Assessment of exercise oxygen consumption as preoperative criterion for lung resection.
Determination of preoperative pulmonary function is crucial in avoiding complications from pulmonary resection. Many have employed static pulmonary function testing in an attempt to decrease morbidity and mortality from lung resections. The purpose of the present study was to correlate preoperative static pulmonary function, one-second forced expiratory volume (FEV1), and exercise O2 consumption (MVO2) with postoperative morbidity and mortality. Fifty consecutive patients underwent preoperative FEV1 and MVO2 determinations. A criterion for surgical resection included an FEV1 greater than 1.7 liters for pneumonectomy, greater than 1.2 liters for lobectomy, and greater than 0.9 liters for wedge resection. The surgeon was blinded as to the results of MVO2 studies. Mean age was 63.8 years (range, 47 to 76 years). There were 10 pneumonectomies, 28 lobectomies, and 12 wedge resections. Among the 50 surgical candidates selected solely on the standard FEV1 values, mortality was 4% (2/50) and morbidity, 12% (6/50). Stratification on the basis of exercise performance showed a 29% mortality (2/7) and a 43% morbidity (3/7) in patients with an MVO2 less than 10 ml/kg/min. Patients with an MVO2 less than 20 but greater than 10 ml/kg/min had a 10.7% morbidity (3/28), and there were no deaths. No patients with an MVO2 greater than 20 ml/kg/min sustained any morbidity or died (p less than 0.001). We conclude that exercise is an important criterion in the preoperative evaluation of patients for pulmonary surgery. An MVO2 less than 10 ml/kg/min is associated with significant morbidity and mortality.


Ca(2+)-dependent enhancement of [3H]noradrenaline uptake in PC12 cells through calmodulin-dependent kinases.
Ca(2+)-dependent regulation of [3H]noradrenaline ([3H]NA) uptake through the NA transporter was studied using PC12 cells. Preincubation for 10 min in the presence of 0.3-10 mM ca2+ in Krebs-Ringer (KR) buffer induced marked enhancement of the uptake (at 1 mM Ca2+, 6.6 times greater than that observed in the absence of Ca2+), which reflected both an increase in Vmax and a decrease in K(m) of the uptake process. Preincubation with 1 mM Ca2+ also induced a significant increase in the Bmax and Kd of [3H]desipramine binding. The uptake was still enhanced after washing cells with Ca(2+)-free buffer following preincubation with 1 mM Ca2+. 1-[N, O-bis(5-Isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), 2-[N-(2-hydroxyethyl)-N-(4-methoxybenzenesulfonyl)]amino-N-(4-c hlo rocinnamyl) -N-methylbenzylamine (KN-93) (inhibitors of Ca2+/calmodulin-dependent kinase II), N-(6-aminohexyl)-5-chloro-1-naphthalenesulonamide (W-7) (a calmodulin antagonist), wortmannin (a myosin light chain kinase inhibitor) significantly reduced Ca(2+)-dependent enhancement of the uptake. Mycalolide B (an inhibitor of actin-myosin interaction) also inhibited the enhancement. Although calphostin C (a protein kinase C (PKC) inhibitor) did not affect the enhancement, 12-o-tetradecanoylphorbol 13-acetate (TPA) inhibited the uptake. A synthetic peptide with a sequence (KKVIYKFFS579 IRGSLW) contained in the intracellular COOH-terminal domain of a rat NA transporter was phosphorylated by purified brain Ca2+/calmodulin-dependent protein kinase II. These results suggest that Ca(2+)-dependent enhancement of the [3H]NA uptake in PC12 cells are mediated by activation of calmodulin-dependent protein kinases, probably through stimulation of translocation of the NA transporter to the plasma membrane and/or direct phosphorylation of the transporter itself.


Immunotoxicity in ascidians: antifouling compounds alternative to organotins: III--the case of copper(I) and Irgarol 1051.
After the widespread ban of TBT, due to its severe impact on coastal biocoenoses, mainly related to its immunosuppressive effects on both invertebrates and vertebrates, alternative biocides such as Cu(I) salts and the triazine Irgarol 1051, the latter previously used in agriculture as a herbicide, have been massively introduced in combined formulations for antifouling paints against a wide spectrum of fouling organisms. Using short-term (60 min) haemocyte cultures of the colonial ascidian Botryllus schlosseri exposed to various sublethal concentrations of copper(I) chloride (LC(50)=281 μM, i.e., 17.8 mg Cu L(-1)) and Irgarol 1051 (LC(50)>500 μM, i.e., >127 mg L(-1)), we evaluated their immunotoxic effects through a series of cytochemical assays previously used for organotin compounds. Both compounds can induce dose-dependent immunosuppression, acting on different cellular targets and altering many activities of immunocytes but, unlike TBT, did not have significant effects on cell morphology. Generally, Cu(I) appeared to be more toxic than Irgarol 1051: it significantly (p<0.05) inhibited yeast phagocytosis at 0.1 μM (∼10 μg L(-1)), and affected calcium homeostasis and mitochondrial cytochrome-c oxidase activity at 0.01 μM (∼1 μg L(-1)). Both substances were able to change membrane permeability, induce apoptosis from concentrations of 0.1 μM (∼10 μg L(-1)) and 200 μM (∼50 mg L(-1)) for Cu(I) and Irgarol 1051, respectively, and alter the activity of hydrolases. Both Cu(I) and Irgarol 1051 inhibited the activity of phenoloxidase, but did not show any interactive effect when co-present in the exposure medium, suggesting different mechanisms of action.


Prosthetic outcomes and clinical performance of CAD-CAM monolithic zirconia versus porcelain-fused-to-metal implant crowns in the molar region: 1-year results of a RCT.
To investigate the clinical performance of monolithic zirconia implant crowns as compared to porcelain-fused-to-metal (PFM) implant crowns. Seventy-six healthy patients received reduced diameter implants in the molar region. Following random allocation, either a monolithic zirconia crown (Mono-ZrO2 ) or a (PFM) was inserted. Crown and implant survival rates, modified USPHS criteria, clinical measurements, and interproximal marginal bone level (MBL) were assessed at crown delivery (baseline, BL) and at the 1-year follow-up (1y-FU). Data were analyzed descriptively. Fisher's exact test and Wilcoxon rank sum test were applied for statistical analysis. The level of statistical significance was set at p < .05. Thirty-nine Mono-ZrO2 and 37 PFM crowns were delivered. At the 1y-FU, one crown in each group was lost due to loss of the implant. Technical complications occurred in the PFM group and were limited to four minor ceramic chippings resulting in a total technical complication rate of 11.1% (p = .024). Anatomical form and color match compared to the adjacent dentition were rated significantly inferior for the Mono-ZrO2 crowns. Patient satisfaction was high in both groups at BL (34 Mono-ZrO2 34 PFM) and at 1y-FU (36 Mono-ZrO2 31 PFM). No significant differences between the groups were detected with respect to the change in MBL and to the soft tissue parameters. Monolithic zirconia crowns are a similarly successful alternative option to PFM crowns for restoring single implants in the posterior area.


Mapping theme trends and knowledge structure of Sjögren's syndrome (SS), a bibliometric analysis from 2010 to 2021.
Sjögren's syndrome is an autoimmune disease with a complicated pathophysiology, and treatment strategies are in desperate need of improvement. In this research, we provide the literature topic trends and knowledge structure connected to Sjögren's syndrome from the perspective of bibliometrics for further research. We acquired 3753 publications from the PubMed database and 3880 catalogs from the Web of Science Core Collection, with a time limit of 2010 to 2021 and the search term as "Sjögren's syndrome." Using the VOSviewer and bibliographic item co-occurrence matrix generator, we conducted cocited analysis, extracted major MeSH terms, generated matrices and performed biclustering analysis, visual matrix, drawn strategy diagram, and social network analysis. Through the clustering of the major MeSH terms, a total of five categories and 10 research topics were identified. Cocitation analysis suggests that diagnosis and clinical manifestations have been the main basis over the past 12 years and also are the mature content in the first quadrant of the strategy map. Ultrasonography, immunosuppressive agents and therapy, mechanism and therapeutic targets, and diagnostic autoantibodies are examples of the third quadrant, which wields great potential to progress. Genetic predisposition and psychology, in the fourth quadrant, need to be developed additionally. The subject keywords near the network's edge, such as "Salivary Glands, Minor/pathology," "Immunosuppressive Agents/therapeutic use," and "Autoantibodies/blood," are all growing research hotspots with much space, according to social network analysis. Through bibliometric analysis of the literature related to Sjögren's syndrome in the past 12 years, we obtained the knowledge basis, undeveloped topics, and emerging hotspots, which can suggest recommendations for future research. Key Points • We disclosed the topic trends and knowledge structure of Sjögren's syndrome literature over the past 12 years. • Clinical manifestations and diagnosis of Sjögren syndrome are included in mature and comprehensive studies, whereas ultrasonography, immunosuppressants and treatments, mechanisms and therapeutic targets, and diagnostic autoantibodies are studies with high potential for advancement. Additional research in genetics and psychology is needed. • We identified potential future research hotspots, including "Salivary Glands, Minor/pathology," "Immunosuppressive Agents/therapeutic use," and "Autoantibodies/blood."


The stroke rehabilitation paradigm.
The matrix of stroke rehabilitation is evolving as we look outside the box of traditional therapy type, timing, and intensity of rehabilitation techniques. For inpatient wards, the goal of medical stability and prompt resolution of complications to maximize participation in therapy remains paramount. In the current medical model, we focus on teaching compensatory strategies and rarely on restorative approaches because of time and financial limitations. Researchers aim to identify new technologic and molecular approaches to improve functional outcomes and more accurately predict disability. This article examines different concepts surrounding the comprehensive rehabilitation paradigm of stroke survivors.


