bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional analysis of cyclophilin PpiB mutants supports an in vivo function not limited to prolyl isomerization activity
Authors: Skagia Aggeliki , Vezyri Eleni , Sigala Markezina , Kokkinou Areti , Karpusas Michael , Venieraki Anastasia , Katinakis Panagiotis , Dimou Maria 
Published: November 2016

Escherichia coli cyclophilin PpiB is a peptidyl‐prolyl cis/trans isomerase (PPIase, EC: 5.2.1.8), involved in the negative modulation of various bacterial processes, such as swimming and swarming motility and biofilm formation ability. In this study, we show that PpiB possesses also a chaperone function as it can prevent the thermal denaturation of citrate synthase even with essentially eliminated PPIase activity. We demonstrate, using active site mutations, that the PPIase activity of PpiB is required in all processes, except for the negative effect on swimming, indicating a possible isomerase‐independent function. Additionally, we show that the reduced PPIase activity of PpiB does not prevent the association with all prey proteins tested and that the PPIase active site is not involved necessarily in each association. We also used a random mutagenesis approach, to identify amino acid residues apart from the catalytic site, which are necessary for PpiB function. The combination of enzymatic studies concerning the PPIase and chaperone activities of each mutant protein, with structural analyses based on 3D models, provided further insights into the effects of the mutations on the function of PpiB and showed the importance of structural features in addition to the catalytic site, for its in vivo role.
Evaluation of the utility of the ISTH‐BAT in haemophilia carriers: a multinational study
Authors: James P. D. , Mahlangu J. , Bidlingmaier C. , Mingot‐Castellano M. E. , Chitlur M. , Fogarty P. F. , Cuker A. , Mancuso M. E. , Holme P. A. , Grabell J. , Satkunam N. , Hopman W. M. , Mathew P. ,   Global Emerging HEmostasis Experts Panel (GEHEP)
Published: November 2016

IntroductionThere has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking.AimOur objective was to validate the ISTH‐BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups.MethodsThis was a prospective, observational, cross‐sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH‐BAT were completed by study personnel.ResultsA total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20–82). Carriers had higher mean bleeding scores (BS) compared with age‐matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2 = −0.36, P < 0.001).ConclusionOur results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH‐BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment.
Unusual cause of hypercalcaemia in end stage renal failure patients
Authors: Teo Hooi Khee , Wong Jiunn 
Published: November 2016

AbstractImmobility‐induced hypercalcaemia is rarely considered in patients on dialysis and is a challenging diagnosis to make. This is especially so due to the lack of biomarkers as well as the notion that calcium metabolism is mostly related to chronic kidney disease‐metabolic bone disorder due to the role of iPTH. We present two cases of our dialysis patients, who were clinically unwell from hypercalcemia. We were initially uncertain of the cause of hypercalcemia as despite our attempts to adjust treatment based on their biochemical findings, we were unable to correct the hypercalcemia. We did not have appropriate bone turnover markers to guide us and out of desperation, anti‐resorptives—calcitonin and bisphosphonate were given with good clinical response. We concluded that the hypercalcemia was related to immobility‐induced hypercalcemia and the inappropriately low iPTH was a red herring. Immobility‐induced hypercalcaemia should be considered in patients with end stage renal failure on renal replacement therapy, especially in those with recent and significant immobility. In these patients, pamidronate can be considered should the hypercalcaemia persist.
Potentially pathogenic circulating autoantibodies to cardiac troponin are present in hemodialysis patients
Authors: Jefferies Helen J. , Tertti Risto , Wittfooth Saara , Burton James O. , Metsärinne Kaj , Pettersson Kim , McIntyre Christopher W. 
Published: November 2016

