bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome and development of symptoms after orthotopic liver transplantation for Wilson disease
Authors: Weiss Karl Heinz , Schäfer Mark , Gotthardt Daniel Nils , Angerer Alexandra , Mogler Carolin , Schirmacher Peter , Schemmer Peter , Stremmel Wolfgang , Sauer Peter
Published: October 2013

Background

Wilson disease (WD) is an autosomal recessive copper storage disease resulting in hepatic and neurologic dysfunction. Liver transplantation is an effective treatment for fulminant cases for patients with chronic liver disease. Reports on the outcome of neuropsychiatric symptoms after orthotopic liver transplantation (OLT) are limited.

Aim

To assess the course of neuropsychiatric and hepatic symptoms after liver transplantation for Wilson disease

Methods

Nineteen patients with Wilson disease received liver transplantation and were followed prospectively from 2005 to 2010 for the development of hepatic, neurological and psychiatric symptoms.

Results

Eight patients (all female) were transplanted for acute liver failure and eleven patients for chronic liver failure. Patient survival rates one and five yr after transplantation were 78% and 65%, respectively. Of the surviving patients, hepatic symptom scores improved in all patients and neurological symptom scores improved in all but one patient after OLT compared to the time of initial diagnosis and compared to pre‐OLT status. Psychiatric symptoms showed moderate improvements.

Conclusion

Survival after OLT for Wilson disease with end‐stage liver disease is excellent. Overall, neuropsychiatric symptoms improved after transplantation, substantiating arguments for widening of the indication for liver transplantation in symptomatic neurologic Wilson disease patients with stable liver function.
Salivary Epithelial Cells as Model to Study Immune Response Against Cutaneous Pathogens
Authors: Negrini Thais C. , Arthur Rodrigo A. , Waeiss Robert A. , Carlosa Iracilda Z. , Srinivasan Mythily
Published: October 2013

The human skin not only provides passive protection as a physical barrier against external injury, but also mediates active surveillance via epidermal cell surface receptors that recognize and respond to potential invaders. Primary keratinocytes and immortalized cell lines, the commonly used sources to investigate immune responses of cutaneous epithelium are often difficult to obtain and/or potentially exhibit changes in cellular genetic make‐up. Here we investigated the possibility of using salivary epithelial cells (SEC) to evaluate the host response to cutaneous microbes. Elevated secretion of IFN‐γ and IL‐12 was observed in the SEC stimulated with Staphylococcus aureus, a transient pathogen of the skin, as mono species biofilm as compared to SEC stimulated with a commensal microbe, the Staphylococcus epidermidis. Co‐culture of the SEC with both microbes as dual species biofilm elicited maximum cytokine response. Stimulation with S. aureus alone but not with S. epidermidis alone induced maximum toll‐like receptor‐2 (TLR‐2) expression in the SEC. Exposure to dual species biofilm induced a sustained upregulation of TLR‐2 in the SEC for up to an hour. The data support novel application of the SEC as efficient biospecimen that may be used to investigate personalized response to cutaneous microflora.
Poor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy
Authors: Merlo Marco , Sinagra Gianfranco , Carniel Elisa , Slavov Dobromir , Zhu Xiao , Barbati Giulia , Spezzacatene Anita , Ramani Federica , Salcedo Ernesto , Di Lenarda Andrea , Mestroni Luisa , Taylor Matthew R. G.
Published: October 2013

Background

In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry.

Methods

DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN were identified. Genotype–phenotype association analysis was performed, and long‐term survival‐free from death or heart transplant was compared between carriers and noncarriers.

Results

We found 24 rare variants (3 in MYH6, 3 in MYH7, 3 in MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families. The phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure deaths, 8 heart transplants, 2 ventricular fibrillations). There was no difference in the overall long‐term survival between carriers and the 33 noncarriers (p = 0.322). However after 50 years of age, the combined endpoint of death or transplant was decreased in carriers as compared to noncarriers (p = 0.026).

Conclusions

Patients with DCM carrying rare variants in sarcomeric genes manifest a poorer prognosis as compared to noncarriers after the age of 50 years. These data further support the role of genetic testing in DCM for risk stratification.
Political Economies of Extractive Industry: From Documenting Complexity to Informing Current Debates
Authors: Bebbington Anthony , Bornschlegl Teresa , Johnson Adrienne
Published: October 2013