Surgical treatment of talar osteo-chondral lesions with micro-fractures, mesenchymal cells grafting on membrane, or allograft: Mid-term clinical and magnetic resonance assessment.
Talar dome osteo-chondral lesions (OCL) are defects of the cartilaginous surface and subchondral bone often associated with sport practice. This retrospective observational work has the purpose of assessing: a) The clinical outcomes in the patients study group and in the three sub-groups; b) medium-term morphological and qualitative outcomes of the newly formed tissue by magnetic resonance imaging; c) if there is the correlation between new formed tissue clinical, morphological RM evaluation and qualitative clinical outcomes.


Does Weight Loss Improve Clinical Outcomes in Overweight and Obese Patients with Heart Failure?
Obesity increases the risk of new onset heart failure (HF), and particularly HF with preserved ejection fraction (HFpEF). Despite the observations of favorable clinical outcomes in HF patients with obesity in general, sometimes referred to as the "obesity paradox," it is important to recognize that severe obesity is associated with worse clinical outcomes. This review summarizes the effects of obesity treatment on cardiovascular health and HF clinical outcomes. Treatment for obesity utilizes a variety of modalities to achieve purposeful weight loss including lifestyle intervention, medications, and bariatric surgery. There are a cluster of benefits of obesity treatment in terms of clinical outcomes in HF. The mechanisms of these benefits include both weight loss-dependent and weight loss-independent mechanisms. Obesity treatment is safe and associated with favorable clinical outcomes across the spectrum of the HF population. The potential benefits are facilitated through multiple mechanisms.


Incidence of Otitis Media with Effusion in Cases of Head and Neck Malignancies Undergoing Radiotherapy: A Prospective Observational Study.
This study was done to evaluate the incidence of otitis media with effusion (OME) in cases of head and neck malignancies who undergo irradiation, excluding nasopharyngeal malignancies. This prospective observational study was done at a tertiary care hospital. Adult patients of head and neck malignancies treated with radiotherapy (RT) with or without concurrent chemotherapy as definitive or adjuvant therapy from September 2017 to August 2018 were included. Cases of nasopharyngeal malignancies and cases of malignancies of other sites extending to nasopharynx causing mechanical obstruction to ET were excluded. The otoscopy, tympanometry and pure tone audiometry findings of these patients were recorded pre RT, immediately after completion of RT and at 6 months post RT. The pre and post RT data were analysed to determine the incidence of OME. 39.3% of ears had retracted tympanic membrane (TM) and 7.1% had air-fluid levels in middle ear at first follow up (FFU). At second follow up (SFU), 13% of ears continued to have retracted TM while none had air-fluid levels. At FFU, 23.2% of ears had 'B' curve on tympanometry, indicative of OME while 19.6% of ears had 'C' curve, indicative of Eustachian tube (ET) dysfunction. At SFU, 1.8% had B curve while 14.3% had C curve, indicating improvement in ET function as compared to that at FFU. There is a considerable percentage of non-nasopharyngeal head and neck malignancy cases who develop OME post RT, however, in most of them it resolves spontaneously.


Piloting the 'Youth Early-intervention Study' ('YES'): Preliminary functional outcomes of a randomized controlled trial targeting social participation and physical well-being in young people with emerging mental disorders.
Young people with mental disorders present with diverse social, vocational, physical, and developmental needs. However, multifaceted interventions are rare. We examine the effectiveness of a clinical trial targeting social participation and physical well-being in young people accessing clinical services. The 'Youth Early-intervention Study' ('YES') was an unblinded, two-phase, pilot randomized controlled trial offered as an adjunct to standard clinical care, consisting of group activities. Mixed effects models were used to examine functional outcomes over time measured by the 'Social and Occupational Functioning Assessment Scale', 'Functioning Assessment Short Test', and 'Brief Disability Questionnaire' (items 7 and 8). 133 participants aged 14-25 were recruited. 87 participants completed both arms and 83 participants completed a 12-month post-trial assessment. Functioning improved across all outcomes. While diagnoses differed in functioning at baseline (lower functioning in psychotic and bipolar disorders compared to depression), they did not differ in the rate of improvement across any measure. Randomization groups did not differ in baseline functioning or the rate of improvement, suggesting a non-specific impact of the intervention. Engagement with education increased from 11% at baseline to 51% at 12-months post-trial and full-time employment increased from 8% at baseline to 20% at 12-months post-trial. Small sample, no control group, and unmeasured potential moderators (e.g. neurocognitive impairment). 'YES' was effective and preliminary positive outcomes were observed across all functional outcomes. Future studies should compare the 'YES' intervention to a treatment-as-usual control condition and conduct a multi-centre trial across early intervention service sites.


Photocatalytic water reduction with copper-based photosensitizers: a noble-metal-free system.
Of noble descent: a fully noble-metal-free system for the photocatalytic reduction of water at room temperature has been developed. This system consists of Cu(I) complexes as photosensitizers and [Fe(3)(CO)(12)] as the water-reduction catalyst. The novel Cu-based photosensitizers are relatively inexpensive, readily available from commercial sources, and stable to ambient conditions, thus making them an attractive alternative to the widely used noble-metal based systems.


Arterial line versus venous line administration of low molecular weight heparin, enoxaparin for prevention of thrombosis in the extracorporeal blood circuit of patients on haemodialysis or haemodiafiltration: A randomized cross-over trial.
The objective of the study is to compare the anti-factor Xa (AXa) level in the blood, after arterial and venous line administration of equivalent doses of enoxaparin for prevention of thrombosis in the extracorporeal blood circuit. The design of the study is a dual centre, prospective, open-labelled randomized crossover, 7 weeks trial. The setting of the study is on a patient on long-term haemodialysis (HD) or haemodiafiltration (HDF) using high-flux membrane. There were eight patients on HD and eight on HDF. Participants were randomly assigned to receive enoxaparin either through the arterial line or venous line of extracorporeal blood circuit for an initial study interval of 2 weeks, followed by 2 weeks of alternate route administration. During the run-in period of 1 week and the follow-up period of 2 weeks, enoxaparin was administered through the arterial line. The primary outcome measure was to compare AXa blood level 4 h after enoxaparin administration. The secondary outcome measures were manual compression time to stop bleeding from arteriovenous fistula, extracorporeal circuit clotting and systemic bleeding episodes. The mean AXa blood level, 4 h after venous circuit administration (0.58 ± 0.21 (HD), 0.82 ± 0.29 (HDF)) of enoxaparin, was significantly greater than that after arterial administration of enoxaparin (0.39 ± 0.25 (HD), 0.39 ± 0.14 (HDF) U/mL), (P < 0.001). In patients on HD or HDF, venous line administration of enoxaparin achieves greater 4 h blood AXa level compared with arterial line administration of equivalent dose. Based on this, we suggest a 25% or 50% reduction in the dose of venous line enoxaparin, compared with the dose administered through arterial line in patients receiving either HD or HDF, respectively.


The susceptibility of chicken kidney and oviduct organ cultures to a vaccine strain of avian infectious bronchitis virus.
The minimal infectious dose of the H52 strain of infectious bronchitis virus for organ cultures of oviduct and kidney was compared in chickens of different ages. Organ cultures of oviduct were found to be highly susceptible to infection regardless of the age of chicken and no difference in susceptibility could be demonstrated between cultures of the magnum and uterus regions of the mature oviduct. Kidney organ cultures were less susceptible and resistance to infection increased significantly (P less than 0.001) with the age of the chicken from which cultures were prepared.


On a new model for inhomogeneous volume growth of elastic bodies.
In general, growth characterises the process by which a material increases in size by the addition of mass. In dependence on the prevailing boundary conditions growth occurs in different, often complex ways. However, in this paper we aim to develop a model for biological systems growing in an inhomogeneous manner thereby generating residual stresses even when growth rates and material properties are homogeneous. Consequently, a descriptive example could be a body featuring homogeneous, isotropic material characteristics that grows against a barrier. At the moment when it contacts the barrier inhomogeneous growth takes place. If thereupon the barrier is removed, some types of bodies keep the new shape mainly fixed. As a key idea of the proposed phenomenological approach, we effort the theory of finite plasticity applied to the isochoric part of the Kirchhoff stress tensor as well as an additional condition allowing for plastic changes in the new grown material, only. This allows us to describe elastic bodies with a fluid-like growth characteristic. Prominent examples are tumours where the characteristic macro mechanical growth behaviour can be explained based on cellular arguments. Finally, the proposed framework is embedded into the finite element context which allows us to close this study with representative numerical examples.


Wheels-in-wheels: Use of gravity in human locomotion.
Although a wheel is an ideal method for transportation and the invention of the spoke wheel made a wheel lighter and swifter, a wheel cannot function well on slanted or rough surfaces; these are common in the natural environment. Further, the load support of the wheel is limited to a point of the whole wheel in contact with the ground. Then, we humans may be using the legs as a part of spoke wheel and place our legs and feet on the ground alternatively to support the body weight while the gravitational torque makes the center of mass (COM) rotate around the hip joint when proper stiffness and balance is made. Through a pulley-like action involving the hamstrings and a lever-like action of back muscles via the psoas muscle, the energy expenditure for locomotion can be reduced to the energy for lifting the swing leg to maintain the proper position of the COM. Further, the stabilizing action of the psoas muscle to the spinal column can be achieved between the stance leg and the swing leg by the weight of the lifted swing leg during the forward movement. This lifting action during swing phase can assist an energy-efficient eccentric contraction of the stance leg. The passive tension generated by gravity (own weight and the carried load) can be the reason for the energy efficiency of both head-carrying and the Nepalese porter method. Using this passive gravitational force via actively synchronized neuromuscular action may be universal for animal locomotion.


