bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizure outcome and its predictors after temporal lobe epilepsy surgery in patients with normal MRI
Authors: Fong Joanna S. , Jehi Lara , Najm Imad , Prayson Richard A. , Busch Robyn , Bingaman William
Published: July 2011

Purpose:  To characterize seizure outcomes following temporal lobe epilepsy (TLE) surgery in patients with normal preoperative brain magnetic resonance imaging (MRI).

Methods:  We reviewed adult patients with pharmacoresistant epilepsy and normal MRI who underwent TLE surgery (1996–2009). Seizure outcomes were analyzed using survival and multivariate regression with Cox proportional hazard modeling. Two analyses were performed using two favorable outcome definitions: complete seizure freedom and Engel classification.

Key Findings:  Sixty‐four patients were analyzed (mean follow‐up 4.1 years; range 1–14.5 years). Most had a standard anterior temporal lobectomy (84%) and unremarkable pathology (45%). At 1 year, the chance of complete seizure freedom was 76% [95% confidence interval (CI) 71–81%] comparable to an 81% (95% CI 76–86%) chance of Engel score of 1. With longer follow‐up, a progressively broadening significant discrepancy between the two outcome measures was observed. The chance of complete seizure freedom was 66% (95% CI 61–71%) at 2 years, and 47% (95% CI 40–54%) at 7 years and beyond, whereas the respective chances of achieving an Engel 1 classification were 76% (95% CI 70–82%), and 69% (95% CI 63–75%) at similar time points. Seizure outcome as defined by either measure was worse in patients with higher baseline seizure frequency (adjusted risk‐ratio 2.7 when >12 seizures/month; p = 0.01) and with preoperative generalized tonic–clonic seizures (adjusted risk ratio 10.8; p = 0.0006). Memory measures declined with dominant hippocampus resections.

Significance:  A normal MRI should not prevent presurgical evaluations in patients with suspected TLE, as favorable long‐term postoperative seizure outcomes are possible. Proposed mechanisms of epileptogenicity and seizure recurrence in this group are discussed.
Definition and natural history of Lennox‐Gastaut syndrome
Authors: Camfield Peter R.
Published: July 2011

Lennox‐Gastaut syndrome (LGS) is a rare epileptic encephalopathy with a peak age of onset of 3–5 years of age. Reported prevalence rates for LGS vary widely from 1–10% of all childhood epilepsies. Incidence rates are much lower. LGS is characterized by intractable, multiple, generalized seizure types and an interictal electroencephalogram showing bursts of slow spike‐and‐wave, paroxysmal bursts of generalized polyspikes, and a slow background. All patients have tonic seizures during sleep that may be subtle, and nearly all have treatment‐resistant, lifelong epilepsy. Cognitive stagnation and behavioral problems are seen in almost all patients and lead to a life of dependency. The differential diagnosis includes other symptomatic generalized epilepsies and pseudo‐Lennox syndrome. Misdiagnosis is common. Children and adults with LGS have an enormous impact on their families, and efforts to improve the quality of life for these patients are complex.
Rational approach to treatment options for Lennox‐Gastaut syndrome
Authors: Montouris Georgia D.
Published: July 2011

Lennox‐Gastaut syndrome (LGS) is an intractable childhood‐onset epileptic encephalopathy. Seizure freedom is rare in LGS. One of the hallmarks of LGS is medical intractability, with generally poor response to antiepileptic drugs (AEDs). Nevertheless, several treatment options are available that can mitigate the severity of seizures and curtail their frequency. New AEDs have been validated in randomized, controlled trials for the treatment of seizures in LGS. In some cases, nonpharmacologic options may be effective, although more data are needed to confirm efficacy outcomes. Comprehensive patient assessments are critical to achieve an optimal AED treatment regimen and minimize the potential for adverse effects.
Does Variance in Drinking Motives Explain the Genetic Overlap Between Personality and Alcohol Use Disorder Symptoms? A Twin Study of Young Women
Authors: Littlefield Andrew K. , Agrawal Arpana , Ellingson Jarrod M. , Kristjansson Sean , Madden Pamela A. F. , Bucholz Kathleen K. , Slutske Wendy S. , Heath Andrew C. , Sher Kenneth J.
Published: July 2011

Background:  Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Although drinking motives have been posited as important mediators of the alcohol–personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e., abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear.

Methods:  Using data from 2,904 young adult female twins, the phenotypic and genetic associations between personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen A, 1982 unpublished data], conscientiousness, neuroticism, and agreeableness [measured by the NEO‐PI; Costa and McCrae, 1985]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; Cooper, 1994]), and AUD symptoms were tested.

Results:  Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant.

Conclusions:  Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms.
The Genetic Effect of Copy Number Variations on the Risk of Alcoholism in a Korean Population
Authors: Bae Joon Seol , Jung Myung Hun , Lee Boung Chul , Cheong Hyun Sub , Park Byung Lae , Kim Lyoung Hyo , Kim Jeong‐Hyun , Pasaje Charisse Flerida A. , Lee Jin Sol , Jung Kyoung Hwa , Chai Young Gyu , Shin Hyoung Doo , Choi Ihn‐Geun
Published: July 2011

Background:  Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism.

Methods:  Using the Illumina HumanHap660W‐Quad BeadChip (∼660 k markers), genome‐wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism‐associated CNV regions, we performed a genome‐wide association analysis, using multivariate logistic regression model controlling for age and gender.