The literature on extractive industries has grown rapidly in recent years both because the empirical significance of resource extraction has increased and because resource extraction necessarily invokes other questions of wider purchase in development studies. This virtual issue brings together articles published in Development and Change on mining, oil and gas extraction since the early 1980s that explore these inter‐connections. They focus on certain interfaces: extraction and rural political economy; extraction and policies of economic adjustment; and extraction and development politics. The articles often document the complexity and contextual specificity of these interconnections, but we draw particular attention here to the insights they offer on broader issues such as the relationship between resource extraction, adjustment and neoliberalization.
Cowden syndrome complicated by a gastrointestinal stromal tumor
Authors: Nakamura Masanao , Hirooka Yoshiki , Yamamura Takeshi , Yamada Koji , Nagura Asuka , Yoshimura Toru , Ohmiya Naoki , Uehara Keisuke , Yoshioka Yuichiro , Nagino Masato , Goto Hidemi
Published: October 2013

To our knowledge, this is the first report of Cowden syndrome complicated by a gastrointestinal stromal tumor (GIST) of the small bowel. A 42‐year‐old female patient was found to have an abdominal mass that was diagnosed as the cause of anemia and was surgically extracted. The surgical specimen was found to be a GIST. During the same period, the patient underwent an endoscopic examination of the entire gastrointestinal tract. She was also diagnosed as having Cowden syndrome based on gastrointestinal polyps and skin, thyroid and breast lesions. Cowden syndrome is associated with germline mutations in the tumorsuppressor gene PTEN. PTEN expression may be essential to tumor growth and is a predictive biomarker of the prognosis of both diseases. The present report of such a case is expected to further the analysis of Cowden syndrome.
Domain‐specific development of face memory but not face perception
Authors: Weigelt Sarah , Koldewyn Kami , Dilks Daniel D. , Balas Benjamin , McKone Elinor , Kanwisher Nancy
Published: October 2013

How does the remarkable human ability for face recognition arise over development? Competing theories have proposed either late maturity (beyond 10 years) or early maturity (before 5 years), but have not distinguished between perceptual and memory aspects of face recognition. Here, we demonstrate a perception–memory dissociation. We compare rate of development for (adult, human) faces versus other social stimuli (bodies), other discrete objects (cars), and other categories processed in discrete brain regions (scenes, bodies), from 5 years to adulthood. For perceptual discrimination, performance improved with age at the same rate for faces and all other categories, indicating no domain‐specific development. In contrast, face memory increased more strongly than non‐face memory, indicating domain‐specific development. The results imply that each theory is partly true: the late maturity theory holds for face memory, and the early maturity theory for face perception.
Antagonistic and synergistic effects of bone morphogenetic protein 2/7 and all‐trans retinoic acid on the osteogenic differentiation of rat bone marrow stromal cells
Authors: Bi Wenjuan , Gu Zhiyuan , Zheng Yuanna , Wang Limin , Guo Jing , Wu Gang
Published: October 2013

The osteogenesis of bone marrow stromal cells (BMSCs) is of paramount importance for the repair of large‐size bone defects, which may be compromised by the dietary‐accumulated all‐trans retinoic acid (ATRA). We have shown that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) could induce bone regeneration in a significantly higher dose‐efficiency in comparison with homodimeric BMPs. In this study, we evaluated the effects of ATRA and BMP2/7 on the proliferation, differentiation, mineralization and osteogenic genes. ATRA and BMP2/7 exhibited both antagonistic and synergistic effects on the osteogenesis of BMSCs. ATRA significantly inhibited proliferation and expression of osteocalcin but enhanced the activity of alkaline phosphatase of BMSCs. On day 21, 50 ng/mL BMP2/7 could antagonize the inhibitive effects of ATRA and significantly enhance osteogenesis of BMSCs. These findings suggested a promising application potential of heterodimeric BMP2/7 in clinic to promote bone regeneration for the cases with dietary accumulated ATRA.
Retracted: Post‐stroke epilepsy in Polish paediatric patients
Authors: Kopyta Ilona , Sarecka‐Hujar Beata
Published: October 2013

The above article, published online on 5 October 2013 in Wiley Online Library Early View (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors, the journal Editor in Chief, Dr Peter Baxter, and John Wiley & Sons Ltd. The retraction has been agreed due to several errors in the statistics. These errors make interpretation of the data difficult and the validity of the conclusions questionable.
Prospective study of activities of daily living outcomes in children with cerebellar atrophy
Authors: Al‐Maawali Almundher , Blaser Susan , Zhao Xiu Y , Yoon Grace
Published: October 2013

Aim

The aim of this study was to identify clinical and radiological predictors of activities of daily living (ADL) outcomes in children with cerebellar atrophy.

Method

Over a period of 5 years, we evaluated 44 participants (25 males, 19 females) children with confirmed cerebellar atrophy using magnetic resonance imaging (MRI). The median age at the time of assessment 9 years; range 16mo–18y. Participants were grouped according to whether the cerebellar atrophy was isolated or associated with other radiological abnormalities. Severity of cerebellar atrophy was graded using qualitative and quantitative scoring systems. A standardized ADL assessment was used to characterize functional outcomes. The characteristics of the participants were analysed using descriptive statistics.