Influence of gel dimensions on resolution and sample throughput on two-dimensional gels.
To achieve high throughput and economical format of 2-D PAGE, comparison between gel size and resolution was conducted on human breast carcinoma cell line (MCF-7/AZ) proteins. SDS gel length showed a weaker influence of separation length on resolution in the second dimension, and there was little benefit of separation distances greater than 15 to 19 cm. IPG strip separation distances were very important with dramatic increase in resolution of longer gels compared with smaller gels, and maximal resolution was obtained using 18- and 24-cm IPG strips. Loading optimal amount of proteins on 2-D gels can also increase the number of detected spots. Therefore, taken together, compromise 2-D gels are crucial for higher capacity and higher throughput.


Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan.
It is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. We determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. Vaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. The progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.


Improving health care, Part 5: Applying the Dartmouth clinical improvement model to community health.
Traditional approaches to community health initiatives provide guidance on community mobilization, health assessment, planning, and intervention. Yet direction in how to frame the action steps to implement and measure results is often missing. Many community health initiatives find implementation overwhelming and ineffectual. FRAMEWORK FOR COMMUNITY HEALTH-THE CLINICAL IMPROVEMENT MODEL: The process--outcome methodology of continuous quality improvement (CQI) can translate large community aims into manageable projects. The sequential application of the clinical improvement model and the Community Health Value Compass for measuring outcomes-in state of health, quality of life, satisfaction, and costs-provides a link between data and action, thereby producing accountability for the community health initiative. USING THE CLINICAL IMPROVEMENT MODEL IN TWIN FALLS: Healthy Magic Valley (Twin Falls, Idaho) is the vision for long-term improvement in health status and reduction of health risks for the Southcentral Idaho Health Network. Since 1996 the Twin Falls Community Health Collaborative and SAFE KIDS Coalition have used the Value Compass model and CQI methods to decrease the rate of motor vehicle collisions, serious injuries, and deaths involving teens, while reducing the health, educational, legal, and financial consequences associated with teen-involved motor vehicle collisions. In 1993 the Twin Falls collaborative convened to apply CQI methods to the health of the community. The team has since met periodically to address the issues of community health, using the Dartmouth value compass model since 1996. Each sequential application of the process-outcome CQI framework exposes a blueprint for action and the unfolding of a health improvement strategy. The interventions should affect one or more dimensions of the value compass for teenage driving and motor vehicle collisions. CASE STUDY OF THE CLINICAL IMPROVEMENT MODEL: The motor vehicle death in October 1997 of a high school football player, who was not wearing a seat belt, led to a call to action for injury prevention. Implementation of a local community health initiative on seat belt use started in 1998. A strategy was developed to address implementation of the project among high school teens (for immediate impact) and elementary school children (for long-term impact) and to promote collaboration between the school and the rest of the community. Observed use of seat belts increased from January to September 1998. Data on fatality rates; injury rates; percentages of teens in crashes, of teens injured, and of teen collisions involving use of alcohol; and comprehensive costs are also monitored. Once coalitions are built and priorities set, the Dartmouth clinical improvement model presents a method that emphasizes measuring the benefits to the individual members of the community. A portfolio composed of a value compass for each health improvement initiative provides ongoing feedback for guiding subsequent strategic planning by the governing community health network.


Platelet reactivity in patients with chronic kidney disease and hemodialysis.
End stage renal disease requiring hemodialysis (HD) is frequent and coronary artery disease (CAD) is a common comorbidity. It is associated with bleeding and ischemic events. Platelet reactivity is a well-known determinant of both. However, the impact of HD due to end stage chronic kidney disease (CKD) on platelet reactivity is unknown. Therefore in this study, we evaluated platelet reactivity during hemodialysis in patients with CKD and coronary artery disease. 22 patients with CKD, HD and CAD were included in this study. Light transmission aggregometry (LTA) and flow cytometry were used for evaluating platelet function immediately before and 2 h after initiation of HD. Arachidonic acid-induced maximum of aggregation (MoApre HD: 27.36% ± 25.23% vs. MoAduring HD: 28.05% ± 23.50%, p value = 0.822), adenosine diphosphate (ADP)-induced platelet aggregation (MoApre HD: 65.36% ± 12.88% vs. MoAduring HD: 61.55% ± 17.17%, p-value = 0.09) and collagen-induced platelet aggregation (MoApre HD: 62.18% ± 18.14% vs. MoAduring HD: 64.82% ± 18.31%, p-value = 0.375) were not affected by HD. P-selectin expression was significantly lower after 2 h of HD (pre HD: 31.56% ± 18.99%, during HD: 23.97% ± 15.28%, p = 0.026). In this pilot study, HD did not enhance platelet aggregation. Baseline platelet reactivity was decreased during HD.


Once cleaved C-C bond was reformed: reversible C-C bond cleavage of dihydroindenyltitanium complexes.
The once cleaved carbon-carbon bond of the Cp moiety in 2 was recombined in indene products. Aslo, we propose a novel mechanism for the cleavage of the carbon-carbon bond of the Cp moiety.


Impact of Aerobika® oscillating positive expiratory pressure in improving small airway resistance, lung function, symptoms and exercise capacity in chronic obstructive pulmonary disease.
Aerobika® oscillating positive expiratory pressure (OPEP) device promotes airway clearance in many respiratory diseases. However, studies have yet to focus on its effectiveness in improving small airway resistance via impulse oscillometry (IOS) measurement in COPD subjects. We aim to evaluate the improvement of small airway resistance (via IOS), lung function (spirometry), exercise capacity [via 6-min walking test (6MWT)], symptoms [COPD assessment test (CAT)] and severe exacerbation events among COPD subjects using Aerobika® OPEP. This was a prospective, single-arm interventional study among COPD subjects with small airway disease. Subjects were instructed to use twice daily Aerobika® OPEP (10 min each session); for 24 weeks; as an additional to standard therapy. IOS, spirometry, 6MWT, CAT score and severe exacerbation events were evaluated at baseline, 12 weeks and 24 weeks. Fifty-three subjects completed the study. Aerobika® usage showed improvement of IOS parameters; e.g. measurement of airway resistance at 5 Hz (R5), cmH20/L/s, (12-week p = 0.008, 24-week p < 0.001), R5% predicted (12-week p = 0.007, 24-week p < 0.001) and small airway resistance (R5-R20), cmH20/L/s, (12-week p = 0.021, 24-week p < 0.001). There were improvement of lung function; e.g. FEV1, L (12-week p = 0.018, 24-week p = 0.001), FEV1% predicted (12-week p = 0.025, 24-week p = 0.001), FEF25-75, L (12-week p = 0.023, 24-week p = 0.002), and FEF25-75% predicted (12-week p = 0.024, 24-week p < 0.001). CAT score improved at 12 weeks (p < 0.001) and 24 weeks (p < 0.001). Subjects had improved exercise capacity (6MWT, metres) after 24 weeks (p = 0.016). However, there was no significant difference in severe exacerbation events 24 weeks before and after Aerobika® usage. Aerobika® OPEP demonstrated significant improvement in small airway resistance as early as 12 weeks of usage, with sustained improvement at 24 weeks. Aerobika® OPEP administration had significantly improved lung function, 6MWT, and CAT scores over 24 weeks. There was no difference in severe exacerbation events.


Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2.
Caffeine is metabolized in the liver by cytochrome P450(CYP)1A2. Recent findings imply that this enzyme may also be of importance for the metabolism of human melatonin (MT). If caffeine and MT are metabolized by the same enzyme, one may expect to find different serum MT levels after ingestion of coffee compared with placebo. Although coffee is consumed by people all over the world, few studies have focused on whether caffeine actually affects serum MT levels in normal subjects. We decided to study that particular topic. For that purpose 12 healthy individuals were tested on two occasions, one week apart. On one of these occasions they were given a capsule containing 200 mg caffeine in the evening. On the other, they received placebo. The experimental order was randomized. Serum MT levels were determined every second hour between 22:00 h and 08:00 h, and the melatonin areas under the curve (MT-AUCs) were calculated. After caffeine the serum MT level rose from 0.09 +/- 0.03 nmol/l at 22:00 h to 0.48 +/- 0.07 nmol/l at 04:00 h. The corresponding rise after placebo was less prominent (from 0.06 +/- 0.01 to 0.35 +/- 0.06 nmol/l). This was reflected by the MT-AUC which was 32% larger after ingestion of caffeine compared with placebo (MT-AUC(caffeine) 3.16 +/- 0.44 nmol/l x h vs MT-AUC(placebo) 2.39 +/- 0.40 nmol/l x h; p < 0.02). These findings imply that caffeine, ingested in the evening at a dose corresponding to two ordinary cups of coffee, augments the nocturnal serum MT level, which in turn supports the notion that cytochrome P450(CYP)1A2 is involved in the hepatic metabolism of human MT.


Revealing the 3-dimensional shape of atom probe tips by atomic force microscopy.
For the very first time, atomic force microscopy is used to determine quantitatively the 3-dimensional shape of an atom probe tip, which is key towards improved accuracy and understanding of artefacts in atom probe tomography. We have successfully measured by atomic force microscopy the apex and shank region of 3 different atom probe tips, of which two show (severe) deviations from a hemisphere due to either non-uniform laser light absorption or the presence of two different materials. Clearly, our method which overcomes the challenge of aligning two very sharp tips on top of each other, offers new pathways to study physical mechanisms in (laser-assisted) atom probe. It represents an important step towards improved reconstruction algorithms as the image formation in atom probe tomography is based on the intricate link between the tip shape (down to the atomic level), the electric field distribution and the ions' flight path towards the detector. Further on, present reconstruction algorithms solely account for a hemispherical tip shape, which does not hold true for most applications and results in complex artefacts. Therefore our method is an attractive novel approach to assess the 3D tip shape.


