bluuebunny/crossref_metadata_2025 huggingface dataset:
Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk
Authors: ten Broeke Sanne W. , Brohet Richard M. , Tops Carli M. , van der Klift Heleen M. , Velthuizen Mary E. , Bernstein Inge , Capellá Munar Gabriel , Gomez Garcia Encarna , Hoogerbrugge Nicoline , Letteboer Tom G.W. , Menko Fred H. , Lindblom Annika , Mensenkamp Arjen R. , Moller Pal , van Os Theo A. , Rahner Nils , Redeker Bert J.W. , Sijmons Rolf H. , Spruijt Liesbeth , Suerink Manon , Vos Yvonne J. , Wagner Anja , Hes Frederik J. , Vasen Hans F. , Nielsen Maartje , Wijnen Juul T.
Published: December 2014

Purpose

The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers.

Methods

Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome–associated cancers.

Results

The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis.

Conclusion

CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.
Impact of Continuous Versus Discontinuous Progesterone on Estradiol Regulation of Neuron Viability and Sprouting After Entorhinal Cortex Lesion in Female Rats
Authors: Barron Anna M. , Brown Meghan A. , Morgan Todd E. , Pike Christian J.
Published: December 2014

Because the estrogen-based hormone therapy (HT) in postmenopausal women typically contains a progestogen component, understanding the interactions between estrogens and progestogens is critical for optimizing the potential neural benefits of HT. An important issue in this regard is the use of continuous vs discontinuous hormone treatments. Although sex steroid hormone levels naturally exhibit cyclic fluctuation, many HT formulations include continuous delivery of hormones. Recent findings from our laboratory and others have shown that coadministration of progesterone (P4) can either attenuate or augment beneficial actions of 17β-estradiol (E2) in experimental models depending in part upon the delivery schedule of P4. In this study, we demonstrate that the P4 delivery schedule in combined E2 and P4 treatments alters degenerative and regenerative outcomes of unilateral entorhinal cortex lesion. We assessed how lesion-induced degeneration of layer II neurons in entorhinal cortex layer and deafferentation in dentate gyrus are affected by ovariectomy and treatments with E2 alone or in combination with either continuous or discontinuous P4. Our results demonstrate the combined efficacy of E2 and P4 is dependent on the administration regimen. Importantly, the discontinuous-combined E2+P4 regimen had the greatest neuroprotective efficacy for both end points. These data extend a growing literature that indicates qualitative differences in the neuroprotective effects of E2 as a function of cotreatment with continuous versus discontinuous P4, the understanding of which has important implications for HT in postmenopausal women.
Mouse and human blastocyst-derived stem cells: vive les differences
Authors: Rossant Janet
Published: December 2014

Lessons learned from conserved vertebrate developmental pathways have catalyzed rapid advances in pluripotent stem cell differentiation towards therapeutically relevant cell types. The most highly conserved phases of development are associated with the early patterning of the body plan – the so-called phylotypic stage. Both prior to and after this stage there is much more divergence across species. Developmental differences between human and mouse at the blastocyst and early post-implantation stages might help explain the differences among the different stem cell lines derived from these embryos. A better understanding of these early stages of human development will aid our ability to generate and manipulate human stem cells and their derivatives.
Modelling sustainable caseloads for MS specialist nurses
Authors: Mynors Geraldine , Bowen Amy
Published: December 2014

Background:

There are 245 Multiple Sclerosis (MS) specialist nurses (MSSNs) across the UK, with variable caseloads, suggesting inequitable and, where caseloads are particularly high, inadequate provision.

Aim:

The MS Trust set out to establish a ‘sustainable’ caseload for an MS specialist nurse, providing a high-quality, proactive service to patients with MS throughout the disease trajectory.

Method:

An expert consensus group agreed standards for MSSN services and assumptions about their working patterns and practices; this process was informed by ‘real world’ data from 40 MSSNs taking part in the MS Trust GEMSS programme. A simple model was then used to determine the sustainable number of cases an MSSN could manage.

Results:

The model showed that a caseload of 358 people with MS per full-time specialist nurse is sustainable.

Conclusions:

A number of conditions must be met, including well thought out job plans, sufficient administrative support, an effective home visit policy and a high level of use of clinic capacity.
The role of botulinum toxin A in the management of neurogenic lower urinary tract symptoms
Authors: Rantell Angie
Published: December 2014

Urinary incontinence associated with neurogenic detrusor overactivity is a common and distressing disorder in patients with chronic neurological conditions. When conservative therapy and antimuscarinic agents fail to treat or improve symptoms, intra-detrusor injections of botulinum toxin A may be considered. This article outlines the history of botulinum toxin A and its use in the management of neurogenic detrusor overactivity. Clinical issues such as patient selection, risks and benefits, and how to appropriately counsel patients prior to considering this treatment are discussed.
Stoma care accessories: don't be overwhelmed
Authors: Cronin Elaine
Published: December 2014