AbstractIntroduction: Repetitive dialysis‐induced cardiac injury is associated with elevated troponin levels, inflammation, and longitudinal reduction in cardiac function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce inflammatory cardiomyopathy in murine models. This study aimed to explore the possibility that analogous autoimmune processes might occur in hemodialysis (HD) patients, by initially investigating cTnAAb prevalence, and exploring potential links with HD‐induced myocardial stunning.Methods: In 130 prevalent HD patients from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac troponins were quantified. Sixty‐four patients underwent serial echocardiography to assess myocardial stunning.Findings: cTnAAb were present in 7% of patients. Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and cTnT, respectively. Patients with cTnAAb had significantly longer dialysis vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P = 0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP‐A (6.4 vs. 3.3 mIU/L, P = 0.038).Discussion: This is the first description of cTnAAb in HD patients, which raises the possibility that longitudinal exposure to repetitive HD‐induced cardiac injury may lead to further autoimmune‐based myocardial insult.
Oral health status of six‐year‐old children in Qatar: findings from the national oral health survey
Authors: Al‐Thani MH , Al‐Thani AA , Al‐Emadi AA , Al‐Chetachi WF , Akram H , Poovelil BV 
Published: November 2016

AbstractIntroductionOral health has a significant impact on physical, social and mental well‐being of an individual. Qatar, like the rest of the world, is experiencing higher prevalence of oral health‐related problems.ObjectivesTo examine the oral health status and extent of preventive and curative needs among six‐year‐old school children in Qatar by key demographic indicators.MethodsSecondary data analysis of 1124 six‐year‐old private and government primary school children from the 2011 Qatar National Oral Health Survey was performed. Dental caries lesions status of primary dentition was assessed according to the WHO criteria. Descriptive statistics were carried out, and comparison among groups was executed by running t statistics. Logistic regression was performed to interpret the impact of various predictors.ResultsOverall, 71.4% children presented with dental caries lesions with a higher prevalence among girls versus boys (73.8% versus 68.9%). The mean overall dmft was recorded as 4.2 with ±4.2 SD. Qatari children had 3.8 time odds of having dental caries lesions compared with non‐Qatari children (P < 0.001). Overall, 18.9% of children showed signs of poor periodontal health. Odds of having more periodontal disease were significant in Qatari boys (OR = 3.1 CI = 2.0, 4.7, P < 0.001) compared to non‐Qatari boys. On average, 3.6 teeth per student were in need of any treatment.ConclusionThis study indicated that only 28.6% of children aged six were free from caries lesions. The results urge to further strengthen the strategies and to improve oral hygiene by various evidence‐based interventions.
Microwave–hot air drying applied to selected cassava cultivars: drying kinetics and sensory acceptance
Authors: Gonçalves Leticia Tinoco , Pereira Nádia Rosa , Almeida Selma Bergara , Freitas Silvio de Jesus , Waldman Walter Ruggeri 
Published: November 2016

SummaryThe effects of three cassava cultivars produced in Brazil were assessed (IAC Espeto, IAC 14 and IAC Caapora) in order to obtain chips by precooking and hot air–microwave drying (70 °C, 95 W). The difference in the composition of cultivars has not influenced the drying of cassava slices. The drying kinetics presented a constant drying rate period followed by a decreasing drying rate with effective diffusion coefficient of 2.8–3.0 × 10−10 m2s−1. The hedonic means of all attributes ranged from ‘neither like nor dislike’ to ‘like moderately’. Therefore, the choice of the more suitable cultivar can be based on plant productivity and product yield. The IAC 14 cultivar resulted in the highest root production per plant, product mass per roots and chips yield.
Genetic diagnosis in Hemophilia A from southern China: five novel mutations and one preimplantation genetic analysis
Authors: Chen J. , Wang J. , Lin X. Y. , Xu Y. W. , He Z. H. , Li H. Y. , Chen S. Q. , Jiang W. Y. 
Published: November 2016

