bluuebunny/crossref_metadata_2025 huggingface dataset:
MAKER-P: A Tool Kit for the Rapid Creation, Management, and Quality Control of Plant Genome Annotations
Authors: Campbell Michael S. , Law MeiYee , Holt Carson , Stein Joshua C. , Moghe Gaurav D. , Hufnagel David E. , Lei Jikai , Achawanantakun Rujira , Jiao Dian , Lawrence Carolyn J. , Ware Doreen , Shiu Shin-Han , Childs Kevin L. , Sun Yanni , Jiang Ning , Yandell Mark
Published: December 2013

We have optimized and extended the widely used annotation engine MAKER in order to better support plant genome annotation efforts. New features include better parallelization for large repeat-rich plant genomes, noncoding RNA annotation capabilities, and support for pseudogene identification. We have benchmarked the resulting software tool kit, MAKER-P, using the Arabidopsis (Arabidopsis thaliana) and maize (Zea mays) genomes. Here, we demonstrate the ability of the MAKER-P tool kit to automatically update, extend, and revise the Arabidopsis annotations in light of newly available data and to annotate pseudogenes and noncoding RNAs absent from The Arabidopsis Informatics Resource 10 build. Our results demonstrate that MAKER-P can be used to manage and improve the annotations of even Arabidopsis, perhaps the best-annotated plant genome. We have also installed and benchmarked MAKER-P on the Texas Advanced Computing Center. We show that this public resource can de novo annotate the entire Arabidopsis and maize genomes in less than 3 h and produce annotations of comparable quality to those of the current The Arabidopsis Information Resource 10 and maize V2 annotation builds.
Do we see what we should see? Describing non-covalent interactions in protein structures including precision
Authors: Gurusaran Manickam , Shankar Mani , Nagarajan Raju , Helliwell John R. , Sekar Kanagaraj
Published: December 2013

The power of X-ray crystal structure analysis as a technique is to `see where the atoms are'. The results are extensively used by a wide variety of research communities. However, this `seeing where the atoms are' can give a false sense of security unless the precision of the placement of the atoms has been taken into account. Indeed, the presentation of bond distances and angles to a false precision (i.e.to too many decimal places) is commonplace. This article has three themes. Firstly, a basis for a proper representation of protein crystal structure results is detailed and demonstrated with respect to analyses of Protein Data Bank entries. The basis for establishing the precision of placement of each atom in a protein crystal structure is non-trivial. Secondly, a knowledge base harnessing such a descriptor of precision is presented. It is applied here to the case of salt bridges,i.e.ion pairs, in protein structures; this is the most fundamental place to start with such structure-precision representations since salt bridges are one of the tenets of protein structure stability. Ion pairs also play a central role in protein oligomerization, molecular recognition of ligands and substrates, allosteric regulation, domain motion and α-helix capping. A new knowledge base, SBPS (Salt Bridges in Protein Structures), takes these structural precisions into account and is the first of its kind. The third theme of the article is to indicate natural extensions of the need for such a description of precision, such as those involving metalloproteins and the determination of the protonation states of ionizable amino acids. Overall, it is also noted that this work and these examples are also relevant to protein three-dimensional structure molecular graphics software.
Improved group‐specific primers based on the full SILVA 16S rRNA gene reference database
Authors: Pfeiffer Stefan , Pastar Milica , Mitter Birgit , Lippert Kathrin , Hackl Evelyn , Lojan Paul , Oswald Andreas , Sessitsch Angela
Published: December 2013

Quantitative PCR (qPCR) and community fingerprinting methods, such as the Terminal Restriction Fragment Length Polymorphism (T‐RFLP) analysis, are well‐suited techniques for the examination of microbial community structures. The use of phylum‐ and class‐specific primers can provide enhanced sensitivity and phylogenetic resolution as compared with domain‐specific primers. To date, several phylum‐ and class‐specific primers targeting the 16S ribosomal RNA gene have been published. However, many of these primers exhibit low discriminatory power against non‐target bacteria in PCR. In this study, we evaluated the precision of certain published primers in silico and via specific PCR. We designed new qPCR and T‐RFLP primer pairs (for the classes Alphaproteobacteria and Betaproteobacteria, and the phyla Bacteroidetes, Firmicutes and Actinobacteria) by combining the sequence information from a public dataset (SILVA SSU Ref 102 NR) with manual primer design. We evaluated the primer pairs via PCR using isolates of the above‐mentioned groups and via screening of clone libraries from environmental soil samples and human faecal samples. As observed through theoretical and practical evaluation, the primers developed in this study showed a higher level of precision than previously published primers, thus allowing a deeper insight into microbial community dynamics.
Insurer Market Structure and Variation in Commercial Health Care Spending
Authors: McKellar Michael R. , Naimer Sivia , Landrum Mary B. , Gibson Teresa B. , Chandra Amitabh , Chernew Michael
Published: December 2013

Objective

To examine the relationship between insurance market structure and health care prices, utilization, and spending.

