)S2 afforded [Fe([13]ane(phenN2)S2)(OTf)2] (1), [Ni([13]ane(phenN2)S2)](ClO4)2 (2(ClO4)2), and [Cu([13]ane(phenN2)S2)(OH2)](ClO4)2 (3(ClO4)2), respectively. The structures of [13]ane(phenN2)S2 and all of its metal complexes were investigated by X-ray crystallography. The [13]ane(phenN2)S2 was found to behave as a tetradentate ligand via its donor atoms N and S.


5-S-cysteinyldopa as a substrate for tyrosinase.
Oxidation of 5-S-cysteinyldopa by mushroom tyrosinase was studied by measuring 5-S-cysteinyldopa consumption with HPLC. 5-S-cysteinyldopa was found to be a substrate for tyrosinase, but our results suggests that a self-catalysed oxidation induced by enzymatically formed 5-S-cysteinyl dopaquinone also takes place. Dopa oxidation by tyrosinase was determined by measuring substrate consumption with HPLC. The oxidation of 5-S-cysteinyldopa was markedly accelerated in the presence of dopa. This could be explained by dopaquinone oxidation of 5-S-cysteinyldopa, which has a lower oxidation potential than dopa.


Relaxation process of magnetic friction under sudden changes in velocity.
Although there have been many studies of statistical mechanical models of magnetic friction, most of these have focused on the behavior in the steady state. In this study, we prepare a system composed of a chain and a lattice of Ising spins that interact with each other, and we investigate the relaxation of the system when the relative velocity v changes suddenly. The situation where v is given is realized by attaching the chain to a spring, the other end of which moves with a constant velocity v. Numerical simulation finds that, when the spring constant has a moderate value, the relaxation of the frictional force is divided into two processes, which are a sudden change and a slow relaxation. This behavior is also observed on regular solid surfaces, although caused by different factors than our model. More specifically, the slow relaxation process is caused by relaxation of the magnetic structure in our model but is caused by creep deformation in regular solid surfaces.


A combination of RNase H and S1 nuclease circumvents an artefact inherent to conventional S1 analysis of RNA splicing.
S1 nuclease mapping is commonly used to analyze transcription and processing of unlabelled RNAs. However, the S1 protocol that appears best suited to demonstrate splicing of a particular RNA (using an intronless probe that is 5' end-labelled in the downstream exon) is not diagnostic as expected. Rather, both intron-containing RNA and intronless RNA confer protection of probe across the splice juncture. To unambiguously demonstrate correctly spliced RNAs that begin at a specific initiation site, we present a procedure in which unspliced RNA molecules are first cleaved by RNase H following annealing to an intronic DNA fragment and the remaining RNA is then subjected to S1 analysis using an intronless probe present in vast excess. Only spliced, correctly initiated transcripts can protect the probe across the splice junction and up to residue +1. This RNase H/S1 method provides a broadly applicable technique with which to demonstrate splicing and initiation of a variety of transcripts, especially ones from transfected genes that can arise both from the normal and from activated cryptic initiation sites.


Expression of P-glycoprotein is positively correlated with p53 in human papilloma virus induced squamous intraepithelial lesions of uterine cervix: poor prognosis association.
This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.


Patient Preferences for Chronic Myeloid Leukemia Medication Regimen Attributes and their Potential Impact on Adherence: Results from a Multi-national Conjoint Study.
Background: Tyrosine kinase inhibitors (TKIs) have significantly improved survival for patients with chronic myeloid leukemia (CML) but require long-term administration and non-adherence due to regimen requirements has been reported. Objectives: This study sought to identify how much patients value more convenient regimens and the potential impact that regimen may have on medication adherence. Methods: This cross-sectional, six-country study utilized a web-based discrete conjoint experiment (DCE) survey in which participants selected between hypothetical treatments that differed on three attributes: meal requirements/restrictions, frequency of administration, and monthly co-pay, to quantify willingness to pay. Attribute percent importance ratings were derived from a multinomial logit model, and utilities were summed for each product profile to determine the most preferred regimen profile. Additional survey questions asked about attributes perceived to affect adherence and the ease and convenience of participants' current regimen. Results: A total of 318 patients completed the survey; median age 53 years (range 18-87); 43.7% male. Four participants were excluded from the conjoint analysis due to illogical responses. The most important regimen attribute driving preferences was the meal requirement/restriction, which was almost twice as important as dose frequency. The majority of participants preferred the profile of a once a day dosing taken with or without a meal, and estimates of willingness-to-pay helped to quantify this preference. In terms of adherence, the majority of participants perceived that having to fast before and after taking medication would be the most likely reason for missing a dose. Conclusions: The results suggest that patients value the convenience of CML treatments and perceive certain regimen characteristics, particularly meal requirements or restrictions, as likely to affect adherence. It is important for healthcare providers to be aware of the potential impact of treatment convenience on non-adherence and communicate closely with patients to decrease this potential.


