bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feedback of personal retinal images appears to have a motivational impact in people with non‐proliferative diabetic retinopathy and suboptimal HbA1c: findings of a pilot study
Authors: Rees G. , Lamoureux E. L. , Nicolaou T. E. , Hodgson L. A. B. , Weinman J. , Speight J. 
Published: March 2013

AbstractAimTo conduct a pilot study to explore the potential impact of visual feedback of personal retinal images on diabetes outcomes.MethodsTwenty‐five participants with non‐proliferative diabetic retinopathy and suboptimal HbA1c (> 53 mmol/mol; > 7%) were randomized to receive visual feedback of their own retinal images or to a control group. At baseline and 3‐month follow‐up, HbA1c, standard measures of beliefs, diabetes‐related distress and self‐care activities were assessed.ResultsIn unadjusted models, relative to controls, the intervention group showed significantly greater improvement in HbA1c at 3‐month follow‐up (–0.6% vs. +0.3%, P < 0.01), as well as enhanced motivation to improve blood glucose management (P < 0.05).ConclusionsThis small pilot study provides preliminary evidence that visual feedback of personal retinal images may offer a practical educational strategy for clinicians in eye care services to improve diabetes outcomes in non‐target compliant patients. A fully powered randomized controlled trial is required to confirm these findings and determine the optimal use of feedback to produce sustained effects.
Clinical status in adolescents: is its impact on oral health‐related quality of life influenced by psychological characteristics?
Authors: Foster Page Lyndie A. , Thomson W. Murray , Ukra Ali , Baker Sarah R. 
Published: March 2013

The objective of this study was to examine, using structural equation modelling, the relationships among clinical characteristics (such as caries experience and malocclusion), oral health‐related quality of life (OHRQoL), and psychological characteristics (mental health, self‐esteem, somatisation, and social perception of body image) in adolescents in New Zealand. Adolescents were examined for malocclusion using the Dental Aesthetic Index (DAI) and for dental caries. Among the 353 (58.8%) 12‐ and 13‐yr‐old adolescents who took part in this cross‐sectional study, the overall mean ± SD decayed, missing, or filled surfaces (DMFS) value was 1.6 ± 3.0, with slightly more than 50% of being caries‐free; the mean ± SD DAI was 31.5 ± 7.6, with one‐quarter of subjects having a ‘handicapping’ malocclusion. The structural equation modelling analysis showed that the structural model was a good fit to the data. As hypothesized, the DAI score significantly predicted OHRQoL. There was no direct relationship between caries experience (DMFS) and OHRQoL, but there was an indirect effect of DMFS on OHRQoL mediated through psychological characteristics. The amount of OHRQoL variance accounted for in the model was substantial, at 62%. It appears that investigating OHRQoL in adolescents is not straightforward; while malocclusion directly affects OHRQoL, the influence of dental caries experience is less direct.
A quantitative study of white matter hypomyelination and oligodendroglial maturation in focal cortical dysplasia type II
Authors: Shepherd Caterina , Liu Joan , Goc Joanna , Martinian Lillian , Jacques Thomas S. , Sisodiya Sanjay M. , Thom Maria 
Published: March 2013

SummaryPurposeA diagnostic feature of focal cortical dysplasia (FCD) type II on magnetic resonance imaging (MRI) is increased subcortical white matter (WM) signal on T2 sequences corresponding to hypomyelination, the cause of which is unknown. We aimed to quantify WM pathology in FCD type II and any deficiency in the numbers and differentiation of oligodendroglial (OL) cell types within the dysplasia.MethodsIn 19 cases we defined four regions of interests (ROIs): ROI1 = abnormal WM beneath dysplasia, ROI2 =dysplastic cortex, ROI3 = normal WM, and ROI4 = normal cortex. We quantified axonal and myelin density using immunohistochemistry for neurofilament, myelin basic protein and quantified mature OL with NogoA, cyclic nucleotide 3‐phosphodiesterase (CNPase) and OL precursor cell (OPC) densities with platelet derived growth factor receptor (PDGFR)α, β and NG‐2 in each region.Key FindingsWe observed a significant reduction in myelin and axons in the WM beneath dysplasia relative to normal WM and there was a correlation between relative reduction of myelin and neurofilament in each case. OL and OPC were present in the WM beneath dysplasia and although present in lower numbers with most markers, were not significantly different from normal WM. Neurofilament and myelin labeling highlighted disorganized orientation of fibers in dysplastic cortex but there were no significant quantitative differences compared to normal cortex. Clinical correlations showed an association between the severity of reduction of myelin and axons in the WM of FCD and duration of epilepsy.SignificanceThese findings indicate a reduction of myelinated axons in the WM of FCD type II rather than dysmyelination as the primary pathologic process underlying WM abnormalities, possibly influenced by duration of seizures. The range of OPC to OL present in FCD type II does not implicate a primary failure of cell recruitment and differentiation of these cell types in this pathology.
Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it
Authors: Kell Douglas B. 
Published: March 2013