Results

The mean age at symptom onset was 20 months (range birth–10y). The group with isolated cerebellar atrophy had better outcomes than the group with cerebellar atrophy associated with other radiological abnormalities, with a mean total ADL score difference of 8.0 points (95% confidence interval 1.8–14.2 points, p=0.01). Age at onset of cerebellar atrophy before 2 years of age, progression of cerebellar atrophy on magnetic resonance imaging, presence of seizures, and decreased size of transverse cerebellar hemisphere diameter were all associated with worse outcomes.

Interpretation

We present a prospective study of clinical and radiological predictors of ADL outcome in children with cerebellar atrophy. This information may be useful in the diagnosis and future management of this complex group of disorders.
Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia
Authors: Simpson Nuala H , Addis Laura , Brandler William M , Slonims Vicky , Clark Ann , Watson Jocelynne , Scerri Thomas S , Hennessy Elizabeth R , Bolton Patrick F , Conti‐Ramsden Gina , Fairfax Benjamin P , Knight Julian C , Stein John , Talcott Joel B , O'Hare Anne , Baird Gillian , Paracchini Silvia , Fisher Simon E , Newbury Dianne F , Consortium SLI
Published: October 2013

Aim

Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia.

Method

Genome‐wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years).

Results

In the clinical language‐impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified.

Interpretation

The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non‐verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals.
The UK service level audit of insulin pump therapy in adults
Authors: White H. D. , Goenka N. , Furlong N. J. , Saunders S. , Morrison G. , Langridge P. , Paul P. , Ghatak A. , Weston P. J.
Published: October 2013

Aims

The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first UK‐wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here.

Methods

All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the UK were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool.

Results

One hundred and eighty‐three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the UK, of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety‐three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0–8), mean whole‐time equivalent diabetes specialist nurses was 0.62 (range 0–3) and mean whole‐time equivalent dietitian services was 0.3 (range 0–2), of which 39, 61 and 60%, respectively, were not formally funded.

Conclusions

The prevalence of continuous subcutaneous insulin infusion use in the UK falls well below the expectation of NICE (15–20%) and that of other European countries (> 15%) and the USA (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users.
Reference values of skin autofluorescence as an estimation of tissue accumulation of advanced glycation end products in a general Slovak population
Authors: Simon Klenovics K. , Kollárová R. , Hodosy J. , Celec P. , Šebeková K.
Published: October 2013

Aims

For decades, Slovakia has maintained a prominent place in mortality rates from cardiovascular diseases among European Union (EU‐27) countries. Determination of skin autofluorescence serves as an estimate of tissue accumulation of advanced glycation end products—substances accumulating in tissues and body fluids that play a pathophysiological role in age‐related diseases and their complications, such as diabetes.

Methods

In 1385 apparently healthy Slovakian subjects aged from a few days old to 77 years, skin autofluorescence was determined using an advanced glycation end product reader and compared with reference data from Dutch Caucasians. The impact of the weekly frequency of recreational physical exercise on skin autofluorescence was investigated in the adults, and the impact of feeding regimen in the infants.

Results

With the exception of 10‐ to 19‐year‐olds, Slovaks had lower skin autofluorescence values in comparison with the Dutch Caucasians. In healthy non‐smokers, physical exercise for > 30 min/day performed ≥ 3 times/week was associated with lower skin autofluorescence levels. In infants, breastfeeding (advanced glycation end product‐poor diet) was associated with lower skin autofluorescence levels in comparison with consumption of infant formulas (advanced glycation end product‐rich diet).

Conclusions

Reference ranges of skin autofluorescence in Slovak Caucasians, detailed for paediatric age groups, are provided. Our data show that, in healthy adults, regular physical exercise associates with lower skin autofluorescence. Infants fed or weaned from infant formulas (advanced glycation end product‐rich diet) have higher skin autofluorescence than their breast milk‐consuming counterparts. It is unclear why Slovaks have lower skin autofluorescence compared with a Dutch population with lower cardiovascular mortality rates. Reference data on skin autofluorescence from diverse populations are needed for the precise clinical interpretation of skin autofluorescence measurements.
Pregnancy losses in women with Type 1 or Type 2 diabetes in the UK: an investigation using primary care records
Authors: McGrogan A. , Snowball J. , de Vries C. S.
Published: October 2013

Aim

This study aims to investigate pregnancy losses in women with Type 1 or Type 2 diabetes and compare this with the general population.

Methods

Pregnancies ending between 1993 and 2006 in those with Type 1 or Type 2 diabetes were identified on the General Practice Research Database. Pregnancy losses were identified from medical records and the cohort described by their characteristics and prescribing for diabetes.