Evaluation of Sysmex XN-1000 hematology analyzer for cell count and screening of malignant cells of serous cavity effusion.
Over the years, with the advancement in hematology analyzer technology, the use of fluid analysis method has seen a drastic increase in clinical examinations. Cell counting and classification in independent body fluid analysis method are conducted by semiconductor laser flow cytometry and nucleic acid fluorescence staining techniques. This study is to evaluate the efficacy of Sysmex XN-1000 hematology analyzer in cell counting and to screen malignant cells with serous cavity effusion. Specimens (N = 206) with serous cavity effusion from our hospital were included in this study. Manual and instrumental methods for cell counting, nucleated cell classification, and high-fluorescent cells (HFC) were used in this study. The correlation between RBC, nucleated cell count (NUC), the percentages of polymorphonuclear cell (PMN%), and mononuclear cells (MN%) was statistically analyzed using manual and instrumental methods. The regression equations of RBC, NUC, PMN%, and MN% in the manual and instrumental methods were RBC y = 0.88x + 426.4; NUC y = 0.85x + 33.4; PMN% y = 0.91x + 4.2; and MN% y = 0.91x + 5.1. Correlation coefficient R was 0.99, 0.98, 0.90, and 0.90 (P < .001). ROC curve analysis showed that when the cut-off value of HFC% was 4.4% and HFC# was 24.5/μL, area under curve (AUC), sensitivity, specificity, and 95% confidence interval were 0.707, 0.792, 0.558, 0.637-0.777; 0.708, 0.753, 0.550, 0.635-0.780, respectively. XN-1000 hematology analyzer body fluid method can accurately and rapidly count cell and nucleated cell classification with serous cavity effusion. HFC can indicate the possible existence of malignant cells; however, further investigations are required to validate its efficacy.


Theoretical analyses of a liquid crystal adaptive lens with optically hidden dielectric double layer.
In this work we theoretically analyze the performance trends of a liquid crystal lens based on the optically hidden dielectric double layer principle. We demonstrate possible ways to optimize the lens as a function of the material and geometric parameters used. The impact of relative dielectric constants, conductivities, and dimensions of the components of the hidden dielectric layer, as well as the thickness and the temperature of the liquid crystal material, are demonstrated. Corresponding trade-offs are briefly discussed.


[Hazard identification of nanomaterials].
It is considered that the materials with new properties may lead to novel biological effects or unknown adverse health effects. To gather proper hazard information, it is important to develop both experimental protocols and detection/measurement methods for nanomaterials in the body, in parallel. Since 2005, we are running research projects to develop methods to monitor health risk effects for the assessment of manufactured nanomaterials funded by the Ministry of Health, Labour and Welfare. For the experimental protocols, these projects focus on the development of 1) in vitro experimental systems, 2) in vivo experimental systems (mainly focusing on long-term health implication, especially carcinogenesis), and 3) proper inhalation system. Firstly, fullerene (C60), titanium dioxide and multi-walled carbon nanotube were chosen to be tested because of their high production volume. Safety issues for new materials such as nanoparticles is a new paradigm. The key is that the full scale exposure to the public has not been started yet. Therefore, there is a good chance that information from hazard identification studies can be directly fed back to the product development plan. Manufacturers can produce safer products without risking themselves waiting for the toxicology studies to be finished after their products are widely marketed.


Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment.
The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding. Simulations indicate that cardiolipin preferentially interacts with the AcrBZ complex, due to increased contact surface, and we observe that chloramphenicol sensitivity of bacteria lacking AcrZ is exacerbated when combined with cardiolipin deficiency. Taken together, the data suggest that AcrZ and lipid cooperate to allosterically modulate AcrB activity. This mode of regulation by a small protein and lipid may occur for other membrane proteins.


Basis set and electron correlation effects on initial convergence for vibrational nonlinear optical properties of conjugated organic molecules.
Using three typical pi-conjugated molecules (1,3,5-hexatriene, 1-formyl-6-hydroxyhexa-1,3,5- triene, and 1,1-diamino-6,6-dinitrohexa-1,3,5-triene) we investigate the level of ab initio theory necessary to produce reliable values for linear and nonlinear optical properties, with emphasis on the vibrational contributions that are known to be important or potentially important. These calculations are made feasible by employing field-induced coordinates in combination with a finite field procedure. For many, but not all, purposes the MP2/6-31+G(d) level is adequate. Based on our results the convergence of the usual perturbation treatment for vibrational anharmonicity was examined. Although this treatment is initially convergent in most circumstances, a problematic situation has been identified.