Despite the sequencing of the human genome, the rate of innovative and successful drug discovery in the pharmaceutical industry has continued to decrease. Leaving aside regulatory matters, the fundamental and interlinked intellectual issues proposed to be largely responsible for this are: (a) the move from ‘function‐first’ to ‘target‐first’ methods of screening and drug discovery; (b) the belief that successful drugs should and do interact solely with single, individual targets, despite natural evolution's selection for biochemical networks that are robust to individual parameter changes; (c) an over‐reliance on the rule‐of‐5 to constrain biophysical and chemical properties of drug libraries; (d) the general abandoning of natural products that do not obey the rule‐of‐5; (e) an incorrect belief that drugs diffuse passively into (and presumably out of) cells across the bilayers portions of membranes, according to their lipophilicity; (f) a widespread failure to recognize the overwhelmingly important role of proteinaceous transporters, as well as their expression profiles, in determining drug distribution in and between different tissues and individual patients; and (g) the general failure to use engineering principles to model biology in parallel with performing ‘wet’ experiments, such that ‘what if?’ experiments can be performedin silicoto assess the likely success of any strategy. These facts/ideas are illustrated with a reasonably extensive literature review. Success in turning round drug discovery consequently requires: (a) decent systems biology models of human biochemical networks; (b) the use of these (iteratively with experiments) to model how drugs need to interact with multiple targets to have substantive effects on the phenotype; (c) the adoption of polypharmacology and/or cocktails of drugs as a desirable goal in itself; (d) the incorporation of drug transporters into systems biology models, en route to full and multiscale systems biology models that incorporate drug absorption, distribution, metabolism and excretion; (e) a return to ‘function‐first’ or phenotypic screening; and (f) novel methods for inferring modes of action by measuring the properties on system variables at all levels of the ‘omes. Such a strategy offers the opportunity of achieving a state where we can hope to predict biological processes and the effect of pharmaceutical agents upon them. Consequently, this should both lower attrition rates and raise the rates of discovery of effective drugs substantially.
Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: a comprehensive Argentine study of inhibitor risks
Authors: Rossetti L. C. , Szurkalo I. , Radic C. P. , Abelleyro M. M. , Primiani L. , Neme D. , Candela M. , Bianco R. P. , de Tezanos Pinto M. , Larripa I. B. , De Brasi C. D. 
Published: March 2013

SummaryInhibitor development against exogenous factor VIII is a severe impairment of replacement therapy affecting 18% of Argentine patients with severe haemophilia A (HA). To study the molecular predisposition for inhibitor development, we genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor‐positive population (19 transients, 15 low responders, LR and 70 high responders, HR) of 104 severe‐HA patients showed 59 Inv22 (intron 22 inversions), 18 small ins/del‐frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2 domain secondary structure. In addition, a patient with mild HA and HR showed the missense p.Glu1704Lys associated with two neutral intronic substitutions potentially affecting the A3 domain. A case/control study (84/143) permitted estimation of F8 genotype–specific inhibitor risks [OR; prevalence (CI)] in severe‐HA patients classifying a high‐risk group including multi‐exon deletions [3.66; 55% (19–100)], Inv22 [1.8; 24% (19–100)] and nonsense in FVIII‐LCh [1.2; 21% (7–59)]; an average risk group including single‐exon deletions, indel frameshifts and nonsense‐HCh; and a low‐risk group represented by missense defects [0.14; 3% (0.6–11)]. Analysis of inhibitor concordance/discordance in related patients indicated additional genetic factors other than F8 genotype for inhibitor formation. No significant inhibitor‐predisposing factors related to FVIII product exposure were found in age‐ and F8 genotype–stratified populations of severe‐HA patients. In conclusion, the Argentine HA patient series presents similar global and mutation‐specific inhibitor risks than the HA database and other published series. This case‐specific information will help in designing fitted therapies and follow‐up protocols in Argentina.
The benefits of exercise for patients with haemophilia and recommendations for safe and effective physical activity
Authors: Negrier C. , Seuser A. , Forsyth A. , Lobet S. , Llinas A. , Rosas M. , Heijnen L. 
Published: March 2013