Results

Of 2001 pregnancies identified in women with Type 1 diabetes, 678 ended in a pregnancy loss: 19.6% were spontaneous, 9.6% were induced and 4.3% were losses for unknown reasons. In women with Type 2 diabetes, there were 240 losses in 669 pregnancies: 21.1% were spontaneous, 10.3% induced and 4.0% were losses for unknown reasons. The proportion of spontaneous losses in women with diabetes was higher than in the general population (13.2%). Women with Type 1 diabetes treated with human and analogue insulins were 60% more likely to have a delivery than a loss (odds ratio 1.6, 95% CI 1.18–2.18) compared with human insulin treatment alone, although numbers were small.

Conclusion

We found that the proportions of spontaneous losses in women with Type 1 or Type 2 diabetes were similar at approximately 20%, which is higher than in the general population and also higher than previous studies have reported. While much emphasis has been placed on pre‐conception care for women with Type 1 diabetes, the same is now needed for those with Type 2 diabetes, given the similarity in outcomes and increasing prevalence of this condition.
Social patterning in knowledge following an informed choice invitation for Type 2 diabetes screening
Authors: Kellar I. , Mason D.
Published: October 2013

Aims

To describe prevalence of knowledge of items specified by the UK General Medical Council as required to make an informed choice following an invitation for screening for Type 2 diabetes and investigate whether knowledge was socio‐economically patterned.

Methods

A 9‐item knowledge questionnaire was employed immediately following an informed choice invitation to Type 2 diabetes screening that was piloted with 278 people between 40 and 69 years in the UK between February and April 2006.

Results

With the exception of post‐diagnosis treatment and the effectiveness of early treatment in preventing long‐term problems, information was typically understood correctly. Social patterning was observed: individuals who left full‐time education before 19 years of age were less likely to understand the most likely test result, the effectiveness of early treatment in preventing long‐term problems or the possible harms of screening.

Conclusions

Even risk communication materials developed for ease of readability can result in inequity, limiting autonomy in healthcare decisions.
Weight change upon once‐daily initiation of insulin detemir with or without dietary intervention in overweight or obese insulin‐naïve individuals with type 2 diabetes: results from the DIET trial
Authors: Niswender K. , Piletic M. , Andersen H. , Conradsen Hiort L. , Hollander P.
Published: October 2013

Aims

Weight gain upon insulin initiation is opposite to clinical goals in diabetes management. This trial aimed to determine the impact of modest dietary intervention on weight change and examine weight change in baseline body mass index strata when initiating once‐daily insulin detemir (IDet) in overweight or obese insulin‐naïve individuals with type 2 diabetes (T2D).

Methods

DIET (Impact of Dietary Intervention on Weight Change in Subjects With Type 2 Diabetes) was a 26‐week, randomized, treat‐to‐target, stratified, controlled, open‐label, multinational trial. Subjects were randomized 1 : 1 to either the IDet group, which received basic dietary and physical exercise advice at baseline, or the Diet+IDet group, which had additional dietary consultations with a certified dietician (three face‐to‐face meetings, three phone contacts).

Results

Mean estimated change in body weight from baseline ± standard error (SE) was −1.05 ± 0.23 kg for Diet+IDet and −0.56 ± 0.23 kg for IDet alone. Estimated mean difference was 0.49 kg (95% confidence interval: −0.15; 1.13, p = 0.132). Glycaemic control, measured by haemoglobin A1c (HbA1c) and fasting plasma glucose, improved similarly in both groups. Both groups reported variable reductions in caloric intake and overall physical activity levels. No difference in hypoglycaemia rates between groups was observed.

Conclusion

This study suggests that a modest dietary intervention plus basic lifestyle advice, compared with basic lifestyle advice alone, resulted in similar weight change, efficacy, safety and tolerability when initiating IDet once daily in overweight or obese insulin‐naïve individuals with T2D.
Asymptomatic Carotid Disease—A New Tool for Assessing Neurological Risk
Authors: Pedro Luís M. , Sanches J. Miguel , Seabra José , Suri Jasjit S. , Fernandes e Fernandes José
Published: October 2013