Totally laparoscopic management of choledochal cysts using a four-hole method.
Choledochal cyst is a rare benign disease of the biliary tract. However, once diagnosed, it must be excised with the gallbladder because of the risk for cancer developing in the biliary tree, including the gallbladder. This report introduces a new surgical technique for totally laparoscopic excision of choledochal cyst and hepaticojejunostomy using a four-hole method. Between October 2003 and May 2005, the authors performed totally laparoscopic choledochal cyst excision for 12 patients. All the patients except one were women, and the mean age was 37.3 years (range, 17-62 years). According to the Todani classification, there were five type Ia cases, four type Ic cases, and three type IV cases. Choledochal cyst excision and Roux-en-Y hepaticojejunostomy were performed laparoscopically using the four-port technique. The mean operation time was 228 min (range, 150-330 min). No operative or postoperative transfusion was required. An oral diet was started on postoperative day 3. The average length of hospital stay was 5.8 days. There was no major complication associated with anastomosis leakage or obstruction. No patient had an adverse response, as determined by clinical or laboratory evaluation during a 2- to 19-month follow-up period. Considering that choledochal cyst is common among young women, who are especially interested in cosmetic results in addition to complete resolution of medical problems, the laparoscopic management of choledochal cyst may be an attractive treatment option.


Service Quality and Customer Satisfaction in the Post Pandemic World: A Study of Saudi Auto Care Industry.
The aim of this research is to examine the impact of service quality on customer satisfaction in the post pandemic world in auto care industry. The car care vendor in the study made effective use of social media to provide responsive updates to the customers in the post pandemic world; such use of social media provides bases for service quality and customer satisfaction. The study examined the relationship between service quality and customer satisfaction using the SERVQUAL framework. According to the findings, empathy, reliability, assurance, responsiveness, and tangibles have a significant positive relationship with customer satisfaction. Our findings suggest that it is critical for workshops to recognize the service quality factors that contribute to customer satisfaction. Findings also suggest that empathy, assurance, reliability, responsiveness, and tangibles contribute to customer satisfaction. Auto repair industry must regularly provide personal attention, greet customers in a friendly manner, deliver cars after services, notify customers when additional repairs are required, and take the time to clarify problems to customers. Furthermore, workshops must screen and hire courteous staff who can clearly communicate the services required to customers both in-person and online and effectively communicate the risks associated with repairs. Service quality seems to be aided by prompt services.


The 3'-terminal region of bacterial 23S ribosomal RNA: structure and homology with the 3'-terminal region of eukaryotic 28S rRNA and with chloroplast 4.5s rRNA.
The sequence of the 110 nucleotide fragment located at the 3'-end of E.coli, P.vulgaris and A.punctata 23S rRNAs has been determined. The homology between the E.coli and P.vulgaris fragments is 90%, whereas that between the E.coli and A.punctate fragments is only 60%. The three rRNA fragments have sequences compatible with a secondary structure consisting of two hairpins. Using chemical and enzymatic methods recently developed for the study of the secondary structure of RNA, we demonstrated that one of these hairpins and part of the other are actually present in the three 3'-terminal fragments in solution. This supports the existence of these two hairpins in the intact molecule. Indeed, results obtained upon limited digestion of intact 23S RNA with T1 RNase were in good agreement with the existence of these two hairpins. We observed that the primary structures of the 3'-terminal regions of yeast 26S rRNA and X.laevis 28S rRNA are both compatible with a secondary structure similar to that found at the 3'-end of bacterial 23S rRNAs. Furthermore, both tobacco and wheat chloroplast 4.5S rRNAs can also be folded in a similar way as the 3'-terminal region of bacterial 23S rRNA, the 3'-end of chloroplast 4.5S rRNAs being complementary to the 5'-end of chloroplast 23S rRNA. This strongly reinforces the hypothesis that chloroplast 4.5S rRNA originates from the 3'-end of bacterial 23S rRNA and suggests that this rRNA may be base-paired with the 5'-end of chloroplast 23S rRNA. Invariant oligonucleotides are present at identical positions in the homologous secondary structures of E.coli 23S, yeast 26S, X.laevis 28S and wheat and tobacco 4.5S rRNAs. Surprisingly, the sequences of these oligonucleotides are not all conserved in the 3'-terminal regions of A.punctata or even P.vulgaris 23S rRNAs. Results obtained upon mild methylation of E.coli 50S subunits with dimethylsulfate strongly suggest that these invariant oligonucleotides are involved in RNA tertiary structure or in RNA-protein interactions.


Peptide Self-Assembled Biofilm with Unique Electron Transfer Flexibility for Highly Efficient Visible-Light-Driven Photocatalysis.
Inspired by natural photosynthesis, biomaterial-based catalysts are being confirmed to be excellent for visible-light-driven photocatalysis, but are far less well explored. Herein, an ultrathin and uniform biofilm fabricated from cold-plasma-assisted peptide self-assembly was employed to support Eosin Y (EY) and Pt nanoparticles to form an EY/Pt/Film catalyst for photocatalytic water splitting to H2 and photocatalytic CO2 reduction with water to CO, under irradiation of visible light. The H2 evolution rate on EY/Pt/Film is 62.1 μmol h(-1), which is about 5 times higher than that on Pt/EY and 1.5 times higher than that on the EY/Pt/TiO2 catalyst. EY/Pt/Film exhibits an enhanced CO evolution rate (19.4 μmol h(-1)), as compared with Pt/EY (2.8 μmol h(-1)) and EY/Pt/TiO2 (6.1 μmol h(-1)). The outstanding activity of EY/Pt/Film results from the unique flexibility of the biofilm for an efficient transfer of the photoinduced electrons. The present work is helpful for designing efficient biomaterial-based catalysts for visible-light-driven photocatalysis and for imitating natural photosynthesis.