Antioxidant properties of a human neuropeptide and its protective effect on free radical-induced DNA damage.
Human catestatin CgA352-372 (SL21) is an endogenous neuropeptide with multiple biological functions. The present study aimed to evaluate the antioxidant, antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide. SL21 neuropeptide generated from the C-terminus of chromogranin A (CgA) was synthesized by solid-phase method. Synthetic peptide was subjected to various in vitro antioxidant assays including the scavenging of 1,1-diphenyl-2-pycryl-hydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(·+) ), and hydroxyl free radicals, metal ion chelation, inhibition of lipid peroxidation, and reducing power. Moreover, protective effect of SL21 on H2 O2 -induced DNA damage was analyzed using pTZ57/RT plasmid. Methylthiazoltetrazolium assay was also performed to study the cytotoxic effect of SL21 neuropeptide on human peripheral blood mononuclear cells. Furthermore, antibacterial and hemolysis assays were conducted. The results demonstrated high activities of SL21 in scavenging free radicals (DPPH, ABTS(·+) , and hydroxyl), chelating of Cu(2+) /Fe(2+) metal ions, reducing power, and inhibition of lipid peroxidation in a concentration-dependent manner. SL21 neuropeptide revealed a protective effect on DNA damage caused by hydroxyl radicals. Interestingly, the peptide exhibited no significant cytotoxicity towards peripheral blood mononuclear cells. Furthermore, SL21 peptide displayed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa without any hemolytic activity on human red blood cells. Conclusively, the present study established SL21 (catestatin) as a novel antioxidative peptide that could further be investigated for its potential use as a pharmaceutical agent.


Calibration system and analytical considerations for quantitative sesquiterpene measurements in air.
Sesquiterpenes (C15H24, SQT) are semi-volatile organic compounds emitted from vegetation and are of interest for air quality considerations because of their suspected contribution to the formation of secondary aerosol. This article investigates the application of a capillary diffusion method for the generation of standard atmospheres of 16 SQT and four other related semi-volatile compounds. This instrument subsequently has been used in the testing of analytical materials, protocols and calibration of air sampling methods. SQT DB-1 retention indices, vapor pressures at 25 and 75 degrees C, and diffusion coefficients were determined. A quantitative, on-line GC method yielded improved results (median relative standard deviation of 5.0-6.1%) for the diffusion rate determination in comparison to a gravimetric approach (median relative standard deviation 18%). The GC method also allowed identifying errors in the gravimetric method stemming from residual solvent evaporation, impurities, and chemical analyte losses. Stainless steel, glass, nickel and PTFE tubing that were tested for transfer lines and a sampling loop had to be kept at temperatures in excess of approximately 110 degrees C in order to prevent significant analytical errors from the stickiness of SQT to these materials. In addition to SQT analysis, results from this research provide general guidelines for gas-phase analysis of related compounds in the C14-C16 volatility range.


Cholesterol assimilation and biotransformation by Lactobacillus helveticus.
Lactobacillus helveticus, grown at 37°C in MRS medium supplemented with 3 mM cholesterol, assimilated all the cholesterol in 42 h having 68 U mg(-1) of intracellular cholesterol oxidase activity. The strain transformed 1 g cholesterol to 0.05 g of androsta-1, 4-diene-3, 17-dione and 0.04 g of androst-4-ene-3, 17 dione within 48 h at 37°C with extracellular cholesterol oxidase activity at 12 U mg(-1) and intracellular oxidase at 0.5 U mg(-1).


Functional role of the interaction between polysialic acid and extracellular histone H1.
Polysialic acid (PSA) is a large and highly negatively charged glycan that plays crucial roles in nervous system development and function in the adult. It has been suggested to facilitate cell migration, neurite outgrowth, and synaptic plasticity because its hydration volume could enhance flexibility of cell interactions. Evidence for receptors of PSA has so far been elusive. We now identified histone H1 as binding partner of PSA via a single-chain variable fragment antibody using an anti-idiotypic approach. Histone H1 directly binds to PSA as shown by ELISA. Surface biotinylation of cultured cerebellar neurons indicated an extracellular localization of histone H1. Immunostaining of live cerebellar neurons and Schwann cells confirmed that an extracellular pool of histone H1 colocalizes with PSA at the cell surface. Histone H1 was also detected in detergent-insoluble synaptosomal membrane subfractions and postsynaptic densities. When applied in vitro, histone H1 stimulated neuritogenesis, process formation and proliferation of Schwann cells, and migration of neural precursor cells via a PSA-dependent mechanism, further indicating that histone H1 is active extracellularly. These in vitro observations suggested an important functional role for the interaction between histone H1 and PSA not only for nervous system development but also for regeneration in the adult. Indeed, histone H1 improved functional recovery, axon regrowth, and precision of reinnervation of the motor branch in adult mice with femoral nerve injury. Our findings encourage investigations on the therapeutic potential of histone H1 in humans.


Sound-direction identification, interaural time delay discrimination, and speech intelligibility advantages in noise for a bilateral cochlear implant user.
To characterize some of the benefits available from using two cochlear implants compared with just one, sound-direction identification (ID) abilities, sensitivity to interaural time delays (ITDs) and speech intelligibility in noise were measured for a bilateral multi-channel cochlear implant user. Sound-direction ID in the horizontal plane was tested with a bilateral cochlear implant user. The subject was tested both unilaterally and bilaterally using two independent behind-the-ear ESPRIT (Cochlear Ltd.) processors, as well as bilaterally using custom research processors. Pink noise bursts were presented using an 11-loudspeaker array spanning the subject's frontal 180 degrees arc in an anechoic room. After each burst, the subject was asked to identify which loudspeaker had produced the sound. No explicit training, and no feedback were given. Presentation levels were nominally at 70 dB SPL, except for a repeat experiment using the clinical devices where the presentation levels were reduced to 60 dB SPL to avoid activation of the devices' automatic gain control (AGC) circuits. Overall presentation levels were randomly varied by +/- 3 dB. For the research processor, a "low-update-rate" and a "high-update-rate" strategy were tested. Direct measurements of ITD just noticeable differences (JNDs) were made using a 3 AFC paradigm targeting 70% correct performance on the psychometric function. Stimuli included simple, low-rate electrical pulse trains as well as high-rate pulse trains modulated at 100 Hz. Speech data comparing monaural and binaural performance in noise were also collected with both low, and high update-rate strategies on the research processors. Open-set sentences were presented from directly in front of the subject and competing multi-talker babble noise was presented from the same loudspeaker, or from a loudspeaker placed 90 degrees to the left or right of the subject. For the sound-direction ID task, monaural performance using the clinical devices showed large mean absolute errors of 81 degrees and 73 degrees, with standard deviations (averaged across all 11 loud-speakers) of 10 degrees and 17 degrees, for left and right ears, respectively. Fore bilateral device use at a presentation level of 70 dB SPL, the mean error improved to about 16 degrees with an average standard deviation of 18 degrees. When the presentation level was decreased to 60 dB SPL to avoid activation of the automatic gain control (AGC) circuits in the clinical processors, the mean response error improved further to 8 degrees with a standard deviation of 13 degrees. Further tests with the custom research processors, which had a higher stimulation rate and did not include AGCs, showed comparable response errors: around 8 or 9 degrees and a standard deviation of about 11 degrees for both update rates. The best ITD JNDs measured for this subject were between 350 to 400 microsec for simple low-rate pulse trains. Speech results showed a substantial headshadow advantage for bilateral device use when speech and noise were spatially separated, but little evidence of binaural unmasking. For spatially coincident speech and noise, listening with both ears showed similar results to listening with either side alone when loudness summation was compensated for. No significant differences were observed between binaural results for high and low update-rates in any test configuration. Only for monaural listening in one test configuration did the high rate show a small significant improvement over the low rate. Results show that even if interaural time delay cues are not well coded or perceived, bilateral implants can offer important advantages, both for speech in noise as well as for sound-direction identification.


Scalp topography of the short latency somatosensory evoked potentials following posterior tibial nerve stimulation in man.
The scalp topography of the short latency somatosensory evoked potentials (SEPs) to unilateral posterior tibial nerve stimulation at the ankle was studied by using a non-cephalic reference in 22 normal young adults. At least 3 components (P28, N31 and N32) were identified preceding the major positive peak (P36). The first 2 components had similar peak latency at all scalp electrodes, and were considered to be generated in deep structures. However, N32 was localized to the hemisphere contralateral to the side of stimulation. P36 was maximal at the midline foot sensory area, or at the contralateral parasagittal area, and its amplitude decreased more steeply anteriorly than posteriorly. The peak latency of P36 progressively increased from ipsilateral to the side of stimulation in the coronal plane. P36 occurred earlier in the somatosensory area, and increased in peak latency anteriorly. Generator source of scalp-recorded far-field potentials (P28 and N31) remains to be elucidated. N32 might reflect activities of the thalamo-cortical pathway or an initial cortical response. P36 appeared to be generated in the somatosensory foot area.


Validation and Cultural Adaptation of the Arabic Version of the Aging Voice Index.
The aging voice index (AVI) is a 23-item self-administered, patient-reported outcome measure. It was developed in the English language to assess the impact of voice disorders on the elderly population. This study aimed to develop an Arabic version of the AVI (A-AVI), test its reliability and validity, and assess its psychometric aspects in Arabic-speaking elderly persons with voice disorders. This was an observational, cross-sectional study involving elderly patients aged ≥60 years. Eighty-two patients with voice disorders were included in the dysphonia group and 77 patients without voice disorders were included in the vocally healthy group. The translated A-AVI and Arabic voice handicap index 10 (A-VHI10) were distributed to the study groups. The A-AVI was tested for its reliability (test-retest reliability and internal consistency) and validity (content, construct, and concurrent with A-VHI10). The A-AVI showed excellent test-retest reliability and internal consistency (intraclass correlation coefficient = 0.987 and Cronbach's alpha = 0.954, respectively). There was a significant difference in A-AVI scores between the elderly in the dysphonia and vocally healthy groups (P < 0.001). In addition, a significant correlation was demonstrated between A-AVI and A-VHI10 (r = 0.89). Unilateral vocal fold immobility and inflammatory laryngeal disorders were most frequently reported by the dysphonia group (28%). A-AVI has excellent validity and reliability in Arab-speaking elderly patients with voice disorders. It can be considered in the assessment of the effect of voice disorders on the quality of life of the elderly.