Active carotid plaques are associated with atheroembolism and neurological events; its identification is crucial for stroke prevention. High‐definition ultrasound (HDU) can be used to recognize plaque structure in carotid bifurcation stenosis associated with plaque vulnerability and occurrence of brain ischemic events. A new computer‐assisted HDU method to study the echomorphology of the carotid plaque and to determine a risk score for developing appropriate symptoms is proposed in this study. Plaque echomorphology characteristics such as presence of ulceration at the plaque surface, juxta‐luminal location of echolucent areas, echoheterogeneity were obtained from B‐mode ultrasound scans using several image processing algorithms and were combined with measurement of severity of stenosis to obtain a clinical score—enhanced activity index (EAI)—which was correlated with the presence or absence of ipsilateral appropriate ischemic symptoms. An optimal cutoff value of EAI was determined to obtain the best separation between symptomatic (active) from asymptomatic (inactive) plaques and its diagnostic yield was compared to other 2 reference methods by means of receiver‐operating characteristic (ROC) analysis. Classification performance was evaluated by leave‐one‐patient‐out cross‐validation applied to a cohort of 146 carotid plaques from 99 patients. The proposed method was benchmarked against (a) degree of stenosis criteria and (b) earlier proposed activity index (AI) and demonstrated that EAI yielded the highest accuracy up to an accuracy of 77% to predict asymptomatic plaques that developed symptoms in a prospective cross‐sectional study. Enhanced activity index is a noninvasive, easy to obtain parameter, which provided accurate estimation of neurological risk of carotid plaques.
A Strategic Approach to Offshoring
Authors: Oladi Reza , Beladi Hamid , Gilbert John
Published: October 2013

In the context of a simple model of strategic offshoring, we investigate the reasons why firms may simultaneously source fragments domestically and internationally. We explore the impacts of offshoring on the production pattern of finished goods, tradable fragment prices, and welfare in a partial equilibrium context. The policy implications of attempts to restrict offshoring are also considered. The analysis shows that an offshoring equilibrium may exist in the absence of comparative advantage in fragments, that offshoring is welfare improving if the costs are sufficiently small, and that attempts (by both countries) to prevent offshoring may paradoxically lower both fragment use and price.
Dental traumas during the military service
Authors: Immonen Matti , Anttonen Vuokko , Patinen Pertti , Kainulainen Marco‐Juhan , Päkkilä Jari , Tjäderhane Leo , Oikarinen Kyösti
Published: October 2013

Background

Dental traumas are most frequent during the first three decades of life and more frequent among males than females. Approximately 80% (n = 28 000) of the male age cohort performs military service annually in Finland. As little is known of dental, head, and neck traumas during the military service, our aim was to study the etiology, number and occurrence of traumas of the Finnish conscripts during one calendar year. Our hypothesis was that above‐mentioned traumas comprise a remarkable proportion of military accidents.

Materials and methods

The data comprised of all the Finnish conscripts' trauma cases in the year 2009 (mean age 20.1 years, SD 1.1). The frequency, mechanism, and time of the incidences were analyzed.

Results

Of the total 1432 trauma cases, 303 (23%) involved head, neck, or dentition. The occurrence rate of dental traumas was 6.5 cases/1000 persons/year. Dental traumas comprised 14.3% of all traumas. The most common mechanism for dental traumas was a blow‐type force. First 4 months of the service and winter time were periods of increased risk of dental traumas. Two‐thirds of the dental traumas, one‐third of the body traumas and a quarter of the head and neck traumas occurred during military field exercises. Most dental traumas required a visit to a military dental clinic and also needed follow‐up care.

Discussion and Conclusion

Head, neck, and dental injuries are common during the military service in Finland. Prevention of dental traumas and need for first aid dental skills of the personnel should be emphasized.
Antimicrobial activity of short‐ and medium‐term applications of polyhexamethylene biguanide, chlorhexidine digluconate and calcium hydroxide in infected immature bovine teeth in vitro
Authors: Zaugg Lucia K. , Zitzmann Nicola U. , Hauser‐Gerspach Irmgard , Waltimo Tuomas , Weiger Roland , Krastl Gabriel
Published: October 2013

Aim

To compare the antimicrobial activity of polyhexamethylene biguanide (Prontosan wound gel, Pr) and chlorhexidine digluconate (CHX) after short‐ and medium‐term application with the disinfection ability of calcium hydroxide (Ca) in a model using immature bovine teeth.

Methods

Sixty immature bovine roots were infected with Enterococcus faecalis and randomly assigned to six groups (n = 10). Disinfectants were applied into the root canal for 10 min (CHX‐10 min and Pr‐10 min) or 7 days (CHX‐7d, Pr‐7d and Ca‐7dg). In the negative control group (Co‐n), no disinfectant was used. Dentine samples were collected, and the total count of bacteria and colony‐forming units were determined. The log10‐transformed Colony‐forming units (CFU) data were analysed using a Kruskal–Wallis test with post hoc Wilcoxon multiple‐comparison tests.

Results

The application of disinfectants led to a significant reduction in CFUs in all groups compared with group Co‐n. When compared to Ca‐7dg, CHX‐7d (P = 0.290), CHX‐10 min (P = 0.963) and Pr‐7d (P = 0.095) revealed no significant differences. Pr‐10 min had a significantly higher CFU value than Ca‐7dg (P = 0.0004), CHX‐10 min (P = 0.0009) and Pr‐7d (P = 0.0006).