Osteonecrosis following renal transplantation.
Subarticular osteonecrosis has been described with increasing frequency after renal transplantation and the use of immunosuppressive corticosteroids. Six cases have been encountered among 170 patients in the Johannesburg renal transplantation programme. The commonly affected sites are the femoral head, the femoral condyles, the humeral head, the talus and the capitulum. The radiological and morbid anatomical features of this complication are described, alternative theories of pathogenesis are considered and an approach to treatment is outlined.


[Risk factors and surgical treatment of recurrent gastrointestinal stromal tumor in the rectum].
To investigate the risk factors and surgical treatment of recurrent gastrointestinal stromal tumors in the rectum. The clinical data of 24 cases,admitted to our hospital, were analyzed retrospectively. The possible risk factors were tested by chi(2)-test. The resectable rate and recurrent rate of recurrent cases were compared with the first-treated cases. The tumors with biggest diameter >or=3 cm and high invasive risk had higher recurrent rates (chi(2)=4.874, P=0.027, chi(2)=6.659, P=0.010). The resectable rate of recurrent gastrointestinal stromal tumors in rectum was 64.3% (9/14), which was significantly lower than that of first-treated ones (23/24) (chi(2)=6.618, P=0.010). There was no significant difference of recurrent rate between the recurrent group and the first-treated group (chi(2)=1.459, P>0.05). The size and invasive risk of tumor are associated with the recurrent rate of gastrointestinal stromal tumors in rectum. The resectable rate of recurrent gastrointestinal stromal tumors in rectum is significantly lower than that of first-treated ones, but recurrent rates are similar in the 2 groups.


Initially transcribed sequences strongly affect the extent of abortive initiation by RNA polymerase II.
We investigated transcript initiation and early elongation by RNA polymerase II using templates mismatched between -9 and +3 (bubble templates). Highly purified RNA polymerase II alone was able to initiate transcription specifically on these templates in the presence of dinucleotide primers. The length distribution of abortively initiated RNAs was similar for purified RNA polymerase II on bubble templates and polymerase II on double-stranded templates in HeLa nuclear extracts. Increasing the U content in the initial portion of the transcript caused similar increases in abortive initiation for transcription of bubble templates by pure polymerase and double-stranded templates in extracts. Thus, the level of abortive initiation by RNA polymerase II is at least partly determined by interactions of the polymerase with the transcript and/or the template, independent of the general transcription factors. Substitution of 5-bromo-UTP for UTP reduced abortive initiation on bubble templates, consistent with the idea that transcription complex stability during early elongation depends on the strength of the initial RNA-DNA hybrid. Interestingly, transcription of bubble templates in HeLa extracts gave very high levels of abortive initiation, suggesting that inability to reanneal the initially melted template segment inhibits transcript elongation in the presence of the initiation factors.


Localization of luteinizing hormone-releasing hormone in the forebrain of the pig.
The distribution of luteinizing hormone-releasing hormone (LHRH)-immunostained perikarya and processes was examined in the forebrains of six sexually mature female pigs by use of indirect biotin-avidin horseradish peroxidase immunocytochemistry. Two primary antisera (Drs. Y.F. Chen and V.D. Ramirez CRR11B73 and Miles-Yeda UZ-4) yielded positive staining. Adjacent sections treated either primary antiserum preabsorbed with LHRH or with normal rabbit serum substituted for primary antiserum lacked positive staining. The greatest proportion of LHRH-immunostained perikarya were found in the medial preoptic area adjacent to the organum vasculosum of the lamina terminalis. The LHRH-immunostained perikarya were also scattered rostrally in the diagonal band of Broca, and within the lateral hypothalamic area, paraventricular nucleus, periventricular zone, suprachiasmatic nucleus, and medial basal hypothalamus. LHRH-immunostained processes, which extended from the medial preoptic area, coursed either along the ventral surface to the median eminence or medially and ventrally along the third ventricular wall ventrally to the median eminence and caudally to the level of the mammillary bodies. Extrahypothalamic processes were located adjacent to the lateral ventricular floor and the third ventricle from the lateral septal area (stria terminalis) to the level of the habenular nucleus. LHRH-immunostained neurons were unipolar, bipolar, and multipolar. Close associations between individual LHRH-immunostained neurons were observed.