Data Sources

Claims for 37.6 million privately insured employees and their dependents from the Truven Health Market Scan Database in 2009. Measures of insurer market structure derived from Health Leaders Inter study data.

Methods

Regression models are used to estimate the association between insurance market concentration and health care spending, utilization, and price, adjusting for differences in patient characteristics and other market‐level traits.

Results

Insurance market concentration is inversely related to prices and spending, but positively related to utilization. Our results imply that, after adjusting for input price differences, a market with two equal size insurers is associated with 3.9 percent lower medical care spending per capita (p = .002) and 5.0 percent lower prices for health care services relative to one with three equal size insurers (p < .001).

Conclusion

Greater fragmentation in the insurance market might lead to higher prices and higher spending for care, suggesting some of the gains from insurer competition may be absorbed by higher prices for health care. Greater attention to prices and utilization in the provider market may need to accompany procompetitive insurance market strategies.
Influence of family history on survival in patients with colon and rectal cancer
Authors: Lee Seong Dae , Kim Byung Chang , Han Kyung Su , Hong Chang Won , Sohn Dae Kyung , Park Ji Won , Park Sung Chan , Kim Sun Young , Baek Ji‐Yeon , Chang Hee Jin , Kim Dae Yong , Oh Jae Hwan
Published: December 2013

Objective

We aimed to investigate the association between a family history (FH) of colorectal cancer (CRC) and cancer recurrence and survival in patients with stage III CRC.

Methods

From April 2001 to December 2007, 1102 patients with stage III CRC were enrolled and their data including FH, clinicopathological characteristics of the tumor were retrospectively analyzed.

Results

Of 971 patients that were finally enrolled, 63 (6.5%) reported CRC in at least one first‐degree relative. Death occurred in 12.7% of the CRC patients with an FH and 21.8% in those without an FH. A multivariate analysis showed that patients with an FH of CRC, compared with those without FH, had an adjusted hazard ratios (HR) of 0.674 (P = 0.281) for overall survival (OS) and 0.672 (P = 0.220) for disease‐free survival (DFS). However, the location of tumor, preoperative carcinoembryonic antigen (CEA) level, tumor invasion (T) stage and lymph node (N) metastasis significantly affected OS and DFS. Furthermore, whereas the FH of CRC patients was associated with a favorable prognosis in stage III colon cancer (HR 0.224, P = 0.040) but not in rectal cancer (HR 1.225, P = 0.640).

Conclusions

In patients with stage III CRC, tumor location (especially in the rectum), a high preoperative CEA level and advanced T and N stages indicate a poor prognosis. However, in stage III colon cancer FH is associated with improved survival.
Identifying QTL and genetic correlations between fur quality traits in mink (Neovison vison)
Authors: Thirstrup J. P. , Anistoroaei R. , Guldbrandtsen B. , Christensen K. , Fredholm M. , Nielsen V. H.
Published: December 2013

Mapping of QTL affecting fur quality traits (guard hair length, guard hair thickness, density of wool, surface of the fur and quality) and skin length was performed in a three‐generation mink population (F2 design). In the parental generation, Nordic Brown mink were crossed reciprocally with American Black short nap mink. In all, 1082 mink encompassing three generations were used for the analyses. The mink were genotyped for 104 microsatellites covering all 14 autosomes. The QTL analyses were performed by least‐square regression implemented in gridqtl software. Genetic and phenotypic correlations and heritabilities were estimated using the average information‐restricted maximum‐likelihood method. Evidence was found for QTL affecting fur quality traits on nine autosomes. QTL were detected for guard hair thickness on chromosomes 1, 2, 3, 6 and 13; for guard hair length on chromosomes 2, 3 and 6; for wool density on chromosomes 6 and 13; for surface on chromosomes 7, 12 and 13; for quality on chromosomes 6, 7, 11 and 13; and for skin length on chromosomes 7 and 9. Proximity of locations of QTL for guard hair length, guard hair thickness and for wool density and quality suggests that some of the traits are in part under the influence of the same genes. Traits under the influence of QTL at close or identical positions also were traits that were strongly genotypically correlated. Based on the results of correlation analyses, the most important single traits influencing the quality were found to be density of wool, guard hair thickness and appearance of the surface.
National Research Strategies: what outcomes are important in peri‐operative elderly care?
Authors: Peden C. J. , Grocott M. P. W.
Published: December 2013

Outcomes are essential measures of healthcare effectiveness and efficiency. Traditional measures of outcome, such as mortality and length of stay, are important and easy to measure but have significant limitations when evaluating the peri‐operative care of elderly patients. Alternative measures, including clinician‐described (e.g. complication rates, functional status, frailty) and patient‐reported outcome and experience measures, are important to provide a comprehensive description of peri‐operative outcome in the older patient. However, few measurement tools have been developed or validated specifically for the elderly surgical patient. This paper describes the outcome measures currently in use, explores how they might be used to improve the quality of care provision, and indicates priority areas for peri‐operative outcomes research in the elderly surgical patients.
The impact of pre‐operative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review
Authors: Partridge J. S. L. , Harari D. , Martin F. C. , Dhesi J. K.
Published: December 2013

