bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic architecture of neurodevelopmental disorders
Authors: Mitchell Kevin J.
Published: September 2014

Neurodevelopmental disorders include rare conditions caused by identified single mutations, such as Fragile X, Down and Angelman syndromes, and much more common clinical categories such as autism, epilepsy and schizophrenia. These common conditions are all highly heritable but their genetics is considered to be “complex”. In fact, this sharp dichotomy in genetic architecture between rare and common disorders may be largely artificial. On the one hand, much of the apparent complexity in the genetics of common disorders may derive from underlying genetic heterogeneity, which has remained obscure until recently. On the other hand, even for supposedly Mendelian conditions, the relationship between single mutations and clinical phenotypes is rarely simple. The categories of monogenic and complex disorders may therefore merge across a continuum, with some mutations being strongly associated with specific syndromes and others having a more variable outcome, modified by the presence of additional genetic variants.
Regulated assembly and disassembly of the yeast telomerase quaternary complex
Authors: Tucey Timothy M. , Lundblad Victoria
Published: September 2014

The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein and two regulatory subunits (Est1 and Est3) in association with the TLC1 RNA, with each of the four subunits essential for in vivo telomerase function. We show here that a hierarchy of assembly and disassembly results in limiting amounts of the quaternary complex late in the cell cycle, following completion of DNA replication. The assembly pathway, which is driven by interaction of the Est3 telomerase subunit with a previously formed Est1–TLC1–Est2 preassembly complex, is highly regulated, involving Est3-binding sites on both Est2 and Est1 as well as an interface on Est3 itself that functions as a toggle switch. Telomerase subsequently disassembles by a mechanistically distinct pathway due to dissociation of the catalytic subunit from the complex in every cell cycle. The balance between the assembly and disassembly pathways, which dictate the levels of the active holoenzyme in the cell, reveals a novel mechanism by which telomerase (and hence telomere homeostasis) is regulated.
The structure of a tetrameric α-carbonic anhydrase fromThermovibrio ammonificansreveals a core formed around intermolecular disulfides that contribute to its thermostability
Authors: James Paul , Isupov Michail N. , Sayer Christopher , Saneei Vahid , Berg Svein , Lioliou Maria , Kotlar Hans Kristian , Littlechild Jennifer A.
Published: September 2014

Carbonic anhydrase enzymes catalyse the reversible hydration of carbon dioxide to bicarbonate. A thermophilicThermovibrio ammonificansα-carbonic anhydrase (TaCA) has been expressed inEscherichia coliand structurally and biochemically characterized. The crystal structure of TaCA has been determined in its native form and in two complexes with bound inhibitors. The tetrameric enzyme is stabilized by a unique core in the centre of the molecule formed by two intersubunit disulfides and a single lysine residue from each monomer that is involved in intersubunit ionic interactions. The structure of this core protects the intersubunit disulfides from reduction, whereas the conserved intrasubunit disulfides are not formed in the reducing environment of theE. colihost cytosol. When oxidized to mimic the environment of the periplasmic space, TaCA has increased thermostability, retaining 90% activity after incubation at 70°C for 1 h, making it a good candidate for industrial carbon-dioxide capture. The reduction of all TaCA cysteines resulted in dissociation of the tetrameric molecule into monomers with lower activity and reduced thermostability. Unlike other characterized α-carbonic anhydrases, TaCA does not display esterase activity towardsp-nitrophenyl acetate, which appears to result from the increased rigidity of its protein scaffold.
Visualization of a substrate-induced productive conformation of the catalytic triad of theNeisseria meningitidispeptidoglycanO-acetylesterase reveals mechanistic conservation in SGNH esterase family members
Authors: Williams Allison H. , Veyrier Frédéric J. , Bonis Mathilde , Michaud Yann , Raynal Bertrand , Taha Muhamed-Kheir , White Stephen W. , Haouz Ahmed , Boneca Ivo G.
Published: September 2014

PeptidoglycanO-acetylesterase (Ape1), which is required for host survival inNeisseriasp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.
Low-dose X-ray radiation induces structural alterations in proteins
Authors: Borshchevskiy Valentin , Round Ekaterina , Erofeev Ivan , Weik Martin , Ishchenko Andrii , Gushchin Ivan , Mishin Alexey , Willbold Dieter , Büldt Georg , Gordeliy Valentin
Published: September 2014

X-ray-radiation-induced alterations to protein structures are still a severe problem in macromolecular crystallography. One way to avoid the influence of radiation damage is to reduce the X-ray dose absorbed by the crystal during data collection. However, here it is demonstrated using the example of the membrane protein bacteriorhodopsin (bR) that even a low dose of less than 0.06 MGy may induce structural alterations in proteins. This dose is about 500 times smaller than the experimental dose limit which should ideally not be exceeded per data set (i.e.30 MGy) and 20 times smaller than previously detected specific radiation damage at the bR active site. To date, it is the lowest dose at which radiation modification of a protein structure has been described. Complementary use was made of high-resolution X-ray crystallography and online microspectrophotometry to quantitatively study low-dose X-ray-induced changes. It is shown that structural changes of the protein correlate with the spectroscopically observed formation of the so-called bR orange species. Evidence is provided for structural modifications taking place at the protein active site that should be taken into account in crystallographic studies which aim to elucidate the molecular mechanisms of bR function.
Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6′)-Ie-APH(2′′)-Ia revealed by crystallographic and small-angle X-ray scattering analysis
Authors: Smith Clyde A. , Toth Marta , Weiss Thomas M. , Frase Hilary , Vakulenko Sergei B.
Published: September 2014

Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6′)-Ie-APH(2′′)-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6′)-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2′′)-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6′)-Ie-APH(2′′)-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2′′)-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6′)-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6′)-Ie enzyme is joined to APH(2′′)-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2′′)-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6′)-Ie-APH(2′′)-Ia enzyme.
Crystal structure of 1,3-bis(4-hexyl-5-iodothiophen-2-yl)-4,5,6,7-tetrahydro-2-benzothiophene
Authors: Linshoeft Julian , Näther Christian , Staubitz Anne
Published: September 2014

In the crystal structure of the title compound, C28H36I2S3, a terthiophene monomer, the central thiophene unit is arrangedanti-coplanar to the two outer thiophene rings. There are two crystallographically independent molecules in the asymmetric unit, which show different conformations. In one molecule, the dihedral angles between the inner and the two outer thiophene rings are 15.7 (3) and 3.47 (3)°, whereas these values are 4.2 (3) and 11.3 (3)° for the second molecule. Differences are also found in the arrangement of the hexyl chains: in one of the two molecules, both chains are nearly in plane to the central moiety, whereas in the second molecule, only one chain is in plane and the other one is nearly perpendicular to the central moiety. Some of the C atoms are disordered and were refined using a split model with occupancy ratios of 0.65:0.35 and 0.70:0.30 in the two molecules.
Crystal structure of di-μ-methanolato-bis{[N′-(1-benzoylprop-1-en-2-yl)thiophene-2-carbohydrazidato-κ3O,N′,O′]oxidovanadium(V)}
Authors: Carroccia Murilo C. , Pesci Rafaela B. P. , Maia Pedro Ivo da S. , Deflon Victor M.
Published: September 2014

The neutral binuclear molecule of the title complex, [V2(C15H12N2O2S)2(CH3O)2O2], exhibits inversion symmetry and consists of two oxidovanadium(V) (VO)3+fragments, each coordinated by a dianionic andO,N′,O′-chelatingN′-(1-benzoylprop-1-en-2-yl)thiophene-2-carbohydrazidate ligand. The V5+cations are bridged by two asymmetrically bonding methanolate ligands [V—O = 1.8155 (12) and 2.3950 (13) Å] originating from the deprotonation of the methanol solvent. The coordination sphere of the VVatom is distorted octahedral, with the equatorial plane defined by the three donor atoms of the thiophene-2-carbohydrazidate ligand and the O atom of a methanolate unit. The axial positions are occupied by the oxide group and the remaining methanolate ligand. The axially bound methanolate ligand shows a longer V—O bond length due to thetransinfluence caused by the tightly bonded oxide group. The packing of the complex molecules is dominated by dispersion forces.
Crystal structure of bis[4-(4-chlorobenzyl)pyridine-κN]bis(thiocyanato-κN)zinc
Authors: Werner Julia , Neumann Tristan , Jess Inke , Näther Christian
Published: September 2014

In the crystal structure of the title compound, [Zn(NCS)2(C12H10ClN)2], the Zn2+cation isN-coordinated by two terminally bonded thiocyante anions and by two 4-(4-chlorobenzyl)pyridine ligands within a slightly distorted tetrahedron. The asymmetric unit consists of half of the discrete complex, the central Zn2+cation of which is located on a twofold rotation axis. The discrete complexes are linked into layersviaa weak intermolecular hydrogen-bonding interaction, with a H...Cl distance of 2.85 Å and a C—H...Cl angle of 151°. These layers extend parallel to theabplane and are held together by dispersion forces only.
Crystal structure of dimethyl 3,3′-[(4-chlorophenyl)methylene]bis(1H-indole-2-carboxylate)
Authors: Li Yu-long , Sun Hong-shun , Jiang Hong , Xu Ning , Xu Hong
Published: September 2014

In the title compound, C27H21ClN2O4, the mean planes of the two indole ring systems (r.m.s. deviations = 0.021 and 0.024 Å) are approximately perpendicular to one another, with a dihedral angle of 79.54 (12)°. The benzene ring is twisted with respect to the mean planes of the two indole ring systems at angles of 80.14 (15) and 86.30 (15)°. In the crystal, molecules are linked by N—H...O hydrogen bonds, forming inversion dimers with anR22(18) ring motif. The dimers are linked by a further N—H...O hydrogen bond, forming chains along [100]. There are intra- and intermolecular C—H...π interactions present, the latter linking the chains to form a three-dimensional supramolecular structure.
Impact of export market orientation on export performance
Authors: Lin Ku-Ho , Huang Kuo-Feng , Peng Yao-Ping
Published: September 2014

Purpose

– The purpose of this paper is to explore the mediating role of export market orientation (EMO) in the relationship between inter-organizational relationships and export performance, and the moderating role of degree of internationalization in the relationship between EMO and export performance.