Results:  We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302‐61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E−05, pcorr = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane‐bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity.

Conclusions:  This is the first genome‐wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism.
A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery
Authors: Shehata Nadine , Burns Laura Alexandra , Nathan Howard , Hebert Paul , Hare Gregory M.T. , Fergusson Dean , Mazer C. David
Published: July 2011

BACKGROUND: It is important to determine the optimal hemoglobin (Hb) concentration for red blood cell (RBC) transfusion for patients undergoing cardiac surgery because increased mortality has been associated with the severity of anemia and exposure to RBCs. Because a definitive trial will require thousands of patients, and because there is variability in transfusion practices, a pilot study was undertaken to determine adherence to proposed strategies.

STUDY DESIGN AND METHODS: A single‐center parallel randomized controlled pilot trial was conducted in high‐risk cardiac patients to assess adherence to two transfusion strategies. Fifty patients were randomly assigned either to a “restrictive” transfusion strategy (RBCs if their Hb concentration was 70 g/L or less intraoperatively during cardiopulmonary bypass [CPB] and 75 g/L or less postoperatively) or a “liberal” transfusion strategy (RBCs if their Hb concentration was 95 g/L or less during CPB and less than 100 g/L postoperatively).

RESULTS: The percentage of adherence overall was 84% in the restrictive arm and 41% in the liberal arm. Twenty‐two (88%) patients were transfused 99 units of RBCs in the liberal group compared to 13 patients who were transfused 50 units in the restrictive group (p < 0.01). There were no significant differences in individual adverse outcomes; however, more adverse events occurred in the restrictive group (38 vs. 15, p < 0.01).

CONCLUSION: Adherence to the evaluated interventions is vital to all randomized controlled trials as it has the potential to affect outcomes. Further pilot studies are required to optimize enrollment and transfusion adherence before a definitive study is conducted.
Alloimmunization to transfused HOD red blood cells is not increased in mice with sickle cell disease
Authors: Hendrickson Jeanne E. , Hod Eldad A. , Perry Jennifer R. , Ghosh Samit , Chappa Prasanthi , Adisa Olufolake , Kean Leslie S. , Ofori‐Acquah Solomon F. , Archer David R. , Spitalnik Steven L. , Zimring James C.
Published: July 2011

BACKGROUND: Increased rates of red blood cell (RBC) alloimmunization in patients with sickle cell disease may be due to transfusion frequency, genetic predisposition, or immune dysregulation. To test the hypothesis that sickle cell pathophysiology influences RBC alloimmunization, we utilized two transgenic mouse models of sickle cell disease.

STUDY DESIGN AND METHODS: Transgenic sickle mice, which express human α and βS globin, were transfused with fresh or 14‐day‐stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffyb) antigen; some recipients were inflamed with poly(I : C) before transfusion. Anti‐HOD alloantibody responses were subsequently measured by enzyme‐linked immunosorbent assay and flow crossmatch; a cohort of recipients had posttransfusion serum cytokines measured by bead array.

RESULTS: Both Berkeley and Townes homozygous (SS) and heterozygous (AS) mice had similar rates and magnitude of anti‐HOD RBC alloimmunization after fresh HOD RBC transfusion compared with control animals; under no tested condition did homozygous SS recipients make higher levels of alloantibodies than control animals. Unexpectedly, homozygous SS recipients had blunted cytokine responses and lower levels of anti‐HOD alloantibodies after transfusion of 14‐day stored RBCs, compared with control animals.

CONCLUSIONS: In sum, homozygous βS expression and the ensuing disease state are not alone sufficient to enhance RBC alloimmunization to transfused HOD RBCs in two distinct humanized murine models of sickle cell disease under the conditions examined. These data suggest that other factors may contribute to the high rates of RBC alloimmunization observed in humans with sickle cell disease.
Reinvestigations of six unusual paternity cases by typing of autosomal single‐nucleotide polymorphisms
Authors: Børsting Claus , Morling Niels
Published: July 2011

BACKGROUND: In some relationship cases, the initial investigations of autosomal short tandem repeats (STRs) lead to an ambiguous conclusion and supplementary investigations become necessary.

STUDY DESIGN AND METHODS: Six unusual paternity cases were previously investigated by other researchers and published as case work examples in forensic journals. Here, the cases were reinvestigated by typing the samples for 49 autosomal single‐nucleotide polymorphisms (SNPs) using the SNPforID multiplex assay.

RESULTS: Three cases were solved by the SNP investigation without the need for any additional testing. In two cases, the SNP results supported the conclusions based on STRs. In the last case, the SNP results spoke in favor of paternity, and the combined paternity index based on autosomal STRs and SNPs was 12.3 billion. Nevertheless, the alleged father was excluded by X‐chromosome typing.

CONCLUSION: The case work examples underline the importance of performing supplementary investigations, and they advocate for the implementation of several panels that may be used in the highly unusual cases. Panels with SNPs or other markers with low mutation probabilities are preferable as supplementary markers, because the risk of detecting (additional) mutations is very low.
A flow cytometric method for platelet counting in platelet concentrates
Authors: van der Meer Pieter F. , Karssing‐van Leeuwen Willy , Kurtz Jim , Spengler Hans‐Peter , Blair AbbeJane , Devine Dana , Harrison Paul , Lambrecht Bernd , VandenBroeke Tania , de Wildt Janny , de Korte Dirk ,   on behalf of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: July 2011

BACKGROUND: The platelets (PLTs) in PLT concentrates are counted with hematology analyzers, but varying results among different hematology analyzers are observed, making comparisons very difficult. Due to the absence of red blood cells in PLT concentrates, the International Council for Standardization in Hematology (ICSH) reference method was modified to be used for PLT concentrates and validated in an international comparative study.