SummaryMost health care professionals involved in the management of people with haemophilia (PWH) believe that exercise is beneficial and its practice is widely encouraged. This article aims to demonstrate that appropriate exercise (adapted to the special needs of the individual PWH) may be beneficial for all PWH through improved physical, psychosocial and medical status. Based on evidence gathered from the literature, many PWH, particularly those using long‐term prophylaxis or exhibiting a mild/moderate bleeding phenotype, are as active as their healthy peers. PWH experience the same benefits of exercise as the general population, being physically healthier than if sedentary and enjoying a higher quality of life (QoL) through social inclusion and higher self‐esteem. PWH can also gain physically from increased muscle strength, joint health, balance and flexibility achieved through physiotherapy, physical activity, exercise and sport. Conversely, very little data exist on activity levels of PWH in countries with limited resources. However, regarding specific exercise recommendations in PWH, there is a lack of randomized clinical trials, and consequently formal, evidence‐based guidelines have not been produced. Based on published evidence from this review of the literature, together with the clinical experience of the authors, a series of recommendations for the safe participation of PWH in regular physical activities, exercises and sport are now proposed. In summary, we believe that appropriately modified programmes can potentially allow all PWH to experience the physical and psychosocial benefits of being physically active which may ultimately lead to an improved QoL.
Radioactive synovectomy with 90yttrium and 153samarium hydroxyapatite in haemophilic joints: preliminary study on radiation safety
Authors: Thomas S. , Mendes J. D. , Souza S. A. , Lorenzato C. S. , Assi P. E. , Pacheco L. R. L. , Gabriel M. B. , Bordim A. , Gutfilen B. , da Fonseca L. M. B. 
Published: March 2013

SummaryMost countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with 90Yttrium Citrate, 90Yttrium hydroxyapatite or 153Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3–51) received 1–3 RS (total 842) and follow‐up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5–10 years for radio‐induction of solid tumours. Moreover, ES is not a typically radio‐induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.
Long‐term trends in the composition of aphidophagous coccinellid communities in Central Europe
Authors: Honek Alois , Martinkova Zdenka , Kindlmann Pavel , Ameixa Olga M. C. C. , Dixon Anthony F. G. 
Published: March 2013

Abstract

Coccinellids (Coleoptera: Coccinellidae) provide important ecosystem services as biocontrol agents in contributing to the regulation of key agricultural pests. It is generally accepted that biodiversity of native coccinellid communities has been declining during recent decades. Here, we present the results of a long‐term study of coccinellid communities and report an attempt to determine whether recent changes in land use have affected their composition.

Coccinellids were sampled in cereal crops, on wild herbaceous plants and deciduous trees during two periods (1976–1983 and 2002–2010).

There are similar species‐rich communities of coccinellids on trees and wild herbaceous plants (average numbers of species 3.18 and 3.06, respectively) and a poorer community on cereals (2.63). Only a few species, associated with particular types of vegetation, differed in their absolute abundance in the first and second period. There was no obvious cause of this variation in abundance. Diversity of coccinellid communities was higher in the second than in the first period (Shannon‐Wiener index 1.32 and 1.14 respectively), although the number of individuals was lower (average catch per sampling session 10.0 and 18.6 individuals respectively).

Over the 35 years of this study, the compositions of the communities remained essentially similar with the numbers of particular species more closely correlated in the two periods on cereals (R2 = 0.97) than on herbaceous plants (R2 = 0.74) and trees (R2 = 0.67).
Gastrocnemius Tendon Strain in a Dog Treated With Autologous Mesenchymal Stem Cells and a Custom Orthosis
Authors: Case J. Brad , Palmer Ross , Valdes‐Martinez Alex , Egger Erick L. , Haussler Kevin K. 
Published: March 2013

AbstractObjectiveTo report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis.Study DesignClinical report.AnimalA 4‐year‐old spayed female Border Collie.MethodsBone‐marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long‐term force‐plate gait analysis were utilized for follow up.ResultsLameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon.ConclusionsFindings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs.
Chromatin remodelling initiation in spermatids: differences among human males
Authors: de Vries M. , Ramos L. , Lacroix R. , D'Hauwers K. , Hendriks J.C.M. , Kremer J.A.M. , van der Vlag J. , de Boer P. 
Published: March 2013

