bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient adherence to evidence‐based pharmacotherapy in systolic heart failure and the transition of follow‐up from specialized heart failure outpatient clinics to primary care
Authors: Gjesing Anne , Schou Morten , Torp‐Pedersen Christian , Køber Lars , Gustafsson Finn , Hildebrandt Per , Videbæk Lars , Wiggers Henrik , Demant Malene , Charlot Mette , Gislason Gunnar H.
Published: February 2013

Aims

Undertreatment with evidence‐based pharmacotherapy for heart failure (HF) is an important problem, and it has been suggested that specialized HF clinics (HFCs) can improve treatment initiation and correct dosing. The objective of this study was to examine long‐term adherence to and dosages of evidence‐based pharmacotherapy during and after participation in specialized HFCs.

Methods and results

Initiation, dosages, and adherence were studied in patients with systolic HF attending HFCs in Denmark from 2002 to 2009. Information was obtained from an electronic patient file and research database used in the HFCs combined with prescription data from the Danish Registry of Medicinal Product Statistics. A total of 8792 patients were included in the study. The mean age was 68 years; with a mean LVEF of 30%, and 72% were males. Long‐term adherence to treatment was high for the patients who initiated renin–angiotensin system (RAS) inhibitors and beta‐blockers. Adherence after 1 year was 93% for RAS inhibitors, 92% for beta‐blockers, and 86% for spironolactone. After 3 years, it was 90% for RAS inhibitors, 88% for beta‐blockers, and 74% for spironolactone. For patients referred back to their general practitioner (GP), adherence 1 year after they left the HFC was 89% for RAS inhibitors, 89% for beta‐blockers, and 72% for spironolactone.

Conclusion

In specialized outpatient HFCs, long‐term adherence to RAS inhibitors and beta‐blockers is close to optimal. Importantly, adherence was maintained after patients were referred back to their GP for continued management. This is likely to provide long‐term benefits for the patients.
IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation
Authors: Lee Jihye , Nakagiri Tomoyuki , Kamimura Daisuke , Harada Masaya , Oto Takahiro , Susaki Yoshiyuki , Shintani Yasushi , Inoue Masayoshi , Miyoshi Shinichiro , Morii Eiichi , Hirano Toshio , Murakami Masaaki , Okumura Meinoshin
Published: February 2013

The IL-6 amplifier, a positive feedback loop for NFκB signaling, which was originally found to be activated by IL-17A and IL-6 stimulation in non-immune cells, is molecularly a simultaneous activator of NFκB and signal transducer and activator of transcription 3 (STAT3), functionally a local chemokine inducer and pathologically a machinery for inflammation development. It has been shown that IL-6 amplifier activation in epithelial cells contributes to rejection responses in a mouse chronic rejection model that develops a bronchiolitis obliterans (BO)-like disease. We investigated whether the IL-6 amplifier is activated in BO regions of a human lung graft after allogeneic transplantation. NFκB and STAT3 molecules were phosphorylated in the epithelial regions of bronchi that localized in the BO regions. Additionally, chemokine ligand 2 (CCL2), and CD4+ T cells and macrophages increased in these regions. Furthermore, human lung epithelial cells expressed CCL2 after stimulation by IFNγ in the presence of IL-6 and epidermal growth factor via enhanced STAT3 signaling, which parallels behavior seen in the mouse model. Thus, our results suggest that the IL-6 amplifier in the epithelial cells of grafts is involved in chronic rejection after lung transplantation, suggesting that the amplifier may be a valuable therapeutic target to prevent chronic rejection after lung transplantation.
Computerized Adaptive Testing for Public Opinion Surveys
Authors: Montgomery Jacob M. , Cutler Josh
Published: February 2013

Survey researchers avoid using large multi-item scales to measure latent traits due to both the financial costs and the risk of driving up nonresponse rates. Typically, investigators select a subset of available scale items rather than asking the full battery. Reduced batteries, however, can sharply reduce measurement precision and introduce bias. In this article, we present computerized adaptive testing (CAT) as a method for minimizing the number of questions each respondent must answer while preserving measurement accuracy and precision. CAT algorithms respond to individuals' previous answers to select subsequent questions that most efficiently reveal respondents' positions on a latent dimension. We introduce the basic stages of a CAT algorithm and present the details for one approach to item selection appropriate for public opinion research. We then demonstrate the advantages of CAT via simulation and empirically comparing dynamic and static measures of political knowledge.
Actinopolyspora

lacussalsi sp. nov., an extremely halophilic actinomycete isolated from a salt lake
Authors: Guan Tong-Wei , Wei Bei , Zhang Yao , Xia Zhan-Fen , Che Zhen-Ming , Chen Xiang-Gui , Zhang Li-Li
Published: February 2013

A novel halophilic, filamentous actinobacterium, designated strain TRM 40139T, was isolated from a hypersaline habitat in Xinjiang Province, north-west China. Its taxonomic status was determined using a polyphasic approach. Phylogenetic analysis based on the almost-complete 16S rRNA gene sequence of the strain showed that it formed a well-separated sub-branch within the radiation of the genus