Is consonance attractive to budgerigars? No evidence from a place preference study.
Consonant tone combinations occur naturally in the overtone series of harmonic sounds. These include sounds that many non-human animals produce to communicate. As such, non-human animals may be attracted to consonant intervals, interpreting them, e.g., as a feature of important social stimuli. There is preliminary evidence of attraction to consonance in various bird species in the wild, but few experimental studies with birds. We tested budgerigars (Melopsittacus undulatus) for attraction to consonant over dissonant intervals in two experiments. In Experiment 1, we tested humans and budgerigars using a place preference paradigm in which individuals could explore an environment with multiple sound sources. Both species were tested with consonant and dissonant versions of a previously studied piano melody, and we recorded time spent with each stimulus as a measure of attraction. Human females spent more time with consonant than dissonant stimuli in this experiment, but human males spent equal time with both consonant and dissonant stimuli. Neither male nor female budgerigars spent more time with either stimulus type. In Experiment 2, we tested budgerigars with more ecologically relevant stimuli comprised of sampled budgerigar vocalizations arranged into consonant or dissonant chords. These stimuli, however, also failed to produce any evidence of preference in budgerigar responses. We discuss these results in the context of ongoing research on the study of consonance as a potential general feature of auditory perception in animals with harmonic vocalizations, with respect to similarities and differences between human and budgerigar vocal behaviour, and future methodological directions.


The optimization of SO2 emissions by the 4DVAR and EnKF methods and its application in WRF-Chem.
Emissions are essential for forecasting air quality and pollution control, but traditional emissions are often not real-time by the statistics of "bottom-up" approach due to high human resource demand. The four-dimensional variational method (4DVAR) and the ensemble Kalman filter (EnKF) are generally used to optimize emissions based on chemical transport models by assimilating observations. Although the two methods solve similar estimation problems, different functions have been developed to address the process of converting the emissions to concentrations. In this paper, we evaluated the performance of the 4DVAR and EnKF methods in optimizing SO2 emissions over China during 23-29 January 2020. The emissions optimized by the 4DVAR and EnKF methods showed a similar spatiotemporal distribution in most regions of China during the study period, suggesting that both methods are useful in reducing uncertainties in the prior emissions. Three forecast experiments with different emissions were conducted. Compared with the forecasts with prior emissions, the root-mean-square error of the forecasts with the emissions optimized by the 4DVAR and EnKF methods decreased by 45.7 % and 40.4 %. This indicates that the 4DVAR method was slightly more effective than the EnKF method in optimizing emissions and improves the accuracy of forecasts. Furthermore, it is found that the 4DVAR method performed better than the EnKF method when the spatial and/or temporal distribution of SO2 observations with strong local characteristics, The EnKF method showed a better performance for the condition of the large difference between prior emissions and real emissions. The results may help to design suitable assimilation algorithms for optimizing emissions and improving model forecasts. The advance data assimilation systems are beneficial for the understanding the effectiveness and value of emission inventories and air quality model.


Targeting of EMILIN-1 and EMILIN-2 to Fibrillin Microfibrils Facilitates their Incorporation into the Extracellular Matrix.
Elastin microfibril interface-located proteins (EMILINs) 1 and 2 belong to a family of structurally related extracellular glycoproteins with unique functions in the extracellular space, such as modulation of pro-transforming growth factor-β processing, activation of the extrinsic apoptotic pathway, and regulation of Hedgehog and Wnt ligand bioavailability. However, little is known about how EMILINs may exert their extracellular functions. We therefore investigated the spatiotemporal localization and deposition of EMILIN-1 and -2 within the extracellular space. By using immunoelectron and immunofluorescence microscopy together with biochemical extraction, we showed that EMILIN-1 and -2 are targeted to fibrillin microfibrils in the skin. In addition, during skin wound healing and in vitro matrix fiber assembly by primary dermal fibroblasts, EMILIN-1 and -2 are deposited on and coregulated with fibrillin. Analysis of wounds and mouse embryonic fibroblast cultures showed that EMILIN-1 and -2 network formation also requires the presence of fibronectin. Disruption of microfibrils in fibrillin-1-deficient mice leads to fragmentation of the EMILIN-1 and -2 networks, suggesting an involvement of EMILINs in fibrillin-related skin disorders. The addition of EMILINs to the ligand repertoire of fibrillin strengthens the concept of fibrillin microfibrils as extracellular scaffolds integrating cellular force transmission and growth factor bioactivity.


Effects of CD20 antibodies and kinase inhibitors on B-cell receptor signalling and survival of chronic lymphocytic leukaemia cells.
Recently, clinical trial results have established inhibitors of B-cell receptor (BCR)-associated kinase (BAKi), with or without CD20 moniclonal antibodies (mAbs), as the preferred first-line treatment for most chronic lymphocytic leukaemia (CLL) patients. Using phosphospecific flow cytometry, we showed that in leukaemic cells from CLL patients the CD20 therapeutic antibodies - rituximab, ofatumumab, and obinutuzumab - inhibited BCR signalling pathways targeting preferentially pBTKY551 - but not BTKY223 - and pAKT. On the contrary, ibrutinib and idelalisib reduced pBTKY223 to a higher extent than pBTKY551 . The strong reduction of pAKT induced by idelalisib was enhanced by its combination with rituximab or ofatumumab. Moreover, CD20 mAbs and BAKi induced the death of leukaemia cells that was significantly potentiated by their combination. Analysis of the enhancement of cell death in these combinations revealed an approximately additive enhancement induced by rituximab or obinutuzumab combined with ibrutinib or idelalisib. Taken together, our data identified negative regulatory effects of CD20 mAbs and their combinations with BAKi on BCR signalling and cell survival in CLL. In conclusion, this study advances our understanding of mechanisms of action of CD20 mAbs as single agents or in combination with BAKi and could inform on the potential of combined therapies in ongoing and future clinical trials in patients with CLL.


Does dysregulated expression of a deregulated viral GPCR trigger Kaposi's sarcomagenesis?
In 1994, the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) was identified as the etiologic agent of Kaposi's sarcoma (KS). KSHV has since been associated with two additional AIDS-related malignancies: primary effusion lymphomas (PEL) and multicentric Castleman's disease (MCD). Although molecular characterization of the KSHV genome has revealed several candidate oncogenes, infection with KSHV alone is not sufficient to cause KS, suggestive of an accomplice in KS initiation. Recent experimental evidence supports a key role for a particular KSHV gene, a constitutively-active G-protein-coupled receptor (vGPCR), in the development of KS. However, it is unclear how a lytic gene expressed in cells destined to die can cause cancer. Here we propose that dysregulation of the viral gene program may lead to nonlytic vGPCR expression. Several candidate cofactors (e.g., HIV-1 Tat, inflammation, aborted lytic cycle progression) are identified that may trigger vGPCR dysregulation, enabling oncogenic signaling pathways up-regulated by vGPCR, combined with the paracrine secretions from vGPCR-expressing cells, to promote the initiation of KS. If KS is indeed dependent on vGPCR dysregulation, then the development of new therapeutic modalities specifically targeting this viral protein or its downstream targets may ultimately prove to be the most effective treatment strategy for this enigmatic disease.


Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations.
A simple, precise, and accurate method is developed and validated for the analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column (5 μm, 125 × 4.6 mm inner diameter) using a mobile phase consisting of methanol/ammonium dihydrogen phosphate buffer (90:10, v/v) at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, robustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r (2) of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r (2) of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r (2) of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r (2) of 0.991. The average recovery of the method is 99.7%, 98.6%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged.


Pulmonary retention of inhaled diesel particles after prolonged exposures to diesel exhaust.
The effect of continuous exposure to diluted diesel exhaust on the pulmonary retention of inhaled diesel particles was studied in male Fischer 344 rats. Test animals were first exposed to clean air or diluted diesel exhaust in exposure chambers at nominal particulate concentrations of 250 micrograms/m3 or 6 mg/m3 for 20 hr/day, 7 days/week, for periods lasting from 7 to 112 days, followed by a nose-only exposure to 14C-tagged diesel particles for 45 min. At preselected time intervals after the radioactive exposure, the 14C-activities in the lungs of groups of four animals were measured to determine the clearance of the 14C-diesel particles up to 1 year. The pulmonary retention of the radioactive diesel particles was greater in animals which had been preexposed to diesel exhaust. The slower alveolar clearance of particle-laden macrophages and leukocytes can be described by a normal biphasic clearance model. Since some of the macrophages were found sequestered as aggregates in the pulmonary region, a slow-clearing residual component was included in a modified lung retention model. When these residual fractions were determined and excluded from the active particulate transport within the lungs, normal alveolar clearance rates were calculated for the animals with a preexposure diesel particulate dose less than 0.8 mg. Slower clearance was observed at a dose of 6.5 mg and no clearance was evident at a dose of 11.8 mg in their lungs.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultrasonic findings in pseudomyxoma peritonei.
The ultrasonic findings of numerous thick-walled intraperitoneal septate cysts, with associated peritoneal liver scalloping, suggest the diagnosis of pseudomyxoma peritonei.