Design/methodology/approach

– The authors sent questionnaires to the 1,000 largest manufacturers listed inCommonWealthmagazine (2009), and a random sample of 500 machinery manufacturers listed in the Taiwan Association of Machinery Industry Directory. The authors received 244 completed questionnaires through which to examine the hypotheses.

Findings

– The findings show that trust and social interaction positively influence EMO, which then enhances export performance. However, the moderating effect of degree of internationalization has no significant impact on the EMO and export performance relationship.

Research limitations/implications

– Future studies should conduct two-way research on focal firms (manufacturers) and overseas partners (agents or distributors) through common variables including trust, commitment, satisfaction, etc. The results indicate that the content validity of the present study is somewhat inadequate, possibly due to the cultural differences involved.

Practical implications

– Overseas information exchange between exporters and partners fosters firms’ export performance. Thus, closer relationships with channel partners or customers via trust and social interactions may help firms to conduct appropriate EMO activities to access overseas market information and improve export performance.

Originality/value

– By investigating Taiwanese exporters, who tend to emphasize relational capital, the authors determine that EMO is important in understanding how inter-organizational relationships influence export performance. The authors also contribute a more comprehensive view to the literature.
Survival of the fattest? Indices of body condition do not predict viability in the brown anole (Anolis sagrei)
Authors: Cox Robert M. , Calsbeek Ryan
Published: September 2014

Measures of body mass and length are commonly used to derive indices of condition, which are often assumed to reflect the energetic state of an animal and, by extension, to predict its fitness. However, the relationship between condition and fitness is rarely quantified, and the appropriate method(s) for deriving indices of condition are frequently debated.

Data from a decade of mark–recapture studies involving over 4,600 individual lizards (Anolis sagrei) and 41 replicates of selection across seven populations were used to test the common assumption that condition, as estimated from body mass and length, is a strong predictor of adult survival, an important component of fitness. Inferences about natural selection were compared between two alternative indices of condition: the popular residual index (Ri), and the scaled mass index (Mi), which was recently proposed as a more appropriate method.

Linear, quadratic and correlational selection gradients obtained using Ri and Mi were highly correlated with one another. Relative to variance in selection among replicates and to error associated with the estimation of selection gradients, variance due to the use of alternative condition indices was minor and effectively negligible.

Contrary to the intuitive prediction that individuals in better condition should exhibit higher survival, there was no evidence for strong or consistent linear (directional) selection for higher condition indices in either males or females. Significant quadratic (stabilizing or disruptive) selection on condition was similarly rare in both sexes. Correlational selection favoured combinations of large size and high condition in males, but not females.

Collectively, these results indicate that inferences about natural selection may be robust to the choice between indices of condition but that indices of condition can be unreliable as proxies for fitness, particularly when relationships between fitness components and condition are contingent upon interactions with other traits.
Predator‐free space, functional responses and biological invasions
Authors: Barrios‐O'Neill Daniel , Dick Jaimie T. A. , Emmerson Mark C. , Ricciardi Anthony , MacIsaac Hugh J.
Published: September 2014

Predator–prey interactions are mediated by the structural complexity of habitats, but disentangling the many facets of structure that contribute to this mediation remains elusive. In a world replete with altered landscapes and biological invasions, determining how structure mediates the interactions between predators and novel prey will contribute to our understanding of invasions and predator–prey dynamics in general.

Here, using simplified experimental arenas, we manipulate predator‐free space, whilst holding surface area and volume constant, to quantify the effects on predator–prey interactions between two resident gammarid predators and an invasive prey, the Ponto‐Caspian corophiidChelicorophium curvispinum.

Systematically increasing predator‐free space alters the functional responses (the relationship between prey density and consumption rate) of the amphipod predators by reducing attack rates and lengthening handling times. Crucially, functional response shape also changes subtly from destabilizingTypeIItowards stabilizingTypeIII, such that small increases in predator‐free space to result in significant reductions in prey consumption at low prey densities.

Habitats with superficially similar structural complexity can have considerably divergent consequences for prey population stability in general and, particularly, for invasive prey establishing at low densities in novel habitats.
The evolution of Hessian fly from the Old World to the New World: Evidence from molecular markers
Authors: Schemerhorn Brandon J. , Crane Yan Ma , Crane Charles F.
Published: September 2014

