bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Receiving Curative-Intent Therapy: A Population-Based Study
Authors: Vijenthira Abi , Mozessohn Lee , Nagamuthu Chenthila , Liu Ning , Blunt Danielle , Alibhai Shabbir , Prica Anca , Cheung Matthew C.
Published: June 2022

Background: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. Methods: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. Results: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70–80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6–2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3–1.7; P<.0001). Conclusions: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.
Welfare institutes in sparsely populated areas
Authors:   Nordregio, Jokinen Johanna Carolina
Published: June 2022

The overall purpose of this Working paper is to clarify and determine the definition of Welfare Institutes in Sparsely Populated Areas (WIiSPA) and identify WIiSPA actors in sparsely populated areas (SPAs) in the Nordic Region and beyond. This working paper aims to shed light on the following project objectives: 1) what components, stakeholders, and visions could constitute a WIiSPA; what elements are necessary for creating a WIiSPA? (Definition of WIiSPA), 2) identifying existing and potential WIiSPA clusters in the Nordic countries and beyond; their prerequisites, strengths, and eventual lack of components for creating a WIiSPA (Mapping of WIiSPA), 3) how could a network of identified WIiSPA clusters best be developed? (WIiSPA network).
The growth and development dynamics of small fraction bulbs of Hyacinthus orientalis
Authors: Okach Mariya Aleksandrovna , Egoshina Evgeniya Alekseevna
Published: June 2022

Hyacinthus orientalis is a valuable decorative bulbous plant. One of the main limitations of its widespread use in landscaping is the low coefficient of vegetative reproduction and the high cost of planting material. Hyacinths are usually grown with the annual digging of bulbs in summer and planting them in autumn. The article presents the results of experience in growing bulbs of small hyacinth fraction with various agricultural techniques. The experiment was carried out in the period 2016-2018 in the open ground in the Botanical Garden-Institute of VSUT (the Mari El Republic). The dynamics of growth and development of 6 hyacinth varieties bulbs was studied during two-year cultivation with annual digging and without digging. It was found that the weight of bulbs of all studied hyacinths varieties increased intensively during two-year cultivation without annual digging. In the experiment variant with annual digging of bulbs weighing 7.3-8.5 g (first size), the formation of baby bulbs was noted only in the varieties ‘Eros’ and ‘Lady Derby’, without annual digging – in the varieties ‘Carnegie’, ‘Lady Derby', ‘Madame Sophie'. The weight of the bulbs of the second size (from 3.8 to 4.5 g) for 1 year of cultivation increased by an average of 1.6 times. Bulbs weighing up to 2 g (third size) for 2 years of cultivation are able to increase their weight by 3 times. Bulbs of terry varieties ‘Rosette’ and ‘Madame Sophie’ weighing up to 2 g grew better during two-year cultivation without annual digging. The data obtained can be used in the cultivation of hyacinths in decorative nurseries.
Designing Customised Bus Routes for Urban Commuters with the Existence of Multimodal Network – A Bi-Level Programming Approach
Authors: CHENG Cheng , WANG Tianzuo , WANG Wei , DING Junqiang
Published: June 2022

Customised bus (CB) is a cutting-edge mean of transportation and has been implemented worldwide. To support the spread of the CB system, methodologies for CB network design have been conducted. However, a majority of them cannot be adopted directly for multi-modal transportation environment. In this paper, we proposed a bi-level programming model to fill this gap. The upper-level problem is to maximise the usage of the CB system with the limitation of operation constraints. Meanwhile, the lower-level problem is to capture the traveller’s choice by minimising traveller’s generalised cost during travel. A solving procedure via genetic algorithm is further proposed and validated via the metro data at Shanghai. The results indicated that the proposed CB route network would attract nearly 5,000 users during morning peak period under the given metro transaction data. We further studied the features of the selected routes and found that the CB network mainly served residence to commercial or industrial parks travellers and would provide travel service with fewer stops, and higher travel efficiency by travelling through expressway.
Loss of Elp1 disrupts trigeminal ganglion neurodevelopment in a model of familial dysautonomia
Authors: Leonard Carrie E , Quiros Jolie , Lefcort Frances , Taneyhill Lisa A
Published: June 2022

Familial dysautonomia (FD) is a sensory and autonomic neuropathy caused by mutations in elongator complex protein 1 (ELP1). FD patients have small trigeminal nerves and impaired facial pain and temperature perception. These signals are relayed by nociceptive neurons in the trigeminal ganglion, a structure that is composed of both neural crest- and placode-derived cells. Mice lacking Elp1 in neural crest derivatives (‘Elp1 CKO’) are born with small trigeminal ganglia, suggesting Elp1 is important for trigeminal ganglion development, yet the function of Elp1 in this context is unknown. We demonstrate that Elp1, expressed in both neural crest- and placode-derived neurons, is not required for initial trigeminal ganglion formation. However, Elp1 CKO trigeminal neurons exhibit abnormal axon outgrowth and deficient target innervation. Developing nociceptors expressing the receptor TrkA undergo early apoptosis in Elp1 CKO, while TrkB- and TrkC-expressing neurons are spared, indicating Elp1 supports the target innervation and survival of trigeminal nociceptors. Furthermore, we demonstrate that specific TrkA deficits in the Elp1 CKO trigeminal ganglion reflect the neural crest lineage of most TrkA neurons versus the placodal lineage of most TrkB and TrkC neurons. Altogether, these findings explain defects in cranial gangliogenesis that may lead to loss of facial pain and temperature sensation in FD.
Convergent mosaic brain evolution is associated with the evolution of novel electrosensory systems in teleost fishes
Authors: Schumacher Erika L , Carlson Bruce A
Published: June 2022