Treatment of symptomatic oral lichen planus (OLP) with 0.1% tacrolimus powder in Oraguard-B - A pilot prospective study.
The purpose of this study was to investigate the efficacy and safety of 0.1% tacrolimus powder in Oraguard-B for the treatment of patients with symptomatic oral lichen planus (OLP). This was a nonrandomized, nonblinded study conducted in the outpatient department. The 20 patients with symptomatic OLP oral lichen planus who were asked to participate in the study were provided with 20-g containers of the study medication. Patients were asked to use the medication over the symptomatic areas three times a day until resolution of the lesion. Patients were recalled to assess the drug response every 15 days. The duration of treatment ranged from 30 to 183 days, with a mean of 81.8 ± 44.4 days; all 20 patients reported a favourable response to the topical tacrolimus therapy. Eleven patients had complete resolution of their lesions. In 16 of 20 patients, there was marked resolution in symptoms as recorded by visual analogue scale. Out of 10 patients followed up for a period of 3 months, 5 had recurrence of their lesions but with less intensity, and the patients were symptomless. No serious side effects were associated with the study medication. Topical tacrolimus 0.1% in Oraguard-B was effective and safe in treating patients with OLP. However, there is still a need to undertake more detailed and objective clinical studies to determine the exact benefit of tacrolimus compared with conventional therapies and examine the influence of different dose regimes and formulations and assess the incidence of recurrence.


Antinociceptive and lethal effects of intraventricularly administered barium and strontium: antagonism by atropine sulfate or naloxone hydrochlorine.
The intracerebroventricular injection of Ba++ and Sr++ produced naloxone and atropine reversible antinociception as measured by the mouse tail-flick test. Naloxone antagonized the antinociception produced by Ba++ more effectively than atropine (pA2 5.9 vs. 7.0, respectively). Naloxone was less efficient than atropine in blocking lethality. Together these results suggest different mechanisms involved in the production of antinociception and lethality by these ions.


Functional development of the parasympathetic innervation of the sino-auricular node in newborn rabbits, cats and guinea pigs.
The effects of supramaximal vagus nerve stimulation on heart rate were studied in newborn rabbits, cats and guinea pigs. The analysis of the stimulus-effect curve revealed that the earlier proposed relationship: log If/IO = H.f (IO is the steady state PP-interval before and If during stimulation, f is the stimulus frequency, and H the slope of the line) accurately summarizes the relation in rabbits, while with minor deviations it also holds for newborn cats and guinea pigs. Thus, the vagus effect for each nerve and animal is characterized by the slope of the line, H. In rabbits and cats the vagus effect decreased during the first postnatal week to about 1/3 and 1/5 of the initial value at birth. Guinea pigs, however, did not show such a postnatal change of the vagus effect. In comparison with rabbits and cats these animals are born at a relatively late ontogenetic stage. Therefore, we hypothesized that the decrease in vagus effect is related to the stage of development and occurs mainly before birth in this species.


Continence rate and oncological feasibility after total transurethral resection of the prostate as an alternative therapy for the treatment of prostate cancer: a pilot study.
The value of total transurethral resection of prostate cancer (TURPC) as an alternative therapy was first recognized by Hans J. Reuter. Thus, we conducted the study of prospectively collected data to verify total TURPC as an alternative therapy forlocalized prostate cancer. From January 2008 to July 2011, 14 patients with a mean age of 76.1 years (range, 66 to 89 years) with clinically localized prostate cancer were treated by prostatic resection by the corresponding author with curative intention. The mean duration of TURPC was 51.7 minutes (range, 30 to 120 minutes) and the mean amount of prostatic tissue resected was 21.2 g (range, 5 to 66 g). An intra- and/or postoperative blood transfusion was necessary in 2 cases. Hyponatremia was found in 7 patients. Six months after TURPC, 3 cases of grade 1 and 1 case of grade 2 incontinence were observed. Three patients in the high-risk group did not achieve a prostate specific antigen (PSA) nadir of ≤0.2 ng/mL. PSA recurrence occurred in one case in our series. Newly developed lymph node or distant metastases were not observed during the follow-up period. According to our results, transurethral resection for prostate cancer can be performed with reasonable oncological results. The PSA nadir levels, and rates of biochemical failure and postoperative complications, including incontinence, were comparable with the published results for other procedures. TURPC is also inexpensive and non-invasive, and requires short hospitalization and a short surgical time without vesicourethral anastomosis.


Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters.
To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer. This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant Ktrans on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR. Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement. • Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response.


Tick paralysis presenting in an urban environment.
We report the case of a 17-month-old female with tick paralysis presenting to an urban Los Angeles emergency department. The tick was later identified as the North American wood tick, Dermacentor andersoni, and was likely obtained while the family was vacationing on a dude ranch in Montana. We discuss the epidemiology of tick paralysis, a differential diagnosis for health care providers, and methods of detection and removal. Given the increasing popularity of outdoor activities and ease of travel, tick paralysis should be considered in cases of acute or subacute weakness, even in an urban setting.


Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor.
Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.


Enhanced effect of vascular endothelial growth factor, thrombopoietin peptide agonist, SCF, and Flt3-L on LTC-IC and reporter gene transduction from umbilical cord blood CD34+ cells.
Hemangioblastic precursors have been identified that give rise to both endothelial cells and HPCs, suggesting that common growth factor requirements may exist. The effect of vascular endothelial growth factor (VEGF) in combination with thrombopoietin peptide agonist (TPOA), Flt-3 L (F), and SCF (S) on long-term culture-initiating cell (LTC-IC), CFU, differentiation, and transduction of cord blood (CB) CD34+ were evaluated up to 4 weeks in culture. At Week 4, in cultures containing T/F/S and VEGF, the LTC-IC increased 1000-fold (from 37 +/- 8 to 37,012 +/- 14,329) with a frequency of 3.4 in 10,000 cells. In the T/F/S cultures without VEGF, the LTC-IC increased 675-fold (to 25,086 +/- 12,102) with a frequency of one LTC-IC in 10,000 cells. The addition of VEGF significantly increased (p < 0.05) the LTC-IC per 10,000 CB CD34+ cells. Transduction with reporter gene enhanced green fluorescent protein (EGFP), resulted in an increase in EGFP+ CFU at Week 1 and EGFP + LTC-IC at Weeks 1 and 4. The cells maintained their multilineage expression when cultured in conditions for erythroid, myeloid, or megakaryocytic differentiation. Peak percentage EGFP coexpression of GlyA and CD11b was 51 +/- 6 percent and 63 +/- 15 percent, respectively, at Week 2, while CD41a was 34 +/- 17 percent at Week 4. T/F/S and VEGF have an enhanced effect on total LTC-IC output and frequency but do not appear to significantly alter the differentiation or transducibility characteristics of CB HPCs in vitro.


Long-term study of ovine pulmonary adenocarcinogenesis in sheep with marginal vs. sufficient nutritional selenium supply: results from computed tomography, pathology, immunohistochemistry, JSRV-PCR and lung biochemistry.
The impact of selenium (Se) in carcinogenesis is still debatable due to inconsistent results of observational studies, recent suspicion of diabetic side effects and e.g. dual roles of glutathione peroxidases (GPx). Previously, our group introduced long-term studies on lung carcinogenesis using the jaagtsiekte sheep retrovirus (JSRV) induced ovine pulmonary adenocarcinoma (OPA) as an innovative animal model. The present report describes the results of sufficient (0.2 mg Se/kg dry weight (dw)) vs. marginal (<0.05 mg Se/kg dw) nutritional Se supply on cancer progression over a two-year period in 16 animals. Computed tomography (CT) evaluation of lung cancer progression, final pathological examination, evidence of pro-viral JSRV-DNA in lung, lymph nodes and broncho-alveolar lavage cells as well as biochemical analysis of Se, GPx1 and thioredoxin reductase (TrxR) activity in lung tissue were recorded. Additionally, immunohistochemical determination of GPx1 expression in unaffected and neoplastic lung cells was implemented. The feeding regime caused significant differences in Se concentration and GPx1 activity in lung tissue between groups, whereas TrxR activity remained unaffected. JSRV was evident in broncho-alveolar lavage cells, lung tissue and lung lymph nodes. Quarterly executed CT could not demonstrate differences in lung cancer proliferation intensity. Necropsy and histopathology substantiated CT findings. Immunohistochemical analysis of GPx1 in lung tissue suggested a coherency of GPx1 immunolabelling intensity in dependence of tumour size. It was concluded that the model proved to be suitable for long-term studies of lung cancer proliferation including the impact of modifiable nutritional factors. Proliferation of OPA was unaffected by marginal vs. sufficient nutritional Se supply.


Annual wellness visits are associated with increased use of preventive services in patients with diabetes living in the Diabetes Belt.
To examine whether Annual Wellness Visits (AWVs) were associated with increased use of preventive services in Medicare patients with diabetes living in the Diabetes Belt. We used a case-control design where outcomes were utilization of preventive services recommended for patients with diabetes (foot exam, eye exam, A1c test, and microalbuminuria test) and the exposure was AWVs using data for Medicare patients with diabetes in 2014 - 2015 residing in the Diabetes Belt (N = 412,009). Only 13.4% of patients in 2014 and 17.4% in 2015 used AWVs. Eye exams (61% vs 53%), foot exams (93% vs 79%), A1c tests (81% vs 71%), and microalbuminuria tests (45% vs 28%) were more common among patients who had an AWV in the preceding year compared with those who did not. These differences remained significant after adjusting for patient demographics, comorbidities, county level medical resources, and geographic factors. AWVs were significantly associated with increased preventive care use among patients with diabetes living in the Diabetes Belt. Low AWV utilization by patients with diabetes in and around the Diabetes Belt is concerning.