SummaryIntroductionAs there is currently no complete cure for hemophilia A (HA), the identification of pathogenic mutations in factor VIII (FVIII) gene from HA patients and carriers, which can contribute to genetic counseling prenatal diagnosis, and preimplantation genetic diagnosis (PGD), is an important step to prevent HA.MethodsA total of 14 unrelated Chinese HA subjects (FVIII activity <40%), 20 carrier subjects, three fetuses, and one PGD were included in this study. We first screened for the presence of FVIII intron 22 and intron 1 inversions. Second, the coding region of the FVIII gene was sequenced. For the novel mutations, FVIII mRNA expression was detected by real‐time PCR and the protein structures were analyzed by bioinformatic tools.ResultsFive novel mutations (c.1A>C, c.304_305insA, c.1594T>A, c.6045G>A, and c.2645_2646insG) were found. The real‐time PCR showed that the expression of FVIII mRNAs was lower in HA patients than in normal subjects. Prenatal diagnosis and PGD were successfully performed: Two of three fetuses and four of eight blastomeres were confirmed to be normal.ConclusionIn conclusion, genetic diagnosis of 14 unrelated HA subjects, 20 carrier subjects, three fetuses, and one PGD was successfully performed in our study.
Skewed, Persistent and High before Death: Medical Spending in Germany
Authors: Karlsson Martin , Klein Tobias J. , Ziebarth Nicolas R. 
Published: November 2016

AbstractWe use claims panel data from a big German private health insurer to provide detailed individual‐level evidence on medical spending between 2005 and 2011. This includes evidence on the distribution of medical spending, the dependence of medical spending on age and other demographic characteristics, its persistence, and how medical spending evolves in the years before death. Our main findings are that health care spending more than doubles between ages 50 and 80 and that spending is very concentrated: the top 10 per cent of all spenders are responsible for 53 per cent of all medical spending in a given year. There is a 50 per cent probability that individual expenditures lie in the same quintile of the distribution after five years, for both very‐high‐ and very‐low‐cost individuals. Medical spending in the year of death is six times higher for the deceased than for everybody else in that year and accounts for 7.9 per cent of lifetime spending. Females use more office‐based care and have higher spending at younger ages, whereas males have higher spending at older ages, particularly for hospital care, and die younger. The presentation of these empirical facts is framed by an institutional discussion of the German health care system, a comparison between publicly‐ and privately‐insured individuals, and a discussion of medical spending trends in aggregate‐level data.
Socio‐Economic Inequalities in Health Care in England
Authors: Cookson Richard , Propper Carol , Asaria Miqdad , Raine Rosalind 
Published: November 2016

AbstractThis paper reviews what is known about socio‐economic inequalities in health care in England, with particular attention to inequalities relative to need that may be considered unfair (‘inequities’). We call inequalities of 5 per cent or less between the most and least deprived socio‐economic quintile groups ‘slight’, inequalities of 5–15 per cent ‘moderate’ and inequalities of more than 15 per cent ‘substantial’. Overall public health care expenditure is substantially concentrated on poorer people. At any given age, poorer people are more likely to see their family doctor, have a public outpatient appointment, visit accident and emergency, and stay in hospital for publicly‐funded inpatient treatment. After allowing for current self‐assessed health and morbidity, there is slight pro‐rich inequity in combined public and private medical specialist visits but not in family doctor visits. There are also slight pro‐rich inequities in overall indicators of clinical process quality and patient experience from public health care, substantial pro‐rich inequalities in bereaved people's experiences of health and social care for recently deceased relatives, and mostly slight but occasionally substantial pro‐rich inequities in the use of preventive care (for example, dental check‐ups, eye tests, screening and vaccination) and a few specific treatments (for example, hip and knee replacement). Studies of population health care outcomes (for example, avoidable emergency hospitalisation) find substantial pro‐rich inequality after adjusting for age and sex only. These findings are all consistent with a broad economic framework that sees health care as just one input into the production of health over the life course, alongside many other socio‐economically patterned inputs including environmental factors (for example, living and working conditions), consumption (for example, diet and smoking), self‐care (for example, seeking medical information) and informal care (for example, support from family and friends).
Medical Spending in Japan: An Analysis Using Administrative Data from a Citizen's Health Insurance Plan
Authors: Ibuka Yoko , Chen Stacey H. , Ohtsu Yui , Izumida Nobuyuki 
Published: November 2016