Actinopolyspora

and the organism was related most closely to the type strains of

Actinopolyspora alba

(97.6 % similarity),

Actinopolyspora xinjiangensis

(97.6 %) and

Actinopolyspora erythraea

(97.1 %). However, it had relatively lower mean DNA–DNA relatedness values with the above strains (36.4, 31.3 and 26.1 %, respectively). Optimal growth occurred at 35 °C, at pH 7.0 and in the presence of 12 % (w/v) NaCl. The whole-cell sugar pattern consisted of xylose, glucose, ribose and arabinose. The major fatty acids were iso-C16 : 0 (28.0 %) and anteiso-C17 : 0 (27.6 %). The diagnostic phospholipids detected were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol and two unknown phospholipids. The predominant menaquinones were MK-9(H4) (49.8 %) and MK-10(H4) (24.2 %). The G+C content of the genomic DNA was 66.4 mol%. Strain TRM 40139T therefore represents a novel species of the genus

Actinopolyspora

, for which the name

Actinopolyspora

lacussalsi sp. nov. is proposed. The type strain is TRM 40139T ( = KCTC 19657T = CCTCC AA 2012020T).
Weissella diestrammenae sp. nov., isolated from the gut of a camel cricket (Diestrammena coreana)
Authors: Oh Sei Joon , Shin Na-Ri , Hyun Dong-Wook , Kim Pil Soo , Kim Joon Yong , Kim Min-Soo , Yun Ji-Hyun , Bae Jin-Woo
Published: February 2013

A novel, Gram-stain-positive, non-motile, facultatively anaerobic, rod- or coccoid-shaped bacterium, designated strain ORY33T, was isolated from the gut of a camel cricket (Diestrammena coreana). The 16S rRNA gene sequence analysis showed that strain ORY33Tbelonged to the genusWeissella, with highest sequence similarity toWeissella koreensisS-5623T(97.7 %). The strain grew optimally at 30 °C and pH 7 in the presence of 0 % (w/v) NaCl. Catalase and oxidase activities were negative. The genomic DNA G+C content of strain ORY33Twas 45.1 mol%. DNA–DNA hybridization values between strain ORY33Tand closely related members of the genusWeissellawere less than 27 %. The major fatty acids of strain ORY33Twere C18 : 1ω9c, C16 : 0and C14 : 0. Based on these phenotypic, phylogenetic and genotypic analyses, strain ORY33Trepresents a novel species belonging to the genusWeissella, for which the nameWeisselladiestrammenaesp. nov. is proposed. The type strain is ORY33T( = KACC 16890T = JCM 18559T).
Actinoplanes siamensis sp. nov., isolated from soil
Authors: Suriyachadkun Chanwit , Ngaemthao Wipaporn , Chunhametha Suwanee , Thawai Chitti , Sanglier Jean-Jacques
Published: February 2013

A Gram-positive filamentous bacterial strain that developed large campanulate sporangia at the ends of sporangiophores on substrate mycelium was isolated from bamboo forest soil in Thailand. According to the results of a polyphasic taxonomic study, our isolate had typical characteristics of members of the genusActinoplanes. The 16S rRNA gene sequence analysis also indicated that strain A-T 6646Tbelonged to the genusActinoplanes, being most closely related toActinoplanes liguriensisDSM 43865T(97.61 %) andActinoplanes octamycinicusNBRC 14524T(97.52 %). The DNA–DNA relatedness values, which differentiate the new strain from the most closely related species, were significantly below 70 %. The cell-wall peptidoglycan containedmeso-diaminopimelic acid. The whole-cell sugars contained xylose and arabinose. The predominant menaquinone was MK-9(H4). The diagnostic phospholipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The predominant cellular fatty acids were iso-C16 : 0, anteiso-C17 : 0, iso-C15 : 0and anteiso-C15 : 0. Following an evaluation of phenotypic, chemotaxonomic and genotypic studies, the isolate is proposed to represent a novel species to be namedActinoplanessiamensissp. nov. The type strain is A-T 6646T( = BCC 46194T = NBRC 109076T).
Vogesella

fluminis sp. nov., isolated from a freshwater river, and emended description of the genus

Vogesella
Authors: Sheu Shih-Yi , Chen Jhen-Ci , Young Chiu-Chung , Chen Wen-Ming
Published: February 2013

A bacterial strain designated Npb-07T was isolated from a freshwater river in Taiwan and characterized using a polyphasic taxonomic approach. Strain Npb-07T was Gram-negative, aerobic, rod-shaped and motile by means of a single polar flagellum. Growth occurred at 10–37 °C (optimum, 20–30 °C), at pH 6.0–9.0 (optimum, pH 6.0–7.0) and with 0–1 % NaCl (optimum, 0.5 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Npb-07T belonged to the genus