Elaine Cronin examines the most commonly used stoma accessory products, discussing how and when they are used. She hopes the article brings knowledge and guidance for those looking after patients with stomas and for carers looking after residents in care homes
Care home insurance: ensuring managers' peace of mind
Authors: Ashurst Adrian
Published: December 2014

In this article, the second in the series on care home insurance matters, Nursing and Residential Care's Consultant Editor Adrian Ashurst, discusses the importance of keeping your care home fit for purpose and insurable
How can your care home comply with the ‘well led’ key question?
Authors: Frankova Helena
Published: December 2014

This article on how CQC will form their view of whether particular social care services are ‘well led’ concludes our review of each of the key questions in CQC's new style comprehensive inspections. What can your care home do to prepare for your inspection?
Viability in using avocado pulp with soy extract in yogurt processing: rheological and sensory analysis.
Authors: Guimarães Daniela Helena Pelegrine , Calado Amanda Ribeiro
Published: December 2014

This paper proposed development of avocado yogurt with soy extract, as well as rheological properties and sensory parameters analysis. The rheological properties were measured in a concentric cylinders rotational. The results showed the different yogurt formulations behaved as a pseudoplástic fluid, presenting also some thixotropy, since the apparent viscosity decreased for the same sample, probably due the suspended particles sedimentation. With regard to sensory analysis results, it could be noted significant difference among the different formulations, especially for flavor attribute, although all the formulations were well accepted by the tasters.

DOI: 10.14685/rebrapa.v5i3.149

 

 
Monitoring the future behaviour of urban drainage
system under climate change: a case study from
north-western England
Authors: Osman Yassin Z.
Published: December 2014

Catchments hydrological conditions and responses
are anticipated to be affected by the changes in
weather patterns, increasing in climate variability and extreme
rainfall. Thus, engineers have no choice but to consider
climate change in their practices in order to adapt
and serve the public interests. This paper is an exploration
of the impacts of climate change on the hydrology that
underlies the hydraulic design of urban drainage system.
Future rainfall has been downscaled from the Global Climate
Model (GCM) employing a hybrid Generalised Linear
Model (GLM) and Artificial Neural Network (ANN) downscaling
techniques under different greenhouse emission
scenarios. The output from this model is applied to a combined
sewer system of an urban drainage catchment in the
Northwest of England during the 21st Century to monitor
its future behaviour in winter and summer seasons. Potential
future changes in rainfall intensity are expected to alter
the level of service of the system, causing more challenges
in terms of surface flooding and increase in surcharge
level in sewers. The results obtained demonstrate
that there is a real chance for these effects to take place
and therefore would require more attention from designers
and catchment managers.
A reliable algorithm for positive solutions of nonlinear boundary value problems by the multistage Adomian decomposition method
Authors: Duan Jun-Sheng , Rach Randolph , Wazwaz Abdul-Majid
Published: December 2014

In this paper, we present a reliable algorithm to calculate positive solutions of homogeneous nonlinear boundary value problems (BVPs). The algorithm converts the nonlinear BVP to an equivalent nonlinear Fredholm– Volterra integral equation.We employ the multistage Adomian decomposition method for BVPs on two or more subintervals of the domain of validity, and then solve the matching equation for the flux at the interior point, or interior points, to determine the solution. Several numerical examples are used to highlight the effectiveness of the proposed scheme to interpolate the interior values of the solution between boundary points. Furthermore we demonstrate two novel techniques to accelerate the rate of convergence of our decomposition series solutions by increasing the number of subintervals and adjusting the lengths of subintervals in the multistage Adomian decomposition method for BVPs.
Frames and constructions enhance text coherence: The case of DNI resolutions in spoken discourse
Authors: Ziem Alexander
Published: December 2014

The paper reports on a corpus-based study investigating the impact of frames and constructions on establishing text coherence. Partly conducted in collaboration with the International Computer Science Institute / FrameNet, Berkeley, the study is based on systematic annotations of so-called Definite Null Instantiations (DNIs). A DNI, sometimes also called anaphoric NI, is a syntactically non-instantiated core frame element (FE), whose identity can be inferred from the co(n)text. By analyzing forms and functions of DNIs in spoken discourse, I will argue that omitted core FEs are often found to be specified in adjacent sentences, yielding frame-triggered text coherence. The case study sheds light on the text-linguistic relevance of frames and constructions. At the same time it paves the way for further investigations of textual reference in a cognitive-linguistic framework.
Figurative processes in meaning interpretation: A case study of novel English compounds
Authors: Onysko Alexander
Published: December 2014