Evaluation of fibrin sealant for biologic mesh fixation at the hiatus in a porcine model.
The ideal method to secure biologic mesh during laparoscopic hiatal hernia repair remains uncertain. Suture or tack fixation can be technically difficult, and serious cardiovascular complications have been reported. Fibrin sealant (FS) offers a potential solution to this problem. We hypothesized that FS provides comparable mesh fixation to suture repair during laparoscopic mesh hiatoplasty. Using a porcine model, laparoscopic hiatal hernia repair was performed with suture reapproximation of the crura and reinforcement with an acellular porcine dermal matrix. Prior to repair, animals were randomized to mesh fixation with sutures (S) or FS. After 30-day survival, an esophagram was performed, the diaphragm harvested, and mesh position, fixation, and incorporation were evaluated histologically and biomechanically using a T-peel test. Twenty (10 S and 10 FS) laparoscopic hiatal hernia repairs were performed. Total operative time was significantly less in the FS group (74.7 versus 127.0 min, p < 0.01). There were no instances of mesh migration in any animal. Mean peel force did not differ significantly between the S and FS groups (0.21 vs. 0.18 N/mm, respectively; p = 0.49). There was no significant difference in cellular repopularization or inflammatory changes around the mesh. Fibrin sealant offers a reasonable alternative to suturing biologic mesh during laparoscopic hiatal hernia repair with equivalent mesh fixation. At 30 days it provides adhesive strength similar to suture fixation, while significantly reducing operative time.


Probenecid-induced protection against acute hexachloro-1,3-butadiene and methyl mercury toxicity to the mouse kidney.
Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3-butadiene (HCBD) or 40 mg/kg methyl mercury (MeHg). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 50% of the proximal tubules after 8 h. Treatment with the organic anion transport inhibitor probenecid (i.p., 3 x 0.75 mmol/kg) did not have any renal effect in normal mice but reduced the number of damaged tubules by 80 and 90% in mice treated with HCBD and MeHg respectively. The results support the conclusion that the toxicity of HCBD and MeHg to the mouse kidney is related to a probenecid-sensitive transport process. It cannot be stated from the present investigation whether the inhibition nephrotoxicity data are related to classic organic anion secretion by the kidney.


Impact of Variability in Echocardiographic Interpretation on Assessment of Adequacy of Repair Following Congenital Heart Surgery: A Pilot Study.
Technical Performance Score (TPS) is based largely on the presence and magnitude of residual lesions on postoperative echocardiograms; this score correlates with outcomes following repair of congenital heart defects. We evaluated reader variability for echocardiographic components of TPS for complete repair of tetralogy of Fallot (TOF) and arterial switch operation (ASO) in two centers and measured its effect on TPS. Postoperative echocardiograms were evaluated in 67 children (39 TOF and 28 ASO). Two readers (one per center) interpreted each echocardiogram. Reader variability in image quality assessments and measurements was compared using weighted kappa (κ), percent agreement, and intra-class correlation. TPS class (1 optimal-no residua, 2 adequate-minor residua, 3 inadequate-major residua) was assigned for each echocardiographic review by an independent investigator. The effect of reader interpretation variability on TPS classification was measured. There was strong agreement for TPS between the two readers (κ = 0.88). The readers were concordant for TPS classes for 57 children (85%) and discordant for classes 2 (minor residua) versus 3 (major residua) in six (9%). Coronary arteries and branch pulmonary arteries were frequently suboptimally visualized. Although inter-reader agreement for TPS was strong, inter-reader variation in echocardiographic interpretations had a small, but important effect on TPS for TOF and ASO, particularly for the distinction between minor and major residua. Further studies of generalizability and reproducibility of TPS and refinement of scoring modules may be needed before it can be used as a tool to assess pediatric cardiac surgical performance and outcomes.


Seasonal changes in photosynthetic characteristics of Anemone raddeana, a spring-active geophyte, in the temperate region of Japan.
Seasonal changes in the photosynthetic characteristics of intact involucral leaves of Anemone raddeana were investigated under laboratory conditions. Net photosynthesis and constant water vapor pressure deficit showed almost the same seasonal trend. They increased rapidly from mid-April immediately after unfolding of the leaves and reached the maximum in late-April, before the maximum expansion of the leaves. They retained the maximum values until early-May and then decreased toward late-May with a progress of leaf senescence. The calculated values of intercellular CO2 concentration and relative stomatal limitation of photosynthesis showed no significant change throughout the season. The carboxylation efficiency as assessed by the initial slope of Ci-photosynthesis curve and the net photosynthesis under a high Ci regime varied seasonally in parallel with the change of the light-saturated photosynthesis. The results indicate that the seasonal changes in light-saturated net photosynthesis are not due to a change of stomatal conductance, but to a change in the photosynthetic capacity of mesophyll. Nevertheless, leaf conductance changed concomitantly with photosynthetic capacity, indicating that the seasonal change in stomatal conductance is modulated by the mesophyll photosynthetic capacity such that the intercellular CO2 concentrations is maintained constant. The shape of light-photosynthesis curve was similar to that of sun-leaf type. The quantum yield also changed simultaneously with the photosynthetic capacity throughout the season.


Factors Associated With Bullying Victimization and Bullying Perpetration in Children and Adolescents With ADHD: 2016 to 2017 National Survey of Children's Health.
To identify characteristics associated with bullying involvement in pediatric ADHD. Data from the 2016 to 2017 National Survey of Children's Health for children aged 6 to 17 years with ADHD were evaluated to assess the association between parent-reported bullying victimization or perpetration and the following potential predictors: demographic characteristics, family factors, school factors, and child conditions/behaviors. Among children with ADHD, 46.9% were bullying victims and 16.2% were perpetrators. Factors associated with victimization included having family financial strain, developmental delay or intellectual disability, friendship difficulties, and school reports about problems. Factors linked to perpetration included being male, receiving government assistance, lack of school engagement, school reports about problems, and having difficulties with friendships, staying calm, and arguing. Children with ADHD frequently were bullying victims and sometimes bullying perpetrators. Factors related to family financial strain, developmental disabilities, emotional regulation, peer relationships, and school functioning may help to identify risk for bullying and opportunities for anti-bullying interventions.


Characterization of a functional recombinant rat liver aldehyde dehydrogenase: expression as a non-fusion protein in E. coli.
A cDNA encoding a rat liver inducible aldehyde dehydrogenase carried in a pUC8 plasmid is expressed in E. coli as a dimeric enzyme molecule functionally and physically identical to the authentic rat enzyme. The cDNA appears to be transcribed using the lac promoter, but is translated from an initiator codon 174 base pairs from the 5' end of the cDNA. The aldehyde dehydrogenase polypeptide is not produced as a fusion protein. This is the first example of the production by E. coli of a catalytically active, multimeric eukaryotic protein which is not a fusion protein.


Faba Bean: Transcriptome Analysis from Etiolated Seedling and Developing Seed Coat of Key Cultivars for Synthesis of Proanthocyanidins, Phytate, Raffinose Family Oligosaccharides, Vicine, and Convicine.
Faba bean (Vicia faba L.) has been little examined from a genetic or genomic perspective despite its status as an established food and forage crop with some key pharmaceutical factors such as vicine and convicine (VC), which provoke severe haemolysis in genetically susceptible humans. We developed next-generation sequencing libraries to maximize information to elucidate the VC pathway or relevant markers as well as other genes of interest for the species. One selected cultivar, A01155, lacks synthesis of the favism-provoking factors, VC, and is low in tannin, while two cultivars, SSNS-1 and CDC Fatima, are wild-type for these factors. Tissues (5- to 6-d-old root and etiolated shoot and developing seed coat) were selected to maximize the utility and breadth of the gene expression profile. Approximately 1.2 × 106 expressed transcripts were sequenced and assembled into contigs. The synthetic pathways for phosphatidylinositol or phytate, the raffinose family oligosaccharides, and proanthocyanidin were examined and found to contain nearly a full complement of the synthetic genes for these pathways. A severe deficiency in anthocyanidin reductase expression was found in the low-tannin cultivar A01155. Approximately 5300 variants, including 234 variants specific to one of the three cultivars, were identified. Differences in expression and variants potentially related to VC synthesis were analyzed using strategies exploiting differences in expression between cultivars and tissues. These sequences should be of high utility for marker-assisted selection for the key traits vicine, convicine, and proanthocyanidin, and should contribute to the scant genetic maps available for this species.


Rationale and design of the EMPYREAN study.
A sodium glucose cotransporter 2 (SGLT2) inhibitor was recently found to reduce heart failure hospitalization in the EMPA-REG OUTCOME trial. We have hypothesized that autonomic nerve activity may be modulated by SGLT2 inhibition. The current study aims to investigate the impact of empagliflozin on sympathetic and parasympathetic nerve activity in patients with type 2 diabetes mellitus. This ongoing study is a prospective, randomized, open-label, multicentre investigation of 134 patients with type 2 diabetes mellitus. The patients are randomly allocated to receive either empagliflozin or sitagliptin with the treatment goal of the Japan Diabetes Society guidelines. Ambulatory electrocardiographic monitoring is performed at the baseline and at 12 and 24 weeks of treatment. Analyses of heart rate variability are conducted using the MemCalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for square analysis. The primary endpoint is the change in the low-frequency (0.04-0.15 Hz)/high-frequency (0.15-0.4 Hz) ratio from baseline to 24 weeks. This investigation on the effect of EMPagliflozin on cardiac sYmpathetic and parasympathetic neRve activity in JapanEse pAtieNts with type 2 diabetes (EMPYREAN study) offers an important opportunity to understand the impact of SGLT2 inhibition on autonomic nerve activity in patients with type 2 diabetes.