Vogesella

and its most closely related neighbour was

Vogesella indigofera

ATCC 19706T with sequence similarity of 98.4 %. The major fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c, 44.4 %) and C16 : 0 (31.9 %). The major respiratory quinone was Q-8. The DNA G+C content of the genomic DNA was 65.3 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two uncharacterized aminophospholipids and an uncharacterized phospholipid. The DNA–DNA relatedness of strain Npb-07T with respect to

V. indigofera

ATCC 19706T was less than 70 %. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Npb-07T represents a novel species in the genus

Vogesella

, for which the name

Vogesella

fluminis sp. nov. is proposed. The type strain is Npb-07T ( = LMG 26669T = BCRC 80377T = KCTC 23713T).
Bacillus

composti sp. nov. and

Bacillus

thermophilus sp. nov., two thermophilic, Fe(III)-reducing bacteria isolated from compost
Authors: Yang Guiqin , Chen Ming , Yu Zhen , Lu Qin , Zhou Shungui
Published: February 2013

Two novel thermophilic bacteria, designated SgZ-9T and SgZ-10T, were isolated from compost. Cells of the two strains were catalase-positive, endospore-forming and Gram-staining-positive rods. Strain SgZ-9T was oxidase-positive and non-motile, and strain SgZ-10T was oxidase-negative and motile. The highest 16S rRNA gene sequence similarity for both strains SgZ-9T and SgZ-10T was observed with

Bacillus fortis

(97.5 % and 96.9 %, respectively). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SgZ-9T formed a cluster with

B. fortis

R-6514T and

Bacillus fordii

R-7190T, and SgZ-10T formed a cluster with

Bacillus farraginis

R-6540T. The DNA–DNA pairing studies showed that SgZ-9T displayed 41.6 % and 30.7 % relatedness to the type strains of

B. fortis

and

B. fordii

, respectively. The 16S rRNA gene sequence similarity between strains SgZ-9T and SgZ-10T was 97.2 %, and the level of DNA–DNA relatedness between them was 39.2 %. The DNA G+C content of SgZ-9T and SgZ-10T was 45.3 and 47.9 mol%, respectively. Chemotaxonomic analysis revealed that both strains contained the menaquinone 7 (MK-7) as the predominant respiratory quinone. The major cellular fatty acids (>5 %) were iso-C15 : 0, anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and iso-C17 : 0 in SgZ-9T and iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 0, anteiso-C17 : 0 and iso-C16 : 0 in SgZ-10T. Based on the phenotypic characteristics, chemotaxonomic features, DNA–DNA hybridization with the nearest phylogenetic neighbours and phylogenetic analysis based on the 16S rRNA gene sequences, the two strains were determined to be two distinct novel species in the genus

Bacillus

, and the names proposed are

Bacillus

composti sp. nov. SgZ-9T ( = CCTCC AB2012109T = KACC 16872T) and

Bacillus

thermophilus sp. nov. SgZ-10T (CCTCC AB2012110T = KACC 16873T).
Wickerhamomyces siamensis sp. nov., a novel yeast species isolated from the phylloplane in Thailand
Authors: Kaewwichian Rungluk , Kawasaki Hiroko , Limtong Savitree
Published: February 2013

Strain DMKU-RK359T, representing a novel yeast species, was isolated from the external surface of a sugar-cane leaf collected in Thailand. On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics, sequence analysis of the D1/D2 region of the large-subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, strain DMKU-RK359T was assigned to a novel Wickerhamomyces species. The novel species was closest to Wickerhamomyces ciferrii, but differed from it by 0.7 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene and 6 % nucleotide substitutions in the ITS region. The name Wickerhamomyces siamensis sp. nov. is proposed (type strain DMKU-RK359T  = BCC 50732T  = NBRC 108900T  = CBS 12570T).
Osmotic Stress Responses and Plant Growth Controlled by Potassium Transporters inArabidopsis
Authors: Osakabe Yuriko , Arinaga Naoko , Umezawa Taishi , Katsura Shogo , Nagamachi Keita , Tanaka Hidenori , Ohiraki Haruka , Yamada Kohji , Seo So-Uk , Abo Mitsuru , Yoshimura Etsuro , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko
Published: February 2013

Osmotic adjustment plays a fundamental role in water stress responses and growth in plants; however, the molecular mechanisms governing this process are not fully understood. Here, we demonstrated that the KUP potassium transporter family plays important roles in this process, under the control of abscisic acid (ABA) and auxin. We generated Arabidopsis thaliana multiple mutants for K+ uptake transporter 6 (KUP6), KUP8, KUP2/SHORT HYPOCOTYL3, and an ABA-responsive potassium efflux channel, guard cell outward rectifying K+ channel (GORK). The triple mutants, kup268 and kup68 gork, exhibited enhanced cell expansion, suggesting that these KUPs negatively regulate turgor-dependent growth. Potassium uptake experiments using 86radioactive rubidium ion (86Rb+) in the mutants indicated that these KUPs might be involved in potassium efflux in Arabidopsis roots. The mutants showed increased auxin responses and decreased sensitivity to an auxin inhibitor (1-N-naphthylphthalamic acid) and ABA in lateral root growth. During water deficit stress, kup68 gork impaired ABA-mediated stomatal closing, and kup268 and kup68 gork decreased survival of drought stress. The protein kinase SNF1-related protein kinases 2E (SRK2E), a key component of ABA signaling, interacted with and phosphorylated KUP6, suggesting that KUP functions are regulated directly via an ABA signaling complex. We propose that the KUP6 subfamily transporters act as key factors in osmotic adjustment by balancing potassium homeostasis in cell growth and drought stress responses.
The Arabidopsis nox Mutant Lacking Carotene Hydroxylase Activity Reveals a Critical Role for Xanthophylls in Photosystem I Biogenesis
Authors: Dall’Osto Luca , Piques Maria , Ronzani Michela , Molesini Barbara , Alboresi Alessandro , Cazzaniga Stefano , Bassi Roberto
Published: February 2013

Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth.
SimAdapt: an individual‐based genetic model for simulating landscape management impacts on populations
Authors: Rebaudo François , Le Rouzic Arnaud , Dupas Stéphane , Silvain Jean‐François , Harry Myriam , Dangles Olivier
Published: February 2013

Simulation models are essential tools in landscape genetics to study how genetic processes are affected by landscape heterogeneity. However, there is still a need to develop different simulation approaches in landscape genetics, so that users may dispose of additional programs to explore further the impact of land‐use and land‐cover changes on population genetics.

We developed a spatially explicit, individual‐based, forward‐time, landscape‐genetic simulation model combined with a landscape cellular automaton to represent evolutionary processes of adaptation and population dynamics in changing landscapes, using the NetLogo environment.

This simulation model represents a unique tool for scientists and scholars looking for a practical and pedagogical framework to explore both empirical and theoretical situations.
Preoperative staging of endometrial cancer using TVS, MRI, and hysteroscopy
Authors: Ørtoft Gitte , Dueholm Margit , Mathiesen Ole , Hansen Estrid S. , Lundorf Erik , Møller Charlotte , Marinovskij Edvard , Petersen Lone K.
Published: February 2013

Objectives

To evaluate the accuracy of different preoperative modalities for staging of endometrial cancer to restrict extensive surgery to patients at high risk of metastatic disease.

Setting

Aarhus University Hospital.

Population

156 women referred in 2006–2011 because of atypical endometrial hyperplasia (G0) or endometrial cancer.

Methods

Patients were offered preoperative transvaginal ultrasonography (TVS), magnetic resonance imaging (MRI), and hysteroscopic‐directed biopsies from the uterine tumor and cervix. Final pathology of the removed uterus was the reference standard. Patients were divided into low risk (<50% myometrial invasion, and grades 0, 1, 2, and no cervical invasion) or high risk (all others).

Main outcome measures

Accuracy, sensitivity, specificity, positive/negative predictive value.

Results

Patients were aged 32–88 years, with a mean body mass index of 29. At final pathology 81% had cancer and 19% G0 or no residual tumor; 54% were high risk. Hysteroscopy‐directed biopsies had a higher accuracy (92%) than endometrial biopsy (58%) for differentiating G0 from cancer (p < 0.001); grade 3 tumor identification had similar accuracy (93 vs. 92%). Deep myometrial invasion was estimated with higher accuracy by MRI (82%) than TVS (74%) (p < 0.02). For cervical involvement, hysteroscopy‐directed biopsies had higher accuracy (94%) than MRI (84%,) and TVS (80%) (p < 0.02). Accuracy for identifying high‐risk women was highest (83%) using a combination of MRI and hysteroscopic‐directed biopsies, compared with TVS and endometrial biopsy (72%) (p < 0.05).

Conclusion

Preoperative staging with MRI and hysteroscopy‐directed biopsy can identify eight of 10 women with high risk of lymph node metastases and spare eight of 10 low‐risk women extended surgery.
Pneumococcemia in children – a retrospective study before universal pneumococcal vaccinations
Authors: Karppa Henna , Vuento Risto , Toropainen Maija , Kaijalainen Tarja , Siira Lotta , Korppi Matti
Published: February 2013

Aim

To evaluate the incidence and characteristics of blood culture‐positive occult pneumococcemia compared with blood culture‐positive pneumococcal pneumonia in children.

Methods

In years 2001–2010, 105 children with positive blood cultures for Streptococcus pneumoniae were identified from hospital electronic files. The patient cards were retrospectively charted for clinical and laboratory data, and 38 patients had and 67 had not pneumonia.

Results

The annual incidence of pneumococcemia was, on average, 29.0/10 000 at 0–12 months, 5.3/10 000 at 13–24 months and 1.9/10 000 at 2–4 years of ages, with no increasing or decreasing trend. The incidence of bacteraemic pneumococcal pneumonia increased (p = 0.022) during the study period. The duration of fever before hospitalization (<24 h 73.9% vs. 25.0%, p = 0.022) and the duration of intravenous antibiotics, usually G‐penicillin (median 72 vs. 96 h, p = 0.021) was shorter in pneumococcemia patients. On admission, blood leucocyte count was higher in pneumococcemia (mean 26.6 vs. 21.9 × 10E9/L, p = 0.012), but serum CRP was higher in pneumonia (median 160 vs. 67.4 mg/L, p < 0.001). The serotypes 6B and 14 caused 53.2% of pneumococcemia cases.