STUDY DESIGN AND METHODS: Five PLT samples were shipped to eight participating centers of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative and counted on the same day. PLTs were stained with fluorescein isothiocyanate–labeled anti‐CD41a in tubes (TruCount, BD Biosciences), measured on a flow cytometer, and analyzed with a uniform template. These samples were also counted on 15 hematology analyzers.

RESULTS: The ICSH method and newly developed BEST method yielded PLT counting results with less than 1% difference (not significant). The intercenter coefficient of variation (CV) of the BEST method was on average 6.3% versus 7.6% on average for hematology analyzers. The CV of individual hematology analyzers was on average 0.9%, which was considerably lower than for the flow cytometers with a mean of 3.7%.

CONCLUSION: The BEST flow cytometric method has a smaller intercenter CV and a smaller center‐to‐center deviation from the group mean compared to hematology analyzers. Conversely, individual hematology analyzers are more precise than the flow cytometric method. Thus, the flow cytometric method provides a calibration tool to allow comparisons between centers, but there is no need to replace routine counting with hematology analyzers.
Increased numbers of total nucleated and CD34+ cells in blood group O cord blood: an analysis of neonatal innate factors in the Korean population
Authors: Lee Hye Ryun , Park Jeong Su , Shin Sue , Roh Eun Youn , Yoon Jong Hyun , Han Kyou Sup , Kim Byung Jae , Storms Robert W. , Chao Nelson J.
Published: July 2011

BACKGROUND: We analyzed neonatal factors that could affect hematopoietic variables of cord blood (CB) donated from Korean neonates.

STUDY DESIGN AND METHODS: The numbers of total nucleated cells (TNCs), CD34+ cells, and CD34+ cells/TNCs of CB in neonates were compared according to sex, gestational age, birth weight, birth weight centile for gestational age, and ABO blood group.

RESULTS: With 11,098 CB units analyzed, blood group O CB showed an increased number of TNCs, CD34+ cells, and CD34+ cells/TNCs compared with other blood groups. Although TNC counts were lower in males, no difference in the number of CD34+ cells was demonstrated because the number of CD34+ cells/TNCs was higher in males. An increase in the gestational age resulted in an increase in the number of TNCs and decreases in the number of CD34+ cells and CD34+ cells/TNCs. The numbers of TNCs, CD34+ cells, and CD34+ cells/TNCs increased according to increased birth weight centile as well as birth weight.

CONCLUSION: CB with blood group O has unique hematologic variables in this large‐scale analysis of Korean neonates, although the impact on the storage policies of CB banks or the clinical outcome of transplantation remains to be determined.
Splanchnic‐cerebral oxygenation ratio as a marker of preterm infant blood transfusion needs
Authors: Bailey Sean M. , Hendricks‐Muñoz Karen D. , Mally Pradeep
Published: July 2011

BACKGROUND: Premature neonates often receive red blood cell (RBC) transfusions to improve tissue perfusion and oxygen delivery. Clinical and laboratory indicators used to guide transfusion therapy are inadequate to determine physiologic need with high predictability and transfusions frequently do not result in clinical improvement. The splanchnic‐cerebral oxygenation ratio (SCOR) provides insight into overall tissue oxygen sufficiency and can be determined using near‐infrared spectroscopy (NIRS). Our aim was to assess the usefulness of SCOR as a marker for transfusion need in preterm infants.

STUDY DESIGN AND METHODS: This study was a prospective observational pilot study utilizing NIRS to analyze the SCOR in symptomatic anemic premature neonates receiving RBC transfusions and nontransfused asymptomatic premature neonates with similarly low hemoglobin (Hb) levels. Subject clinical status was determined based on frequency of apnea, bradycardia, pulse‐oximetry desaturation events, heart rate, respiratory support, and feeding tolerance. We then assessed for any difference between baseline (pretransfusion) SCOR of 1) symptomatic subjects who improved after transfusion, 2) symptomatic subjects who did not improve, and 3) asymptomatic subjects.

RESULTS: The study included 52 subjects (34 transfused, 18 asymptomatic): mean birth weight was 1164 g, mean gestational age was 28.6 weeks, and mean Hb level was 9.0 g/dL. Of 34 transfused subjects, 19 improved (56%). Mean baseline SCOR values were lower in neonates who improved with transfusion, 0.61 ± 0.22, when compared to those without improvement, 0.75 ± 0.17, and asymptomatic neonates, 0.77 ± 0.16 (p = 0.03). Infants with a low baseline SCOR (≤0.73) were more likely to improve after transfusion (likelihood ratio, 2.8; 95% confidence interval, 1.1‐6.7).

CONCLUSION: SCOR may help identify premature infants who will benefit from RBC transfusion.
All Middle‐Class Families Are Not Created Equal: Explaining the Contexts that Black and White Families Face and the Implications for Adolescent Achievement*
Authors: Lindsay Constance A.
Published: July 2011

Objectives.This article examines the relationship between race, socioeconomic status, and achievement using an ecological perspective.