Patients hospitalized with acute heart failure, worsening renal function, and persistent congestion are at high risk for adverse outcomes despite current medical therapy.
Approximately 1/3 of patients with acute decompensated heart failure (ADHF) are discharged with persistent congestion. Worsening renal function (WRF) occurs in approximately 50% of patients hospitalized for ADHF and the combination of WRF and persistent congestion are associated with higher risk of mortality and HF readmissions. We designed a multicenter, prospective registry to describe current treatments and outcomes for patients hospitalized with ADHF complicated by WRF (defined as a creatinine increase ≥0.3 mg/dL) and persistent congestion at 96 h. Study participants were followed during the hospitalization and through 90-day post-discharge. Hospitalization costs were analyzed in an economic substudy. We enrolled 237 patients hospitalized with ADHF, who also had WRF and persistent congestion. Among these, the average age was 66 ± 13 years and 61% had a left ventricular ejection fraction (LVEF) ≤ 40%. Mean baseline creatinine was 1.7 ± 0.7 mg/dL. Patients with persistent congestion had a high burden of clinical events during the index hospitalization (7.6% intensive care unit transfer, 2.1% intubation, 1.7% left ventricular assist device implantation, and 0.8% dialysis). At 90-day follow-up, 33% of patients were readmitted for ADHF or died. Outcomes and costs were similar between patients with reduced and preserved LVEF. Many patients admitted with ADHF have WRF and persistent congestion despite diuresis and are at high risk for adverse events during hospitalization and early follow-up. Novel treatment strategies are urgently needed for this high-risk population.


Similar nicotinic excitability responses across the developing hippocampal formation are regulated by small-conductance calcium-activated potassium channels.
The hippocampal formation forms a cognitive circuit that is critical for learning and memory. Cholinergic input to nicotinic acetylcholine receptors plays an important role in the normal development of principal neurons within the hippocampal formation. However, the ability of nicotinic receptors to stimulate principal neurons across all regions of the developing hippocampal formation has not been determined. We show in this study that heteromeric nicotinic receptors mediate direct inward current and depolarization responses in principal neurons across the hippocampal formation of the young postnatal mouse. These responses were found in principal neurons of the CA1, CA3, dentate gyrus, subiculum, and entorhinal cortex layer VI, and they varied in magnitude across regions with the greatest responses occurring in the subiculum and entorhinal cortex. Despite this regional variation in the magnitude of passive responses, heteromeric nicotinic receptor stimulation increased the excitability of active principal neurons by a similar amount in all regions. Pharmacological experiments found this similar excitability response to be regulated by small-conductance calcium-activated potassium (SK) channels, which exhibited regional differences in their influence on neuron activity that offset the observed regional differences in passive nicotinic responses. These findings demonstrate that SK channels play a role to coordinate the magnitude of heteromeric nicotinic excitability responses across the hippocampal formation at a time when nicotinic signaling drives the development of this cognitive brain region. This coordinated input may contribute to the normal development, synchrony, and maturation of the hippocampal formation learning and memory network. NEW & NOTEWORTHY This study demonstrates that small-conductance calcium-activated potassium channels regulate similar-magnitude excitability responses to heteromeric nicotinic acetylcholine receptor stimulation in active principal neurons across multiple regions of the developing mouse hippocampal formation. Given the importance of nicotinic neurotransmission for the development of principal neurons within the hippocampal formation, this coordinated excitability response is positioned to influence the normal development, synchrony, and maturation of the hippocampal formation learning and memory network.


Calcium Control of the Sign of Phototaxis in Brown Algal Gametes of Mutimo cylindricus.
Brown algal swarmers usually exhibit positive or negative phototaxis. Such behaviors influence the increasing or decreasing dispersal distance or colonization on the new substratum. We confirmed that the sign of phototaxis (negative or positive) in male gametes of Mutimo cylindricus was affected by extracellular Ca2+ influx through Ca2+ channels. Under the control condition (10-2 m [Ca2+ ]), male gametes swimming with a helical rotation of their cell body mostly showed positive phototaxis. At 10-3 m [Ca2+ ], more than half of the male gametes showed positive phototaxis, whereas the others showed negative phototaxis. From 10-4 -10-5 m [Ca2+ ], the phototactic sign changed to negative. When these negative phototactic gametes were transferred back to the control condition, the phototactic sign reverted to positive. At 10-6 m [Ca2+ ], some of male gametes showed negative phototaxis, but most showed no phototaxis or flagellar beating. Lanthanum, a Ca2+ channel blocker, affected the sign of phototaxis at 10-4 m [La3+ ] under 10-2 m [Ca2+ ], and male gametes mostly showed negative phototaxis. A further increase in [La3+ ] inhibited phototaxis and flagellar beating. These results pointed out the involvement of Ca2+ channels that were blocked by La3+ in phototaxis and flagellar beating.