Conclusions

Within the limitations of this study, sufficient antimicrobial effect may be reached by a short‐term application of CHX. For the application of 1% Prontosan wound gel, a medium‐term use (7 day) is required, while short‐term use (10 min) is less effective.
Management of crown‐related fractures in children: an update review
Authors: Güngör Hamdi Cem
Published: October 2013

Traumatic dental injuries (TDIs) are a serious public health problem. Epidemiology of dental trauma indicates that these injuries are more prevalent in child population of the world. Children are the sufferers in two‐thirds of all TDIs observed. Although being a major fraction, crown‐related fractures are a less severe form of TDIs with respect to their complications and sequelae. However, as with other types of traumatic injuries, the delay in seeking for immediate care following a traumatic injury and the lack of appropriate treatment may compromise long‐term outcomes. This article reviews the occurrence, management, and prognosis of crown‐related fractures in primary and permanent teeth in light of the recent literature.
Age‐specific maternal effects interact with larval food supply to modulate life history in Coleomegilla maculata
Authors: VARGAS GERMAN , MICHAUD J. P. , NECHOLS JAMES R. , MORENO CARLOS A.
Published: October 2013

Maternal effects can modify progeny phenotypes to improve their survival under variable conditions, such as changes in food supply. In aphidophagous coccinellids, maternal effects can influence egg size, developmental rate, and final adult body size.

Four cohorts of Coleomegilla maculata De Geer larvae were reared from four different points in their mothers' reproductive lives (1st, 12th, 24th, and 36th oviposition days) and divided into two diet treatments for rearing; 30‐min daily access to eggs of Ephestia kuehniella Zeller or ad libitum.

Progeny survival was lower on restricted food but increased over the first 12 oviposition days in both treatments, suggesting mothers did not conform to the theoretical norm of producing their ‘best’ progeny first.

Larval development was delayed on the restricted diet, but there was no effect of oviposition day on total developmental time, although pupation was faster in the final cohort than in the first.

The results suggest that mothers employ a mixed strategy and produce subsets of progeny that vary in response to food limitation. A small fraction adopt an ‘optimistic’ strategy and undergo an additional instar to take advantage of any possible improvement in the food supply, whereas a larger fraction adopt a ‘pessimistic’ strategy, forgoing an instar and the costs of a moult to pupate at a small size.

The restricted diet increased the percentage of larvae that added or subtracted an instar, but larvae from later clutches were more likely to pupate after only three instars, independent of treatment, suggesting that a larger proportion of later‐hatching progeny are maternally programmed for pessimism, as would be adaptive for larvae exploiting aphid populations in decline.
Depression in young adult psychiatric outpatients: delimiting early onset
Authors: Ramirez Adriana , Ekselius Lisa , Ramklint Mia
Published: October 2013

Aim

The aim of this study was to examine differences in childhood, adolescent and adult onset of depression.

Methods

Young psychiatric outpatients (n = 156) diagnosed with a lifetime depressive episode were divided into three groups according to age of onset of their first depressive episode: childhood (≤12 years, n = 21), adolescent (13–17 years, n = 58) and early adult onset (18–25 years, n = 77). Participants were assessed by diagnostic interviews and by questionnaires measuring previous life events and childhood developmental delays. Clinical characteristics and various risk factors were compared between groups.

Results

This clinical sample was dominated by women, with onset of their first depressive episode occurring during adolescence. Childhood onset was related to an increased number of depressive episodes, higher prevalence of personality disorders, more current social problems and more reported development delays during childhood regarding literacy learning, social skills and memory. They also reported more separation anxiety symptoms and neglect during childhood and more experiences of teenage pregnancies and abortions.

Conclusions

Childhood onset of depression is associated with more severe symptoms, more psychosocial risk factors and childhood developmental delays. Because all onset groups shared many features, the results are inconclusive if there are distinct subgroups according to age of onset.
Pathways to (specialized) care: patient costs and contacts en route to a first‐episode psychosis clinic
Authors: Cheung Desmond , Roper Leslie , Purdon Scot E.
Published: October 2013

Aim

To estimate the public health costs of specific help‐seeking pathways into an early intervention psychosis clinic.

Methods

The sequence of police, emergency and mental health contacts utilized by 50 patients up to 1 year prior to admission was characterized using chart reviews and structured interviews. Cost estimates for contacts were obtained from provincial health/public service cost reports.

Results

A high‐cost inpatient pathway and a low‐cost outpatient pathway were identified, with the former exceeding the latter by a factor of 18.5 in cost. This discrepancy was attributable to both the high cost of inpatient services and the long duration of inpatient admissions, as well as more frequent inpatient use of high‐cost urgent services (e.g. police, emergency services).