Comprehensive geriatric assessment is an established clinical approach. It reduces mortality and improves the physical wellbeing of older people in the community or hospitalised for medical reasons. Pre‐operative comprehensive geriatric assessment seems a plausible method for reducing adverse postoperative outcomes. The objectives of this systematic review and narrative synthesis are to describe how pre‐operative comprehensive geriatric assessment has been used in surgical patients and to examine the impact of comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery. We searched MEDLINE, EMBASE and Web of Science from 1980 to 2013 (week 26). We included five studies: two randomised controlled trials and three before‐and‐after intervention quasi‐experimental studies. Patient populations, interventions and outcome measures varied between studies. Both the randomised trials showed benefit on postoperative outcomes, including medical complications. Two of the before‐and‐after studies reported a positive impact on postoperative length of stay and other outcomes. The heterogeneity of study methods, populations, interventions and outcomes precluded meta‐analysis. Based on this narrative synthesis, pre‐operative comprehensive geriatric assessment is likely to have a positive impact on postoperative outcomes in older patients undergoing elective surgery, but further definitive research is required. Clinical services providing pre‐operative comprehensive geriatric assessment for older surgical patients should be considered.
Peri‐operative care of the elderly 2014
Authors:   Membership of the working party: R. Griffiths, Beech F. , Brown A. , Dhesi J. , Foo I. , Goodall J. , Harrop‐Griffiths W. , Jameson J. , Love N. , Pappenheim K. , White S.
Published: December 2013

Increasing numbers of elderly patients are undergoing an increasing variety of surgical procedures.

There is an age‐related decline in physiological reserve, which may be compounded by illness, cognitive decline, frailty and polypharmacy.

Compared with younger surgical patients, the elderly are at relatively higher risk of mortality and morbidity after elective and (especially) emergency surgery.

Multidisciplinary care improves outcomes for elderly surgical patients. Protocol‐driven integrated pathways guide care effectively, but must be individualised to suit each patient. The AAGBI strongly supports an expanded role for senior geriatricians in coordinating peri‐operative care for the elderly, with input from senior anaesthetists (consultants/associate specialists) and surgeons.

The aims of peri‐operative care are to treat elderly patients in a timely, dignified manner, and to optimise rehabilitation by avoiding postoperative complications. Effective peri‐operative care improves the likelihood of very elderly surgical patients returning to their same pre‐morbid place of residence, and maintains the continuity of their community care when in hospital.

Postoperative delirium is common, but underdiagnosed, in elderly surgical patients, and delays rehabilitation. Multimodal intervention strategies are recommended for preventing postoperative delirium.

Peri‐operative pain is common, but underappreciated, in elderly surgical patients, particularly if they are cognitively impaired. Anaesthetists should administer opioid‐sparing analgesia where possible, and follow published guidance on the management of pain in older people.

Elderly patients should be assumed to have the mental capacity to make decisions about their treatment. Good communication is essential to this process. If they clearly lack that capacity, proxy information should be sought to determine what treatment, if any, is in the patient's best interests.

Anaesthetists must not ration surgical or critical care on the basis of age, but must be involved in discussions about the utility of surgery and/or resuscitation.

The evidence base informing peri‐operative care for the elderly remains poor. Anaesthetists are strongly encouraged to become involved in national audit projects and outcomes research specifically involving elderly surgical patients.
Intergroup Ideology and Environmental Inequality
Authors: Jackson Lynne M. , Bitacola Lisa M. , Janes Leslie M. , Esses Victoria M.
Published: December 2013

Three studies showed that social dominance orientation could contribute to environmental inequality through its association with environmental and economic ideologies, pursuit of ingroup interest, and relative indifference toward groups with low economic standing. Study 1 showed that social dominance orientation is correlated with a lack of concern for the natural environment and with the endorsement of free‐market ideology. In Study 2, people higher in social dominance orientation endorsed a polluting industry that hurt a foreign population when the industry benefited their ingroup. Study 3 demonstrated that, given a choice of locations to site an environmentally problematic industry, people higher in social dominance orientation chose to direct the dangerous environmental footprint toward economically vulnerable foreign populations, and this was because of their relative lack of concern for human justice.
Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR‐ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission
Authors: van Kooten Niekerk Peter B. , Petersen Charlotte C. , Nyvold Charlotte G. , Ommen Hans B. , Roug Anne S. , Nederby Line , Hokland Peter , Kjeldsen Eigil
Published: December 2013