Methods.Conventional theory suggests that as parent human capital increases, family resources increase, and therefore student achievement should increase. However, differential academic achievement is still observed between black and white adolescents in similar middle‐class families. I first provide a descriptive analysis of three domains of the local ecology that I theorize influence adolescent achievement: neighborhoods, parenting styles, and time use. I then use OLS regression analysis to explore whether the inclusion of various domains of adolescents' environments eliminates the black‐white test score differential.

Results.I find that the inclusion of the three domains lessens, but does not eliminate, the black‐white test score differential.

Conclusion.Black and white adolescents at all socioeconomic levels face different contexts; these different contexts are associated with differences in achievement.
Cooperative Institutions and Inequality in the OECD: Bringing the Firm Back In*
Authors: Alemán José A.
Published: July 2011

Objective. To examine the relationship between firm‐level cooperation, inequality, and redistribution in 18 advanced industrialized democracies.

Methods. The relationships are investigated using multiple regression analyses of institutional, political, and economic variables.

Results. Multilevel models reveal that contrary to neocorporatism, firm‐level cooperative ties have significant inegalitarian effects, particularly in the distribution of pretax, pretransfer market income. The effects, however, are also felt in the distribution of posttax, posttransfer income.

Conclusion. By paying attention to the effect of firm‐level cooperation, the study sheds new light on inequality in the OECD as a result of both market‐based and nonmarket coordination.
Recession of an EB‐PVDYSZ Coated Turbine Blade by CaSO4 and Fe, Ti‐Rich CMAS‐Type Deposits
Authors: Braue Wolfgang , Mechnich Peter
Published: July 2011

An in‐service high‐pressure turbine blade with a columnar, Y2O3‐stabilized ZrO2 (YSZ) thermal barrier coating (TBC) fabricated by electron‐beam physical vapor deposition was investigated to access the TBC hot corrosion mechanisms during turbine operation. The TBC exhibits a through‐thickness pore filling with anhydrite‐type CaSO4. Chemical analysis of the CMAS‐type particle deposits reveals relatively low SiO2 but high CaO contents and substantial amounts of Fe2O3 and TiO2. The hot corrosion scenario observed at the YSZ column tips involves newly formed CaZrO3 and the garnet‐type phase Ca3(Zr,Mg,Ti)2(Fe,Al,Si)3O12, also known as the mineral kimzeyite. The phase relationships were confirmed in laboratory experiments. CaSO4 as well as the particle deposits prove to be effective solvents for YSZ introducing distinct solid‐state reactions. The results support the idea of a dual YSZ hot corrosion process. A first stage controlled by a SiO2‐free Ca‐source, most likely primary CaSO4 produces a thin CaZrO3 layer. A second, CMAS‐type stage providing high concentrations of Fe2O3, TiO2, and SiO2 favors the formation of kimzeyite. The melting temperature of kimzeyite presumably defines a thermal operation limit for YSZ‐based TBCs.
Use of Styryl 11 and STaR 11 for the Luminescence Enhancement of Cyanoacrylate‐Developed Fingermarks in the Visible and Near‐Infrared Regions*
Authors: Chadwick Scott , Maynard Philip , Kirkbride Paul , Lennard Chris , Spindler Xanthe , Roux Claude
Published: July 2011

Abstract:  In current casework, most post‐cyanoacrylate stains rely on luminescence emission in the visible region (400–700 nm). While traditional stains such as rhodamine 6G work well under most circumstances, some surfaces may generate background luminescence under the same conditions. Detection in the near‐infrared region (NIR > 700 nm) has shown to be effective in minimizing the interferences from such surfaces. The laser dye styryl 11 generated strongly luminescent fingermarks when applied after cyanoacrylate fuming on all surfaces tested. When compared to rhodamine 6G, the dye was superior only when viewed in the NIR. Styryl 11 was subsequently combined with rhodamine 6G, and the mixed stain formulation (named StaR 11 by the authors) induced stronger luminescence compared with styryl 11 alone with an ability to visualize in both the visible and NIR regions. Reliable and consistent results were obtained when using either styryl 11 alone or the STaR 11 mixture. The enhancement achieved did not otherwise vary depending on the source of the fingermark secretions. With visualization possible in both the visible and NIR regions, the styryl 11/rhodamine 6G mixture showed significant potential as a post‐cyanoacrylate stain.
How mathematics warp biology: round‐off of umbilical cord blood gas case value decimals distorts calculation of metabolic acidosis at birth
Authors: OLOFSSON PER , MOKARAMI PARISA , KÄLLÉN KARIN , WIBERG NANA
Published: July 2011