Conclusion

Given the substantial cost differential between inpatient and outpatient routes, additional clarification of modifiable factors that determine pathways to care could have significant implications to health service delivery costs for this population.
Can I be a student again? How medical graduates make the decision to return to dental school prior to a career in oral and maxillofacial surgery
Authors: Tahim A. S. , Payne K. F. B. , Goodson A. M. C. , Cabot L. B. , Fan K.
Published: October 2013

Introduction

Oral and maxillofacial surgery (OMFS) trainees in the UK have traditionally completed their dental undergraduate studies prior to returning to medical school. Recently, there have been increasing numbers of medical graduates who return to dental school before embarking on OMFS specialist training. There is limited research into the career motivation within this group and little guidance on how they may integrate the dental undergraduate course into their postgraduate training path. This study aims to evaluate these factors in more detail.

Methods

Questionnaires and focus groups were used to evaluate prior surgical experience of qualified medics who return to dental school with the intention of pursuing a career in OMFS, along with the factors that affect the timing of their return to dental school.

Results

The average age of medical graduates entering dental school decreased during the study period. The average number of months each cohort of students spent as a practicing doctor prior to starting dentistry also reduced. Postgraduate experience in OMFS was highly variable, but the numbers of students who received alternative exposure to OMFS, such as undergraduate special study modules, medical school elective or taster weeks, increased. The key barriers that were carefully considered by these trainees before returning to university included the perceived increase in the length of training, trainees' prior surgical experience, financial implications and the impact on quality of life.

Conclusions

A trainee's decision to return to study dentistry is a multifactorial process. Understanding when trainees decide to return to sit their dental degree is vital not only to provide guidance for future trainees but also to assist future workforce planning, thus aiding training, education and development within OMFS.
An introduction to clinical practice guideline for Chinese undergraduates in stomatology
Authors: Li C. , Zheng J. , Guo C. , Ling J. , Yu H. , Zhang J. , Tai B. , Hou T. , Tang G. , Sun W. , Wang S.
Published: October 2013

The Society of Dental Education, Chinese Stomatological Association has formulated the Standards of Clinical Practice for Chinese Undergraduate Students Majoring in Stomatology, on the basis of extensively soliciting the views of experts in various fields. The aim of this standard is to guide clinical teaching and improve teaching quality in schools of stomatology in China. The standards include eight parts: the standard of clinical practice for oral and maxillofacial surgery, for cariology and endodontics, for periodontics, for the oral mucosa diseases, for preventive dentistry, for pedodontology, for prosthodontics and for oral imageology. Each part includes introduction to subjects, the clinical practice time period, the purpose and requirements of practice, the disease types of practice and items of clinical operation, the index of the lowest workload of practice and the major methods of assessment. These standards are not only the basic requirements and guiding principles for clinical teaching, but also the major criteria for assessing the clinical teaching quality of stomatological colleges/schools of China.
Phenotypic expression of Hb F in common high Hb F determinants in Thailand: roles of α‐thalassemia, 5′ δ‐globin BCL11A binding region and 3′ β‐globin enhancer
Authors: Prakobkaew Nattaphol , Fucharoen Supan , Fuchareon Goonnapa , Siriratmanawong Nirut
Published: October 2013

Background

Deletions of δ‐ and β‐globin genes are associated with different Hb F levels. To address this, we have examined hematological and molecular characteristics in a large cohort of high Hb F determinants in Thailand.

Methods

A total of 160 unrelated adult subjects with heterozygous trait for high Hb F determinants and another 10 patients with compound heterozygous trait for Hb E were selectively recruited. Hematological parameters and Hb analysis were recorded, and α‐thalassemia mutations were investigated. DNA deletions causing δβ0‐thalassemia and hereditary persistence of fetal hemoglobin (HPFH) were identified using multiplex PCR and denaturing high‐performance liquid chromatography (HPLC) assays developed.

Results

Four different DNA deletions were detected including the 12.6 kb deletion δβ0‐thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)‐6 (n = 65), Indian deletion‐inversion Gγ(Aγδβ)‐thalassemia (n = 15) and 78 kb deletion Chinese Gγ(Aγδβ)‐thalassemia (n = 1). Eighteen cases were found to carry α‐thalassemia with 10 different genotypes. All 10 patients who had similar hematological phenotype with that of Hb E‐β0‐thalassemia were found to be compound Hb E‐δβ0‐thalassemia. Differences in hematological features as well as Hb F levels were noted and are presented comparatively.