The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34+ stem cell and progenitor cell subpopulations were isolated by fluorescence‐activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph+) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4‐log reduction in BCR‐ABL1 expression (MR4), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA‐based qPCR in detecting residual Ph+ stem cells (P = 0·005), and detected Ph+ stem‐ and progenitor cells in 9/10 patients at frequencies of 2–14%. Moreover, while all qPCR+ samples also were iFISH+, 9/33 samples were qPCR‐/iFISH+, including all positive samples from MR4 patients. Our findings show that residual Ph+ cells are low BCR‐ABL1 producers, and that DNA‐based methods are required to assess the content of persisting Ph+ stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR4, and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.
Stability of Core Language Skill from Early Childhood to Adolescence: A Latent Variable Approach
Authors: Bornstein Marc H. , Hahn Chun‐Shin , Putnick Diane L. , Suwalsky Joan T. D.
Published: December 2013

This four‐wave prospective longitudinal study evaluated stability of language in 324 children from early childhood to adolescence. Structural equation modeling supported loadings of multiple age‐appropriate multisource measures of child language on single‐factor core language skills at 20 months and 4, 10, and 14 years. Large stability coefficients (standardized indirect effect = .46) were obtained between language latent variables from early childhood to adolescence even when accounting for child nonverbal intelligence and social competence and maternal verbal intelligence, education, speech, and social desirability. Stability coefficients were similar for girls and boys. Stability of core language skill was stronger from 4 to 10 to 14 years than from 20 months to 4 years, so early intervention to improve lagging language is recommended.
Genotype–phenotype analysis of Jervell and Lange‐Nielsen syndrome in six families from Saudi Arabia
Authors: Al‐Aama J.Y. , Al‐Ghamdi S. , Bdier A.Y. , AlQarawi A. , Jiman O.A. , Al‐Aama N. , Al‐Aata J. , Wilde A.A.M. , Bhuiyan Z.A.
Published: December 2013

We sought to explore the genotype–phenotype of Jervell and Lange‐Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS‐affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β‐Blockers abolished the cardiac‐related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region‐specific cascade screening of LQTS in Saudi Arabia.
Residual ridge dimensions at edentulous maxillary first molar sites and periodontal bone loss among two ethnic cohorts seeking tooth replacement
Authors: Acharya Aneesha , Hao Jia , Mattheos Nikos , Chau Anson , Shirke Prashant , Lang Niklaus P.
Published: December 2013

Objectives

To study residual ridge dimensions at edentulous first molar sites in relation to periodontal bone loss among cohorts of partially edentulous Asian Indian and Hong Kong Chinese subjects seeking tooth replacement.

Materials and methods

A total of 628 edentulous maxillary first molar sites were analyzed on Cone Beam Computed Tomography scans of 225 Asian Indian (I) and 232 Hong Kong Chinese (C) partially edentulous adults seeking tooth replacement. Age, ethnicity, gender, total tooth loss, the presence or absence of adjacent teeth, categories of periodontal status defined according to radiographic alveolar bone loss (P0: periodontal health, P1: incipient to moderate disease, P2: severe periodontal disease) and sinus membrane abnormalities were noted. Alveolar ridge height (RH), widths at 1 and 3 mm from crest (RW1; RW3), and relative position of the bone crest (RR) were measured.

Results

Prevalence of P2 status was most frequent in both cohorts(C: 50.4% I: 49.2%). P2 had lowest ridge heights; 13.1% C P2 and 14%I P2 had RH < 2 mm. Sites with both RH <8 mm and RW1 < 6 mm occurred at 59%C P2 and 68%I P2. Sinus membrane abnormalities were most frequent in P2. Periodontal status and sinus membrane abnormality increased the odds of RH <5 mm and RH <8 mm more than 2‐fold; additionally, gender and ethnicity significantly impacted RH <8 mm. Gender and adjacent tooth status significantly affected RW1.

Conclusion

Incident advanced periodontal disease was common among Asian Indian and Hong Kong Chinese subjects seeking tooth replacement and associated with lower available bone heights. Ethnicity, gender, sinus membrane thickening affected available bone height in the subsinus region, while the presence of adjacent teeth‐ and age‐affected residual ridge width.
Old age is associated with increased severity of complications in endoscopic biliary stone removal
Authors: Nishikawa Takao , Tsuyuguchi Toshio , Sakai Yuji , Sugiyama Harutoshi , Sakamoto Dai , Nakamura Masato , Yokosuka Osamu
Published: December 2013

Background and Aim

Various techniques are required in endoscopic biliary stone removal. Because the presence of biliary stones is a benign disease, it is essential to minimize procedure‐related complications. Having a sound knowledge of the risk factors can help reduce the number and severity of complications. We determined the risk factors for complications in patients undergoing endoscopic biliary stone removal.

Methods

This was a retrospective observational cohort study. We analyzed 743 consecutive patients with biliary stones who were treated with endoscopic retrograde cholangiopancreatography and identified the independent risk factors for complications.