Light, sleep and circadian rhythms in older adults with Alzheimer's disease and related dementias.
Alzheimer's disease and related dementias (ADRD) can cause sleep and behavioral problems that are problematic for ADRD patients and their family caregivers. Light therapy has shown promise as a nonpharmacological treatment, and preliminary studies demonstrate that timed light exposure can consolidate and improve nighttime sleep efficiency, increase daytime wakefulness and reduce evening agitation without the adverse effects of pharmacological solutions. Compliance with light treatment and the accurate measurement of light exposures during treatment, however, have presented barriers for the adoption of light therapy for ADRD. Recent research showing that the circadian system is maximally sensitive to short-wavelength light opens the way for the potential application of lower, more-targeted light intensities to maximize compliance and individualize light dose/timing in therapeutic settings.


Evidence-based, multifactorial approach to addressing non-adherence to antiretroviral therapy and improving standards of care.
Near-perfect adherence to antiretroviral therapy over time is critical to achieve viral suppression and recovery of functional immunity in individuals infected with HIV. The concept of adherence as a dynamic behaviour influenced by multiple biopsychosocial factors motivated us to implement an integrated, multifactorial programme in our hospital-based setting. The aims of this study were to survey the scope and determinants of non-adherence in patients attending the Ambulatory HIV Service at Royal Perth Hospital, to develop a method for longitudinal monitoring and to implement measures tailored to support individuals. The US Adult AIDS Clinical Trials Group self-report baseline adherence, follow-up and side-effect questionnaires were used to survey 247 patients at two time-points between September 2002 and February 2003. A longitudinal monitoring method was developed and the WA HIV Cohort Study database used to collate results with clinical markers up to December 2005. Adherence was associated with viral suppression and CD4 T-cell recovery and improved over the 3-year period under observation (all P < 0.001). Diminishing adherence was associated with younger age (P = 0.002), substance use (P < 0.01), perceived stress (P = 0.04) and indicators of depression (P = 0.03). The analyses showed relationships between personal experience of side-effects and the depression indicator scale in patients on antiretroviral therapy. The programme resulted in an improvement in adherence in our cohort even after adjusting for pill burden, dosing frequency and highly active antiretroviral therapy regimen and has enhanced focus on patients vulnerable to non-adherence while supporting those not currently at risk.


Glucocorticoid treatment decreases muscarinic receptor expression in canine airway smooth muscle.
Corticosteroids upregulate the beta-adrenergic pathway, but little is known about corticosteroid regulation of muscarinic pathways. Basenji-greyhound (BG) dogs treated for 3 days with methylprednisolone (MPS) but not deoxycorticosterone (DOC) had decreased numbers of muscarinic receptors in airway smooth muscle homogenates as determined by radioligand binding with 1-[3H]quinuclidinyl benzilate (vehicle control, 578 +/- 53 fmol/mg protein; MPS, 290 +/- 22 fmol/mg protein; DOC, 565 +/- 141 fmol/mg protein). Competition radioligand binding with the M2-selective antagonist tripitramine showed a decrease in both the M2 and M3 muscarinic receptors with no changes in receptor affinities (M2: vehicle control, 478 +/- 41 fmol/mg protein; MPS, 265 +/- 20 fmol/mg protein, M3: vehicle control, 89 +/- 13 fmol/mg protein; MPS, 25 +/- 16 fmol/mg protein). In vitro treatment of airway smooth muscle from control BG dogs with MPS had no effect on muscarinic receptor number, despite increased expression of beta-adrenergic receptors. Thus glucocorticoids indirectly decrease the expression of M2 and M3 muscarinic receptors in airway smooth muscle, which, in part, may account for their beneficial effects in the treatment of asthma.


[Average blood glucose construction: a multi-level Bayes model approach and application].
To explore the average blood glucose construction method based on the multi-level Bayes model and evaluate the example application. We generate simulated data with multi-level Bayes model. Three methods were utilized to construct the average blood glucose at the same time, then we compared the result with each other. A cohort study method was used to select 12321 participants aged over 45 y who without stroke in a community in Suzhou and was followed up from 2011 to 2018, of which 53. 7% were male. Mean blood glucose calculated by the most accurate complete Bayesian method was divided into six groups. The Cox regression model was used to analyze the effect of mean blood glucose on the incidence of fatal stroke. 1000 times of simulation result showed that the average mean blood glucose estimation calculated by the complete Bayesian method was 0. 278, the average of blood glucose estimation was 0. 527 mmol/L, and the average correlation coefficient with the actual blood glucose was r=0. 898. During the follow-up period, 153 fatal strokes occurred. Association was found between the mean blood glucose and the risk of fatal stroke(P<0. 05). The average risk of blood glucose over 140 mg/dL was 2. 304 times that of 90-99 mg/dL(HR=2. 304, 95%CI 1. 151-4. 613) after the adjustment of effects. The complete Bayesian multi-level latent variable model can accurately estimate the average blood glucose.


Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis.
Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. Adults with HDM-associated allergic rhinitis were randomized in a double-blind, placebo-controlled study to receive 500 index of reactivity (IR) tablets, 300IR tablets, or placebo administered once daily for 1 year and were followed for the subsequent year. The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period (ie, October 1 to December 31). Symptoms and rescue medication scores, onset of action, patient-reported outcomes, and safety were secondary variables. The same end points were evaluated during the immunotherapy-free year. The primary efficacy end point was analyzed by using analysis of covariance. Five hundred nine participants were randomized, and 427 continued in the immunotherapy-free year. Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2% (P = .0066) and -17.9% (P = .0150), respectively. Efficacy of both doses was maintained during the treatment-free follow-up phase. The onset of action was at 4 months. Participants' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group (P = .0206 and P = .0001, respectively). Adverse events were generally application-site reactions. There were no reports of anaphylaxis. Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated. Efficacy was maintained during the treatment-free follow-up year.


Monitoring the Cerebral Oximetry Index Along With In-line Cardiopulmonary Bypass Parameters in a High-Risk Patient Undergoing Cardiac Surgery: A Case Report.
The quest to minimize the morbidity and mortality of patients undergoing cardiac surgery is ongoing. Impaired cerebral autoregulation and tissue malperfusion are linked with neurological complications. The cerebral oximetry index (COx) has been introduced as an index of cerebral autoregulation, while in-line monitoring enables the detection and prevention of metabolic disturbances during cardiopulmonary bypass (CPB). This report presents the case of a 58-year-old female patient scheduled for aortic valve replacement under minimally invasive extracorporeal circulation (MiECC). Her medical history consisted of epilepsy, multiple ischemic strokes, heavy smoking, and brachiocephalic artery stenosis. We sought to investigate the limits of autoregulation and the role of metabolic indices of perfusion on COx. Mean arterial blood pressure (ABP), cerebral oximetry (rSO2), and in-line perfusion data during CPB were recorded at 10s intervals. The lower limit of autoregulation was 44mmHg on both sides and the upper limit was 98mmHg on the right and 107mmHg on the left side. A multiple linear regression analysis was performed to identify any potential predictors of COx values. Hemoglobin (Hb), PCO2, flow, DO2 index (DO2i), Ο2 extraction ratio (O2ER), and perfusion ratio (PR) were included in the analysis. Significant equations were found on both sides. Predicted COx left was equal to 5.8 - 11.04O2ER - 0.04Hb (p=0.001, R2= 0.15). Predicted COx right was equal to 3.06 - 0.3flow - 6.8O2ER -0.03Hb + 0.02PCO2 + 0.004DO2i(p=0.03, R2=0.13). Targeting physiological perfusion and monitoring perfusion during CPB may have an additional impact on cerebral autoregulation and should be studied further.


Nursing care delivery models and outcomes: A literature review.
The purpose of this literature review was to determine the types of nursing care delivery models currently being used in acute care hospitals to determine the effectiveness of the model and the outcomes being measured. A literature search was conducted, and databases searched included CINAHL, Nursing and Allied Health, Medline, EMBASE, ProQuest Theses, and Dissertations for the years 2000-2020. Sixteen studies were retrieved. Patient outcomes measured included falls, adverse events, and infections. Nursing outcomes measured included satisfaction, communication, and perceived quality of care. Findings from this review showed there was no single model of nursing care delivery that resulted in positive patient or nurse outcomes, thus a "one size fits all" approach to selecting or utilizing a model of care is not realistic. Given the number of nursing care delivery models that were hybrids, clearer descriptions of each model and further research on patient and nursing outcomes is warranted.


Genotype by environment interaction for fertility, survival, and milk production traits in Australian dairy cattle.
The existence of a genotype x environment interaction (G x E) for fertility traits, survival, and milk yield traits was examined by considering performance recorded in different calving systems (seasonal, split, and year round) or regions as different traits. For fertility traits and survival, G x E were also investigated by applying a random regression model using continuous environmental variables, such as level of herd milk production, temperature-humidity index, and herd size as environmental descriptors. The traits considered were calving interval, calving to first service interval (CFS), 25-d nonreturn rate at first service, pregnancy rate, survival, milk yield, fat yield, and protein yield and percentage. Data on Holstein-Friesian cows that calved between 1997 and 2005 were analyzed. The number of cows included in the analyses ranged from approximately 21,000 for pregnancy rate to approximately one-half million for survival. For all traits, heterogeneity in additive and phenotypic variances was observed. For example, for CFS the additive genetic and phenotypic variance in seasonal calving herds was only 9 and 15% of that in year-round calving herds, respectively. Genetic correlations among calving systems for milk yield traits were greater than 0.96. For calving interval, the lowest genetic correlation, of 0.83, was between split and year-round calving herds, but for CFS and pregnancy rate, genetic correlations as low as 0.37 were observed, although these estimates were associated with large standard errors. Genetic correlations between traits recorded in different Australian regions were greater than 0.89. Heritability and phenotypic variance for milk yield traits were the greatest in region 1, which consisted of Queensland, West Australia, South Australia, and New South Wales, and were least in region 3, which included Gippsland and Tasmania, in accordance with mean milk yield levels. Genetic correlations as low as 0.5 for some fertility traits between the 5th and 95th percentile of the distribution of the environmental descriptors, such as herd size and average herd milk production, were also observed. However, these estimates had large standard errors. Regardless of the environmental descriptor used, there was no evidence for the presence of a large G x E that resulted in economically significant reranking of bulls.