Eighteen polymorphic microsatellite loci and 11 single‐nucleotide polymorphisms were genotyped in 1 095 individual Hessian fly specimens representing 23 populations from North America, southern Europe, and southwest Asia. The genotypes were used to assess genetic diversity and interrelationship of Hessian fly populations. While phylogenetic analysis indicates that the American populations most similar to Eurasian populations come from the east coast of the United States, genetic distance is least between (Alabama and California) and (Kazakhstan and Spain). Allelic diversity and frequency vary across North America, but they are not correlated with distance from the historically documented point of introduction in New York City or with temperature or precipitation. Instead, the greatest allelic diversity mostly occurs in areas with Mediterranean climates. The microsatellite data indicate a general deficiency for heterozygotes in Hessian fly. The North American population structure is consistent with multiple introductions, isolation by distance, and human‐abetted dispersal by bulk transport of puparia in infested straw or on harvesting equipment.
Genetic identification of endangered North African ungulates using noninvasive sampling
Authors: Silva Teresa Luísa , Godinho Raquel , Castro Diana , Abáigar Teresa , Brito José Carlos , Alves Paulo Célio
Published: September 2014

North African ungulates include several threatened and emblematic species, yet are poorly studied mainly due to their remoteness and elusiveness. Noninvasive sampling provides a useful approach to obtain ecological and genetic information essential to guide conservation actions. The very first and most important step in conservation planning is to accurately identify species, and molecular genetics has been proved to be a useful tool. Several molecular genetics protocols are available for species identification, even for samples with poor quality DNA, such as faeces, hairs or bones. Most of these protocols use mitochondrial DNA for barcoding despite this marker being especially prone to problems, including mtDNA introgression, nuclear insert copies, high intraspecific diversity or heteroplasmy. In this work, we developed a molecular method based on polymorphisms in small fragments of the mitochondrial cytochrome b (cytb, mtDNA) and the nuclear kappa casein genes (KCAS, nDNA) for identifying endangered North African ungulates. These fragments revealed polymorphisms, including species‐specific variation, which allowed species identification of nine ungulate species that co‐occur in North Africa. The method was validated across more than 400 samples, including different types of noninvasive samples collected in the field. The simplicity, high reliability and relative low cost of the described method make it a promising tool to improve ecological studies of the North African ungulates and consequently, the implementation of more efficient management and conservation plans for these endangered ungulates.
Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden
Authors: Westman J. , Wahlbeck K. , Laursen T. M. , Gissler M. , Nordentoft M. , Hällgren J. , Arffman M. , Ösby U.
Published: September 2014

Objective

To analyse mortality and life expectancy in people with alcohol use disorder in Denmark, Finland and Sweden.

Method

A population‐based register study including all patients admitted to hospital diagnosed with alcohol use disorder (1 158 486 person‐years) from 1987 to 2006 in Denmark, Finland and Sweden.

Results

Life expectancy was 24–28 years shorter in people with alcohol use disorder than in the general population. From 1987 to 2006, the difference in life expectancy between patients with alcohol use disorder and the general population increased in men (Denmark, 1.8 years; Finland, 2.6 years; Sweden, 1.0 years); in women, the difference in life expectancy increased in Denmark (0.3 years) but decreased in Finland (−0.8 years) and Sweden (−1.8 years). People with alcohol use disorder had higher mortality from all causes of death (mortality rate ratio, 3.0–5.2), all diseases and medical conditions (2.3–4.8), and suicide (9.3–35.9).

Conclusion

People hospitalized with alcohol use disorder have an average life expectancy of 47–53 years (men) and 50–58 years (women) and die 24–28 years earlier than people in the general population.
Microorganisms in the Female Genital Tract during Pregnancy: Tolerance versus Pathogenesis
Authors: Ramos Bruna de Andrade , Kanninen Tomi T. , Sisti Giovanni , Witkin Steven S.
Published: September 2014

Microorganisms in the pregnant female genital tract are not always associated with pathology. The factors that influence the maternal response to microorganisms remain ill defined. We review the state of knowledge of microbe–host interactions in gestational tissues and highlight mechanisms that promote tolerance or pathogenesis. Tolerance to microorganisms is promoted during pregnancy by several mechanisms including upregulation of anti‐inflammatory mediators, induction of endotoxin tolerance, and possibly by regulation of autophagy. Conversely, an altered vaginal microbiota or a pre‐existing viral presence may result in induction of excessive inflammation and preterm labor. Although infections play a prevalent role in preterm birth, microbes are present in gestational tissues of women with healthy outcomes and may provide beneficial functions. The complex interactions between different microbial species and the maternal immune system during gestation remain incompletely elucidated.
Adolescent alcohol use: Social comparison orientation moderates the impact of friend and sibling behaviour
Authors: Litt Dana M. , Stock Michelle L. , Gibbons Frederick X.
Published: September 2014

Objectives

Research has indicated that both peers and siblings influence adolescents’ alcohol use (e.g., Windle, 2000, Appl. Dev. Sci., 4, 98). The present two studies examined whether social comparison orientation (SCO) moderates the effects of perceived friend and sibling alcohol use on adolescents’ alcohol use cognitions and behaviours.

Design and methods

Two studies examined the role of SCO as a moderator of social influence (perceived friend alcohol use in Study 1 and both perceived friend use and sibling‐reported alcohol use in Study 2) on prototype perceptions and willingness to drink alcohol (Studies 1 and 2) as well as actual alcohol consumption (Study 2) among early adolescents.