Objective. To illustrate the impact on settling neonatal metabolic acidosis diagnosis by rounding off pH and base deficit (BD) case value decimals. Design. Comparative study. Setting. University maternity units. Sample. Umbilical cord arterial blood gas values from 18 831 newborns. Main outcome measures. Prevalences of pH <7.05 and metabolic acidosis diagnosis (pH <7.05 plus BD >12.0 mmol/L). Methods. Calculation of BD from pH and pCO2 values, and calculating the prevalences of metabolic acidosis before and after rounding off three‐decimal values to two or one decimals. The ‘round to half even’ and ‘round half up’ round‐off rules were used for digit 5. Results. Arterial pH was ≤7.049 in 339 newborns (1.8%). In 27 (8.0%) pH was 7.045–7.049, rounded off to 7.05 when truncated to two decimals (crude vs. round‐off values; McNemar's test, p<0.000001). Depending on round‐offs of pH case value decimals before or after calculation of BD, and round‐offs of resulting three‐decimal BD values to one decimal, metabolic acidosis ‘disappeared’ or ‘appeared’ in eight of 75 metabolic acidosis cases (10.7%). With different modes of calculation, the number of metabolic acidosis cases varied between 75 and 71 cases (p≥0.1). Conclusion. Due to pH and BD case value decimal round‐offs, a diagnostic discrepancy of acidotic pH values occurred in 8%, and of metabolic acidosis diagnosis in 10.7% of cases. A drift of a dichotomy parameter value cut‐off due to decimal round‐offs will result in a shift in distribution of positive and negative cases in a population sample.
Colonization of the Galápagos Islands by plants with no specific syndromes for long‐distance dispersal: a new perspective
Authors: Vargas Pablo , Heleno R. , Traveset A. , Nogales M.
Published: July 2011

Since nobody has witnessed the arrival of early plant colonists on isolated islands, the actual long‐distance dispersal (hereafter LDD) has historically been a matter of speculation. In the present study, we offer a new approach that evaluates whether particular syndromes for LDD (i.e. the set of traits related to diaspore dispersal by animals, wind and sea currents) have been favourable in the natural colonization of the Galápagos Islands by plants. Dispersal syndromes of the 251 native genera (509 angiosperm species) presently acknowledged as native were carefully studied, combining data from floristic lists of the Galápagos Islands, diaspore traits, characteristics of continental relatives and our own observations. We used these genera (and occasionally infrageneric groups) as the working units to infer the number of introductions and colonists. A final number of native plants was inferred and analysed after correcting by pollen records of six species from six genera previously considered exotic (palaeobotanical correction). The number of early colonists was also corrected by incorporating information from the few (n= 12) phylogenetic studies of genera from both the Galápagos Islands and the Americas (phylogenetic correction). A total of 372 colonization events were inferred for the native flora using the latest check‐list. The proportions of native colonists grouped into five categories were: endozoochory 16.4%, epizoochory 15.7%, hydrochory 18.6%, anemochory 13.3%, and unassisted diaspores 36.0%. These figures did not vary significantly on analysing only the 99 genera that include endemic species in order to rule out any human‐mediated introductions. Irrespective of the roles of the different agents involved in LDD, diaspores with no special syndrome for LDD (unassisted diapores), such as many dry fruits, have been successful in reaching and colonizing the Galápagos archipelago. This finding leads us to suggest that unpredictable and so far unknown LDD mechanisms should be further considered in the theory of island biogeography.
Licorice and its potential beneficial effects in common oro‐dental diseases
Authors: Messier C , Epifano F , Genovese S , Grenier D
Published: July 2011

Oral Diseases (2011) 18, 32–39

Licorice, the name given to the roots and stolons of Glycyrrhiza species, has been used since ancient times as a traditional herbal remedy. Licorice contains several classes of secondary metabolites with which numerous human health benefits have been associated. Recent research suggests that licorice and its bioactive ingredients such as glycyrrhizin, glabridin, licochalcone A, licoricidin, and licorisoflavan A possess potential beneficial effects in oral diseases. This paper reviews the effects of licorice and licorice constituents on both the oral microbial pathogens and the host immune response involved in common ora‐dental diseases (dental caries, periodontitis, candidiasis, and recurrent aphthous ulcers). It also summarizes results of clinical trials that investigated the potential beneficial effects of licorice and its constituents for preventing/treating oro‐dental diseases.
Molecular findings in oral premalignant fields: update on their diagnostic and clinical implications
Authors: Gonzalez‐Moles MA , Scully C , Ruiz‐Avila I
Published: July 2011

Oral Diseases (2011) 18, 40–47

The development of multiple oral tumours, seen in up to 30% of patients with a primary oral squamous cell carcinoma, is sometimes attributable to the presence of genetically altered premalignant fields and has important prognostic implications. Molecular techniques available for the definitive diagnosis of such a field (loss of heterozygosity analysis of 3p, 9p and 17p and study of TP53 tumour suppressor gene mutation) are expensive, complex and not universally available, hampering their routine application. Nevertheless, molecular diagnosis is essential for modern assessment of the risk of multiple tumours and for decisions on the appropriate preventive and therapeutic approaches. This article reviews current knowledge on molecular findings in premalignant fields in the oral cavity and oropharynx and provides an update on criteria for their identification, discussing the clinical and therapeutic implications.
Planting a misdiagnosis of Alzheimer's disease in a person's mind
Authors: Merckelbach Harald , Jelicic Marko , Jonker Cees
Published: July 2011

Objective: There is an extensive corpus of knowledge about how misinformation may distort autobiographical memories. A diagnostic error can be conceptualised as a form of misinformation.

Methods: The authors discuss the case of a 58-year-old woman who was given a misdiagnosis of Alzheimer's disease.

Results: The patient was deeply convinced that the diagnosis was correct, even when she was confronted with contradictory evidence.