Non-adiabatic dynamics of isolated green fluorescent protein chromophore anion.
On-the-fly ab initio molecular dynamics calculations have been performed to investigate the relaxation mechanism of green fluorescent protein chromophore anion under vacuum. The CASSCF surface hopping simulation method based on Zhu-Nakamura theory is applied to present the real-time conformational changes of the target molecule. The static calculations and dynamics simulation results suggest that not only the twisting motion around bridging bonds between imidazolinone and phenoxy groups but the strength mode of C=O and pyramidalization character of bridging atom are major factors on the ultrafast fluorescence quenching process of the isolated chromophore anion. The abovementioned factors bring the molecule to the vicinity of conical intersections on its potential energy surface and to finish the internal conversion process. A Hula-like twisting pattern is displayed during the relaxation process and the entire decay process disfavors a photoswitching pattern which corresponds to cis-trans photoisomerization.


Survival and Incidence Patterns of Pancreatic Neuroendocrine Tumors Over the Last 2 Decades: A SEER Database Analysis.
Pancreatic neuroendocrine tumors (pNETs) are rare cancers with outcomes determined by multiple factors including grade, stage, and clinical presentation. In this study, we aimed to determine the prognosis of patients with pNETs using a large population-based database. In this population-based study, we identified patients with pNETs from the SEER 18 registry (2000-2016) using a combination of ICD-O-3 and histology codes. We calculated age-adjusted incidence rates using SEER*Stat 8.3.5. In addition, we analyzed overall survival (OS) using the Kaplan-Meier method, and investigated prognostic factors using a multivariable Cox proportional hazards model. A total of 8944 pNETs patients were identified. Annual incidence rates increased from 0.27 to 1.00 per 100 000. This was largely explained by an increase in number of patients diagnosed with localized disease in more recent years (2012-2016). Median OS was 68 months (95% CI [64, 73]) and 5-year OS rates in localized, regional, and metastatic disease were 83%, 67%, and 28%, respectively. There was a significant improvement in OS for patients diagnosed between 2009 and 2016 (median OS 85 months) compared with those diagnosed between 2000 and 2008 (median OS 46 months) (HR 0.66; 95% CI [0.62, 0.70]). This improvement in OS was consistent across all stages. This study shows a steady increase pNETs incidence with notable stage migration to earlier stages in recent years. This increase in incidence is accompanied by a significant improvement in survival across different disease stages.


Monolith or Powder: Improper Sample Pretreatment May Mislead the Understanding of Industrial V2O5-WO3/TiO2 Catalysts Operated in Stationary Resources.
Although various characterizations are widely applied to commercial V2O5-WO3/TiO2 catalysts, the influence of the catalyst physical structure, i.e., monolith or powder, on the characterization results has not been investigated. Several important catalytic behaviors and phenomena were observed in this study using V2O5-WO3/TiO2 monolithic catalysts employed for over 5000 h in various stationary flue gases, and many of the results were only observable on monolithic catalysts, such as depth-dependent distribution of external elements, penetration of As2O3, and the formation of Tl2O-TiO2 p-n junctions. If the monolith is ground into powder states, it will alter or destroy the catalyst surface and remove important clues closely related to catalytic performance under working conditions. The redox and acidity properties of V2O5-WO3/TiO2 obtained from powder samples may be significantly different from their true state under working conditions, resulting in a misperception of catalyst performance. Therefore, a cautious pretreatment should be taken into careful consideration when analyzing commercial honeycomb V2O5-WO3/TiO2 catalysts.


Buckling of liquid columns.
Under appropriate conditions, a column of viscous liquid falling onto a rigid surface undergoes a buckling instability. Here we show experimentally and theoretically that liquid buckling exhibits a hitherto unsuspected complexity involving three different modes-viscous, gravitational, and inertial-depending on how the viscous forces that resist bending of the column are balanced. We also find that the nonlinear evolution of the buckling exhibits a surprising multistability with three distinct states: steady stagnation flow, "liquid rope coiling," and a new state in which the column simultaneously folds periodically and rotates about a vertical axis. The transitions among these states are subcritical, leading to a complex phase diagram in which different combinations of states coexist in different regions of the parameter space.


[Is dilatation of the papilla a differential diagnostic or therapeutic intervention?].
Calculations were made to establish the action of probes of different thickness on both cicatric tissue and unstriated muscles of the major duodenal papilla. The findings are graphically represented. These calculations were based on histopathological findings recorded from the major duodenal papilla, expandibility, of collagenic fibres and unstriated muscles, and morphometric measurements. The conclusion was drawn that passage of a probe of more than 3 mm in diameter through a cicatrically narrowed papilla constituted an act of therapy or at least had a therapeutic component in addition to probing. The therapeutic range of papillary dilatation is limited to something from three to six millimetres.