AbstractHealth care spending growth in Japan has accelerated in recent years, unlike in most OECD countries. It is thus important to characterise the structure of recent medical spending using individual‐level data. We use medical claim bill data from a citizen's health insurance plan in Japan to examine the concentration in and persistence of medical spending. We find that medical spending is disproportionately distributed across individuals, with the top 10 per cent of spenders responsible for over 60 per cent of total expenditures. We also find a high correlation in spending over time: the top 20 per cent of spenders have a probability of over 60 per cent of remaining in the same rank in the following year. Further, medical spending is more concentrated among those aged 0–64 years than among the older age group. The results also show a difference in income gradient of health expenditures across age groups. Specifically, individuals aged 25–64 in low‐income families spend more on medical care than those in high‐income families, whereas there is no clear association between income and health expenditures among the elderly. Finally, consistent with previous studies, we find increased medical expenses in the year of death, accounting for 17 per cent of total expenditures among those aged 65 and over.
Recent Trends in Taiwanese Medical Spending
Authors: Chen Stacey H. , Chuang Hongwei 
Published: November 2016

AbstractSince the creation of National Health Insurance (NHI) in 1995, Taiwan's medical spending has been increasing rapidly, as has been the case in most countries worldwide. This paper follows international standards in documenting recent trends in Taiwan's medical spending by category, relying on official statistics, Surveys of Family Income and Expenditure (SFIE) data and administrative reimbursement panel data from the NHI Universal Database (NHIUD). Two findings are noteworthy. First, we find a rapidly widening gap since 1996 between rich and poor in terms of out‐of‐pocket payments and those by private health insurance; meanwhile, the gap between them in terms of NHI expenditure has remained roughly constant. This trend can be attributed mainly to a positive income gradient in personal health care expenditure among elderly individuals (aged 65 or older). Second, end‐of‐life hospital spending is large in both magnitude and proportion. Average end‐of‐life hospital spending is more than 30 times average hospital spending by the total population, and it accounts for 15.9 per cent of total hospital care expenditure (or 5.0 per cent of overall medical spending), even though the population near death accounts for only 0.51 per cent of the overall population. Two‐thirds of end‐of‐life hospital spending is on the elderly, who also constitute two‐thirds of the population near death. For both the elderly and working‐age adults, the share of end‐of‐life hospital spending strikingly aligns with the share of deaths.
Medical Spending in Denmark
Authors: Christensen Bent Jesper , Gørtz Mette , Kallestrup‐Lamb Malene 
Published: November 2016

AbstractUsing full population longitudinal data from merged administrative registers for Denmark, we document that medical spending is highly concentrated in the population and is persistent through time at the individual level. In addition, we provide overviews of institutional details of the Danish health care system, aggregate trends in health care expenditures and the relevant register data. Nearly two‐thirds of expenditures are on hospitals and one‐fifth on long‐term care, with the remainder roughly equally split between primary care and prescription drugs. Health expenditures are higher for men than for women from ages 61 to 78, and otherwise higher for women. Between ages 50 and 80, hospital expenditures more than triple for men while more than doubling for women, and total health expenditures quadruple for men while tripling for women. The top 1 per cent of all spenders account for nearly one‐quarter of total spending in a given year, and averaging over three years only reduces this fraction to one‐fifth. The top 20 per cent of spenders in a given year are more likely to remain in that category two years later than not. The poorest fifth of the population aged 25 and above are responsible for more than twice as much spending on health as the richest, and this reverse social gradient is even stronger for long‐term care and is stronger among men than among women, especially in hospital expenses. Expenditures in the year (over the three years) before death are nearly 12 times (respectively nine times) higher than average, but nevertheless are only 11 per cent (respectively a quarter) of lifetime spending. Out‐of‐pocket expenses on prescription drugs only amount to 3 per cent of total health expenditures and are less concentrated than these.
Speciation in a keystone plant genus is driven by elevation: a case study in New Guinean Ficus
Authors: Segar S. T. , Volf M. , Zima Jnr J. , Isua B. , Sisol M. , Sam L. , Sam K. , Souto‐Vilarós D. , Novotny V. 
Published: November 2016

AbstractMuch of the world's insect and plant biodiversity is found in tropical and subtropical ‘hotspots’, which often include long elevational gradients. These gradients may function as ‘diversity pumps’ and contribute to both regional and local species richness. Climactic conditions on such gradients often change rapidly along short vertical distances and may result in local adaptation and high levels of population genetic structure in plants and insects. We investigated the population genetic structure of two species of Ficus (Moraceae) along a continuously forested elevational gradient in Papua New Guinea. This speciose plant genus is pollinated by tiny, species‐specific and highly coevolved chalcid wasps (Agaonidae) and represented by at least 73 species at our study gradient. We present results from two species of Ficus sampled from six elevations between 200 m and 2700 m a.s.l. (almost the entire elevational range of the genus) and 10 polymorphic microsatellite loci. These results show that strong barriers to gene flow exist between 1200 m and 1700 m a.s.l. Whereas lowland populations are panmictic across distances over 70 km, montane populations can be disjunct over 4 km, despite continuous forest cover. We suggest that the limited gene flow between populations of these two species of montane Ficus may be driven by environmental limitations on pollinator or seed dispersal in combination with local adaptation of Ficus populations. Such a mechanism may have wider implications for plant and pollinator speciation across long and continuously forested elevational gradients if generalist insect pollinators and vertebrate seed dispersers also form populations based on elevation.
Physical Exercise for Late‐Life Depression: Customizing an Intervention for Primary Care
Authors: Zanetidou Stamatula , Belvederi Murri Martino , Menchetti Marco , Toni Giulio , Asioli Fabrizio , Bagnoli Luigi , Zocchi Donato , Siena Matteo , Assirelli Barbara , Luciano Claudia , Masotti Mattia , Spezia Carlo , Magagnoli Monica , Neri Mirco , Amore Mario , Bertakis Klea D. ,   the Safety Efficacy of Exercise for Depression in Seniors Study Group
Published: November 2016

ObjectivesTo identify which individual‐ and context‐related factors influence the translation into clinical practice of interventions based on physical exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late‐life major depression (LLMD).DesignSecondary analysis of a randomized controlled trial.SettingPrimary care with psychiatric consultation‐liaison programs (PCLPs)—organizational protocols that regulate the clinical management of individuals with psychiatric disorders.ParticipantsIndividuals aged 65 and older with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (N = 121).InterventionParticipants with LLMD were randomized to AD (sertraline) or AD plus PE (AD + PE).MeasurementsParticipant characteristics that were associated with greater effectiveness of AD + PE (moderators) were identified, and effect sizes were calculated from success rate differences. Whether the characteristics of the study setting influenced participant flow and attendance at exercise sessions was then explored, and primary care physicians (PCPs) were surveyed regarding their opinions on PE as a treatment for LLMD.ResultsThe following participant characteristics were associated with greater likelihood of achieving remission from depression with AD + PE than with AD alone: aged 75 and older (effect size 0.32), polypharmacy (0.35), greater aerobic capacity (0.48), displaying psychomotor slowing (0.49), and less‐severe anxiety (0.30). The longer the PCLP had been established at a particular center, the more individuals were recruited at that center. After participating in the study, PCPs expressed positive views on AD + PE as a treatment for LLMD and were more likely to use this as a therapeutic strategy.ConclusionsThe combination of PE and sertraline could improve the management of LLMD, especially when customized for individuals with specific clinical features. Liaison programs might influence the implementation of similar interventions in primary care, and PCPs viewed them positively.