Results

Complications occurred in 66 patients (8.9%). Pancreatitis occurred in 26 patients (3.5%), cholangitis in 16 (2.2%), bleeding in 12 (1.6%) and other in 12 (1.6%). Independent risk factors for overall complications were multiple biliary stones (P = 0.0480) and anti‐thrombotic drugs (P = 0.0186).Independent risk factors for moderate or severe complications were old age (P = 0.0201), multiple biliary stones (P = 0.0300), anti‐thrombotic drugs (P = 0.0131), and cirrhosis of the liver (P = 0.0013). The respective risk factors for pancreatitis, cholangitis, and bleeding were precut technique (P = 0.0005), endoscopic mechanical lithotripsy (P = 0.0421), and both anti‐thrombotic drugs (P = 0.0228) and cirrhosis of the liver (P = 0.0115).

Conclusions

Old age was associated with a similar complication rate to younger age but increased the severity of complications following endoscopic biliary stone removal. Improved awareness of the severity of complications may be of benefit during periprocedural management. Further studies are warranted.
Does a 2.5‐year self‐management education and support intervention change patterns of healthcare use in African‐American adults with Type 2 diabetes?
Authors: Yeung R. O. , Oh M. , Tang T. S.
Published: December 2013

Aims

To investigate the impact of a 2.5‐year diabetes self‐management education and support intervention on healthcare use and to examine factors associated with patterns of healthcare use.

Methods

We recruited 60 African‐American adults with Type 2 diabetes who completed a 2.5‐year empowerment‐based diabetes self‐management education and support intervention. Primary healthcare use outcomes included acute care visits, non‐acute care visits and days lost to disability. Acute care was a composite score calculated from the frequency of urgent care visits, emergency department visits and hospitalizations. Non‐acute care measured the frequency of scheduled outpatient visits. To examine change in patterns of healthcare use, we compared the frequency of healthcare visits over the 6‐month period preceding the intervention with that in the last 6 months of the intervention.

Results

No significant changes in patterns of healthcare use were found for acute care, non‐acute care or days lost to disability. Multiple regression models found higher levels of depression (P = 0.001) to be associated with a greater number of non‐acute healthcare visits, and found longer duration of diabetes (P = 0.019) and lower levels of diastolic blood pressure (P = 0.025) to be associated with fewer days lost to disability.

Conclusions

Participation in a long‐term diabetes self‐management education and support intervention had no impact on healthcare use in our sample of African‐American subjects.
Efficacy and safety of sodium glucose co‐transport‐2 inhibitors in type 2 diabetes: a meta‐analysis of randomized clinical trials
Authors: Monami M. , Nardini C. , Mannucci E.
Published: December 2013

Aims

Sodium glucose co‐transport‐2 (SGLT‐2) inhibitors, a new class of glucose‐lowering agents, reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of the present meta‐analysis is the assessment of the overall efficacy and safety profile of these drugs.

Methods

A meta‐analysis was performed including all trials with a duration of at least 12 weeks, comparing a SGLT‐2 inhibitor with a non‐SGLT‐2 inhibitor agent in type 2 diabetes. The principal outcome of this analysis was the effect of SGLT‐2 inhibitors on HbA1c at 12, 24 and 52 weeks. Hypoglycaemia, genital and urinary infections were retrieved and combined to calculate Mantel–Haenszel odds ratio (MH‐OR). Furthermore, data on body mass index (BMI), endpoint fasting plasma glucose, systolic and diastolic blood pressure, creatinine, hematocrit and lipid profile were collected.

Results

Among placebo‐controlled trials, HbA1c reduction at 12, 24 and 52 weeks was 0.5 [0.4; 0.6], 0.6 [0.6; 0.5] and 0.6 [0.7; 0.5]%. In placebo‐controlled studies, 24‐week reduction of HbA1c with SGLT‐2 inhibitors was greater in trials enrolling patients with a lower mean age and duration of diabetes, and a higher baseline BMI, HbA1c and fasting glucose. In placebo‐controlled trials, SGLT‐2 inhibitors determined a weight loss during the first 24 weeks, which was maintained up to 52 weeks.

Conclusions

SGLT‐2 inhibitors are effective in the treatment of type 2 diabetes, providing additional benefits, such as weight loss, reduction of blood pressure and increase in high‐density lipoprotein (HDL)‐cholesterol. Apart from genital and urinary infections, rather frequent but usually mild, SGLT‐2 inhibitors appear to be well tolerated.
The dipeptidylpeptidase‐IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses
Authors: Anz D. , Kruger S. , Haubner S. , Rapp M. , Bourquin C. , Endres S.
Published: December 2013