Brain region size generally scales allometrically with brain size, but mosaic shifts in brain region size independent of brain size have been found in several lineages and may be related to the evolution of behavioral novelty. African weakly electric fishes (Mormyroidea) evolved a mosaically enlarged cerebellum and hindbrain, yet the relationship to their behaviorally novel electrosensory system remains unclear. We addressed this by studying South American weakly electric fishes (Gymnotiformes) and weakly electric catfishes (Synodontis spp.), which evolved varying aspects of electrosensory systems, independent of mormyroids. If the mormyroid mosaic increases are related to evolving an electrosensory system, we should find similar mosaic shifts in gymnotiforms and Synodontis. Using micro-computed tomography scans, we quantified brain region scaling for multiple electrogenic, electroreceptive, and non-electrosensing species. We found mosaic increases in cerebellum in all three electrogenic lineages relative to non-electric lineages and mosaic increases in torus semicircularis and hindbrain associated with the evolution of electrogenesis and electroreceptor type. These results show that evolving novel electrosensory systems is repeatedly and independently associated with changes in the sizes of individual major brain regions independent of brain size, suggesting that selection can impact structural brain composition to favor specific regions involved in novel behaviors.
An adaptive dimension differential evolution algorithm based on ranking scheme for global optimization
Authors: Sung Tien-Wen , Zhao Baohua , Zhang Xin
Published: June 2022

In recent years, evolutionary algorithms based on swarm intelligence have drawn much attention from researchers. This kind of artificial intelligent algorithms can be utilized for various applications, including the ones of big data information processing in nowadays modern world with heterogeneous sensor and IoT systems. Differential evolution (DE) algorithm is one of the important algorithms in the field of optimization because of its powerful and simple characteristics. The DE has excellent development performance and can approach global optimal solution quickly. At the same time, it is also easy to get into local optimal, so it could converge prematurely. In the view of these shortcomings, this article focuses on the improvement of the algorithm of DE and proposes an adaptive dimension differential evolution (ADDE) algorithm that can adapt to dimension updating properly and balance the search and the development better. In addition, this article uses the elitism to improve the location update strategy to improve the efficiency and accuracy of the search. In order to verify the performance of the new ADDE, this study carried out experiments with other famous algorithms on the CEC2014 test suite. The comparison results show that the ADDE is more competitive.
Patient deaths during the period of prolonged stay in cases of delayed discharge for nonclinical reasons at a university hospital: a cross sectional study
Authors: Pellico-López Amada , Herrero-Montes Manuel , Cantarero Prieto David , Fernández-Feito Ana , Cayon-De las Cuevas Joaquin , Parás-Bravo Paula , Paz-Zulueta María
Published: June 2022

Background

Delayed discharge for non-clinical reasons also affects patients in need of palliative care. Moreover, the number of people dying in hospitals has been increasing in recent years. Our aim was to describe characteristics of patients who died during prolonged stay, in comparison with the rest of patients with delayed discharge, in terms of length of hospital stay, patient characteristics and the context of care.

Methods

A descriptive cross-sectional study at a high complexity public hospital in Northern Spain (2007–2015) was conducted. To compare the differential characteristics of the groups of patients died during delayed discharge with the rest, Student’s T test and Pearson’s chi-square test (χ2) were used.

Results

A total of 198 patients died (6.57% of the total), with a mean total stay of 27.45 days and a prolonged stay of 10.69 days. Mean age 77.27 years. These were highly complex cases, 77.79% resided in the urban area, were admitted urgently (95.45%), to internal medicine or oncology wards, and the most common diagnosis was pneumonia. In people with terminal illness, clinicians can better identify when therapeutic possibilities are exhausted and acute hospitalization is not an adequate resource for their needs. Living in an urban area with the availability of palliative care hospital beds is related to the decision to die in hospital.
Rabbit hindlimb kinematics and ground contact kinetics during the stance phase of gait
Authors: Hall Patrick , Stubbs Caleb , Anderson David E. , Greenacre Cheryl , Crouch Dustin L.
Published: June 2022