Conclusion

The incidence of pneumococcemia was highest in 1–2‐year‐old children, and typical for pneumococcemia was rapid onset of fever, high blood leucocyte count and a modestly elevated CRP on admission.
Relations between denudation, glaciation, and sediment deposition: implications from the Plio‐Pleistocene Central Alps
Authors: Reiter Wolfgang , Elfert Simon , Glotzbach Christoph , Bernet Matthias , Spiegel Cornelia
Published: February 2013

Despite abundant data on the early evolution of the Central Alps, the latest stage exhumation history, potentially related to relief formation, is still poorly constrained. We aim for a better understanding of the relation between glaciation, erosion and sediment deposition. Addressing both topics, we analysed late Pliocene to recent deposits from the Upper Rhine Graben and two modern river sands by apatite fission‐track and (U‐Th‐Sm)/He thermochronology. From the observed age patterns we extracted the sediment provenance and paleo‐erosion history of the Alpine‐derived detritus. Due to their pollen and fossil record, the Rhine Graben deposits also provide information on climatic evolution, so that the erosion history can be related to glacial evolution during the Plio‐Pleistocene. Our data show that Rhine Graben deposits were derived from Variscan basement, Hegau volcanics, Swiss Molasse Basin, and the Central Alps. The relations between glaciation, Alpine erosion, and thermochronological age signals in sedimentary rocks are more complex than assumed. The first Alpine glaciation during the early Pleistocene did not disturb the long‐term exhumational equilibrium of the Alps. Recent findings indicate that main Alpine glaciation occurred at ca. 1 Ma. If true, then main Alpine glaciation was coeval with an apparent decrease of hinterland erosion rates, contrary to the expected trend. We suggest that glaciers effectively sealed the landscape, thus reducing the surface exposed to erosion and shifting the area of main erosion north toward the Molasse basin, causing sediment recycling. At around 0.4 Ma, erosion rates increased again, which seems to be a delayed response to main glaciation. The present‐day erosion regime seems to be dominated by mass‐wasting processes. Generally, glacial erosion rates did not exceed the pre‐glacial long‐term erosion rates of the Central Alps.
Geographical distribution of Slovenian BRCA1/2 families according to family origin: implications for genetic screening
Authors: Krajc M , Zadnik V , Novaković S , Stegel V , Teugels E , Bešič N , Hočevar M , Vakselj A , De Grève J , Žgajnar J
Published: February 2013

Knowledge of the geographical distribution of highly recurrent mutations may be useful for efficient screening in cancer families. Since the cloning of the BRCA1/2 genes, it is known that the wide spectrum of deleterious mutations shows high ethnic and geographic heterogeneity. In this study, we have tested probands from 582 breast/ovarian cancer families and positioned all 156 BRCA1/2 families on the map according to the family origin. We observed that high‐risk families with the same recurrent mutation present a typical geographical distribution and that different recurrent mutations may show different distribution patterns. We then evaluated the genetic screening implications of this heterogeneous prevalence of the most recurrent mutations found [300T>G(c.181T>G), 1806C>T(c.1687C>T), 969ins7(c.844_850dupTCATTAC), 5382insC(c.5266dupC), 235G>A(c.116G>A) in BRCA1 and IVS16‐2A>G(c.7806‐2A>G) in BRCA2]. On the basis of these results, specific testing procedures for new incident cases may be offered according to their family origins and, according to the information regarding clusters revealed in this study, the individuals (especially those at low risk), originating from regions with clusters, might be screened preferentially for cluster mutations and analysis may be simplified according to the family origin.
Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene
Authors: Liu Z.‐J. , Sun Y.‐M. , Ni W. , Dong Y. , Shi S.‐S. , Wu Z.‐Y.
Published: February 2013

Patients with Huntington's disease (HD) carrying CAG repeats beyond 60 are less frequently seen and clinical features of them have been rarely reported. We identified four unrelated patients carrying CAG repeats beyond 60 (84.0 ± 13.76, ranging from 74 to 104) from 119 Chinese HD patients via direct sequencing. These four were all early onset with a mean age at presenting symptom of 9.8 ± 1.71 years. Paternal transmission was found in three of them and the fourth was apparently sporadic. In addition, they had atypical onset symptoms including epilepsy, intellectual decline, tics and walking instability, which might lead the clinicians to make the wrong diagnosis in the early stage of disease. Our work explores clinical features of Chinese HD patients with an expanded CAG repeat over 60 and may help the clinicians make a correct diagnosis in the early stage of disease.
No bridge too high: Infants decide whether to cross based on the probability of falling not the severity of the potential fall
Authors: Kretch Kari S. , Adolph Karen E.
Published: February 2013