Inhibitors of dipeptidylpeptidase IV (DPP‐IV) represent a novel class of frequently used anti‐diabetic drugs. In addition to its function in metabolic regulation, DPP‐IV also plays a role in the immune system. Whether the DPP‐IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. Here, we investigated the effect of these agents on both innate and adaptive immunity. We found that the DPP‐IV inhibitors did not affect the innate immune response induced by Toll‐like receptor (TLR) ligands, as cytokine secretion and induction of co‐stimulatory molecules by human blood mononuclear cells was not impaired. Furthermore, proliferation of T cells and suppressive function of regulatory T cells was preserved. Mice treated with vildagliptin showed normal cytokine production, immune cell activation and lymphocyte trafficking upon TLR activation. Thus, crucial immunological parameters remain unaffected upon treatment with DPP‐IV inhibitors, a fact that is reassuring with respect to safety of these drugs.
Differing effects of liraglutide on gastric emptying in Japanese patients with type 2 diabetes
Authors: Nagai Y. , Hashimoto E. , Oikawa R. , Asai S. , Terashima Y. , Nakamura Y. , Sasaki Y. , Tsukiyama H. , Fukuda H. , Ohshige T. , Kato H. , Ohta A. , Tanaka Y.
Published: December 2013

This study was performed to clarify the influence of liraglutide on gastric emptying in Japanese patients with type 2 diabetes. In 16 patients, the [13C]‐acetate breath test was performed to compare gastric emptying before and after liraglutide treatment. We found two patterns of response, with gastric emptying being delayed by liraglutide in seven patients (delayers) and not delayed in nine patients (non‐delayers). The mean increase of the maximum gastric emptying time was 31 ± 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 ± 3 min (p = 0.60 vs. baseline) in the non‐delayers. The delayers showed a greater early decrease of AUC‐PG from 0 to 60 min, despite no increase of the plasma insulin level compared with non‐delayers. In conclusion, the effect of liraglutide treatment on gastric emptying shows heterogeneity, and patients can be classified as delayers or non‐delayers.
Movement rules for juvenile steelhead: dynamic linking of movement behaviour to habitat and density
Authors: Hayes Daniel B. , Thompson Bradley E.
Published: December 2013

We incorporated explanatory factors including stream habitat type and fish density into individual‐based models with dynamic connections among adjacent habitat units to infer dispersal behaviour of juvenile steelheadOncorhynchus mykissin a Great Lakes watershed. We used mark–recapture data and an inverse modelling approach to estimate daily probability of steelhead moving out of a habitat unit, P(move),according to four competing models. The models used included (i) a null model where all fish had equal movement probability; (ii) a habitat‐dependent model where P(move) depended on the habitat type; (iii) a density‐dependent model of P(move); and (iv) a model where P(move) depended on both density and habitat type. The habitat‐dependent model provided the most parsimonious fit to the observed data according to Akaike's information criteria (AICc). In the null model, P(move) averaged 0.70, whereas P(move) averaged 0.75 in pools, 0.68 in riffles and 0.73 in runs in the habitat‐dependent model.
Widespread microRNA dysregulation in multiple system atrophy – disease‐related alteration in miR‐96
Authors: Ubhi Kiren , Rockenstein Edward , Kragh Christine , Inglis Chandra , Spencer Brian , Michael Sarah , Mante Michael , Adame Anthony , Galasko Douglas , Masliah Eliezer
Published: December 2013

MicroRNA (miRNA) are short sequences of RNA that function as post‐transcriptional regulators by binding to target mRNA transcripts resulting in translational repression. A number of recent studies have identified miRNA as being involved in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the role of miRNA in multiple system atrophy (MSA), a progressive neurodegenerative disorder characterized by oligodendroglial accumulation of alpha‐synuclein remains unexamined. In this context, this study examined miRNA profiles in MSA cases compared with controls and in transgenic (tg) models of MSA compared with non‐tg mice. The results demonstrate a widespread dysregulation of miRNA in MSA cases, which is recapitulated in the murine models. The study employed a cross‐disease, cross‐species approach to identify miRNA that were either specifically dysregulated in MSA or were commonly dysregulated in neurodegenerative conditions such as Alzheimer's disease, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration or the tg mouse model equivalents of these disorders. Using this approach we identified a number of miRNA that were commonly dysregulated between disorders and those that were disease‐specific. Moreover, we identified miR‐96 as being up‐regulated in MSA. Consistent with the up‐regulation of miR‐96, mRNA and protein levels of members of the solute carrier protein family SLC1A1 and SLC6A6, miR‐96 target genes, were down‐regulated in MSA cases and a tg model of MSA. These results suggest that miR‐96 dysregulation may play a role in MSA and its target genes may be involved in the pathogenesis of MSA.
Severe polyuria and polydipsia as major clinical signs in a horse with unilateral renal adenocarcinoma
Authors: Birkmann K. , Trump M. , Dettwiler M. , Rütten M. , Wehrli Eser M.
Published: December 2013

A 14‐year‐oldSwissWarmblood gelding was presented with chronic severe polyuria, polydipsia and weight loss. At the time of admission, water intake was 240 l/day. On rectal examination, a large mass was identified in the left dorsal abdominal quadrant, which was shown to originate from the left kidney by transabdominal ultrasonographic examination. Unilateral nephrectomy via flank incision was performed under general anaesthesia. Histopathological examination of the tumour revealed a papillary renal adenocarcinoma. Successful outcome and survival was documented 13 months after surgery. Severe polyuria and polydipsia should be considered as major clinical signs for renal carcinoma in horses, which can be successfully treated with unilateral nephrectomy if no signs of metastatic spread are evident.
Variation and linkage disequilibrium between a structurally polymorphic Alu located near the OR12D2 gene of the extended major histocompatibility complex class I region and HLA‐A alleles
Authors: Kulski J. K. , Shigenari A. , Inoko H.
Published: December 2013