Results

In Study 1, cross‐sectional results indicated that SCO moderated the effect of perceived friend alcohol use on favourable images of drinkers and willingness to drink. Study 2 found that SCO moderated the effects of perceived friend use and sibling use on favourable images of alcohol users, willingness to use alcohol, and change in alcohol use over 3 years such that adolescents who reported engaging in social comparison more often reported greater willingness, more favourable images, and increases in alcohol use when perceived friend use or sibling use was high.

Conclusions

These studies highlight the importance of SCO as a moderator of susceptibility to the social influences of friends and siblings and may hold important implications for adolescent alcohol use prevention programmes and models of health risk behaviour.

Statement of contribution

What is already known on this subject? The prevalence of adolescent alcohol use continues to be a public health concern and research has indicated that alcohol use during adolescence is often influenced by the behaviour of friends and siblings.

What does this study add? Results add to the literature on the importance of examining person‐level moderators such as of peer and sibling influence on alcohol use cognitions and behaviour according to the prototype/willingness model. Results suggest that considering social comparison orientation as an individual difference variable that may influence adolescents’ decisions to engage in alcohol use can potentially increase the efficacy of existing alcohol use programs.
Do people with shortened dental arches have worse oral health‐related quality of life than those with more natural teeth? A population‐based study
Authors: Tan Haiping , Peres Karen G. , Peres Marco A.
Published: September 2014

Objective

To test whether people with shortened dental arches (SDA) have impaired oral health‐related quality of life than those with more natural teeth.

Method

We analysed data from the 2004–2006 Australian National Survey of Adult Oral Health (including telephone interview, oral epidemiological examinations and mailed questionnaire). Participants aged ≥15 years and with intact anterior teeth were eligible in this study. We used multivariable negative binomial regression analyses to test the association of SDA, according to two alternative definition (1. having intact teeth and 3‐5 natural occlusal units; 2. having intact anterior teeth and four natural occlusal units), with OHIP‐14 severity and extent, adjusting for potential confounders, including demographic variables (age and sex), socioeconomic variables (income and education), behaviour characteristics (time since last visit, reason for the last dental visit, difficult in paying $100 dental bill and dental insurance possession), and dental outcomes (coronal and root caries, and periodontal disease).

Result

We analysed on 2,750 dentate participants that were eligible for the study. When SDA was classified as intact anterior teeth, four occlusal units and no dental prosthesis, no statistical difference in OHIP‐14 severity or extent was identified compared with those with intact anterior teeth, over four occlusal units and no dental prosthesis. Participants who presented intact anterior teeth, 3‐5 occlusal units and no prosthesis showed 50% higher rates of OHIP‐14 severity than those with intact anterior teeth, over five occlusal units and no prosthesis while their OHIP‐14 extent was similar to that of the reference group.

Conclusion

SDA is not associated with negative impacts on quality of life, according to both OHIP‐14 severity and extent, when SDA is defined as four occlusal units and no dental prosthesis. When SDA is defined as 3‐5 occlusal units and no dental prosthesis, it is only associated with OHIP‐14 severity, but not OHIP‐14 extent.
Food consumption, obesity and abnormal glycaemic control in a Canadian Inuit community
Authors: Singer J. , Putulik Kidlapik C. , Martin B. , Dean H. J. , Trepman E. , Embil J. M
Published: September 2014

Dietary and lifestyle factors may contribute to diabetes and obesity in the Canadian Inuit. We documented dietary patterns, physical activity level, obesity, blood glucose abnormalities and diabetes prevalence in a Canadian Inuit community. There were 250 Inuit residents of Repulse Bay, Nunavut, who had an interview about diet and physical activity, measurement of weight and height, and laboratory studies (194 subjects). Children, adolescents and younger adults (aged < 48 years) consumed significantly less country food and more processed snack foods and sweet drinks than older adults (aged ≥ 48 years). Only 88 of 250 subjects (35%) reported that they went out on the land once or more per week. Of the 85 children and adolescent subjects (aged 7–17 years), 11 (13%) were obese. Average body mass index for adults (aged ≥ 18 years) was 29 ± 6 kg m–2, and 61 adults (37%) were obese (body mass index ≥30 kg m–2). In the 140 adults who had laboratory studies, 18 adults (13%) had a blood glucose abnormality, including 10 adults (7%) with impaired fasting glucose, four adults (3%) with impaired glucose tolerance and six adults (4%) with diabetes (five adults previously undiagnosed). Twelve of the 194 subjects tested (6%) had fasting insulin ≥140 pmol L–1 (mean, 196 ± 87 pmol L–1). In summary, there was a high prevalence of poor dietary choices, limited physical activity, obesity and type 2 diabetes in this Inuit community. Public health programmes are needed to improve the dietary and health status of this community.
Expression of the p40 isoform of p63 has high specificity for cutaneous sarcomatoid squamous cell carcinoma
Authors: Ha Lan Thanh T. , Chen Stephanie J. T. , Arps David P. , Fullen Douglas R. , Patel Rajiv M. , Siddiqui Javed , Carskadon Shannon , Palanisamy Nallasivam , Harms Paul W.
Published: September 2014