Conclusion: A diagnosis is not a neutral piece of information. It profoundly affects the lives of patients. The consequences of a misdiagnosis may be similar to persistent false memories.
Effect of caesarean section on brain maturation
Authors: Kapellou Olga
Published: July 2011

The rates of caesarean section (CS) are increasing worldwide. The short‐term effects of CS in the newborn have been described and long‐term reported risks of alterations of pathophysiology include altered microflora, increased risk of childhood asthma and childhood‐onset type I diabetes mellitus. There has been emphasis on the respiratory morbidity related to the timing of elective CS. More recently, a population study demonstrated dose‐dependent effect of each week of gestation on the need for special education. This highlights the importance of intrauterine brain development towards the end of pregnancy and hitherto largely unexplored possible effects on neurodevelopment if it is interrupted.

Conclusion:  The timing of CS is important not only because delivery before 39 weeks can increase respiratory morbidity, but also owing to the fact that ongoing intrauterine brain maturation could be significant for future neurodevelopment.
Parental psychological well‐being and cognitive development of very low birth weight infants at 2 years
Authors: Huhtala Mira , Korja Riikka , Lehtonen Liisa , Haataja Leena , Lapinleimu Helena , Munck Petriina , Rautava Päivi ,   the PIPARI Study Group
Published: July 2011

Aim:  To assess the associations between cognitive development of very low birth weight (VLBW) infants and measures of parental psychological well‐being.

Methods:  In this prospective cohort study, 182 VLBW infants born 1/2001–12/2006 at the Turku University Hospital, Finland, were followed up. At 2 years corrected age, cognitive development of the child was assessed using the Mental Development Index of Bayley Scales, and both parents filled in validated questionnaires defining parental psychological well‐being (Beck Depression Inventory, Parenting Stress Index and Sense of Coherence Scale).

Results:  The cognitive delay of the infant was associated with paternal symptoms of depression (p = 0.007) and parenting stress (p = 0.03). Mothers of the infants with cognitive delay reported increased parenting stress related to the difficulty to accept the child (p = 0.001). Weak sense of coherence predicted depressive symptoms in both parents (p < 0.0001).

Conclusion:  Even if the fathers of VLBW infants experienced depressive symptoms less often than the mothers, the ability of the fathers to cope was significantly associated with the cognitive development of the infant. In addition, the fathers reported more parenting stress if the infant had a cognitive delay. The mothers reported more parenting stress related to accepting the VLBW infant with cognitive delay.
Differences in the behavior of the crossbred steers of different sire lines of Japanese Black cattle
Authors: UETAKE Katsuji , ISHIWATA Toshie , KILGOUR Robert J. , TANAKA Toshio
Published: July 2011

We determined differences in the behavior of the progeny of two major sire lines of Japanese Black cattle by recording the behavior of 35 and 70 half‐sib steers of sires from fast (FG) and slow (SG) growing lines, respectively. Two sire lines of steers were mixed and allocated to nine pens with 11–12 animals per pen. The proportion of steers lying was significantly (P < 0.001) higher in the SG line (43.4 ± 5.7% compared to 40.3 ± 6.0%). The proportion of time spent eating concentrate feed (FG: 12.1 ± 2.3%; SG: 11.4 ± 2.1%), drinking (FG: 0.8 ± 1.1%; SG: 0.4 ± 0.6%), licking the feed trough (FG: 0.4 ± 0.6%; SG: 0.2 ± 0.4%) and performing tongue‐playing (FG: 3.1 ± 4.6%; SG: 1.0 ± 1.9%) was significantly higher in FG, whereas the proportion of time spent resting (FG: 41.5 ± 12.8%; SG: 43.7 ± 10.9%) and performing self‐licking (FG: 1.7 ± 1.4%; SG: 2.1 ± 1.3%) was higher in SG (all P < 0.05). These results show progeny of the FG sire engaged in more active behaviors compared to the progeny of the SG sire line.
Effects of fermented mushroom (Flammulina velutipes) by‐product diets on growth performance and carcass traits in growing‐fattening Berkshire pigs
Authors: CHU Gyo Moon , YANG Jeong Mo , KIM Hoi Yun , KIM Chung Hui , SONG Young Min
Published: July 2011

This study was conducted to investigate effects of fermented mushroom (Flammulina velutipes) by‐product diets on the growth performance and carcass traits in growing‐fattening Berkshire pigs. The fermented diets mainly contained 40.0% mushroom by‐product, 20.0% formula feed, 26.0% rice bran and supplemental 0.1% probiotics. The mixed ingredients were fermented for 5 days at room temperature. Berkshire pigs (n = 225) were divided into five groups and three replications. The basal diets (C) were substituted by 10% (T1), 30% (T2), 50% (T3) and 70% (T4) fermented mushroom by‐product diets. Crude protein concentration and total calorie in fermented diets were significantly increased (P < 0.05) at the end of fermentation days compared with initial fermentation day. Body weight gain, feed efficiency and carcass weight were significantly lower (P < 0.05) in the T2, T3 and T4 groups than in the control group. Carcass grade was significantly better (P < 0.05) in the pigs fed fermented diets than in the pigs fed control diet and the ratio of high grade (1 plus 2 grades) was higher in the fermented diet groups compared with the control group. Therefore, although a diet of fermented mushroom by‐product decreased growth performance and feed efficiency, it improved the carcass grade in Berkshire pigs.
Effects of plane of nutrition on growth, feed intake, digestibility and nitrogen balance in Murrah graded male buffalo (Bubalus bubalis) calves in Nepal
Authors: KUMAGAI Hajime , BARAL Bodh R. , SHIINO Tatsu , DEVKOTA Naba R. , OISHI Kazato , HIROOKA Hiroyuki , KOLACHHAPATI Mana R. , TIWARI Ishwor C. P.
Published: July 2011