This article contributes to cognitive semantic research on the construal of figurative meaning in noun-noun compounds. Previous studies in this field have shown a predilection towards using conceptual blending theory in order to describe the process of meaning formation in nominal compounds. Observations have largely been based on analyses of established compounds and their conventionalized meanings. The current paper explores an alternative approach and methodology. A study was conducted in which participants were asked to interpret the meaning of a set of novel noun-noun compounds. These meaning descriptions are taken as an empirical base to investigate figurative interpretations. Since previous applications of conceptual blending theory have highlighted some limitations of describing meaning construal in compounds, and since the relation between conceptual blending and related processes of conceptual metaphor and metonymy has not been clarified yet, the analysis in the current study takes a step back and relies on conceptual metaphor and metonymy. Besides providing an overview of the amount of figurative meaning interpretations given to the different test items, the paper pays particular attention to the methodological challenges of applying conceptual metaphor and metonymy theory in the attempt to capture the figurative nature of the meaning descriptions. A close analysis of selected meaning interpretations provides a first impression on how applying conceptual metaphor and metonymy can pave the way towards a more differentiated understanding of associative complexity in figurative meaning interpretations.
Geographic variation of quite + ADJ in twenty national varieties of English: A pilot study
Authors: Levshina Natalia
Published: December 2014

This paper aims to show how large-scale corpus data can be used for bottom-up modelling of semantic differences between geographical variants of one construction. More specifically, it investigates the geographic variation of quite as a degree modifier of adjectives in twenty national written varieties of English. Based on semantic classes of more than 6,000 adjectives in almost 240,000 occurrences of quite + ADJ from the Global Web-based English corpus, as well as additional data collected directly from the World Wide Web, the quantitative analyses reveal systematic geographic differences in the use of quite. In addition, a distributional Vector Space Model is created that represents the aggregate similarities and differences between the geographic variants of quite + ADJ in a clustering solution, which is interpreted with the help of a distinctive collexeme analysis.
A usage-based study of the just me construction
Authors: Bai Yinchun
Published: December 2014

A number of recent studies have emphasized the need for Construction Grammar to address the discourse-pragmatic characteristics of grammatical constructions. Much of how Construction Grammar incorporates pragmatic considerations of contextual factors into its descriptions of speakers’ linguistic knowledge remains to be worked out. In order to take a step towards that goal, this corpus-based study presents the just me construction and analyzes it from compositional, semantic and pragmatic perspectives. The study first delivers an in-depth description of the constrained and conventionalized composition of the construction. Then it proposes that the intricate semantic content is the result of formal and conceptual blending of the alternative question construction and the truncated it-cleft construction. Third, the pragmatic aspects of the just me construction are analyzed in terms of its hedging function, possible response patterns, and the conventionalized nature of its non-compositional meaning. All contribute to the recognition of the just me construction as a symbolic unit in the grammar of English. In conclusion, after a summary of the points made in previous sections, the insights gleaned from the present case study will be used to reflect in more general terms on the role of pragmatic considerations of contextual factors in Construction Grammar.
Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls
Authors: Chin Vivian L. , Cai Ziyong , Lam Leslie , Shah Bina , Zhou Ping
Published: December 2014

Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test.

To determine the best predictive model for detecting puberty in girls.

Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15).

Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed.

The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%.

The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.
Determinants of (–1,1)-matrices of the skew-symmetric type: a cocyclic approach
Authors: Álvarez Víctor , Armario José Andrés , Frau María Dolores , Gudiel Félix
Published: December 2014

An n by n skew-symmetric type (-1; 1)-matrix K =[ki;j ] has 1’s on the main diagonal and ±1’s elsewhere with ki;j =-kj;i . The largest possible determinant of such a matrix K is an interesting problem. The literature is extensive for n ≡ 0 mod 4 (skew-Hadamard matrices), but for n ≡ 2 mod 4 there are few results known for this question. In this paper we approach this problem constructing cocyclic matrices over the dihedral group of 2t elements, for t odd, which are equivalent to (-1; 1)-matrices of skew type. Some explicit calculations have been done up to t =11. To our knowledge, the upper bounds on the maximal determinant in orders 18 and 22 have been improved.
Absolutely strongly star-Hurewicz spaces
Authors: Song Yan-Kui
Published: December 2014

A space X is absolutely strongly star-Hurewicz if for each sequence (Un :n ∈ℕ/ of open covers of X and each dense subset D of X, there exists a sequence (Fn :n ∈ℕ/ of finite subsets of D such that for each x ∈X, x ∈St(Fn; Un) for all but finitely many n. In this paper, we investigate the relationships between absolutely strongly star-Hurewicz spaces and related spaces, and also study topological properties of absolutely strongly star-Hurewicz spaces.
Nonrecursive solution for the discrete algebraic Riccati equation and X + A*X-1A=L
Authors: Adam Maria , Assimakis Nicholas
Published: December 2014

In this paper, we present two new algebraic algorithms for the solution of the discrete algebraic Riccati
equation. The first algorithm requires the nonsingularity of the transition matrix and is based on the solution of a
standard eigenvalue problem for a new symplectic matrix; the proposed algorithm computes the extreme solutions
of the discrete algebraic Riccati equation. The second algorithm solves the Riccati equation without the assumption
of the nonsingularity of the transition matrix; the proposed algorithm is based on the solution of the matrix equation
X + A*X-1A=L, where A is a singular matrix and L a positive definite matrix.
Pointwise density topology
Authors: Górajska Magdalena
Published: December 2014