Cutaneous spindle cell malignancies such as sarcomatoid squamous cell carcinoma (SCC), leiomyosarcoma, desmoplastic melanoma (DM) and atypical fibroxanthoma (AFX) may be morphologically indistinguishable, yet accurate diagnosis is important for appropriate clinical management. The distinction among these entities relies on immunohistochemical evaluation for epidermal, muscle or melanocytic differentiation. Epidermal differentiation markers include cytokeratins and p63. p63 is expressed as two distinct isoforms, ΔNp63 (p40) and TAp63. p40 positivity is highly specific for pulmonary SCC and head and neck sarcomatoid SCC. We examined the utility of p40 vs. p63 immunostaining in the differentiation of a variety of cutaneous spindle cell malignancies, including sarcomatoid SCC (n = 27), AFX (n = 34) and DM (n = 10). p40 was less sensitive than p63 for detecting sarcomatoid SCC (56% and 81%, respectively). p63 and p40 were comparably specific for sarcomatoid SCC relative to AFX, with only rare weak staining of tumor cells for p63 and/or p40 in a minority of AFX cases, including one case with approximately 10% of cells staining weakly for p40. All cases of DM were negative for p40 and p63. Our results support continued use of p63 for diagnosis of cutaneous sarcomatoid SCC because of greater sensitivity relative to p40.
Psychosis patients' knowledge, adherence and attitudes towards the naming of antipsychotic medication inHongKong
Authors: Lau Karen Chi‐Kwan , Lee Edwin Ho‐Ming , Hui Christy Lai‐Ming , Chang Wing‐Chung , Chan Sherry Kit‐Wa , Chen Eric Yu‐Hai
Published: September 2014

Aim

Non‐adherence to medication is a common and significant challenge to successful treatment of psychosis. Knowledge of prescribed antipsychotic medication may influence psychosis patients' willingness to adhere to prescriptions. This study aimed to assess knowledge of psychosis patients on their prescribed antipsychotic medication with regard to drug name, type, dosage, purpose, side effects and reasons for taking medication, so as to investigate the associations between knowledge and adherence. The study also aimed to evaluate patient attitudes towards the currentChinese name of ‘anti‐psyche drug’ for antipsychotic medication inHongKong, and survey patients' opinions on alternative names for antipsychotic medication.

Methods

A questionnaire was administered to 70 consecutive patients from the psychiatric ward and outpatient clinic atQueenMaryHospital inHongKong.

Results

Current knowledge ofHongKong psychosis patients falls short in areas of drug name (51.4% unaware), drug type (40% unaware) and prescribed dosage (28.6% unaware). The rate of self‐reported non‐adherence in the study sample was 38.6%. Adherence to medication was found to be positively associated with knowledge of purpose for taking medication. The current Chinese name ‘anti‐psyche drug’ had a rating of 47/100 among psychosis patients.

Conclusion

Measures should be taken to improve patient knowledge in areas of drug name, type and prescribed dosage. Reminding patients about the purpose of medication may also benefit adherence and overall treatment. Finally, because of the possible stigma of the current name of antipsychotic medication, an alternative term may be more favourable in promoting its acceptance inHongKong.
Delimiting Family in Syntheses of Research on Childhood Chronic Conditions and Family Life
Authors: Knafl Kathleen , Leeman Jennifer , Havill Nancy , Crandell Jamie , Sandelowski Margarete
Published: September 2014

Synthesis of family research presents unique challenges to investigators who must delimit what will be included as a family study in the proposed review. In this paper, the authors discuss the conceptual and pragmatic challenges of conducting systematic reviews of the literature on the intersection between family life and childhood chronic conditions. A proposed framework for delimiting the family domain of interest is presented. The framework addresses both topical salience and level of relevance and provides direction to future researchers, with the goal of supporting the overall quality of family research synthesis efforts. For users of synthesis studies, knowledge of how investigators conceptualize the boundaries of family research is important contextual information for understanding the limits and applicability of the results.
Sex‐ and age‐related differences in mid‐thigh composition and muscle quality determined by computed tomography in middle‐aged and elderly Japanese
Authors: Kasai Takehiro , Ishiguro Naoki , Matsui Yasumoto , Harada Atsushi , Takemura Marie , Yuki Atsumu , Kato Yuki , Otsuka Rei , Ando Fujiko , Shimokata Hiroshi
Published: September 2014

Aim

Sex‐ and age‐related differences in mid‐thigh composition and muscle quality remain unclear. The present study aimed to clarify these differences using computed tomography in middle‐aged and elderly Japanese.

Methods

A total of 2310 participants (age 40–89 years), who were randomly selected from the local residents, underwent computed tomography examination of the right mid‐thigh. Thigh circumference and cross‐sectional areas of the thigh, muscle, quadriceps, non‐quadriceps, fat, and bone were measured. Knee extension strength and muscle quality index (knee extension strength/quadriceps cross‐sectional area) were also assessed. Sex‐ and age‐related differences in these indices were analyzed.