Do infants, like adults, consider both the probability of falling and the severity of a potential fall when deciding whether to cross a bridge? Crawling and walking infants were encouraged to cross bridges varying in width over a small drop‐off, a large drop‐off, or no drop‐off. Bridge width affects the probability of falling, whereas drop‐off height affects the severity of the potential fall. For both crawlers and walkers, decisions about crossing bridges depended only on the probability of falling: As bridge width decreased, attempts to cross decreased, and gait modifications and exploration increased, but behaviors did not differ between small and large drop‐off conditions. Similarly, decisions about descent depended on the probability of falling: Infants backed or crawled into the small drop‐off, but avoided the large drop‐off. With no drop‐off, infants ran straight across. Results indicate that experienced crawlers and walkers accurately perceive affordances for locomotion, but they do not yet consider the severity of a potential fall when making decisions for action.
Endovascular therapy in 201 patients with acute symptomatic occlusion of the internal carotid artery
Authors: Fischer U. , Mono M.‐L. , Schroth G. , Jung S. , Mordasini P. , El‐Koussy M. , Weck A. , Brekenfeld C. , Findling O. , Galimanis A. , Heldner M. R. , Arnold M. , Mattle H. P. , Gralla J.
Published: February 2013

Background and purpose

Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest.

Methods

From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra‐arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively.

Results

There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA‐T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2–3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2–3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91 = 86% and 64/78 = 82%) compared with pharmacological thrombolysis only (15/32 = 47%; P < 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3‐month outcome was favourable [modified Rankin score (mRS) 0–2] in 54/28% patients and moderate (mRS 0–3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA‐T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (P = 0.001). In multivariate analysis age [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93–0.98], NIHSS on admission (OR = 0.9, 95% CI = 0.83–0.98) and functional ICA‐T occlusion (OR = 0.35, 95% CI = 0.16–0.77) were non‐modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (OR = 9.30, 95% CI = 2.03–42.63).

Conclusions

The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.
Stroke recurrence patterns are predicted by the subtypes and mechanisms of the past, non‐cardiogenic stroke
Authors: Yoon Y. , Lee D. H. , Kang D. W. , Kwon S. U. , Suh D. C. , Bang O. Y. , Kim J. S.
Published: February 2013

Background and purpose

The association between past stroke subtypes and recurrent stroke subtypes in non‐cardiogenic stroke remains unknown.

Methods

Patients with ischaemic stroke who had a past history of large‐artery disease (LAD) or small‐artery disease (SAD) subtypes were assessed. LAD was subdivided into intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS). LAD stroke mechanisms were categorized as artery‐to‐artery embolism, in situ thrombotic occlusion and local branch occlusion, while SAD was subdivided into lacunar infarction (LI) and branch atheromatous disease (BAD) on the basis of magnetic resonance imaging findings. The relationship between past and current strokes was analyzed.

Results

Among the 202 patients enrolled, the LAD group (n = 111) had 64 and 47 patients with ICAS and ECAS, and the SAD group (n = 91) had 63 and 28 patients with LI and BAD, respectively, at the time of past stroke. Patients with LAD developed LAD‐associated strokes most often (n = 99, 89.2%), and patients with SAD developed SAD most often (n = 69, 75.8%; P < 0.001). Patients with ICAS were more likely to develop ICAS later (n = 46, 79.3%), whereas those with ECAS developed ECAS more often (n = 31, 75.6%; P < 0.001). Patients with ICAS presenting with artery‐to‐artery embolism more often developed artery‐to‐artery embolism later (n = 26, 72.2%), whereas those with local branch occlusion developed recurrent local branch occlusion most often (n = 10, 66.7%, P = 0.005). In the SAD group, patients with BAD developed LAD more frequently than the LI group (n = 11, 39.3% vs. n = 9, 14.3%, P = 0.022).

Conclusions

The subtypes and mechanisms of recurrent stroke are significantly influenced by those of the past stroke.
Association between multiple sclerosis and chronic periodontitis: a population‐based pilot study
Authors: Sheu J.‐J. , Lin H.‐C.
Published: February 2013

Background and purpose

The pathogenesis of multiple sclerosis (MS) is still not fully understood, but multiple infections are known to be crucial in the development of the disease. Periodontitis caused by periodontopathic polymicrobial infections is among the most common chronic infectious disorders. This case–control study aimed to investigate the association between chronic periodontitis (CP) and MS using a population‐based dataset in Taiwan.

Methods

This study included 316 cases who had a diagnosis of MS and 1580 randomly selected controls. We performed conditional logistic regressions to investigate the association between MS and having been previously diagnosed with CP.

Results

The results reveal that the prevalence of earlier CP was 25.6% and 15.4% for cases and controls, respectively (P < 0.001). Conditional logistic regression analysis revealed that cases were 1.86 [95% confidence interval (CI) = 1.39–2.48] times as likely as controls to have been previously diagnosed with CP, after adjusting for sociodemographic characteristics as well as hyperlipidemia, hypertension, coronary heart disease, alcohol abuse/alcohol‐dependence syndrome, tobacco use disorder and chronic obstructive pulmonary disease. After analyzing by gender, it was realized that while female cases had a higher chance than female controls of having earlier CP (adjusted odds ratio = 2.08; 95% CI = 1.49–2.95), there was no statistical association detected between these two conditions in men.