Though the rabbit is a common animal model in musculoskeletal research, there are very limited data reported on healthy rabbit biomechanics. Our objective was to quantify the normative hindlimb biomechanics (kinematics and kinetics) of six New Zealand White rabbits (three male, three female) during the stance phase of gait. We measured biomechanics by synchronously recording sagittal plane motion and ground contact pressure using a video camera and pressure-sensitive mat, respectively. Both foot angle (i.e., angle between foot and ground) and ankle angle curves were unimodal. The maximum ankle dorsiflexion angle was 66.4 ± 13.4° (mean ± standard deviation across rabbits) and occurred at 38% stance, while the maximum ankle plantarflexion angle was 137.2 ± 4.8° at toe-off (neutral ankle angle = 90 degrees). Minimum and maximum foot angles were 17.2 ± 6.3° at 10% stance and 123.3 ± 3.6° at toe-off, respectively. The maximum peak plantar pressure and plantar contact area were 21.7 ± 4.6% BW/cm2 and 7.4 ± 0.8 cm2 respectively. The maximum net vertical ground reaction force and vertical impulse, averaged across rabbits, were 44.0 ± 10.6% BW and 10.9 ± 3.7% BW∙s, respectively. Stance duration (0.40 ± 0.15 s) was statistically significantly correlated (p < 0.05) with vertical impulse (Spearman’s ρ = 0.76), minimum foot angle (ρ = −0.58), plantar contact length (ρ = 0.52), maximum foot angle (ρ = 0.41), and minimum foot angle (ρ = −0.30). Our study confirmed that rabbits exhibit a digitigrade gait pattern during locomotion. Future studies can reference our data to quantify the extent to which clinical interventions affect rabbit biomechanics.
Ectopic Thymic Cyst Presenting as Lateral Neck Mass in a Young Boy: A Case Report
Authors: Walke Vaishali A , Datar Sonali , Meshram Sonal , Jacob Roshni , Kowe Balwant
Published: June 2022

The thymus is derived from ectoderm and endoderm of third pharyngeal pouches. It descends down along the cervical region to anterior mediastinum and involutes by increasing age. The ectopic thymic tissue in neck is a rarity and few mentioned in literature are described as sporadic case reports. Ectopic thymic cyst accounts for less than 1% of all cystic neck masses in children and even more rare in adults. Worldwide literature states that there are about 150 cases of congenital ectopic thymic tissue. It can occur anywhere along the path of its descent, from mandible to mediastinum. This entity being unusual is infrequently considered in the differential diagnosis of cervical cystic masses. Histopathology forms the mainstay in confirmation of diagnosis. Here, we report a case of 12-year-old boy who presented with right-sided neck mass. The excised specimen revealed presence of lymphoid tissue with Hassalls corpuscles in the wall of cyst. This hallmarking feature is the pointer to arrive at a correct diagnosis of thymic cyst and to exclude its closest differential at this anatomical location including branchial cyst, cystic hygroma, lymphadenopathy and epidermoid cyst. The literature is reviewed and differentials of ectopic thymic cyst in cervical region are being discussed.
A Prospective Study of Ultrasound Guided Fine Needle Aspiration Cytology of Focal Lesions in Liver
Authors: Shruthi HY , Chavan Sateesh S
Published: June 2022

Introduction: Many hepatic lesions which are detected clinically or by imaging technique are easily accessible to Fine Needle Aspiration Cytology (FNAC). Swift diagnosis by FNAC helps to save precious time and allow clinicians to duly plan treatment. Ultrasound guided FNAC of the liver is a safe, cheap, relatively non invasive procedure with minimum complication and can be routinely done for evaluation of liver diseases. Aim: To evaluate hepatic lesions by ultrasound guided FNAC and classifying into inflammatory or non inflammatory, benign or malignant, primary or secondary tumour and also to find novel cytological features. Materials and Methods: The present two year descriptive cross- sectional prospective study was carried out in the Department of Pathology, Karnataka Institute of Medical Sciences, Hubli, India. A total of 90 patients who satisfied the inclusion criteria during the two years study (August 2012 to July 2014) were assessed for clinical history and subjected to FNAC under ultrasound guidance. Descriptive statistical analysis was performed to calculate the percentage and frequency for the categorical variable included in the study. Results: Out of 90 cases, majority 73 (81.1%) cases were neoplastic and 11 (12.2%) cases were non-neoplastic and the remaining 6 (6.6%) cases were inconclusive. Out of 73 cases, four cases were benign tumours and 69 cases were malignant tumours. Out of 69 cases, 33 cases were Hepatocellular Carcinoma (HCC), 32 cases were metastatic deposits, three cases were cholangiocarcinoma, one case was suggestive of malignancy. Among 33 cases of metastatic deposits, adenocarcinoma was most common (32 cases) and Squamous Cell Carcinoma (SCC) the least (one case). The most consistent cytological findings in HCC were macronucleoli (32 cases) and trabecular pattern of arrangement (32 cases). The most consistent finding in metastatic adenocarcinoma was coarse clumping of nuclear chromatin (32 cases). Conclusion: The study concludes that the ultrasound-guided FNAC of the liver is a safe, simple, cost-effective, and accurate method that permits the categorisation of non-neoplastic (inflammatory) and neoplastic lesions (non inflammatory), primary and secondary malignancy in a simple and rational manner which is helpful for the management of hepatic lesions.
The Effects of Exercise on Weight among School Children in Amai Ukwuani, Delta State Nigeria
Authors: Eboh O. J. , Onuoha T. , Adeola M. O. , James G. C.
Published: June 2022