An experiment was conducted using 17 male buffalo calves to assess the effects of plane of nutrition on dry matter intake (DMI), daily gain (DG), body size measurement, apparent digestibility and nitrogen (N) balance. To attain 250 kg BW, the calves were allocated into three groups: H, L‐H and L, receiving the concentrate at 1.50% of BW, 0.75% of BW until 190 kg BW and 1.50% thereafter and 0.75% of BW, respectively. The animals had ad libitum access to urea‐treated rice straw (UTRS). The DMI of UTRS through the experiment was higher in L and L‐H than H, showing 3.52, 2.90 and 2.62 kg/day, respectively (P < 0.01), but the total DMI did not differ among the treatment groups. The DG throughout the experiment was high in the order of H, L‐H and L, showing 0.72, 0.57 and 0.45 kg, respectively (P < 0.01). The digestibility of DM, organic matter, crude protein, neutral and acid detergent fiber and N retention were higher in H than in L (P < 0.05). The findings of this study thus revealed the greater DG has an advantage of shortening the growing period around 3 months, and consequently increasing benefit in fattening of buffalo calves in Nepal.
Cellular vacuolation induced by Clostridium perfringens epsilon‐toxin
Authors: Nagahama Masahiro , Itohayashi Yukari , Hara Hideki , Higashihara Masahiro , Fukatani Yusuke , Takagishi Teruhisa , Oda Masataka , Kobayashi Keiko , Nakagawa Ichiro , Sakurai Jun
Published: July 2011

The epsilon‐toxin of Clostridium perfringens forms a heptamer in the membranes of Madin–Darby canine kidney cells, leading to cell death. Here, we report that it caused the vacuolation of Madin–Darby canine kidney cells. The toxin induced vacuolation in a dose‐dependent and time‐dependent manner. The monomer of the toxin formed oligomers on lipid rafts in membranes of the cells. Methyl‐β‐cyclodextrin and poly(ethylene glycol) 4000 inhibited the vacuolation. Epsilon‐toxin was internalized into the cells. Confocal microscopy revealed that the internalized toxin was transported from early endosomes (early endosome antigen 1 staining) to late endosomes and lysosomes (lysosomal‐associated membrane protein 2 staining) and then distributed to the membranes of vacuoles. Furthermore, the vacuolation was inhibited by bafilomycin A1, a V‐type ATPase inhibitor, and colchicine and nocodazole, microtubule‐depolymerizing agents. The early endosomal marker green fluorescent protein–Rab5 and early endosome antigen 1 did not localize to vacuolar membranes. In contrast, the vacuolar membranes were specifically stained by the late endosomal and lysosomal marker green fluorescent protein–Rab7 and lysosomal‐associated membrane protein 2. The vacuoles in the toxin‐treated cells were stained with LysoTracker Red DND‐99, a marker for late endosomes and lysosomes. A dominant negative mutant of Rab7 prevented the vacuolization, whereas a mutant form of Rab5 was less effective. These results demonstrate, for the first time, that: (a) oligomers of epsilon‐toxin formed in lipid rafts are endocytosed; and (b) the vacuoles originating from late endosomes and lysosomes are formed by an oligomer of epsilon‐toxin.

Structured digital abstract

 Epsilon‐toxin colocalizes with Epsilon‐toxin by cosedimentationthroughdensitygradient (View interaction)
A protein oxidase catalysing disulfide bond formation is localized to the chloroplast thylakoids
Authors: Feng Wei‐Ke , Wang Liang , Lu Ying , Wang Xiao‐Yun
Published: July 2011

In chloroplasts, thiol/disulfide‐redox‐regulated proteins have been linked to numerous metabolic pathways. However, the biochemical system for disulfide bond formation in chloroplasts remains undetermined. In the present study, we characterized an oxidoreductase, AtVKOR‐DsbA, encoded by the gene At4g35760 as a potential disulfide bond oxidant in Arabidopsis. The gene product contains two distinct domains: an integral membrane domain homologous to the catalytic subunit of mammalian vitamin K epoxide reductase (VKOR) and a soluble DsbA‐like domain. Transient expression of green fluorescent protein fusion in Arabidopsis protoplasts indicated that AtVKOR‐DsbA is located in the chloroplast. The first 45 amino acids from the N‐terminus were found to act as a transit peptide targeting the protein to the chloroplast. An immunoblot assay of chloroplast fractions revealed that AtVKOR‐DsbA was localized in the thylakoid. A motility complementation assay showed that the full‐length of AtVKOR‐DsbA, if lacking its transit peptide, could catalyze the formation of disulfide bonds. Among the 10 cysteine residues present in the mature protein, eight cysteines (four in the AtVKOR domain and four in the AtDsbA domain) were found to be essential for promoting disulfide bond formation. The topological arrangement of AtVKOR‐DsbA was assayed using alkaline phosphatase sandwich fusions. From these results, we developed a possible topology model of AtVKOR‐DsbA in chloroplasts. We propose that the integral membrane domain of AtVKOR‐DsbA contains four transmembrane helices, and that both termini and the cysteines involved in catalyzing the formation of disulfide bonds face the oxidative thylakoid lumen. These studies may help to resolve some of the issues surrounding the structure and function of AtVKOR‐DsbA in Arabidopsis chloroplasts.