The paper presents a new type of density topology on the real line generated by the pointwise convergence, similarly to the classical density topology which is generated by the convergence in measure. Among other things, this paper demonstrates that the set of pointwise density points of a Lebesgue measurable set does not need to be measurable and the set of pointwise density points of a set having the Baire property does not need to have the Baire property. However, the set of pointwise density points of any Borel set is Lebesgue measurable.
Complete and sufficient statistics and perfect families in orthogonal and error orthogonal normal models
Authors: Areia Aníbal , Carvalho Francisco , Mexia João T.
Published: December 2014

We will discuss orthogonal models and error orthogonal models and their algebraic structure, using as background, commutative Jordan algebras. The role of perfect families of symmetric matrices will be emphasized, since they will play an important part in the construction of the estimators for the relevant parameters. Perfect families of symmetric matrices form a basis for the commutative Jordan algebra they generate. When normality is assumed, these perfect families of symmetric matrices will ensure that the models have complete and sufficient statistics. This will lead to uniformly minimum variance unbiased estimators for the relevant parameters.
Generalizations of Nekrasov matrices and applications
Authors: Cvetković Ljiljana , Kostić Vladimir , Nedović Maja
Published: December 2014

In this paper we present a nonsingularity result which is a generalization of Nekrasov property by using two different permutations of the index set. The main motivation comes from the following observation: matrices that are Nekrasov matrices up to the same permutations of rows and columns, are nonsingular. But, testing all the permutations of the index set for the given matrix is too expensive. So, in some cases, our new nonsingularity criterion allows us to use the results already calculated in order to conclude that the given matrix is nonsingular. Also, we present new max-norm bounds for the inverse matrix and illustrate these results by numerical examples, comparing the results to some already known bounds for Nekrasov matrices.
Computing the numerical range of Krein space operators
Authors: Bebiano Natalia , da Providência J. , Nata A. , da Providência J.P.
Published: December 2014

Consider the Hilbert space (H,〈• , •〉) equipped with the indefinite inner product[u,v]=v*J u,u,v∈ H, where J is an indefinite self-adjoint involution acting on H. The Krein space numerical range WJ(T) of an operator T acting on H is the set of all the values attained by the quadratic form [Tu,u], with u ∈H satisfying [u,u]=± 1. We develop, implement and test an alternative algorithm to compute WJ(T) in the finite dimensional case, constructing 2 by 2 matrix compressions of T and their easily determined elliptical and hyperbolical numerical ranges. The numerical results reported here indicate that this method is very efficient, since it is faster and more accurate than either of the existing algorithms. Further, it may yield easy solutions for the inverse indefinite numerical range problem. Our algorithm uses an idea of Marcus and Pesce from 1987 for generating Hilbert space numerical ranges of matrices of size n.
Rare types of breast carcinoma
Authors: Gudaviciene Daiva , Steponaviciene Laura , Meskauskas Raimundas , Smailyte Giedre , Aleknavicius Eduardas
Published: December 2014

Breast cancer (BC) is a heterogeneous disease
that encompasses several distinct entities with remarkably
different characteristics. Histological type is one of
important BC characteristics. Histological type is associated
with differences in epidemiology, diagnostic issues,
clinical course, prognosis. When we talk about BC, ductal
and lobular carcinoma is usually what we have in mind.
However, the other types that comprise less than 10% of
BC are also very important. The rarity of many of these
neoplasms does not allow large or randomized studies
to define the optimal treatment. Many of the descriptions
are from case reports and small series. The aim of this retrospective
study was to analyze the data on rare breast
cancers, to describe their main characteristics, and to
calculate survival rates. We believe that the experience of
our institution will contribute to the available data about
these rare breast cancers and help in better understanding
of this subgroup.
Preparation and application of fluorinated-siloxane protective surface coating material for stone inscriptions
Authors: Li Pengling , Qiu Fengxian , Zhang Xiaoying , Wang Lili , Chen Qian , Yang Dongya
Published: December 2014

A series of fluorinated-siloxane protective surface coating materials (FPA/SiO2) were prepared with different contents of dodecafluoroheptyl methacrylate (DFMA) and fixed content of siloxane. The properties of FPA/SiO2 protective materials were investigated by the methods of Fourier transform infrared spectroscopy (FT-IR) spectra, UV-Vis spectrum, transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The surface morphology and mineralogical analysis of the fresh and weathered stone samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. The artificial ageing test, which was commonly used as a criterion for the evaluation of the protective ability of FPA/SiO2 coating material, was performed. The results indicate that when the content of DFMA is 30 wt.% and the content of SiO2 is 10 wt.%, the prepared coating material has good comprehensive performances. The artificial ageing test shows that the protective surface coating material has good compatibility with and similar appearance to stone relics. The effect of FPA/SiO2 protective coating material for protection of Jiaoshan Steles Grove (China) is noticeable and it can be widely applied to the protection of stone relics.
Combination of montmorillonite and a Schiff-base polyphosphate ester to improve the flame retardancy of ethylene-vinyl acetate copolymer
Authors: Liu Yan , Fang Zhengping
Published: December 2014