Results

The thigh cross‐sectional area in men and women decreased by 0.6% and 0.5%/year, respectively, because of a decrease in muscle cross‐sectional area (men 75.2%, women 40.6%), fat cross‐sectional area (men 24.4%, women 59.6%) and bone cross‐sectional area (men 0.5%, women −0.2%). Muscle cross‐sectional area in men and women decreased by 0.6% and 0.4%/year, respectively, because of a decrease in quadriceps cross‐sectional area (men 65.6%, women 81.6%) and non‐quadriceps cross‐sectional area (men 34.4%, women 18.4%). Muscle quality in men and women decreased by 0.4% and 0.3%/year, respectively.

Conclusion

Thigh cross‐sectional area decreased with age mainly because of a decrease in muscle cross‐sectional area in men and fat cross‐sectional area in women. The rate of decrease in muscle cross‐sectional area was 1.5‐fold higher in men than in women. Muscle cross‐sectional area decreased with age mainly because of a decrease in quadriceps cross‐sectional area, especially in women. Decrease in muscle quality with age was similar in both sexes. Geriatr Gerontol Int 2015; 15: 700–706.
Senescence is involved in the pathogenesis of chronic obstructive pulmonary disease through effects on telomeres and the anti‐aging molecule fibroblast growth factor 23
Authors: Ishii Takeo , Gemma Akihiko , Kida Kozui
Published: September 2014

Aim

Fibroblast growth factor 23 knockout mice develop premature aging and emphysema, indicating that dysregulation of the normal aging process is involved in the pathobiology of chronic obstructive pulmonary disease. Thus, we explored the association among a coding single‐nucleotide polymorphism of fibroblast growth factor 23, its protein concentration in serum and telomere length in patients with chronic obstructive pulmonary disease.

Methods

The study involved 361 smokers; among whom, 244 were patients with chronic obstructive pulmonary disease. We genotyped a coding single‐nucleotide polymorphism of fibroblast growth factor 23, rs7955866, and measured the telomere length of the peripheral blood cells. We also determined emphysema severity and airflow obstruction using computed tomography and pulmonary function tests, respectively. Furthermore, we analyzed the association between the disease phenotypes and fibroblast growth factor 23 genotypes or telomere length of peripheral blood leukocytes, as well as the association between the serum level of the studied protein and its genotypes.

Results

The mice with A alleles on rs7955866 showed severe upper lung emphysema (P = 0.008). The serum concentration of the tested protein was lower in the mice with A allele than in the G homozygotes (P = 0.004). Telomere shortening was associated with airflow obstruction (P = 0.009), but not with upper lung emphysema.

Conclusions

A variation of fibroblast growth factor 23 with a reduced serum concentration appeared to promote emphysema formation. Telomere shortening in peripheral blood leukocytes was not associated with emphysema, but with airflow obstruction in chronic obstructive pulmonary disease through an independent mechanism. Geriatr Gerontol Int 2015; 15: 827–833.
Prognostic factors associated with adverse outcome among critically ill elderly patients admitted to the intensive care unit
Authors: Orsini Jose , Butala Ashvin , Salomon Say , Studer Sean , Gadhia Shardul , Shamian Ben , Prajapati Ramesh , Blaak Christa
Published: September 2014

Introduction

Despite concerns over the appropriateness and quality of care provided in the intensive care unit (ICU) at the end of life, the number of elderly patients who receive critical care is increasing. Despite this, many physicians have doubts as to whether elderly patients are good candidates for ICU care because of the apparently poor outcome during and after critical care in this population. The objective of the present study was to describe the clinical characteristics and outcome of a geriatric population admitted to the ICU.

Materials and methods

A single‐center, prospective, observational study was carried out among geriatric patients, aged 75 years or older, admitted to ICU.

Results

A total of 71 patients were admitted to ICU during the study period. Their mean age was 83 years (range 75–98 years), with a mean Acute Physiology and Chronic Health Evaluation‐II score of 21.8 (range 8–39) on admission to ICU. A total of 48 patients (68%) required mechanical ventilation, and 39 (55%) received at least one vasoactive drug. The mean ICU length of stay was 4.6 days (range 1–18 days), and it was similar for ICU survivors and non‐survivors (4.7 vs 4.5). A total of 14 patients (19.7%) were admitted after cardiac arrest, and eight (57.1%) of them died in ICU. A total of 28 patients (39.4%) died in the hospital, and 18 (25.4%) died in ICU.