The study was carried out to determine the effect of exercise on the body among primary school pupils in Amai. Fifty school pupils were selected from Gods will school for the study. Twenty-five of the pupils engaged in exercise (jogging of 400 meters) for 10 consecutive days. While the remaining twenty-five pupils did not exercise. The weights of the pupils were taken for the 10 days. The result showed that at the end of day 5, majority of the pupils who exercised reduced weight by at least 1kg and at the end of day 10, no pupils added an extra kg of weight. The mean weight lost by the pupils who exercised was 3.04kg. the result also showed that all the pupils who did not exercise kept on adding weight from Day1 till the Day 10. The mean weight gained by pupils who did not exercise was 3.44kg. However, the body mass index of the pupils indicated that none was overweight or obese. This study has shown that regular physical exercise is an important way of controlling weight. Physical exercise should be a part of the curriculum in all schools as childhood obesity is becoming rampant and an issue of global concern due to its health hazards.
Screening of Zinc Solubilizing Plant Growth Promoting Rhizobacteria (PGPR) as Potential Tool for Biofortification in Rice
Authors: Rion Md Shafiul Islam , Rahman Atiqur , Khatun Mst. Julekha , Zakir H. M. , Rashid M. Harun , Quadir Quazi Forhad
Published: June 2022

Aims: Plant growth-promoting rhizobacteria enhance growth by making plant nutrients available to plants under a variety of growing conditions. The study was designed to screen zinc (Zn) solubilizing rhizobacteria and test their colonization ability in the rice rhizosphere.

Place and Duration of Study: The experiments were conducted in the Department of Agricultural Chemistry, Bangladesh Agricultural University, Mymensingh-2202, from January 2019 to July 2019.

Methodology: Initially, thirty-two previously isolated rhizobacteria were used for screening Zn solubilizing ability under a solid medium. Selected rhizobacteria from previous screening were used to quantify Zn solubilization in broth culture and evaluate their root colonization in rice using water agar media in a growth chamber. Early seedling growth was monitored for two weeks, and root-shoot lengths were recorded. Eleven of the tested rhizobacteria responded positively to ZnO-containing media.

Results: The Zn solubilizing index (ZSI) of the positive isolates ranged between 1.08-2.25 after 5 days of incubation. Isolate MQ1 solubilized the highest Zn both in solid medium (ZSI=2.25) and culture broth (solubilized 220.20 ppm Zn). The colonization of bacteria in the root zone was also investigated via bio-primed rice seeds of Binadhan-20. Eight of 11 isolates (MQ1, MQ2, MQ3, MQ4, OSbr5, OSbr6, EC1, and MQL9) showed substantial colonization in the rhizosphere after two weeks. The germination percentage of bio-primed seeds was not increased over the control, however, in most cases, bio-priming boasted early seedling growth. The OSbr5, OSbr6, and MQ6 isolates were superior performers in case of root and shoot growth.

Conclusion: The study identified some Zn solubilizing isolates, revealed their root colonizing ability, and observed early plant growth promotion. These isolates could be used as a potential tool for the Zn biofortification approach in rice.
CD63 associates with CD11/CD18 in large detergent‐resistant complexes after translocation to the cell surface in human neutrophils1
Authors: Skubitz Keith M. , Campbell Kenneth D. , Skubitz Amy P.N.
Published: July 2002

CD63 antibody binding to the neutrophil surface triggers a transient activation signal that regulates the adhesive activity and surface expression of CD11/CD18. Gel permeation chromatography demonstrated that all of the cell surface CD11/CD18 associated with CD63 eluted in the void volume, indicating that they were present in large detergent‐resistant complexes. In contrast, the majority of the total cellular CD63, CD11 and CD18, which are largely intracellular, was not present in complexes. The data suggest that intracellular CD11, CD18 and CD63 are not in detergent‐resistant complexes, but enter such complexes following translocation to the cell surface.
Distinct versus redundant properties among members of the INK4 family of cyclin‐dependent kinase inhibitors
Authors: Thullberg Minna , Bartkova Jirina , Khan Selina , Hansen Klaus , Rönnstrand Lars , Lukas Jiri , Strauss Michael , Bartek Jiri
Published: July 2002

p16INK4a, p15INK4b, p18INK4c and p19INK4d comprise a family of cyclin‐dependent kinase inhibitors and tumor suppressors. We report that the INK4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity. In contrast, only p18 and particularly p19 are phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non‐overlapping properties, suggesting distinct regulatory modes, and diverse roles for the individual INK4 family members in cell cycle control, cellular differentiation, and multistep oncogenesis.
Inactivation of p53 and life span extension of human diploid fibroblasts by mot‐2
Authors: Kaul Sunil C. , Reddel Roger R. , Sugihara Takashi , Mitsui Youji , Wadhwa Renu
Published: July 2002