Conclusion

Comparison of phenotypes, genotypes, and the deletion breakpoints of these Thai high Hb F determinants indicates that differences in Hb F expression are correlated with the existence of α‐thalassemia, the loss of BCL11A binding region located 5′ to the δ‐globin gene and the 3′ β‐globin enhancer, which confirms their important roles in fetal Hb expression.
Quantification of HBG mRNA in primary erythroid cultures: prediction of the response to hydroxyurea in sickle cell and beta‐thalassemia
Authors: Pecoraro Alice , Rigano Paolo , Troia Antonio , Calzolari Roberta , Scazzone Concetta , Maggio Aurelio , Steinberg Martin H. , Marzo Rosalba Di
Published: October 2013

Background and Objective

Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies like sickle cell disease (SCD) and β‐thalassemia. Hydroxyurea (HU) can stimulate HbF production in these diseases but the response is highly variable indicating the utility of developing an in vitro test to predict the patient's response to HU. We assessed whether the HbF response of patients with SCD and thalassemia intermedia (TI) to HU correlates with HBG (both γ‐globin genes) expression in their cultured erythroid progenitors following exposure to HU.

Patients and Methods

We exposed primary erythroid cultures from peripheral blood mononuclear cells from 30 patients with SCD and 15 with TI to HU and measured HBG mRNA by real‐time quantitative PCR. The same patients were then treated with HU and their HbF response after treatment with a stable dose of HU was compared with the mRNA results in cultured cells.

Results and Conclusion

The fold increase in HBG mRNA in erythroid progenitors was similar to the fold increase in HbF in vivo. Quantification of HBG mRNA in erythroid progenitor cell cultures from patients with SCD and TI is predictive of their clinical response to HU.
Refractory thrombotic thrombocytopenic purpura in a 16‐year‐old girl: successful treatment with bortezomib
Authors: van Balen Tessa , Schreuder Michiel F. , de Jong Huib , van de Kar Nicole C. A. J.
Published: October 2013

We present a case of a 16‐year‐old girl with autoimmune thrombotic thrombocytopenic purpura (TTP), refractory to plasma exchange and high‐dose prednisone. Despite the additional treatment with rituximab, she developed renal and neurological complications with ongoing hemolysis and thrombocytopenia. Bortezomib, a proteasome inhibitor and thereby blocking plasma cells, was added, and our patient recovered. We suggest that bortezomib can be of additional value in severe immunologically mediated TTP in adolescents. Its use may prevent the necessity of other invasive therapies, such as splenectomy, with significant side effects.
Oral administration of the flavanol (−)‐epicatechin bolsters endogenous protection against focal ischemia through the Nrf2 cytoprotective pathway
Authors: Leonardo Christopher C. , Agrawal Megha , Singh Nilendra , Moore J. Russell , Biswal Shyam , Doré Sylvain
Published: October 2013

Consumption of flavan‐3‐ols, notably (−)‐epicatechin (EC), has been highly recommended in complementary and alternative medicine (CAM) due to reports that flavan‐3‐ols boost antioxidant activity, support vascular function, and prevent cardiovascular disease. To date, in vivo efficacy and mechanisms of action for many CAM therapies, including EC, remain elusive in brain ischemia. In contrast to its purported direct antioxidant role, we hypothesized protection through activation of the endogenous transcriptional factor Nrf2. To screen cellular protection and investigate Nrf2 activation, we adopted a pretreatment paradigm using enriched primary neuronal cultures from mice and washed out EC prior to oxygen glucose deprivation to attenuate direct antioxidant effects. EC protected primary neurons from oxygen glucose deprivation by increasing neuronal viability (40.2 ± 14.1%) and reducing protein oxidation, effects that occurred concomitantly with increased Nrf2‐responsive antioxidant protein expression. We also utilized wildtype and Nrf2 C57BL/6 knockout mice in a permanent model of focal brain ischemia to evaluate glial cell regulation and complex sensorimotor functioning. EC‐treated wildtype mice displayed a reduction or absence of forelimb motor coordination impairments that were evident in vehicle‐treated mice. This protection was associated with reduced anatomical injury (54.5 ± 8.3%) and microglia/macrophage activation/recruitment (56.4 ± 13.0%). The protective effects elicited by EC in both model systems were abolished in tissues and neuronal cultures from Nrf2 knockout mice. Together, these data demonstrate EC protection through Nrf2 and extend the benefits to improved performance on a complex sensorimotor task, highlighting the potential of flavan‐3‐ols in CAM approaches in minimizing subsequent stroke injury.
Blocking brain‐derived neurotrophic factor inhibits injury‐induced hyperexcitability of hippocampal CA3 neurons
Authors: Gill Raminder , Chang Philip K.‐Y. , Prenosil George A. , Deane Emily C. , McKinney Rebecca A.
Published: October 2013

Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin‐related kinase B (TrkB), a receptor for brain‐derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF‐mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury‐induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB‐Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB‐Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two‐fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB‐Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB‐Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury‐induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post‐traumatic epilepsy. Therefore, our data suggest that blocking the BDNF–TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post‐traumatic epilepsy.