SummaryDuring the last phase of spermatogenesis, called spermiogenesis, the nucleosome‐based chromatin structure is replaced by a protamine‐based DNA packaging. Not much is known about the chromatin remodelling involved in humans and animals. Here, we have investigated initiation of chromatin remodelling over seven probands of which five were diagnosed with non‐obstructive azoospermia (NOA) and two with obstructive azoospermia (OA) (failed vaso‐vasostomy patients with proven fertility prior to vasectomy, Johnsen scores ≥9). Chromatin remodelling was studied evaluating the presence of nucleosomes, histone H3, pre‐protamine 2 and protamine 1. This approach was feasible since the local initiation of nucleosome eviction in the sub acrosomal domain, which was visible in alkaline nuclear spread preparations. The patterns of nucleosome and H3 loss were largely congruent. Nucleus wide incorporation of protamine 1 could already be observed at the late round spermatid stage. Both for nucleosome loss and for protamine 1 incorporation, there was distinct variation within and between probands. This did not relate to the efficiency of sperm production per meiocyte. Pre‐protamine 2 was always confined to the subacrosomal domain, confirming the role of this area in chromatin remodelling.
The prognostic role of the new entity butterfly‐like facial rash and cutaneous findings in patients with crimean congo haemorrhagic fever
Authors: Pancar G.S. , Duygu F. , Kalkan G. 
Published: March 2013

AbstractBackgroundCrimean Congo Haemorrhagic Fever (CCHF) is a deadly fever caused by Nairovirus (family Bunyaviridae). It is an important public health problem in hyperendemic regions with a high mortality rate. There have been many studies on cutaneous findings in other viral infections, however, our knowledge is limited regarding CCHF. The aim of this study was to evaluate the cutaneous manifestations of CCHF and their relationship with mortality.MethodsPatients who were diagnosed CCHF between April 1 and September 1, 2011 were enrolled in this study. Dermatologic examination and laboratory analysis were obtained during hospitalization.ResultsA new entity that is first reported in this study as a butterfly‐like facial rash was recognized in 76 patients (42.9%). It was not correlated with mortality but could coexist with other dermatological signs of CCHF. The major outcome was the increased mortality rate with other cutaneous findings (especially ecchymosis, purpura and petechia) (P < 0.01). While 12 deceased individuals had one or more skin findings, only one patient died without any cutaneous manifestations. Mortality rate was higher in patients with purpura than the patients with pethesia. The statistically significant correlation was observed between cutaneous manifestations and elevation of aspartate aminotransferase (AST) levels (P = 0.009). Platelet levels were lower in patients with cutaneous involvement (P < 0.01). No statistically significant relationship was found between cutaneous findings and alanine aminotransferase (ALT), white blood cell (WBC), Haemoglobin (Hb), creatinine kinase (CK) and lactate dehydrogenase (LDH) levels.LimitationsHistopathologic examination of facial rash could not be done because of haemostatic failure.ConclusionThe results of this study confirm that cutaneous findings can be a clue regarding the prognosis of the patients with CCHF. Physicians should be aware that CCHF may present with a butterfly‐like rash on the face.
Water availability and population origin affect the expression of the tradeoff between reproduction and growth in Plantago coronopus
Authors: Hansen C. F. , García M. B. , Ehlers B. K. 
Published: March 2013

AbstractInvestment in reproduction and growth represent a classic tradeoff with implication for life history evolution. The local environment can play a major role in the magnitude and evolutionary consequences of such a tradeoff. Here, we examined the investment in reproductive and vegetative tissue in 40 maternal half‐sib families from four different populations of the herb Plantago coronopus growing in either a dry or wet greenhouse environment. Plants originated from populations with an annual or a perennial life form, with annuals prevailing in drier habitats with greater seasonal variation in both temperature and precipitation. We found that water availability affected the expression of the tradeoff (both phenotypic and genetic) between reproduction and growth, being most accentuated under dry condition. However, populations responded very differently to water treatments. Plants from annual populations showed a similar response to drought condition with little variation among maternal families, suggesting a history of selection favouring genotypes with high allocation to reproduction when water availability is low. Plants from annual populations also expressed the highest level of plasticity. For the perennial populations, one showed a large variation among maternal families in resource allocation and expressed significant negative genetic correlations between reproductive and vegetative biomass under drought. The other perennial population showed less variation in response to treatment and had trait values similar to those of the annuals, although it was significantly less plastic. We stress the importance of considering intraspecific variation in response to environmental change such as drought, as conspecific plants exhibited very different abilities and strategies to respond to high versus low water availability even among geographically close populations.