Different flame retardant ethylene-vinyl acetate copolymer (EVA) formulations were prepared to evaluate the synergistic effect between organo-montmorillonite (OMMT) and a Schiff-base polyphosphate ester (PAB) on the combustion behavior of EVA. X-ray diffraction (XRD) and transmission electron microscopy (TEM) results revealed that montmorillonite platelets selectively dispersed in the PAB phase. EVA/PAB/OMMT(80/15/5) had better thermal stability and flame retardancy than EVA/PAB(80/20), as indicated by the results of thermogravimetric analysis (TGA), limited oxygen index (LOI), vertical burning test (UL-94) and microscale combustion colorimeter (MCC), showing a synergism between OMMT and PAB. For example, the onset decomposition temperature (T
5%) increased from 233°C to 296°C, the char residue at 600°C increased from 6.6% to 11.0%, and the peak heat release rate (PHRR) decreased from 718.1 W/g to 706.6 W/g. This is caused by the silicoaluminophosphate (SAPO) structure formed by reactions between the phosphoric acid generated from PAB and OMMT.
Eloquence and Education. School Rhetoric in Eighteenth-Century Sweden
Authors: Rimm Stefan
Published: December 2014

The following contribution will examine the form and content of school rhetoric in the Latin schools of early modern Sweden. After an introduction to the schools, an outline of their curricular heritage will be given, situating school rhetoric in the classical trivium. Three components of rhetorical education are identified: the theoretical teaching, the reading of exemplary texts, and the exercises, all three components displaying a striking traditionalism and stability during the eighteenth century. Furthermore, it will be shown that rhetorical education also served as a means of instilling virtue in pupils and that rhetoric was an essential component in the reproduction of a representative learned culture and in the formation of virtuous character and erudite identity.
Böcke, Bunkel und Tantenbekehrer. Johann Friedrich Löwens Beredsamkeit des Leibes und die Bockiade August Friedrich Cranz‘. Eine Lesart
Authors: Palm Mathias
Published: December 2014

The following contribution will demonstrate the differences between Löwen’s theory in his Kurzgefaste Grundsatze von der Beredsamkeit des Leibes and the satirical Fragment eines Schreibens uber den Ton in den Schriften einiger teutschen Gelehrten und Schongeister by August Friedrich Cranz. Löwen’s Kurzgefaste Grundsatze is concerned with the art of physical expression on the stage, provides also information on facets of the contemporary image of the body. These facets should be traced in Fragment eines Schreibens, which became known as Bockiade. August Friedrich Cranz, only ten years younger than Löwen, was an representative of the Berlin Enlightenment. He commented on the social and cultural developments in the last three decades of the 18th century. His satire not only mentioned the great minds of the time. He commented the feud between the Berlin publisher, bookseller and author Friedrich Nicolai and the poet, translator and editor Christoph Martin Wieland in Weimar in his satirical writing.
On His Terms, In My Words
Authors: Jenkins David M.
Published: December 2014

This narrative is an exploration of the complicated relationship between my father and me as he battled cancer. It hopefully contributes to the field of qualitative inquiry at large, particularly in the domains of family, loss, and grief. This text shifts in time, tense, and voice. Part homage, part confession, it looks at the notion of voice from different angles.
Mutations in the ‘DRY’ motif of the CB1 cannabinoid receptor result in biased receptor variants
Authors: Gyombolai Pál , Tóth András D , Tímár Dániel , Turu Gábor , Hunyady László
Published: December 2014

The role of the highly conserved ‘DRY’ motif in the signaling of the CB1cannabinoid receptor (CB1R) was investigated by inducing single-, double-, and triple-alanine mutations into this site of the receptor. We found that the CB1R-R3.50A mutant displays a partial decrease in its ability to activate heterotrimeric Goproteins (∼80% of WT CB1R (CB1R-WT)). Moreover, this mutant showed an enhanced basal β-arrestin2 (β-arr2) recruitment. More strikingly, the double-mutant CB1R-D3.49A/R3.50A was biased toward β-arrs, as it gained a robustly increased β-arr1 and β-arr2 recruitment ability compared with the WT receptor, while its G-protein activation was decreased. In contrast, the double-mutant CB1R-R3.50A/Y3.51A proved to be G-protein-biased, as it was practically unable to recruit β-arrs in response to agonist stimulus, while still activating G-proteins, although at a reduced level (∼70% of CB1R-WT). Agonist-induced ERK1/2 activation of the CB1R mutants showed a good correlation with their β-arr recruitment ability but not with their G-protein activation or inhibition of cAMP accumulation. Our results suggest that G-protein activation and β-arr binding of the CB1R are mediated by distinct receptor conformations, and the conserved ‘DRY’ motif plays different roles in the stabilization of these conformations, thus mediating both G-protein- and β-arr-mediated functions of CB1R.
Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity
Authors: Kooptiwut Suwattanee , Hanchang Wanthanee , Semprasert Namoiy , Junking Mutita , Limjindaporn Thawornchai , Yenchitsomanus Pa-thai
Published: December 2014

Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin–angiotensin–aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47phox mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47phox mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47phox. In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.
Family-Initiated Dialogue About Medications During Family-Centered Rounds
Authors: Benjamin Jessica M. , Cox Elizabeth D. , Trapskin Philip J. , Rajamanickam Victoria P. , Jorgenson Roderick C. , Weber Holly L. , Pearson Rachel E. , Carayon Pascale , Lubcke Nikki L.
Published: December 2014

BACKGROUND AND OBJECTIVE:

Experts suggest family engagement in care can improve safety for hospitalized children. Family-centered rounds (FCRs) can offer families the opportunity to participate in error recovery related to children’s medications. The objective of this study was to describe family-initiated dialogue about medications and health care team responses to this dialogue during FCR to understand the potential for FCR to foster safe medication use.

METHODS:

FCR were video-recorded daily for 150 hospitalized children. Coders sorted family-initiated medication dialogue into mutually exclusive categories, reflecting place of administration, therapeutic class, topic, and health care team responses. Health care team responses were coded to reflect intent, actions taken by the team, and appropriateness of any changes.

RESULTS:

Eighty-three (55%) of the 150 families raised 318 medication topics during 347 FCR. Most family-initiated dialogue focused on inpatient medications (65%), with home medications comprising 35%. Anti-infectives (31%), analgesics (14%), and corticosteroids (11%) were the most commonly discussed medications. The most common medication topics raised by families were scheduling (24%) and adverse drug reactions (11%). Although most health care team responses were provision of information (74%), appropriate changes to the child’s medications occurred in response to 8% of family-initiated dialogue, with most changes preventing or addressing adverse drug reactions or scheduling issues.

CONCLUSIONS:

Most families initiated dialogue regarding medications during FCRs, including both inpatient and home medications. They raised topics that altered treatment and were important for medication safety, adherence, and satisfaction. Study findings suggest specific medication topics that health care teams can anticipate addressing during FCR.
Vitamin D in Fetal Development: Findings From a Birth Cohort Study
Authors: Hart Prue H. , Lucas Robyn M. , Walsh John P. , Zosky Graeme R. , Whitehouse Andrew J.O. , Zhu Kun , Allen Karina L. , Kusel Merci M. , Anderson Denise , Mountain Jenny A.
Published: December 2014

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks’ pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989–1991. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 36% (323 of 901) of the pregnant women. After adjusting for relevant covariates, maternal vitamin D deficiency during pregnancy was associated with impaired lung development in 6-year-old offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at 20 years. In summary, vitamin D may have an important, multifaceted role in the development of fetal lungs, brain, and bone. Experimental animal studies support an active contribution of vitamin D to organ development. Randomized controlled trials of vitamin D supplementation in pregnant women with long-term follow-up of offspring are urgently required to examine whether the correction of vitamin D deficiency in pregnant women is beneficial for their offspring and to determine the optimal level of maternal serum 25(OH)D for fetal development.
Core Symptoms of Autism Improved After Vitamin D Supplementation
Authors: Jia Feiyong , Wang Bing , Shan Ling , Xu Zhida , Staal Wouter G. , Du Lin
Published: December 2014

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. Among the environmental factors, vitamin D3 (cholecaliferol) seems to play a significant role in the etiology of ASD because this vitamin is important for brain development. Lower concentrations of vitamin D3 may lead to increased brain size, altered brain shape, and enlarged ventricles, which have been observed in patients with ASD. Vitamin D3 is converted into 25-hydroxyvitamin D3 in the liver. Higher serum concentrations of this steroid may reduce the risk of autism. Importantly, children with ASD are at an increased risk of vitamin D deficiency, possibly due to environmental factors. It has also been suggested that vitamin D3 deficiency may cause ASD symptoms. Here, we report on a 32-month-old boy with ASD and vitamin D3 deficiency. His core symptoms of autism improved significantly after vitamin D3 supplementation. This case suggests that vitamin D3 may play an important role in the etiology of ASD, stressing the importance of clinical assessment of vitamin D3 deficiency and the need for vitamin D3 supplementation in case of deficiency.
“Hospitality of the Heart – Hospitality for the Human Spirit”
Authors: Connell Sharon , Beardsley Christina
Published: December 2014