We investigated the genetic structure and population frequency of an Alu repeat dimorphism (absence or presence) located near the OR12D2 gene within the olfactory receptor gene region telomeric of the alpha HLA class I region (HLA‐J, ‐A, ‐G, ‐F). The structurally polymorphic Alu insertion (POALIN) locus rs33972478 that we designated as AluOR and its allele and haplotype frequencies and association with HLA‐A and six other structurally polymorphic retroelements (3 Alu, 2 SVA and an HERVK9) were determined in 100 Japanese, 174 Caucasians and 100 African American DNA samples. The AluOR insertion varied in population frequency between 14.4% and 31.5% with significant differences between the Japanese and Caucasians, but not between the Caucasian and African Americans. Although AluOR is located 600 kb from the HLA‐A gene, there was a significant linkage disequilibrium between the two loci and a high percentage association of the AluOR insertion with HLA‐A29 (79%) in Caucasians and HLA‐A31 (69.4%) in Japanese. Inferred haplotypes among three‐locus to eight‐locus haplotype structures showed maximum differences between the populations with the eight‐locus haplotypes. The most frequent multilocus haplotype shared between the populations was the HLA‐A2 allele in combination with the AluHG insertion. The AluOR whether investigated alone or together with the HLA class I alleles and other dimorphic retroelements is an informative ancestral marker for the identification of lineages and variations within the same and/or different populations and for examining the linkage and crossing‐over between the HLA and OR genomic regions in the extended MHC.
Impact of symptom improvement on patients' bother and quality of life in female patients with overactive bladder treated by solifenacin (SET‐Q)
Authors: Gotoh Momokazu , Kobayashi Toshimitsu , Sogabe Keizo
Published: December 2013

Objectives

To analyze the relationship between symptom improvement and health‐related quality of life in female overactive bladder patients treated with solifenacin.

Methods

We carried out a prospective, multicenter, open‐label study. Eligible patients were treatment‐naive female patients with overactive bladder, with an urgency episode at least once a week. Symptoms were quantitatively assessed by the Overactive Bladder Symptom Score, and quality of life by the Overactive Bladder questionnaire. Changes of symptom severity, bother, and quality of life were assessed at baseline and 12 weeks after treatment with solifenacin 5, 7.5 or 10 mg once daily.

Results

Data from 523 patients (mean age 66 years) were analyzed. Solifenacin significantly improved the total Overactive Bladder Symptom Score and also all subscores for the four symptoms (daytime frequency, urgency, night‐time frequency and urgency incontinence). Solifenacin also significantly improved the four quality of life subscales, total quality of life and symptom bother scores of the Overactive Bladder questionnaire. The severity of night‐time frequency at baseline positively affected the improvement in the quality of life subscale of Sleep, and the severity of daytime frequency at baseline positively affected the improvement of coping and social interaction. Improvement of severity in various symptoms positively affected the improvement of bother and the quality of life subscales.

Conclusions

Solifenacin provides an overall improvement of bother and quality of life in female overactive bladder patients. Symptom severity before treatment and improvement of symptom severity seem to variably affect this improvement.
“Aiding Defeated Migrants”: Institutional Strategies to Assist Polish Returned Migrants
Authors: Czerniejewska Izabela , Goździak Elżbieta M.
Published: December 2013

This article is based on an exploratory study of Polish “returned” migrants aided by the Barka Foundation, carried out in 2010 shortly after the men were returned to Poland, during the liminal stage of readjustment and decision‐making about whether to remain in Poland, return to the UK or migrate elsewhere. The interviews centred on migrants' assessment of their migration projects; engagement with Barka outreach workers; decision‐making processes about returning to Poland; assessment of most pressing needs; evaluation of provided services once they returned to Poland; and plans for the future. Discussions with service providers mirrored these themes to compare the emic or insiders' (migrants) and etic or outsiders' (programme staff's) assessment of the strategies employed to aid Polish “returned” migrants.
Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model
Authors: Guzman‐Bautista Edgar R. , Garcia‐Ruiz Carlos E. , Gama‐Espinosa Alicia L. , Ramirez‐Estudillo Carmen , Rojas‐Gomez Oscar I. , Vega‐Lopez Marco A.
Published: December 2013

Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA) ‐specific MatAb on the anti‐OVA antibody response in sera, nasal secretions and saliva from specific pathogen‐free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen‐specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti‐OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen‐specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination.
Early clearance of Mycobacterium tuberculosis: a new frontier in prevention
Authors: Verrall Ayesha J. , G. Netea Mihai , Alisjahbana Bachti , Hill Philip C. , van Crevel Reinout
Published: December 2013