Validation of the new venous severity scoring system in varicose vein surgery.
We performed this observational study to validate the three components of a new venous severity scoring (VSS) system, ie, venous clinical severity score (VCSS), venous segmental disease score (VSDS), and venous disability score (VDS), and to evaluate VCSS, VDS, and CEAP clinical class and score in quantifying outcome of varicose vein surgery. Patients and methods The study included 45 patients who underwent superficial venous surgery in 48 legs with primary varicose veins. Venous color duplex scanning, clinical examination, and a questionnaire were used preoperatively and at 6 weeks and 6 months postoperatively to assign VSS and CEAP clinical class and score. CEAP clinical score, VCSS, and VDS demonstrated a linear association with CEAP clinical class (P <.001, P <.001, P =.002, respectively). Good correlation among all severity scores was found, particularly between CEAP clinical score and VCSS (r = 0.94; P <.001). CEAP clinical score was also highly correlated with CEAP clinical class (r = 0.84; P <.001) and VDS (r = 0.70; P <.001). Similarly, VCSS correlated with CEAP clinical class (r = 0.83; P <.001) and also VDS (r = 0.72; P <.001). The anatomic severity marker VSDS demonstrated a weak correlation with clinical severity indicators VCSS (r = 0.29; P =.048) and VDS (r = 0.31; P =.03) but not with age, gender, or CEAP clinical class and score. Six months after surgery the median (interquartile range) percent change in VCSS (73%; range, 50%-100%) and CEAP clinical score (70%; range, 50%-100%) were both significantly greater (P <.001) than the corresponding change in CEAP clinical class (17%; range, 0%-50%). In legs with high VDS at baseline, median (interquartile range) percent change in VDS was 100% (range, 50%-100%), significantly greater (P <.001) than the corresponding change in CEAP clinical class (0%; range, 0%-17%). Venous severity scores are significantly higher in advanced venous disease, demonstrating correlation with anatomic extent. Both venous clinical severity scores, VCSS and CEAP clinical score, are equally sensitive and significantly better for measuring changes in response to superficial venous surgery than is the already in use CEAP clinical class. VDS demonstrated comparable and even better performance. Although the assignment of CEAP clinical class might be adequate for daily clinical purposes, venous severity scoring systems should be used in clinical studies to quantify venous outcome.


Cascades of pile-up and dead time.
Count loss through a cascade of pile-up and dead time is studied. Time interval density-distribution functions and throughput factors are presented for counters with a series arrangement of pile-up and extending or non-extending dead time. A counter is considered, where an artificial dead time is imposed on every counted event, in order to control the length and type of dead time. For such a system, it is relatively easy to determine an average count-loss correction factor via a live-time clock gated by the imposed dead-time signal ('live-time mode'), or otherwise to apply a correction factor based on the inversion of the throughput function ('real-time mode'). However, these techniques do not account for additional loss through pulse pile-up. In this work, counting errors associated with neglecting cascade effects are calculated for measurements in live-time and real-time mode.


Crystallization of Recombinant Fimbrial Proteins of Porphyromonas gingivalis.
Porphyromonas gingivalis fimbriae play a critical role in colonization. Elucidation of the fimbrial structure in atomic detail is important for understanding the colonization mechanism and to provide means to combat periodontitis. X-ray crystallography is a technique that is used to obtain detailed information of proteins along with bound ligands and ions. Crystallization of the protein of interest is the first step toward structure determination. Unfortunately it is not possible to predict the crystallization condition of a certain protein or even if the protein can be crystallized. Protein crystallization is, on the contrary, a matter of trial and error. However, the best strategy for success is to focus on the protein purification step to obtain a sample that is pure, stable, homogeneous and of high concentration. This chapter addresses general methods for crystallization of fimbrial proteins.


Quantification of choroidal blood-flow parameters using indocyanine green video-fluorescence angiography and statistical picture analysis.
A method for indocyanine green video-fluorescence angiography of the human choroid is described using a 30 degrees fundus camera (C. Zeiss) with external light supply, a low-light-level TV camera, and a video recorder. Bloodflow parameters for the choroid were obtained from the video recording using a picture-analysis system (IBAS, Kontron). These included: the mean time for arterial, capillary and venous filling and a parameter corresponding to the amount of perfused capillaries in the choroid. Angiograms were performed on normal, healthy subjects at normal and increased intraocular pressures and on patients with dry senile macular degeneration. Examples of the results are shown and discussed.


Biochemical characterization of an acidophilic β-mannanase from Gloeophyllum trabeum CBS900.73 with significant transglycosylation activity and feed digesting ability.
Acidophilic β-mannanases have been attracting much attention due to their excellent activity under extreme acidic conditions and significant industrial applications. In this study, a β-mannanase gene of glycoside hydrolase family 5, man5A, was cloned from Gloeophyllum trabeum CBS900.73, and successfully expressed in Pichia pastoris. Purified recombinant Man5A was acidophilic with a pH optimum of 2.5 and exhibited great pH adaptability and stability (>80% activity over pH 2.0-6.0 and pH 2.0-10.0, respectively). It had a high specific activity (1356 U/mg) against locust bean gum, was able to degrade galactomannan and glucomannan in a classical four-site binding mode, and catalyzed the transglycosylation of mannotetrose to mannooligosaccharides with higher degree of polymerization. Besides, it had great resistance to pepsin and trypsin and digested corn-soybean meal based diet in a comparable way with a commercial β-mannanase under the simulated gastrointestinal conditions of pigs. This acidophilic β-mannanase represents a valuable candidate for wide use in various industries, especially in the feed.


Nitrate-stimulated mineralization of ammonium in anaerobic soils.
Nitrate addition to soil stimulated mineralization of soil organic nitrogen more than twenty-fold over controls to which no nitrate was added. Addition of 15NO 3- showed that very little of the increased ammonium came from nitrate reduction.


Effects of insulin on plasma fibrinogen levels in rats submitted to tissue injury or ACTH administration.
Insulin is necessary to produce an increase of plasma fibrinogen in rats submitted to tissue injury or ACTH administration. This increase is more significant when endogenous or exogenous excess of insulin is present, while in uninjured rats the absence or excess insulin does not modify plasma fibrinogen.


Nutritional status and lung function in children with pancreatic-sufficient cystic fibrosis.
There is a strong association between nutrition and long-term FEV1 in cystic fibrosis (CF), but studies have been driven by data from subjects with pancreatic insufficiency (PI-CF). We thus evaluated the association between body mass index (BMI) and FEV1 percent-predicted (FEV1pp) in children with pancreatic sufficiency (PS-CF) and contrasted it with the association in PI-CF. We utilized data from the CF Foundation Patient Registry. The cohort included children born 1995-2010, diagnosed <2 years of age, and who had annualized data on BMI percentile and FEV1pp at ages 6-16 years. Pancreatic status was defined based on pancreatic enzyme replacement therapy. The association between BMI and FEV1 was evaluated using linear and mixed-effects longitudinal regression. There were 424 children with PS-CF and 7,849 with PI-CF. The association between BMI and FEV1 differed significantly by pancreatic status: each 10-pct higher BMI was associated with 2% [95%CI = 1.9-2.1] higher FEV1pp in PI-CF, compared to just 0.9% [0.5-1.3] in PS-CF (PINTERACTION < 0.001). Within the at-risk nutritional category (BMI <25pct), each 10-pct higher BMI was associated with 5% higher FEV1pp in PI-CF, but no significant increase in PS-CF. Moreover, in PS-CF, overweight/obesity (BMI ≥85pct) was associated with decreasing FEV1pp. In addition, FEV1pp decline through age 20 years in youth with PS-CF was modest (-0.6% per year) and independent of BMI (BMI*age PINTERACTION = 0.37). In children with PS-CF, BMI remains an important determinant of lung function. However, it may be less critical to attain a BMI >50th percentile; and BMI ≥85th percentile may be detrimental.


Electrophysiologic effects of propranolol in intraventricular conduction disturbance.
Sixteen patients underwent electrophysiologic studies before and after intravenous infusion of propranolol, 0.1 mg/kg. All of them had intraventricular conduction disturbances. A significant (p less than 0.01) increase occurred after propranolol in the mean spontaneous cycle length (mean change 122 ms) and the AH interval (mean 28 ms). The HV interval did not change significantly. The effective refractory period of the His-Purkinje system increased in 4 of 5 patients (mean net change 44 ms, p greater than 0.10). In 7 patients with phase 3 infranodal block, the longest cycle length for producing block increased after propranolol in 5 and remained unchanged in 2 (mean increase 40 ms, p less than 0.02). Two patients showed phase 4 atrioventricular block. Propranolol increased the critical cycle length by an average of 120 ms. Propranolol-induced bradycardia restored stable atrioventricular conduction in 2 patients with intermittent 2:1 block but facilitated the occurrence of high grade infranodal block in 1 patient. Thus, propranolol can impair His-Purkinje conduction in patients with preexisting infranodal abnormalities.


Patient navigation and financial incentives to promote smoking cessation in an underserved primary care population: A randomized controlled trial protocol.
Despite the high risk of tobacco-related morbidity and mortality among low-income persons, few studies have connected low-income smokers to evidence-based treatments. We will examine a smoking cessation intervention integrated into primary care. To begin, we completed qualitative formative research to refine an intervention utilizing the services of a patient navigator trained to promote smoking cessation. Next, we will conduct a randomized controlled trial combining two interventions: patient navigation and financial incentives. The goal of the intervention is to promote smoking cessation among patients who receive primary care in a large urban safety-net hospital. Our intervention will encourage patients to utilize existing smoking cessation resources (e.g., quit lines, smoking cessation groups, discussing smoking cessation with their primary care providers). To test our intervention, we will conduct a randomized controlled trial, randomizing 352 patients to the intervention condition (patient navigation and financial incentives) or an enhanced traditional care control condition. We will perform follow-up at 6, 12, and 18 months following the start of the intervention. Evaluation of the intervention will target several implementation variables: reach (participation rate and representativeness), effectiveness (smoking cessation at 12 months [primary outcome]), unintended consequences (e.g., purchase of illicit substances with incentive money), adoption (use of intervention across primary care suites), implementation (delivery of intervention), and maintenance (smoking cessation after conclusion of intervention). Improving the implementation of smoking cessation interventions in primary care settings serving large underserved populations could have substantial public health impact, reducing cancer-related morbidity/mortality and associated health disparities.


Life span differences in digoxin uptake and excretion.
Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occurring at 45 min. The rate in the mature 12-month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescence. On the other hand, digoxin uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and an increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age.