This article is based on action research conducted with the Multi-faith Chaplaincy team at Chelsea and Westminster Hospital, south-west London. The research began by exploring the question “In what kind of spaces does spiritual care take place and how do chaplains discover, offer, or create such spaces?” The method was Ballard and Pritchard’s pastoral cycle – experience, exploration, reflection and action – and a focus group model. Discussion centred on how chaplains can enable spiritual care to happen in prescribed places, in spaces of opportunity, and how they can discover, create and offer such spaces. The theme of hospitality was identified as an essential aspect of the chaplain’s role, which is both to give and to receive. Further reflection has highlighted actions which have been taken forward to change, enhance and renew the provision of spiritual care provided by the Multi-faith Chaplaincy Team, particularly on the Trust’s Neo-Natal Unit. It has also informed further opportunities for multi-disciplinary working to enhance spiritual care. We recommend action research both for chaplaincy and multi-disciplinary teams, as well as the use of the pastoral or reflective cycle which offers a dynamic combination of experience, exploration reflection – including theological themes – and action.
LABORATORINIŲ TYRIMŲ PREANALIZĖS PERIODU SLAUGYTOJŲ DAŽNIAUSIAI DAROMOS KLAIDOS
Authors: Jerdiakova Natalja , Mikaliūkštienė Aldona , Gierasimovič Zita , Kalibatienė Danutė
Published: December 2014

Reikšminiai žodžiai: preanalizės periodas, analitė, ėminių technika, venos punkcija. Tikslas. Šiuo tyrimu buvo siekiama išanalizuoti klinikinių laboratorinių veninio kraujo tyrimų preanalizės periodu slaugytojų dažniausiai daromas klaidas. Tyrimo medžiaga ir metodai. Tyrime buvo stebėti 104 laboratorinių tyrimų preanalizės periodo etapai renkant kraują skirtingiems tyrimams. Tyrimo metodus apima: veninio kraujo ėminių preanalizės periodų stebėjimas bei slaugytojų atliekamų veiksmų fiksavimas, medicininės paciento dokumentacijos nagrinėjimas. Slaugytojų atliekamiems veiksmams fiksuoti buvo sudarytas stebėjimo dienynas, paruoštas remiantis moksline literatūra bei galiojančiais Lietuvoje teisės aktais. Stebėjimo dienynas apima: analitės paskirtį, slaugytojų veiksmus iki veninio kraujo ėminio, punkcijos vietos parinkimą ir paruošimą, ėminių saugojimo laiką ir sąlygas, transportavimo būdas. Duomenų analizė atlikta naudojant „SPSS Windows (v. 20.0)“, „Excel 2010“ (v. 14.0) programas. Kintamųjų ir klaidų dažnių pasiskirstymui vertinti sudarytos dažnių lentelės, kuriose pateiktas absoliutus skaičius ir procentinės reikšmės. Kokybinių bei kiekybinių kintamųjų reikšmių grupėms palyginti sudarytos požymių dažnių kryžminės lentelės. Statistinio ryšio stiprumui nustatyti skaičiuotas Spirmeno koreliacijos koeficientas (rs). Skirtumai laikyti statistiškai reikšmingi, kai paklaidos tikimybės reikšmė p ≤ 0,05. Rezultatai ir išvados. Ruošdamosi paimti kraujo slaugytojos padarė 220 klaidų, iš jų priemonių paruošimo etape 186 (84,5 proc.), vertinant ir pažymint tyrimą veikiančius veiksnius – 34 (15,5 proc.). Dažniausiai daromos klaidos (n = 104): priemonių galiojimo termino netikrinimas (100 proc.), netinkamas mėgintuvėlių skaičius (45,2 proc.), tyrimą veikiančių veiksnių ignoravimas (25,9 proc.). Kraujo ėminio paėmimo metu padaryta 971 klaida. Dažniausios klaidos (n = 104): punkcijos vietos valymas netinkama kryptimi (91,3 proc.), mažo kiekio tamponų naudojimas (88,5 proc.), pripildytų mėgintuvėlių guldymas horizontaliai (79,8 proc.). Daugiau klaidų darė vyresnės nei 35 metų, dirbusios daugiau nei 10 metų bei turinčios aukštąjį neuniversitetinį išsilavinimą (p 0,0001) slaugytojos. Saugant ir transportuojant ėminius į laboratoriją, padarytos 178 klaidos. Dažniausiai daromos klaidos: mėgintuvėlių saugojimas horizontalioje padėtyje (65,4 proc.), įvyniotų į lydraštį mėgintuvėlių transportavimas rankoje (46,2 proc.), mėgintuvėlių transportavimas rankoje (n = 7; 6,7 proc.). Saugant ėminius, daugiau klaidų darė vyresnės, ilgiau dirbančios ir turinčios aukštąjį neuniversitetinį išsilavinimą slaugytojos (p 0,001).
VAIKŲ NEAIŠKIOS KILMĖS KARŠČIAVIMAS
Authors: Batulevičiūtė Lina , Radžiūnienė Violeta , Vankevičienė Ramunė , Kinčinienė Odeta , Panavienė Violeta
Published: December 2014