Structured digital abstract

 AtVKOR‐DsbA and D1 colocalize by cosedimentation in solution (View interaction)
Intein lacking conserved C‐terminal motif G retains controllable N‐cleavage activity
Authors: Volkmann Gerrit , Liu Xiang‐Qin
Published: July 2011

A split‐intein consists of two complementary fragments (N‐intein and C‐intein) that can associate to carry out protein trans‐splicing. The Ssp GyrB S11 split‐intein is an engineered unconventional split‐intein consisting of a 150‐amino‐acid N‐intein and an extremely small six‐amino‐acid C‐intein, which comprises the conserved intein motif G. Here, we show that fusion proteins containing the 150‐amino‐acid N‐intein could be triggered to undergo controllable N‐cleavage in vitro when the six‐amino‐acid C‐intein or a derivative thereof was added as a synthetic peptide in trans. More importantly, we discovered, unexpectedly, that the 150‐amino‐acid N‐intein could be induced by strong nucleophiles to undergo N‐cleavage in vitro, and in Escherichia coli cells, in the absence of the motif G‐containing six‐amino‐acid C‐intein. This finding indicated that the first step of the protein splicing mechanism (acyl shift) could occur in the absence of the entire motif G. Extensive kinetic analyses revealed that both the motif G residues and the Ser+1 residue positively influenced N‐cleavage rate constants and yields. The 150‐amino‐acid N‐intein could also tolerate various unrelated sequences appended to its C‐terminus without disruption of the N‐cleavage function, suggesting that the catalytic pocket of the intein has considerable structural flexibility. Our findings reveal interesting insights into intein structure–function relationships, and demonstrate a new and potentially more useful method of controllable, intein‐mediated N‐cleavage for protein engineering applications.
Synergy between the N‐terminal and C‐terminal domains of Mycobacterium tuberculosis HupB is essential for high‐affinity binding, DNA supercoiling and inhibition of RecA‐promoted strand exchange
Authors: Sharadamma N. , Khan Krishnendu , Kumar Sandeep , Neelakanteshwar Patil K. , Hasnain Seyed E. , Muniyappa K.
Published: July 2011

The occurrence of DNA architectural proteins containing two functional domains derived from two different architectural proteins is an interesting emerging research theme in the field of nucleoid structure and function. Mycobacterium tuberculosis HupB, unlike Escherichia coli HU, is a two‐domain protein that, in the N‐terminal region, shows broad sequence homology with bacterial HU. The long C‐terminal extension, on the other hand, contains seven PAKK/KAAK motifs, which are characteristic of the histone H1/H5 family of proteins. In this article, we describe several aspects of HupB function, in comparison with its truncated derivatives lacking either the C‐terminus or N‐terminus. We found that HupB binds a variety of DNA repair and replication intermediates with Kd values in the nanomolar range. By contrast, the N‐terminal fragment of M. tuberculosis HupB (HupBMtbN) showed diminished DNA‐binding activity, with Kd values in the micromolar range, and the C‐terminal domain was completely devoid of DNA‐binding activity. Unlike HupBMtbN, HupB was able to constrain DNA in negative supercoils and introduce negative superhelical turns into relaxed DNA. Similarly, HupB exerted a robust inhibitory effect on DNA strand exchange promoted by cognate and noncognate RecA proteins, whereas HupBMtbN, even at a 50‐fold molar excess, had no inhibitory effect. Considered together, these results suggest that synergy between the N‐terminal and C‐terminal domains of HupB is essential for its DNA‐binding ability, and to modulate the topological features of DNA, which has implications for processes such as DNA compaction, gene regulation, homologous recombination, and DNA repair.

Structured digital abstract

 hupB binds to hupB by cross‐linking study (View interaction)
Guidance of pharmacotherapy in a complex psychiatric case by CYP450 DNA typing
Authors: Landino Joan , Buckley Jane , Roy John M. , Villagra David , Gorowski Krystyna , Kocherla Mohan , Windemuth Andreas , Ruaño Gualberto
Published: July 2011

Purpose: To illustrate the utility of CYP450 genotyping to guide clinical psychopharmacological treatment decisions and minimize or avoid harmful and costly adverse drug reactions (ADRs).

Data sources: DNA was extracted from a whole blood sample from the case study subject and tested for CYP450 gene polymorphisms in the CLIA certified Laboratory of Personalized Health at Genomas, Inc. Clinical data were obtained from patient records and clinician observations.

Conclusions: We present a case in which the ascertainment of multiple CYP450 isoenzyme deficiencies resulted in a dramatic change in psychotropic treatment approach. Shortly after making these adjustments, the patient saw a significant improvement in most of her debilitating psychiatric symptoms.

Implications for practice: In complex cases, CYP450 DNA testing can guide pharmacotherapy by exposing innate hepatic metabolic deficiencies as a result of DNA polymorphism. In such cases, clinicians can favor treatments that target functional isoenzyme pathways rather than deficient or null pathways thus leading to decreased risk of ADRs and improved patient response.