Early clearance (EC) is the successful eradication of inhaled Mycobacterium tuberculosis before an adaptive immune response develops. Evidence for EC comes from case contact studies that consistently show that a proportion of heavily exposed individuals do not develop M. tuberculosis infection. Further support for the existence of this phenotype comes from genetic loci associated with tuberculin reactivity. In this review we discuss aspects of the innate response that may underpin EC and hypotheses that can be tested through field laboratory link studies in M. tuberculosis case contacts. Specifically, we consider mechanisms whereby alveolar macrophages recognize and kill intracellular M. tuberculosis, and how other cell types, such as neutrophils, natural killer T cells, mucosa‐associated invariant T cells and γδ T cells may assist. How EC may be impaired by HIV infection or vitamin D deficiency is also explored. As EC is a form of protective immunity, further study may advance the development of vaccines and immunotherapies to prevent M. tuberculosis infection.
The Characteristics Approach to the Measurement of Population Aging
Authors: Sanderson Warren C. , Scherbov Sergei
Published: December 2013

Conventional measures of population aging, such as proportions over age 65, can present a misleading picture of the aging process by not taking account of changes in people's characteristics beyond their chronological age—for example, changes in remaining life expectancy, health and morbidity, disability rates, and cognitive functioning. The “characteristics approach” set out in this article encompasses multiple features of population aging, yielding new measures that can better inform both demographic analysis and public policy debate. We relate the brief history of this approach, examine its basic mathematical structure, and give empirical examples of the insights it offers, drawing on data from West Germany, Japan, Russia, and the United States.
Regulatory variant of the TPH2 gene and early life stress are associated with heightened attention to social signals of fear in infants
Authors: Forssman Linda , Peltola Mikko J. , Yrttiaho Santeri , Puura Kaija , Mononen Nina , Lehtimäki Terho , Leppänen Jukka M.
Published: December 2013

Background

Cross‐species evidence suggests that genetic and experiential factors act early in development to establish individual emotional traits, but little is known about the mechanisms that emerge during this period to mediate long‐term outcomes. Here, we tested the hypothesis that known genetic and environmental risk conditions may heighten infants' natural tendency to attend to threat‐alerting stimuli, resulting in a cognitive bias that may contribute to emotional vulnerability.

Methods

Data from two samples of 5–7‐month‐old infants (N = 139) were used to examine whether established candidate variations in the serotonin‐system genes, i.e., TPH2 SNP rs4570625 (‐703 G/T) and HTR1A SNP rs6295 (‐1019 G/C), and early rearing condition (maternal stress and depressive symptoms) are associated with alterations in infants' attention to facial expressions. Infants were tested with a paradigm that assesses the ability to disengage attention from a centrally presented stimulus (a nonface control stimulus or a neutral, happy, or fearful facial expression) toward the location of a new stimulus in the visual periphery (a geometric shape).

Results

TPH2 ‐703 T‐carrier genotype (i.e., TT homozygotes and heterozygotes), presence of maternal stress and depressive symptoms, and a combination of the T‐carrier genotype and maternal depressive symptoms were associated with a relatively greater difficulty disengaging attention from fearful facial expressions. No associations were found with infants' temperamental traits.

Conclusions

Alterations in infants' natural attentional bias toward fearful facial expressions may emerge prior to the manifestation of emotional and social behaviors and provide a sensitive marker of early emotional development.
Factors associated with good glycemic control among patients with type 2 diabetes mellitus
Authors: Ahmad Nur Sufiza , Islahudin Farida , Paraidathathu Thomas
Published: December 2013

Aims/Introduction

The aim of the present study was to determine the status of glycemic control and identify factors associated with good glycemic control among diabetic patients treated at primary health clinics.

Materials and Methods

A systematic random sample of 557 patients was selected from seven clinics in the Hulu Langat District. Data were collected from patients' medication records, glycemic control tests and structured questionnaires. Logistic regression analysis was carried out to predict factors associated with good glycemic control.

Results

Variables associated with good glycemic control included age (odds ratio 1.033; 95% confidence interval 1.008–1.059) and duration of diabetes mellitus (odds ratio 0.948; 95% confidence interval 0.909–0.989). Compared with the patients who were receiving a combination of insulin and oral antidiabetics, those receiving monotherapy (odds ratio 4.797; 95% confidence interval 1.992–11.552) and a combination of oral antidiabetics (odds ratio 2.334; 95% confidence interval 1.018–5.353) were more likely to have good glycemic control. In the present study, the proportion of patients with good glycemic control was lower than that in other published studies. Older patients with a shorter duration of diabetes who were receiving monotherapy showed better glycemic control.

Conclusions

Although self‐management behavior did not appear to influence glycemic control, diabetic patients should be consistently advised to restrict sugar intake, exercise, stop smoking and adhere to medication instructions. Greater effort by healthcare providers in the primary health clinics is warranted to help a greater number of patients achieve good glycemic control.