Reikšminiai žodžiai: neaiškios kilmės karščiavimas, sisteminis jaunatvinis idiopatinis artritas, vaikai. Santrumpos: sJIA – sisteminis jaunatvinis idiopatinis artritas, MAS – makrofagų aktyvacijos sindromas, NKK – neaiškios kilmės karščiavimas. Neaiškios kilmės karščiavimas – karščiavimas ≥ 38,3 °C, trunkantis ilgiau nei 8 dienas, kai, įvertinus anamnezę, klinikinės apžiūros bei pradinių laboratorinių tyrimų duomenis, priežastis lieka nenustatyta. Pagrindinės karščiavimo priežastys vaikų amžiuje yra infekcijos, autoimuninės ligos ir navikai. Tarp reumatinių ligų dažniausias yra sisteminis jaunatvinis idiopatinis artritas. sJIA būdinga ne trumpiau kaip 2 savaites, mažiausiai 3 dienas iš eilės trunkantis karščiavimas, trumpalaikis bėrimas, difuzinė limfadenopatija, hepatosplenomegalija, serozitas ir, žinoma, artritas ar artralgija [1]. Ligos pradžioje apie trečdaliui sJIA sergančių pacientų dar nebūna artrito, o tai neretai sukelia diagnostinių sunkumų. Laboratorinių ir vaizdinių tyrimo metodų duomenys yra nespecifiniai. Nustatant diagnozę, remiamasi klinikiniais simptomais, kurie pasižymi didele įvairove bei vertinimo subjektyvumu. Diferencinei diagnostikai svarbiausia ekskliuduoti kitas ligas: infekciją, leukemiją, neuroblastomą, periodinius karščiavimo sindromus, vaskulitus, sistemines jungiamojo audinio ligas [1]. Makrofagų aktyvacijos sindromas (MAS) – gyvybei grėsminga sJIA komplikacija. Nediagnozavus laiku, paciento ligos išeitis fatališka. Naujausias gydymas pagrįstas citokinų (IL-1, IL-6) slopinimu. Šiame straipsnyje bus nagrinėjamas NKK atvejis, kurio priežastis buvo jaunatvinis idiopatinis artritas.
Uma Perspectiva Bioética sobre a Criação de Banco de Dados de Perfis Genéticos para Investigações Criminais no Brasil
Authors: Renata de Araújo Coelho  , José Renato Salviato  , Tânia Mara Volpe Miele  , Rogério Scandiuzzi
Published: December 2014

A aplicação de técnicas de genética e de biologia molecular representa significativa contribuição para a identificação humana e investigações criminais, a partir do armazenamento de perfis genéticos. No Brasil, país que ocupa a sexta posição no ranking de taxas de homicídios, com apenas 20% de apuração de crimes, foi instituído o Banco Nacional de Perfis Genéticos e a Rede Integrada de Bancos de Perfis Genéticos, a partir da Lei n° 12.654/12, regulamentada pelo Decreto n° 7.950/13. Esta pesquisa contempla a análise do cenário atual em termos de criminalidade no Brasil e adoção dos citados dispositivos legais, em face dos princípios de bioética médica conhecidos por Autonomia e Não Maleficência. Há críticas no sentido de que o Princípio da Autonomia é ferido, na medida em que a atual legislação permite a coleta compulsória de material genético, afetando outro princípio, constitucional, de que ninguém é obrigado a produzir provas contra si mesmo. Na mesma linha há a preocupação relativamente ao uso inadequado das informações contidas naquele Banco de Dados, o que, todavia, representa um cuidado adotado pelo legislador. Outro princípio da bioética que necessariamente deve ser rigorosamente observado, até porque representa exigência moral da profissão médica, é o da Não Maleficência. Significa dizer que a coleta compulsória de material genético deve afastar qualquer risco de dano e, por óbvio, de vida. Assim, há de se concluir que a adoção de bancos de DNA representa importante meio de prova para afastar incertezas, seja na identificação criminal, seja na identificação de pessoas desaparecidas.
The Use of DNA Barcoding to Identify Feathers from Illegally Traded Birds
Authors: Carlos Benigno Vieira de Carvalho
Published: December 2014

The illegal trade of animals threatens the survival of wild populations, including birds, one of the most targeted groups. Brazilian native birds are protected by the current legislation, and their illegal trade is a crime that can be punished with imprisonment. However, in some cases, it is not easy to identify seized specimens, making the characterization of the crime difficult and so the punishment of the offenders. When morphological identification is compromised, genetic identification can be used to associate unknown samples to a reference sample by comparing sequences of mitochondrial genes. In this study I used a 650 bp region from the subunit I of cytochrome c oxidase gene (COI) associated with the Barcode of Life Database (BOLD) to identify five feathers seized by the Brazilian Federal Police in 2012. The DNA Laboratory of the Brazilian Federal Police was able to match four of the five feathers to the species Triclaria malachitacea, the Blue-bellied Parrot, a member of the family Psittacidae. The results support the idea that members of this group are preferred targets for the illegal trade of wild birds and proved that DNA barcoding is a valuable tool for forensic casework.