Conclusions

This study provides evidence for an association between CP and MS in female, but not male, subjects. Further epidemiological studies are needed to confirm the association and gender‐specific differences found in the present study.
PRRT2 mutations and paroxysmal disorders
Authors: Méneret A. , Gaudebout C. , Riant F. , Vidailhet M. , Depienne C. , Roze E.
Published: February 2013

In the past year, mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on PRRT2 mutation‐associated disorders. Our objectives were to describe the wide clinical spectrum associated with PRRT2 mutations, and to present the current hypotheses on the underlying pathophysiology. PRRT2 mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The PRRT2 protein, through its interaction with SNAP‐25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by PRRT2 loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age‐dependent expression. The clinical spectrum of PRRT2 mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.
Acute cerebral microbleeds in refractory status epilepticus
Authors: Jeon Sang‐Beom , Parikh Gunjan , Alex Choi H. , Lee Kiwon , Lee Jong Hwan , Schmidt J. Michael , Badjatia Neeraj , Mayer Stephan A. , Claassen Jan
Published: February 2013

Cerebral microbleeds (CMBs) are commonly found in patients with stroke and cerebral amyloid angiopathy. However, there have been no reports of CMBs or their acute appearance in patients with status epilepticus. Herein we describe two patients with refractory status epilepticus of uncertain origin. Both patients were previously healthy, and their initial imaging showed no underlying CMBs. One patient's follow‐up susceptibility‐weighted imaging 29 days after initial imaging showed 63 new CMBs. The other patient's follow‐up susceptibility‐weighted imaging 41 days after initial imaging showed 14 new CMBs. Multimodal neuromonitoring revealed increase in lactate–pyruvate ratio, decrease in partial brain tissue oxygen tension, increase in pressure reactivity index, and fluctuations of blood pressure and cerebral perfusion pressure. This report demonstrates that multiple new CMBs may develop in patients with refractory status epilepticus (SE).
FDG‐PET and magnetoencephalography in presurgical workup of children with localization‐related nonlesional epilepsy
Authors: Widjaja Elysa , Shammas Amer , Vali Reza , Otsubo Hiroshi , Ochi Ayako , Snead O. Carter , Go Cristina , Charron Martin
Published: February 2013

Purpose

2‐[18F]Fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) and magnetoencephalography (MEG) may assist in identifying the epileptogenic zone in children with nonlesional localization‐related epilepsy. The aim of this study was to evaluate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG‐PET, MEG, FDG‐PET + MEG, and FDG‐PET/MEG in children with nonlesional localization‐related epilepsy.

Methods

Twenty‐six children with localization‐related epilepsy and who had normal or subtle changes on magnetic resonance imaging (MRI) underwent FDG‐PET and MEG. Twenty‐two patients had surgical resection, and surgical outcome was assessed using Engel classification. In patients with Engel I seizure outcome, we assessed the sensitivity, specificity, PPV, and NPV of lobar localization of MEG, FDG‐PET, FDG‐PET + MEG, and FDG‐PET/MEG.

Key Findings

Sixteen (72.7%) of 22 had Engel I seizure outcome. MEG was concordant with surgical resection in 18 patients, 14 had Engel I, and four had Engel II–IV outcomes. MEG was nonlocalizing or nonconcordant in four patients; two patients had Engel I and two had Engel II–IV outcomes. FDG‐PET was concordant with surgical resection in 14 patients; 9 had Engel I outcome, and 5 had Engel II–IV outcome. FDG‐PET was nonlocalizing or nonconcordant in seven patients with Engel I, and one with Engel III outcome. The sensitivity, specificity, PPV, and NPV of MEG were 85.0%, 99.1%, 94.4%, and 97.3%, respectively. The sensitivity, specificity, PPV, and NPV of FDG‐PET were 65.0%, 94.4%, 68.4%, and 93.6%, respectively. There was no significant difference between MEG and FDG‐PET for concordance with surgical resection (χ2 = 2.794, p = 0.095). FDG‐PET + MEG, defined as two tests concordant with surgical resection, had reduced sensitivity and NPV, but increased specificity and PPV (55.0%, 92.3%, 100%, and 100%, respectively) relative to individual tests. FDG‐PET/MEG, defined as one or both test(s) concordant with surgical resection, had increased sensitivity and NPV but reduced specificity (95.0%, 99.0%, and 93.5%, respectively) relative to individual tests.