Normal human lung fibroblasts were transfected with expression plasmids encoding mot‐2, an hsp70 family member that is associated with the immortal phenotype. After the empty vector‐transfected controls had become senescent and positive for senescence‐associated β‐galactosidase (SA‐β‐gal), the mot‐2‐expressing cells continued to proliferate for an additional 12–18 population doublings and showed a young cell morphology and much lower SA‐β‐gal activity. The tumor suppressor p53 was found to be transcriptionally inactivated in life span‐extended cells. We have thus shown for the first time that overexpression of mot‐2 in normal human cells is able to permit their temporary escape from senescence.
The importance of being knotted: effects of the C‐terminal knot structure on enzymatic and mechanical properties of bovine carbonic anhydrase II1
Authors: Alam Mohammad Taufiq , Yamada Takafumi , Carlsson Uno , Ikai Atsushi
Published: July 2002

In order to better understand the contribution of the knotted folding pattern to the enzymatic and mechanical properties of carbonic anhydrases, we replaced Gln‐253 of bovine carbonic anhydrase II with Cys, which allowed us to measure the mechanical strength of the protein against tensile deformation by avoiding knot tightening. The expressed protein, to our surprise, turned out to contain two conformational isomers, one capable of binding an enzymatic inhibitor and the other not, which led to their separation through affinity chromatography. In near‐ and far‐UV circular dichroism and fluorescence spectra, the separated conformers were very similar to each other and to the wild‐type enzyme, indicating that they both had native‐like conformations. We describe new evidence which supports the notion that the difference between the two conformers is likely to be related to the completeness of the C‐terminal knot formation.
Metabolic Inhibitors, Elicitors, and Precursors as Tools for Probing Yield Limitation in Taxane Production by Taxuschinensis Cell Cultures
Authors: Srinivasan V. , Ciddi V. , Bringi V. , Shuler M. L.
Published: July 2002

Inhibition of biosynthetic enzymes and translation and translocation processes, elicitation, and precursor feeding were used to probe biosynthetic pathway compartmentation, substrate−product relationships, and yield limitation of the diterpenoid taxanes in cell cultures of Taxus chinensis (PRO1–95). The results suggest the following: (i) the source of isopentenyl pyrophosphate in taxane production is likely plastidic rather than cytoplasmic; (ii) baccatin III may not be a direct precusor of Taxol (Taxol is a registered trademark of Bristol‐Myers Squibb for paclitaxel); (iii) baccatin III appears to have cytoplasmic and plastidic biosynthetic components, while Taxol production is essentially plastidic; and (iv) arachidonic acid specifically stimulates Taxol production but does not have a significant effect on baccatin III yield. Semiempirical mathematical models were used to describe these results and predict potential yield‐limiting steps. Model simulations suggest that, under current operating conditions, Taxol production in Taxus chinensis (PRO1–95) cultures is limited by the ability of the cells to convert phenylalanine to phenylisoserine rather than by the branch‐point acyl transferase. This result is supported by the lack of improvement of Taxol yield by feeding phenylalanine or benzoylglycine. The methods described in this article, while specifically expanding our knowledge of taxane production in PRO1–95 cultures, could be generally useful in investigating complex aspects of secondary metabolic pathways in plant cell cultures, especially when details of the pathway and compartmentation are sparse.
Conformational study of an Aib‐rich peptide in DMSO by NMR
Authors: Bellanda M. , Peggion E. , Mammi S. , Bürgi R. , Van Gunsteren W.
Published: July 2002

Abstract:The strong propensity of 2‐amino‐2‐methyl propanoic acid (Aib)‐rich peptides to form stable helical structures is well documented. NMR analysis of the short peptide Z‐(Aib)5‐L‐Leu‐(Aib)2‐OMe indicates the presence of a well‐characterized 310‐helix even in dimethylsulfoxide (DMSO), a solvent known to disrupt helical structures. The structure remains stable at least up to 348 K. Stereospecific assignment of the diastereotopic methyls of Aib was achieved, with the assumption of a specific helical screw sense. The methyl more eclipsed with respect to the CO vector resonates at a higher field in the carbon dimension. Molecular dynamics simulations successfully predict the3JCHNHcoupling constant of Leu6and most of the H‐bonding pattern. Discrepancies were found for Aib3and Aib7amide protons which can be explained by a higher sensitivity of the simulations to the helix fraying at the end of the peptide and by the presence of extended conformations for Leu6during most of the simulations.
Mass spectrometric evaluation of synthetic peptides as primary structure models for peptide and protein deamidation
Authors: Robinson N.E. , Robinson A.B. , Merrifield R.B.
Published: July 2002

Abstract: Solid‐phase peptide synthesis and deamidation measurements using a novel mass spectrometric technique were carried out for 94 model asparaginyl peptides from 3 to 13 residues in length. Deamidation rates of these peptides in pH 7.4, 37.0°C, 0.15 m Tris−HCl buffer were measured and evaluated. It was found that they validate the use of pentapeptide models as surrogates for the primary sequence dependence of peptide and protein deamidation rates and the discovery by difference of secondary, tertiary and quaternary structure effects. Deamidation of the pentapeptide models, compared with that of longer peptides of more intricate structure, is discussed, and the application of this technique to deamidation measurement of intact proteins is demonstrated.
Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV‐infected patients
Authors: Campo J. , Del Romero J. , Castilla J. , García S. , Rodríguez C. , Bascones A.
Published: July 2002

Background:  High viral load is currently considered to be one of the main indicators of the progression of HIV‐induced immunodepression, but few studies have analysed its relationship to the presence of oral candidiasis (OC). The aim of this cross‐sectional study is to analyse the relationship between viral load, total CD4 lymphocyte count, and percentage of CD4 lymphocytes to the occurrence of OC.

Methods:  The present cross‐sectional study included 156 HIV‐infected patients seen at a clinic for sexually transmitted diseases and HIV. We assesed the presence or absence of OC, and microbiological samples were obtained from the palatine mucosa and dorsal tongue for a smear stained with KOH (potassium hydroxide) and culture on Sabouraud's dextrose agar in all patients. Viral load was determined by quantification of viral RNA in peripheral blood with a minimum detectable level of 500 RNA copies/ml. CD4+ counts/CD4+ percentage were categorized as <200/<14%, 200–499/14–28%, and >500/>29%, and HIV viral loads were categorized as <500, 500–10,000, >10,000 copies/ml.

Results:  Thirty‐eight percent (37.8%) of the patients had OC. Patients with CD4+ lymphocyte counts below 200×106/l and CD4+ percentages below 14% showed a significantly higher frequency of OC (57.9% and 48.0%, respectively). Patients with a viral load over 10,000 copies/ml also had OC more frequently (44.8%). In the multiple logistic regression analysis, OC showed a statistically significant association with high viral load [>10,000 vs <500, odds ratio (OR)=11.4], low percentage of CD4+ lymphocytes (<14% vs >28%, OR=5), and injection drug use (IDU vs heterosexual transmission, OR=10.2). In HIV‐infected patients, high viral load was associated with more frequent OC, regardless of CD4+ lymphocyte level.

Conclusions:  These findings suggest that oral candidiasis could be a useful clinical marker of patients with high viral load. In view of these results, emphasis should be placed on the importance of systematic examination of the oral cavity in all medical follow‐up examinations of HIV‐infected patients.
Crystal structure of a staphylokinase variant
Authors: Chen Yuhang , Song Gang , Jiang Fan , Feng Liang , Zhang Xiaoxuan , Ding Yi , Bartlam Mark , Yang Ao , Ma Xiang , Ye Sheng , Liu Yiwei , Tang Hong , Song Houyan , Rao Zihe
Published: July 2002

Staphylokinase (SAK) is a 15.5‐kDa protein from Staphylococcus aureus that activates plasminogen by forming a 1 : 1 complex with plasmin. Recombinant SAK has been shown in clinical trials to induce fibrin‐specific clot lysis in patients with acute myocardial infarction. However, SAK elicits high titers of neutralizing antibodies. Biochemical and protein engineering studies have demonstrated the feasibility of generating SAK variants with reduced antigenicity yet intact thrombolytic potency. Here, we present X‐ray crystallographic evidence that the SAK(S41G) mutant may assume a dimeric structure. This dimer model, at 2.3‐Å resolution, could explain a major antigenic epitope (residues A72–F76 and residues K135‐K136) located in the vicinity of the dimer interface as identified by phage‐display. These results suggest that SAK antigenicity may be reduced by eliminating dimer formation. We propose several potential mutation sites at the dimer interface that may further reduce the antigenicity of SAK.
Incidence and associations of acute renal failure complicating high‐dose intravenous immunoglobulin therapy
Authors: Sati H. I. A. , Ahya R. , Watson H. G.
Published: July 2002

In a formal study, we have identified increasing age, pretreatment renal impairment and diabetes mellitus as risk factors for the development of intravenous immunoglobulin‐induced renal failure. Identification of these characteristics in potential recipients should alert clinicians to the associated increased risk of this serious complication.
Development of a sensitive diagnostic assay for fish nervous necrosis virus based on RT‐PCR plus nested PCR
Authors: Dalla Valle L , Zanella L , Patarnello P , Paolucci L , Belvedere P , Colombo L
Published: July 2002

A polymerase chain reaction (PCR)‐based assay to detect nervous necrosis virus (NNV) in fish was developed by using two sets of primers designed on a highly conserved region of the coat protein gene encoded by RNA2 of NNV. The first pair of primers amplified a fragment of 605 bp by one‐step reverse‐transcription (RT)‐PCR, while the second pair amplified an internal segment of 255 bp by nested PCR. Addition of nested PCR increased the assay sensitivity 100‐fold when carried out in a separate tube (two‐step assay) and 10‐fold when performed in the same tube (one‐step assay). The sensitivity of the two‐step assay was 104 times higher than that of virus cultivation. Nested PCR served also to confirm the specificity of the first amplification, as verified also by Southern hybridization analysis and direct sequencing. In species known to be susceptible to infection, such as European sea bass, Dicentrarchus labrax, and gilthead seabream, Sparus aurata, NNV was often detectable in brain tissue by RT‐PCR alone but only by the two‐step assay in blood, sperm, ovarian tissue or larvae. The same was true for sperm and ovarian tissue of shi drum, Umbrina cirrosa. NNV was also detected in the brains of Japanese red seabream, Pagrus major and brown meagre, Sciaena umbra, suggesting that these species can also be infected. No NNV was detected in samples of Artemia salina nauplii and rotifers obtained from a fish farm with an NNV outbreak. The inclusion of nested PCR in the assay appears to be necessary to screen out NNV‐positive broodfish by blood sampling and testing of their larval progeny.
Baseline ophthalmic findings in the Vitamin E, Cataract and Age‐Related Maculopathy (VECAT) study
Authors: PhD L D Robman , GradDip G Tikellis , BapplSc S K M Garrett , Fraco C A Harper , Fracp J J McNeil , Fraco H R Taylor , PhD C A McCarty
Published: July 2002

Purpose: To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E, Cataract and Age‐Related Maculopathy (VECAT) study participants.

Methods: A sample of volunteers from an urban area of Melbourne, Australia, were recruited to participate in a randomized, controlled trial investigating the effect of vitamin E on the development of cataract and age‐related maculopathy. Standardized eye examinations involved clinical assessment, which included Wilmer grading of the lens, digital photography of the lens with Nidek EAS‐1000 lens camera and stereo photography of the macular area with the Nidek 3‐DX fundus camera. All cases of ophthalmic findings were determined on the basis of pathology in the worse eye.

Results: Most eyes were free from abnormalities. The most frequent findings were cataract and age‐related macular changes. Nuclear cataract (nuclear opacity grade ≥2) was present in 4.5%, cortical cataract (cortical opacity grade ≥2) in 14.3% and posterior subcapsular cataract in 3.0% of participants; in addition, coronary cataract was observed in 13.6%. Soft drusen larger than 125 μm were found in 11.4%, retinal pigment epithelium changes in 9.5%, epiretinal membrane in 6.6% and age‐related macular degeneration in 0.5% of participants.

Summary: Due to the selection criteria, the majority of participants had clear or minor lens changes and/or minor retinal age‐related changes. Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation.
A child and adolescent psychiatric outreach service for rural New South Wales: A telemedicine pilot study
Authors: Dossetor DR , Nunn KP , Fairley M , Eggleton D
Published: July 2002

Objective: To examine the feasibility of a tertiary outreach service in child and adolescent psychiatry to two rural health centres in New South Wales, Australia.

Methods: Following a site visit to Dubbo Hospital and Bourke Hospital, telemedical videoconferencing was provided for 2 h/week for 32 weeks. Details of referrers, patients’ diagnosis and outcome, and satisfaction with the service were obtained.

Results: Cases were triaged by a nominated rural adolescent mental health worker. The service provided detailed assessment and management of severe, complex, mental and neuropsychiatric disorders. Fifty‐four young people were assessed and 72 joint consultative videoconferencing interviews were undertaken, including 26 initial consultations. Twenty‐three initial consultations were undertaken on the visit to the rural centres. Clinical descriptions illustrate the flexibility and sensitivity of the service.

Conclusion: Telepsychiatry provides access to a flexible, effective tertiary service for those with special, complex needs, including the disadvantaged or isolated. It makes a valuable, economic contribution to supporting and educating rural health professionals, thereby enriching rural mental health services.
Teaching patients to monitor their risk factors retards the progression of vascular complications in high‐risk patients with Type 2 diabetes mellitus—a randomized prospective study
Authors: Rachmani R. , Levi Z. , Slavachevski I. , Avin M. , Ravid M.
Published: July 2002

Aims Intensive management of risk parameters in diabetic patients may retard the progression of both micro‐ and macrovascular complications. Intensified care requires expert staff and is expensive. The aim of the present study was to examine whether sharing the therapeutic responsibility with the patients will improve the outcome.

Methods A randomized prospective study of 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL‐C > 120 mg/dl). Patients were randomly allocated to standard annual consultation (SC) or to a patient participation programme (PP). The medical care for both groups was administered by primary care physicians, who were unaware of the nature of the intervention.

Results At 4 years the mean blood pressure was 148/88 (± 6.1/1.7) mmHg in the SC patients vs. 142/84 (± 5.8/1.8) mmHg in the PP group (P = 0.02). The mean LDL‐C was 124 ± 8 and 114 ± 6 mg/dl (P = 0.01) and the mean HbA1c was 8.9 ± 1.2% and 8.2 ± 1.5% (P = 0.04) in the SC and PP groups, respectively. The average annual fall in estimated glomerular filtration rate was 3.5 ml/min per year in the SC group vs. 2.25 in the PP group (P < 0.05). Albumin/creatinine ratio > 300 mg/g developed in four SC patients vs. none of the PP patients. There was a total of 36 cardiovascular events in the SC group vs. 23 in the PP group (P = 0.04). All patients in the PP group received ACE inhibitors (or AII blockers) and statins vs. 52% and 43%, respectively, in the SC group. Glucose‐lowering regimens were similar.

Conclusions Well‐informed and motivated patients were more insistent to reach and maintain target values of the main risk factors of diabetic complications. The differences between the PP and SC groups were of the same order of magnitude as those between intensive and standard care groups in other studies albeit with, comparatively, a very modest cost.
Glyceryl trinitrate induced headache in migraineurs – relation to attack frequency
Authors: Christiansen I. , Daugaard D. , Lykke Thomsen L. , Olesen J.
Published: July 2002

Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate headache in healthy subjects, whilst migraineurs develop a more severe headache, resembling spontaneous migraine attacks. In order to investigate whether this increased nitric oxide sensitivity depends upon the frequency of spontaneously occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5 µg/kg/min) was given to 15 migraine patients with rare attacks (≤4 attacks/year) of migraine without aura. Fourteen age‐matched migraine patients with frequent attacks of migraine without aura (≥12 attacks/year) and 14 healthy subjects served as controls. No significant difference between the migraine groups for any of several parameters was detected, although the trend was always towards more headaches in frequent migraineurs. Both migraineurs with frequent and rare attacks experienced a headache that was significantly more severe, longer lasting, and fulfilled the diagnostic criteria for migraine without aura more often, compared to the healthy subjects (P = 0.0001). Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be related to a basic – probably genetically determined – pathophysiological mechanism involving nitric oxide, and not to the environmental influences, which to a large extent determine the expression of migraine.
Skin involvement in chronic myelomonocytic leukaemia as a predictor of transformation into acute myeloid leukaemia
Authors: Pont V , Miquel FJ , Grau C , Hernández F , Sánchez‐Carazo JL , Aliaga A
Published: July 2002

We report on the case of a patient with myelodysplastic syndrome (MDS) who presented with leukaemia cutis preceding development of acute myeloid leukaemia. Leukaemic infiltration of the skin should be considered an early manifestation of leukaemic transformation and an indicator of poor prognosis in MDS.
Accommodation to static chromatic simulations of blurred retinal images
Authors: Lee John H. , Stark Lawrence R. , Cohen Sara , Kruger Philip B.
Published: July 2002

The eye’s longitudinal chromatic aberration (LCA) is known to drive ‘reflex’ accommodation to moving objects, but the evidence is not as clear for stationary objects. The present study examined whether accommodation can be driven by static simulations of the effects of defocus and LCA. Accommodation was recorded continuously while each of 12 subjects viewed images (through a 0.75 mm pinhole) that simulated the appearances of blurred sine wave gratings (3.9 c.p.d.). In two experimental conditions, an eye with normal LCA was assumed and defocus of +1 D or −1 D was simulated. In a control condition, an eye with neutralised LCA was assumed and target defocus of 1 D was simulated. Subjects’ accommodation responses were consistent with the hypothesis that LCA provides a stimulus to accommodation. Chromatic aberration drives accommodation to both moving and stationary objects, and thus is an important stimulus for accommodation in everyday situations. The study findings are discussed in relation to colour vision, visual display terminals and emmetropization.
Within‐Patient Early Versus Delayed Treatment of Migraine Attacks With Almotriptan: The Sooner the Better
Authors: Pascual Julio , Cabarrocas Xavier
Published: July 2002

Background.—Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial.

Objective.—To address the potential “within‐patient” benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity.

Methods.—We performed a post hoc analysis of a subgroup of patients from a large, open‐label, long‐term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 “mild” attacks and 3 “moderate/severe” attacks, examining rates of pain‐free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated.

Results.—There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain‐free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain‐free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%).

Conclusion.—These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain‐free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.
Substance P
Authors: Snijdelaar Dirk G. , Dirksen Ris , Slappendel Rob , Crul Ben J.P.
Published: July 2002

Substance P is considered to be an important neuropeptide in nociceptive processes. Although substance P was described more than 60 years ago, there is still controversy about its exact role in nociception. This article reviews the current knowledge about the function of substance P in pain. Special emphasis is put on how to use this knowledge in the development of new ways to treat pain.
Nonlinear optical susceptibilities of high-index glasses
Authors: Hall D. W. , Newhouse M. A. , Borrelli N. F. , Dumbaugh W. H. , Weidman D. L.
Published: July 2002

We report results of degenerate four-wave mixing measurements of nonresonant nonlinearities in a variety of high-index lead and bismuth containing oxide glasses and the chalcogenide As2S3. The third-order nonlinear susceptibilities of the oxide glasses are found to scale with the heavy metal content. A lead-bismuth-gallate glass was identified with a nonresonant χ3 equal to 42±7×10−14 esu, which is approximately three times larger than that of any glass previously reported.