Conclusion

Advanced age, critical illness, cardiopulmonary resuscitation, and needs for mechanical ventilation and/or vasopressor therapy are independent risk factors associated with adverse outcome in elderly patients admitted to ICU. Alternatives for ICU admission should be considered in geriatric patients with severe critical illnesses. Geriatr Gerontol Int 2015; 15: 889–894.
Association between the physical activity and heart rate corrected‐QT interval in older adults
Authors: Michishita Ryoma , Fukae Chika , Mihara Rikako , Ikenaga Masahiro , Morimura Kazuhiro , Takeda Noriko , Yamada Yosuke , Higaki Yasuki , Tanaka Hiroaki , Kiyonaga Akira ,   The Nakagawa Study Group
Published: September 2014

Aim

Increased physical activity can reduce the incidence of cardiovascular disease and the mortality rate. In contrast, a prolonged heart rate corrected‐QT (QTc) interval is associated with an increased risk of arrhythmias, sudden cardiac death and coronary artery disease. The present cross‐sectional study was designed to clarify the association between the physical activity level and the QTc interval in older adults.

Methods

The participants included 586 older adults (267 men and 319 women, age 71.2 ± 4.7 years) without a history of cardiovascular disease, who were taking cardioactive drugs. Electrocardiography was recorded with a standard resting 12‐lead electrocardiograph, while the QTc interval was calculated according to Hodges' formula. The physical activity level was assessed using a triaxial accelerometer. The participants were divided into four categories, which were defined equally quartile distributions of the QTc interval.

Results

After adjusting for age, body mass index, waist circumference and the number of steps, the time spent in inactivity was higher and the time spent in light physical activity was significantly lower in the longest QTc interval group than in the shortest QTc interval group in both sexes (P < 0.05, respectively). However, there were no significant differences in the time spent in moderate and vigorous physical activities among the four groups in either sex.

Conclusions

These results suggest that a decreased physical activity level, especially inactivity and light intensity physical activity, were associated with QTc interval in older adults. Geriatr Gerontol Int 2015; 15: 895–901.
Independent association between serum C‐peptide levels and fat mass‐to‐lean mass ratio in the aging process
Authors: Li Ying , Zheng Lian Shun , Li Yue , Zhao Duo Duo , Meng Lu
Published: September 2014

Aim

The changes in body composition and biomarker levels that occur during the aging process are complex and remain poorly understood. The present study aimed to evaluate changes in serum C‐peptide levels and fat mass‐to‐lean mass ratio (FM/LM ratio) with increasing age, and to explore the associations between serum C‐peptide levels and FM/LM ratio.

Methods

This was a population‐based cross‐sectional study that included 3912 participants aged 30–85 years. Body composition was measured using dual‐energy X‐ray absorptiometry. Analysis of covariance was used to evaluate how the serum C‐peptide level and FM/LM ratio change with increasing age, as well as how the FM/LM ratio changes in line with increasing serum C‐peptide level. A multiple linear regression analysis was carried out to determine the association between serum C‐peptide level and FM/LM ratio.

Results

Analysis of covariance showed that serum C‐peptide levels, and most regional FM/LM ratios tended to increase in line with increasing age. Total fat mass, total lean mass, percentage total fat mass and total FM/LM ratio were significantly elevated, and percentage total lean mass decreased significantly with increasing serum C‐peptide levels in both men and women. Multiple linear regression analysis showed that serum C‐peptide level was strongly associated with the total FM/LM ratio.

Conclusions

The findings showed that both serum C‐peptide level and FM/LM ratio increased with increasing age, and the serum C‐peptide level was closely associated with changes in the total FM/LM ratio. Geriatr Gerontol Int 2015; 15: 918–926.
Comorbidities in elderly patients with asthma: Association with control of the disease and concomitant treatment
Authors: Wardzyńska Aleksandra , Kubsik Beata , Kowalski Marek Leszek
Published: September 2014

Aim

The incidence of concomitant conditions increases with age. In elderly patients, the presence of comorbidities has been related to the course and severity of asthma. The aim of the present study was to assess the impact of comorbidities and concomitant treatment on asthma control and severity in older adults.

Methods

A total of 93 elderly (age >65 years) and 78 younger (age 30–50 years) asthmatic patients were randomly selected from a database including 1755 asthmatics. Evaluation consisted of a questionnaire, spirometry and skin prick testing.

Results

In elderly asthmatics, a higher incidence of chronic comorbidities (mean 8.4 vs 4.7; P < 0.001) and a higher number of prescribed medicines (7.4 vs 4.5, P < 0.001) were observed, but the severity of asthma and the intensity of anti‐asthma treatment were similar to that seen in younger patients. Asthma control was not strikingly different between the groups. There was no correlation between the presence of comorbid conditions and asthma control, severity or frequency of exacerbations in older patients. Elderly patients treated with statins had a lower risk of asthma exacerbation (OR 0.39, 95% CI 0.18–0.84, P = 0.017), whereas treatment with proton pump inhibitors was associated with a higher risk of exacerbations in older adults (OR 1.84, 95% CI 1.07–3.18, P = 0.029) and higher disease severity in younger patients (OR 2.49, 95% CI 1.1–5.67, P = 0.029).

Conclusion

The higher prevalence of comorbidities observed in elderly asthmatics under specialist care do not seem to be associated with worsened asthma control or severity. However, concomitant medications can significantly affect asthma control in both elderly and younger asthmatics. Geriatr Gerontol Int 2015; 15: 902–909.