Significance

The two tests FDG‐PET and MEG were complementary in the assessment of children with localization‐related epilepsy, particularly when one test was nonlocalizing or nonconcordant.
Variability of EEG‐fMRI findings in patients with SCN1A‐positive Dravet syndrome
Authors: Moehring Jan , von Spiczak Sarah , Moeller Friederike , Helbig Ingo , Wolff Stephan , Jansen Olav , Muhle Hiltrud , Boor Rainer , Stephani Ulrich , Siniatchkin Michael
Published: February 2013

Purpose

Dravet syndrome (DS) or severe myoclonic epilepsy of infancy is an intractable epileptic encephalopathy of early childhood that is caused by a mutation in the SCN1A gene in most patients. The aim of this study was to identify a syndrome‐specific epileptic network underlying interictal epileptiform discharges (IEDs) in patients with DS.

Methods

Ten patients with the diagnosis of DS associated with mutations in the SCN1A gene were investigated using simultaneous recording of electroencephalography and functional magnetic resonance imaging ((EEG‐fMRI). Time series of IEDs were used as regressors for the statistical fMRI analysis.

Key Findings

In nine patients with DS, individual blood oxygenation level–dependent (BOLD) signal changes were seen. In three patients the thalamus was involved. Furthermore, regions of the default mode network were activated in seven patients. However, a common activation pattern associated with IEDs could not be detected.

Significance

The study demonstrates that, despite a common genetic etiology in DS, different neuronal networks underlie the individual IEDs.
Detection of generalized tonic–clonic seizures by a wireless wrist accelerometer: A prospective, multicenter study
Authors: Beniczky Sándor , Polster Tilman , Kjaer Troels W. , Hjalgrim Helle
Published: February 2013

Our objective was to assess the clinical reliability of a wrist‐worn, wireless accelerometer sensor for detecting generalized tonic–clonic seizures (GTCS). Seventy‐three consecutive patients (age 6–68 years; median 37 years) at risk of having GTCS and who were admitted to the long‐term video–electroencephalography (EEG) monitoring unit (LTM) were recruited in three centers. The reference standard was considered the seizure time points identified by experienced clinical neurophysiologists, based on the video‐EEG recordings and blinded to the accelerometer sensor data. Seizure time points detected real‐time by the sensor were compared with the reference standard. Patients were monitored for 17–171 h (mean 66.8; total 4,878). Thirty‐nine GTCS were recorded in 20 patients. The device detected 35 seizures (89.7%). In 16 patients all seizures were detected. In three patients more than two thirds of the seizures were detected. The mean of the sensitivity calculated for each patient was 91%. The mean detection latency measured from the start of the focal seizure preceding the secondarily GTCS was 55 s (95% confidence interval [CI] 38–73 s). The rate of false alarms was 0.2/day. Our results suggest that the wireless wrist accelerometer sensor detects GTCS with high sensitivity and specificity. Patients with GTCS have an increased risk for injuries related to seizures and for sudden unexpected death in epilepsy (SUDEP), and many nocturnal seizures remain undetected in unattended patients. A portable automatic seizure detection device will be an important tool for helping these patients.
Divergent effects of the T1174S SCN1A mutation associated with seizures and hemiplegic migraine
Authors: Cestèle Sandrine , Labate Angelo , Rusconi Raffaella , Tarantino Patrizia , Mumoli Laura , Franceschetti Silvana , Annesi Grazia , Mantegazza Massimo , Gambardella Antonio
Published: February 2013

Purpose

To report the identification of the T1174S SCN1A (NaV1.1) mutation in a three‐generation family with both epileptic and familial hemiplegic migraine (FHM) phenotypes and clarify the pathomechanism.

Methods

The five affected individuals underwent detailed clinical analyses. Mutation analyses was performed by direct sequencing of SCN1A; functional studies by expression in tsA‐201 cells. A computational model was used to compare the effects of T1174S with those of a typical FHM mutation (Q1489K).

Key Findings

The proband had benign occipital epilepsy (BOE); two relatives had simple febrile seizures (FS) and later developed BOE. Two additional relatives had FHM without epilepsy or FS. All affected members and one obliged carrier carried the T1174S mutation. Functional effects were divergent: positive shift of the activation curve and deceleration of recovery from fast inactivation, consistent with loss of function, and increase of persistent current (INaP), consistent with gain of function. The INaP increase was inhibited by dialysis of the cytoplasm, consistent with a modulation. Therefore, as shown by the computational model, T1174S could in some conditions induce overall loss of function, and in others gain of function; Q1489K induced gain of function in all the conditions.

Significance

Modulation of the properties of T1174S can lead to a switch between overall gain and loss of function, consistent with a switch between promigraine end epileptogenic effect and, thus, with coexistence of epileptic and FHM phenotypes in the same family. These findings may help to shed light on the complex genotype–phenotype relationship of SCN1A mutations.
Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β‐structure formation
Authors: Shimizu Youské , Shimizu Takashi , Nara Masayuki , Kikumoto Mahito , Kojima Hiroaki , Morii Hisayuki
Published: February 2013

Members of the kinesin‐13 sub‐family, including KIF2C, depolymerize microtubules. The positive charge‐rich ‘neck’ region extending from the N‐terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182–E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182–D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion‐rich C‐termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C‐termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation‐rich region (K190–A204) forms β‐structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules.