bluuebunny/crossref_metadata_2025 huggingface dataset:
Incontrovertible proof that the “discrepancies” in thin-shell-buckling studies are in the classical theory, not the test data
Authors: Hart-Smith LJ
Published: February 2014

It is shown here that the classical shell-buckling analyses have been fatally flawed since they were first derived. One reason cited is a failure to freeze the buckling stresses at the values at which buckling commenced, which resulted in consistent over estimates of the true buckling stresses by large factors. Another is the misinterpretation of the inextensibility criterion, which is customarily expressed in terms of the linear equations pertaining prior to buckling instead of the nonlinear equations that govern once buckling has commenced. The consequence of not acknowledging these errors is that, for many decades, it has been assumed incorrectly that the classical analyses for the various shell geometries are valid and that the major discrepancies can all be attributed to imperfections in the testing. It is shown here that this is not the case, by deriving different governing equations for shell buckling, starting from the geometrically nonlinear equilibrium equations for thin shells. These equilibrium equations are shown to include both the linear terms governing prior to buckling, with the remaining terms pertaining during buckling. This shows that buckling is resisted entirely by bending stresses alone, just as is known to be the case for flat-plate buckling, instead of by the combination of membrane and bending stresses. Specific equations are included for cylindrical shells, along with test data showing that the correct buckling stress for longitudinally compressed unpressurized cylinders is only half the classical prediction. Future papers will include full analyses of the buckling of spherical shells under external pressure at half the classical prediction, and of cylindrical shells under external pressure at one third of the classical prediction, as well as the buckling of pressurized and unpressurized cylindrical shells under longitudinal compression showing how, as the internal pressure is increased, the diamond-buckling stress increases from half the classical prediction for zero pressure to the classical ring-buckling stress for high pressure.
The defence of journalistic legitimacy in media discourse in China: An analysis of the case of Deng Yujiao
Authors: Tong Jingrong
Published: February 2014

This article examines the response of Chinese mainstream journalists towards their citizen counterparts, through an analysis of how journalists constructed a discourse of ‘netizens’ and journalism in the case of Deng Yujiao. The analysis is mainly drawn from a discourse analysis of the newspaper coverage of this case in the Southern Metropolitan Daily (SMD) and the relevant journalists’ reflexive articles on the same topic published in the Journal of Southern Media Studies (JSMS). The discourse analysis is supplemented by interviews with 60 journalists in 2011 concerning their views of netizens in general and of the conflict between journalism and netizens in this particular case. Based on these three elements of analysis, this article offers an account of how institutionally-shaped journalistic norms and values have been used to set up and maintain the occupational boundaries of Chinese journalism, in an attempt to defend journalistic legitimacy by making a clear distinction between ‘amateur netizens/them’ and ‘professional journalists/us’.
Resting-State Functional Connectivity and Its Association With Multiple Domains of Upper-Extremity Function in Chronic Stroke
Authors: Urbin M. A. , Hong Xin , Lang Catherine E. , Carter Alex R.
Published: February 2014

Background. Recent work has shown that resting-state functional connectivity (rsFC) between homotopic, motor-related brain regions is associated with upper-extremity control early after stroke. Objectives. This study examined various patterns of rsFC in chronic stroke, a time at which extensive neural reorganization has occurred. Associations between homotopic somatomotor connectivity and clinical measures, representing separate domains of upper-extremity function, were determined. Methods. A total of 19 persons ≥6 months poststroke participated. Four connectivity patterns within a somatomotor network were quantified using functional magnetic resonance imaging. Upper-extremity gross muscle activation, control, and real-world use were evaluated with the Motricity Index, Action Research Arm Test, and accelerometry, respectively. Results. Connectivity between homotopic regions was stronger than that in the contralesional and ipsilesional hemispheres. No differences in connectivity strength were noted between homotopic pairs, indicating that a specific brain structure was not driving somatomotor network connectivity. Homotopic connectivity was significantly associated with both upper-extremity control ( r = 0.53; P= .02) and real-world use ( r = 0.54; P= .02); however, there was no association with gross muscle activation ( r = 0.23; P=.34). The combination of clinical measures accounted for 40% of the variance in rsFC (= .05). Conclusions. The results reported here expand on previous findings, indicating that homotopic rsFC persists in chronic stroke and discriminates between varying levels of upper-extremity control and real-world use. Further work is needed to evaluate its adequacy as a biomarker of motor recovery following stroke.
Endovenous laser ablation for saphenous vein insufficiency: Short- and mid-term results of 230 procedures
Authors: Altin Firat H , Aydin Selim , Erkoc Kamuran , Gunes Tevfik , Eygi Bortecin , Kutas Baris H
Published: February 2014

Objective

The present study aimed to evaluate the efficacy of endovenous laser ablation with a 1470-nm laser and to analyze the short- to mid-term results of endovenous laser ablation procedures to treat great saphenous vein insufficiency.

Method

In this retrospective study, 200 patients (230 limbs) with symptomatic varicose veins secondary to great saphenous vein insufficiency treated with 1470-nm endovenous laser ablation were studied. Patients were evaluated clinically on the first day, first week, first month, and sixth month after the operation. Treated limbs were evaluated as separate treatment events.

Results

The short-term occlusion rate was 99% and mid-term occlusion rate was 100%. Induration or swelling was the most common minor complication (13%). No major complication such as deep venous thrombosis and pulmonary embolus occurred. Preoperatively documented mean venous clinical severity score significantly reduced from 4.9 ± 2.3 to 2.5 ± 1.1 ( p < 0.05).

Conclusion

Endovenous laser ablation procedure of great saphenous vein with a 1470-nm diode laser is a minimally invasive, safe, and efficient treatment option in all-suitable patients with high short- and mid-term success rate.
Campylobacter infection in chickens modulates the intestinal epithelial barrier function
Authors: Awad Wageha A , Molnár Andor , Aschenbach Jörg R , Ghareeb Khaled , Khayal Basel , Hess Claudia , Liebhart Dieter , Dublecz Károly , Hess Michael
Published: February 2014

Asymptomatic carriage of Campylobacter jejuni is highly prevalent in chicken flocks. Thus, we investigated whether chronic Campylobacter carriage affects chicken intestinal functions despite the absence of clinical symptoms. An experiment was carried out in which commercial chickens were orally infected with C. jejuni (1 × 108 CFU/bird) at 14 days of life. Changes in ion transport and barrier function were assessed by short-circuit current ( Isc) and transepithelial ion conductance ( Gt) in Ussing chambers. Gt increased in cecum and colon of Campylobacter-infected chicken 7 d post-infection (DPI), whereas Gt initially decreased in the jejunum at 7 DPI and increased thereafter at 14 DPI. The net charge transfer across the epithelium was reduced or tended to be reduced in all segments, as evidenced by a decreased Isc. Furthermore, the infection induced intestinal histomorphological changes, most prominently including a decrease in villus height, crypt depth and villus surface area in the jejunum at 7 DPI. Furthermore, body mass gain was decreased by Campylobacter carriage. This study demonstrates, for the first time, changes in the intestinal barrier function in Campylobacter-infected chickens and these changes were associated with a decrease in growth performance in otherwise healthy-appearing birds.
Assessment of carers of people with dementia
Authors: Dow Johanne , Robinson Louise
Published: February 2014

There are currently 800 000 people in the UK with dementia, two-thirds of whom live in the community supported by family carers. As the number of people with dementia is expected to double, and costs of care treble, in the next 30 years, carers of people with dementia should be recognised as a vital resource to society and the economy. Carers suffer adverse physical, psychological, financial and social consequences due to their role. GPs are well placed to identify and assess carers, and refer them to relevant health, social and voluntary sector services if needed. The aim of this article is to summarise the current needs of carers of people with dementia and explore how GPs can conduct a holistic and comprehensive assessment.
The osteocyte as a therapeutic target in the treatment of osteoporosis
Authors: Rochefort Gaël Y.
Published: February 2014

Osteoporosis is characterized by a low bone-mineral density associated with skeletal fractures. The decrease in bone-mineral density is the consequence of an unbalanced bone-remodeling process, with higher bone resorption than bone formation. The orchestration of the bone-remodeling process is under the control of the most abundant cell in bone, the osteocyte. Functioning as an endocrine cell, osteocytes are also a source of soluble factors that not only target cells on the bone surface, but also target distant organs. Therefore, any drugs targeting the osteocyte functions and signaling pathways will have a major impact on the bone-remodeling process. This review discusses potential advances in drug therapy for osteoporosis, including novel osteocyte-related antiresorptive and anabolic agents that may become available in the coming years.
Can Glucose Be Monitored Accurately at the Site of Subcutaneous Insulin Delivery?
Authors: Ward W. Kenneth , Castle Jessica R. , Jacobs Peter G. , Cargill Robert S.
Published: February 2014

Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome.
Insulin Pump Patient Characteristics and Glucose Control in the Hospitalized Setting
Authors: Kannan Subramanian , Satra Ankita , Calogeras Ellen , Lock Patricia , Lansang M. Cecilia
Published: February 2014

Introduction:

Patients’ knowledge of their insulin pumps and glucose control during hospitalization has not been studied.

Aim:

The aim was to study the determinants of glycemic control in patients using continuous subcutaneous insulin infusion (CSII) in the hospital.

Methods:

Three groups of patients were identified: those who did not need any inpatient education and continued on CSII (gorup A), those who received education then continued on CSII (group B), and those for whom CSII was not appropriate and were treated with multiple daily insulin injections (gorup C). We compared the measures of glycemic control between the 3 groups and analyzed which variables impacted glucose control.

Results:

There were 50 patients, with 51 hospital admissions, 57% males, mean age 48 ± 13 years, 86% had type 1 diabetes (T1DM). The mean DM duration was 26 ± 14 years, mean duration of CSII use was 8.7 ± 6 years, and mean HbA1c was 7.6 ± 1.4%. The mean duration of hospital stay was 5.6 ± 4.6 days. Mean blood glucose (BG) and frequency of hyperglycemia and hypoglycemic events among the 3 groups adjusted for their duration of hospital stay were not statistically different. None of the patients developed diabetic ketoacidosis while using their pump. Stepwise multivariate analysis revealed knowledge of hypoglycemia correction was the single most important predictor of mean BG (P < .001).

Conclusion:

Patients who received inpatient education performed similarly to patients who did not need inpatient education. Patients who receive inpatient education on CSII fare similar as patients who did not require inpatient education.
Agency Resistance to Outcome Measurement
Authors: Strickhouser Sara M. , Wright James D.
Published: February 2014

We are now well into the second decade of the “outcomes” revolution, the increasing expectation on the part of funders that social and human services agencies report on the impacts or outcomes of their programs. It is no longer enough to “do good” poorly; rather, the expectation these days is that the agencies report on program outcomes and the impact they have on the communities they serve. Unfortunately, however sensible such expectations would seem to be, agencies continue to resist, and in some cases sabotage, these more complex reporting requirements. Program outcomes, it turns out, are often difficult for agencies to conceptualize and even more difficult for them to attain. This study explores the sources of agency resistance to outcomes measurement and management through qualitative interviews with directors and staff of eight human service nonprofit agencies and their one common funder in a large southeastern metropolitan area. Along with the usual logistical issues, we find that a lack of communication between agencies and funders about their intended goals leads to frustration on both sides, ultimately making it more difficult to measure community-level impact than it truly needs to be.
A Possible Case of Gabapentin-Induced Mild Hyperglycemia
Authors: Andres Jennifer , Clements Jennifer N. , Salmiery Donna
Published: February 2014

Objective: A possible case of gabapentin-induced mild hyperglycemia is reported. Case Summary: A 63-year-old Caucasian gentleman was treated in a pharmacist-run pharmacotherapy clinic for type 2 diabetes management. His comorbidities included type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, peripheral vascular disease, Barrett’s esophagus, chronic back pain, and obesity. His medications for these comorbidities were continued throughout his care. The patient had no known drug allergies. After 3 months of pharmacist-managed diabetes management, the patient’s glucose levels had improved and were within the desired range for a majority of the readings. The patient was consulted to the pain clinic for uncontrolled pain and initiated and titrated on gabapentin from 300 mg per day to 600 to 900 mg 3 times per day. Two weeks later, the patient’s glucose levels increased to levels of 150 to 165 mg/dL. The patient’s increasing blood glucose values were treated with NPH insulin, which was titrated for several months until he was switched to insulin glargine. Gabapentin was not discontinued since it provided adequate pain control. Discussion: An objective causality assessment revealed that the adverse effect was possible. No other new medications were introduced, current medications were not adjusted, and no alternate causes could be found for increased glucose values. Conclusion: A 63-year-old Caucasian gentleman with type 2 diabetes mellitus developed a possible case of gabapentin-induced mild hyperglycemia after receiving gabapentin for several months with a dose titration. Gabapentin could be considered as a cause for otherwise unexplained hyperglycemia in a patient.
Endothelial Smad4 restrains the transition to hematopoietic progenitors via suppression of ERK activation
Authors: Lan Yu , He Wenyan , Li Zhuan , Wang Yu , Wang Jun , Gao Jiao , Wang Weili , Cheng Tao , Liu Bing , Yang Xiao
Published: February 2014

Key Points

Endothelial Smad4 is a physiological suppressor that functions specifically during the transition to hematopoietic progenitors. Endothelial Smad4 lies upstream of the subaortic microenvironment to control the hematopoietic fate of aortic endothelium.
Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients
Authors: Geyer Holly L. , Scherber Robyn M. , Dueck Amylou C. , Kiladjian Jean-Jacques , Xiao Zhijian , Slot Stefanie , Zweegman Sonja , Sackmann Federico , Fuentes Ana Kerguelen , Hernández-Maraver Dolores , Döhner Konstanze , Harrison Claire N. , Radia Deepti , Muxi Pablo , Besses Carlos , Cervantes Francisco , Johansson Peter L. , Andreasson Bjorn , Rambaldi Alessandro , Barbui Tiziano , Vannucchi Alessandro M. , Passamonti Francesco , Samuelsson Jan , Birgegard Gunnar , Mesa Ruben A.
Published: February 2014

Key Points

Distinct clusters exist within polycythemia vera, essential thrombocythemia, and myelofibrosis. Clusters are not direct surrogates for current prognostic scores.
Genotype-specific small-molecule therapy for cystic fibrosis
Authors: Thursfield Rebecca M. , Davies Jane C.
Published: February 2014

Educational aims

To allow the reader to refresh their knowledge of the underlying gene and protein defects in cystic fibrosis

To provide an understanding of new therapies developed and those in development

To attain a thorough understanding of the need for different therapies for different mutations

To inform the reader of the potential benefits for their patients of this new class of drugs

The prognosis for patients with cystic fibrosis (CF) has improved greatly over the past 30 years but the median age of survival is still only to the patients late 30s. New treatments are required to decrease morbidity and improve mortality. The basic defect in CF lies in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, mutations of which lead to a dysfunctional CFTR protein. The way in which the protein is defective differs between the six so-called mutation classes. An understanding of these classes has led to the development of mutation-specific small-molecule treatments.

Class I mutations are caused by the presence of a premature termination codon. Ataluren is a systemic agent that allows read-through of the mutated mRNA and translation of full-length protein. A phase III clinical trial has recently been completed. In class II mutations, the most common of which is Phe508del (previously termed ΔF508), the resulting CFTR protein is misfolded and is not trafficked through the cytoplasm to the cell membrane. CFTR-corrector drugs seek to facilitate such trafficking; recently increased understanding of the complex nature of the misfolding events may explain why this approach is, to date, rather difficult. Improvements in CFTR protein function have been achievedin vivoand clinical trial data are beginning to emerge. It may be necessary to use correctors with potentiators and combination trials of two correctors, VX-809 and VX-661, with or without the CFTR potentiator ivacaftor are underway. The latter was initially developed and tested in patients with the class III mutation Gly551Asp (previously termed G551D). In cells with this mutation, CFTR protein reaches the cell surface but fails to respond to cellular signals to open and conduct chloride. Ivacaftor increases the probability that the channel is open and has led to significant clinical benefit in patients with the Gly551Asp mutation; it is now being investigated in other class III and some class IV mutations.

Ivacaftor is the first genotype-specific treatment to demonstrate clinical efficacy and to be approved for licence. Other compounds are currently in development and the field is optimistic that drugs for other genotypes will not be far behind.
Nabla discrete fractional Grüss type inequality
Authors: Güvenilir A Feza , Kaymakçalan Billur , Peterson Allan C , Taş Kenan
Published: February 2014

Properties of the discrete fractional calculus in the sense of a backward difference are introduced and developed. Here, we prove a more general version of the Grüss type inequality for the nabla fractional case. An example of our main result is given.

MSC: 39A12, 34A25, 26A33, 26D15, 26D20.
Autocrine ligands of the epithelial growth factor receptor mediate inflammatory responses to diesel exhaust particles
Authors: Parnia Sam , Hamilton Lynnsey M , Puddicombe Sarah M , Holgate Stephen T , Frew Anthony J , Davies Donna E
Published: February 2014

Background

Diesel exhaust is associated with cardiovascular and respiratory mortality and morbidity. Acute exposure leads to increased IL-8 expression and airway neutrophilia, however the mechanism of this response is unknown. Objectives: As cigarette smoke-induced IL-8 expression by epithelial cells involves transactivation of the epidermal growth factor receptor (EGFR), we studied the effects of diesel exhaust particles (DEP) on IL-8 release and the role of the EGFR.

Methods

Primary bronchial epithelial cells (PBEC) were exposed to DEPs or carbon black. IL-8 and EGFR ligand expression (transforming growth factor alpha (TGFα), heparin-binding EGF-like growth factor, and amphiregulin (AR)) were assessed by quantitative RT-PCR and ELISA.

Results

DEP, but not carbon black, caused a dose-dependent increase in mitogen-activated protein kinase (MAPK) activation and IL-8 expression, however above 50 μg/ml there was an increase in cytotoxicity. At 50 μg/ml, DEPs stimulated transcription and release of IL-8 and EGFR ligands. IL-8 release was blocked by EGFR neutralizing antibodies, an EGFR-selective tyrosine kinase inhibitor and by the metalloprotease inhibitor, GM6001, which blocks EGFR ligand shedding. Neutralizing antibodies to AR, TGFα and heparin-binding (HB)-EGF reduced DEP-induced IL-8 by >50%. Conclusion Expression of IL-8 in response to DEPs is dependent on EGFR activation and that autocrine production of EGFR ligands makes a substantial contribution to this response. Capsule Summary: This study identifies a mechanism whereby diesel particles stimulates IL-8 release from bronchial epithelial cells. This mechanism may help to explain the recruitment of neutrophils into the airways of people exposed to particulate air pollution.
DNA methylation profiling in the thalamus and hippocampus of postnatal malnourished mice, including effects related to long-term potentiation
Authors: Weng Xiaoling , Zhou Daizhan , Liu Fatao , Zhang Hong , Ye Junyi , Zhang Zhou , Zhang Di , Wang Yinan , Tao Liming , Cao Lan , Kan Mengyuan , Wang Ting , Feng Guoyin , Qin Xiaolan , Sun Jihui , He Lin , Liu Yun
Published: February 2014

Background

DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development. Postnatal brains appear to exhibit stimulus-induced methylation changes because of factors such as environment, lifestyle, and diet (nutrition). The purpose of this study was to examine how extensively the brain DNA methylome is regulated by nutrition in early life.

Results

By quantifying the total amount of 5-methylcytosine (5mC) in the thalamus and the hippocampus of postnatal malnourished mice and normal mice, we found the two regions showed differences in global DNA methylation status. The methylation level in the thalamus was much higher than that in the hippocampus. Then, we used a next-generation sequencing (NGS)-based method (MSCC) to detect the whole genome methylation of the two regions in malnourished mice and normal mice. Notably, we found that in the thalamus, 500 discriminable variations existed and that approximately 60% were related to neuronal development or psychiatric diseases. Pathway analyses of the corresponding genes highlighted changes for 9 genes related to long-term potentiation (5.3-fold enrichment, P = 0.033).

Conclusions

Our findings may help to indicate the genome-wide DNA methylation status of different brain regions and the effects of malnutrition on brain DNA methylation. The results also indicate that postnatal malnutrition may increase the risk of psychiatric disorders.
Italian family paediatricians’ approach and management of celiac disease: a cross-sectional study in Puglia Region, 2012
Authors: Fortunato Francesca , Martinelli Domenico , Cozza Vanessa , Ciavarella Pierpaolo , Valente Anna , Cazzato Teresa , Piazzolla Ruggiero , Prato Rosa , Pedalino Biagio
Published: February 2014

Background

Celiac disease (CD) is a chronic autoimmune illness of the small intestine triggered by gluten consumption in genetically predisposed individuals. CD presentation is not limited to the gastrointestinal tract and it is still under-diagnosed. Complete resolution of clinical manifestations follows if a gluten-free diet is adopted. In western countries, CD prevalence is approximately 1%. Age of onset is often between 6 months and 7 years.

We assessed the approach to diagnosis and management of celiac patients by the paediatricians in Puglia Region, Italy.

Methods

We conducted a cross-sectional survey among the 589 Apulian Family Paediatricians (FPs) during January 2011-January 2012 using a self-administered web-based standardized questionnaire including self-assessment of their knowledge, diagnostic path and type of management they would follow for CD, clinical information on their celiac patients. We assessed associations among the explored variables by defining double-entry contingency tables and calculating Odds Ratio (OR) with 95% Confidence Intervals (CIs).

Results

The 218 (37%) FPs participating in the study reported 1,020 CD patients (representing approximately 1% of the child population covered by the enrolled FPs). Of them, 55% were female; 45% were aged 5–10 years. Weight loss and stunting were the main reported symptoms at diagnosis (41%). The majority (98%) of FPs requested anti-transglutaminase antibody (tTG-Ab) titres for CD diagnosis. Approximately 78% of FPs recommended gluten introduction in the diet of infants at the age of 6 months; 12% and 8% recommended introduction of gluten before and after 6 months of age respectively.

The degree of knowledge for either CD diagnosis making process or CD related diseases was medium/high in 97% and 82% of the participating FPs respectively. FPs (83%) who had a medium or high degree of knowledge of CD patients’ diet were more likely to experience low or no difficulty in providing their patients with dietary advices (OR:5.5; 95%CI:1.7-17.5).

Conclusions

Apulian FPs report a good degree of knowledge of CD, its diagnosis and its management. We will diffuse results and recommendations to all paediatricians in the Region. Actions aiming to continued education on CD in medical under and postgraduate trainings are crucial to prevent under-diagnosis.
Evidence for synergistic effects of PRNP and ATP7Bmutations in severe neuropsychiatric deterioration
Authors: Forbes Nauzer , Goodwin Susan , Woodward Kevin , Morgan David G , Brady Lauren , Coulthart Michael B , Tarnopolsky Mark A
Published: February 2014

Background

Wilson’s disease (WD), a rare cause of neuropsychiatric deterioration, is associated with mutations in theATP7Bgene. Prion diseases are also rare causes of neuropsychiatric deterioration that can occur sporadically without an identifiable cause, or can be attributed to mutations in thePRNPgene.

Case presentation

Here we describe a biological “experiment of nature” in which a patient presented with severe neuropsychiatric decline and strong biochemical evidence of WD. Genetic analysis revealed that he was a compound heterozygote for twoATP7Bsequence variants (c.2165dupT, p.Arg723Glufs*32; and c.4039G > A, p.Gly1347Ser), the first having been reported once previously, and the second being novel. In addition, the patient was heterozygous for aPRNPvariant, c.160G > A, p.Gly54Ser, that has been reported in a neuropsychiatric patient only once previously in association with a similarly severe clinical course of neuropsychiatric disease and early age of onset, but no accompanying information onATP7Bgenotype. Of particular interest was the observation that the patient’s older sister, who carried the sameATP7Bgenotype and laboratory evidence for biochemical WD but was clinically asymptomatic, lacked thePRNPvariant allele.

Conclusions

We propose that synergism may occur between at least some allelic variants ofATP7BandPRNP, possibly exerted through effects on cellular copper metabolism.
Severe maternal morbidity and maternal near miss in the extremes of reproductive age: results from a national cross- sectional multicenter study
Authors: Oliveira Fernando César , Surita Fernanda Garanhani , Pinto e Silva João Luiz , Cecatti José Guilherme , Parpinelli Mary Angela , Haddad Samira M , Costa Maria Laura , Pacagnella Rodolfo Carvalho , Sousa Maria Helena , Souza João Paulo ,   The Brazilian Network for Surveillance of Severe Maternal Morbidity Study Group
Published: February 2014

Background

The aim of this study was to assess severe maternal morbidity (SMM) and near miss (NM) cases among adolescent girls and women over 35 years of age in the Brazilian Network for Surveillance of Severe Maternal Morbidity, using a set of standard criteria, compared to pregnant women aged 20 to 34 years.

Methods

A cross-sectional multicenter study conducted in 27 referral obstetric units in Brazil. All pregnant women admitted to these centers during a one-year period of prospective surveillance were screened to identify cases of maternal death (MD), NM and other SMM. Indicators of maternal morbidity and mortality were evaluated for the three age groups. Sociodemographic, clinical and obstetric characteristics, gestational and perinatal outcomes, main causes of morbidity and delays in care were also compared. Two multiple analysis models were performed, to estimate the adjusted prevalence ratio for identified factors that were independently associated with the occurrence of severe maternal outcome (SMO = MNM + MD).

Results

Among SMM and MD cases identified, the proportion of adolescent girls and older women were 17% each. The risk of MNM or death was 25% higher among older women. Maternal near miss ratio and maternal mortality ratios increased with age, but these ratios were also higher among adolescents aged 10 to 14, although the absolute numbers were low. On multivariate analysis, younger age was not identified as an independent risk factor for SMO, while this was true for older age (PR 1.25; 1.07-1.45).

Conclusions

SMO was high among women below 14 years of age and increased with age in Brazilian pregnant women.
The use of a modified Delphi approach to engage stakeholders in zoonotic disease research priority setting
Authors: Sawford Kate , Dhand Navneet K , Toribio Jenny-Ann LML , Taylor Melanie R
Published: February 2014

Background

After the 2011 cluster of Hendra virus cases in horses in Australia, public health targeted education initiatives at people in the equine industry to reduce human exposure to potentially infected horses. ‘Horse owners and Hendra Virus: A Longitudinal cohort study To Evaluate Risk’ aims to enhance public health measures through improved understanding of Hendra virus risk perception and risk mitigation strategies among horse owners and horse care providers. This paper describes the stakeholder consultation that was undertaken to ensure the cohort study outcomes were relevant to diverse groups who play a role in Hendra virus policy development and implementation.

Methods

A two-round modified Delphi study with online questionnaires was conducted. In round one, stakeholders identified priority research areas. In round two, stakeholders rated and ranked topics that emerged from thematic analysis of the round one responses. Round two data were analysed using logistic regression.

Results

Of the 255 stakeholders contacted, 101 responded to round one. Over 450 topics were proposed. These were organized into 18 themes. Approximately two thirds of the round one respondents participated in round two. ‘Hendra virus-related risk awareness and perception’, ‘personal health and safety’, ‘emergency preparedness’, ‘risk prevention, mitigation, and biosecurity’, and ‘Hendra virus vaccination in horses – attitudes/uptake’ were the top five areas identified according to probability of being ranked extremely important.

Conclusions

In this study, a modified Delphi approach was effective in guiding research into Hendra virus, a zoonotic disease of animal and human health significance. The findings support the notion that stakeholders should be engaged in zoonotic disease research priority setting. Such consultation will help to ensure that research initiatives are relevant and useful to stakeholders in the position to make use of new findings.
Kcnq 1-5 (Kv7.1-5) potassium channel expression in the adult zebrafish
Authors: Wu Calvin , Sharma Kanishk , Laster Kyle , Hersi Mohamed , Torres Christina , Lukas Thomas J , Moore Ernest J
Published: February 2014

Background

KCNQx genes encode slowly activating-inactivating K+ channels, are linked to physiological signal transduction pathways, and mutations in them underlie diseases such as long QT syndrome (KCNQ 1), epilepsy in adults (KCNQ 2/3), benign familial neonatal convulsions in children (KCNQ 3), and hearing loss or tinnitus in humans (KCNQ 4, but not KCNQ 5). Identification of kcnqx potassium channel transcripts in zebrafish (Danio rerio) remains to be fully characterized although some genes have been mapped to the genome. Using zebrafish genome resources as the source of putative kcnq sequences, we investigated the expression of kcnq1-5 in heart, brain and ear tissues.

Results

Overall expression of the kcnq x channel transcripts is similar to that found in mammals. We found that kcnq1 expression was highest in the heart, and also present in the ear and brain. kcnq2 was lowest in the heart, while kcnq3 was highly expressed in the brain, heart and ear. kcnq5 expression was highest in the ear. We analyzed zebrafish genomic clones containing putative kcnq4 sequences to identify transcripts and protein for this highly conserved member of the Kcnq channel family. The zebrafish appears to have two kcnq4 genes that produce distinct mRNA species in brain, ear, and heart tissues.

Conclusions

We conclude that the zebrafish is an attractive model for the study of the KCNQ (Kv7) superfamily of genes, and are important to processes involved in neuronal excitability, cardiac anomalies, epileptic seizures, and hearing loss or tinnitus.
Assessment of reproductive health and violence against women among displaced Syrians in Lebanon
Authors: Reese Masterson Amelia , Usta Jinan , Gupta Jhumka , Ettinger Adrienne S
Published: February 2014

Background

The current conflict in Syria continues to displace thousands to neighboring countries, including Lebanon. Information is needed to provide adequate health and related services particularly to women in this displaced population.

Methods

We conducted a needs assessment in Lebanon (June-August 2012), administering a cross-sectional survey in six health clinics. Information was collected on reproductive and general health status, conflict violence, stress, and help-seeking behaviors of displaced Syrian women. Bivariate and multivariate analyses were conducted to examine associations between exposure to conflict violence, stress, and reproductive health outcomes.

Results

We interviewed 452 Syrian refugee women ages 18–45 who had been in Lebanon for an average of 5.1 (± 3.7) months. Reported gynecologic conditions were common, including: menstrual irregularity, 53.5%; severe pelvic pain, 51.6%; and reproductive tract infections, 53.3%. Among the pregnancy subset (n = 74), 39.5% of currently pregnant women experienced complications and 36.8% of those who completed pregnancies experienced delivery/abortion complications. Adverse birth outcomes included: low birthweight, 10.5%; preterm delivery, 26.5%; and infant mortality, 2.9%. Of women who experienced conflict-related violence (30.8%) and non-partner sexual violence (3.1%), the majority did not seek medical care (64.6%). Conflict violence and stress score was significantly associated with reported gynecologic conditions, and stress score was found to mediate the relationship between exposure to conflict violence and self-rated health.

Conclusions

This study contributes to the understanding of experience of conflict violence among women, stress, and reproductive health needs. Findings demonstrate the need for better targeting of reproductive health services in refugee settings, as well as referral to psychosocial services for survivors of violence.
Optical absorption, induced bleaching, and photoluminescence of CdSe nanoplatelets grown in cadmium octanoate matrix
Authors: Lyashchova Alina , Dmytruk Andriy , Dmitruk Igor , Klimusheva Gertruda , Mirnaya Tetyana , Asaula Vitaliy
Published: February 2014

CdSe nanoparticles (NPs) are chemically synthesized in thermotropic ionic liquid crystalline (LC) phase of cadmium octanoate that was used as a nanoreactor. The nanocomposite samples are obtained by the rapid cooling of the LC phase to room temperature. Observed doublet structure in absorption spectra of the nanocomposites is characteristic for the two-dimensional CdSe nanoplatelets (NPLs). The thicknesses of the CdSe NPLs are 1.6, 1.9 and 2.3 nm as determined from the absorption spectra, and correspond to 4, 5 and 6 CdSe monolayers, respectively. Induced simultaneous bleaching of the doublet components observed under femtosecond laser excitation, as well as photoluminescence spectra and their kinetics are found compatible with the model of excitons with heavy- and light-hole valence bands confined in nanoplatelets.
Poorly differentiated component in gastric pinch biopsies predicts submucosal invasion
Authors: Lee Sun-Mi , Yang Sun , Joo Mee , Kim Kyoung-Mee , Park Cheol Keun , Ahn Soomin , Min Byung-Hoon , Lee Jun Haeng , Kim Seonwoo , Rhee Jong Chul , Kim Jae J , Lauwers Gregory Y
Published: February 2014

Background

Endoscopic resection has become standard therapy for selected patients with early gastric carcinoma (EGC). However, the preoperative diagnostic accuracy for excluding submucosal (SM) invasion is not precise. Moreover, histologic features predicting SM invasion in gastric carcinomas (SMiGC) have not been studied extensively.

Methods

Pre-treatment gastric biopsies from 60 patients with SM invasion who underwent endoscopic resection were reviewed and compared to 58 biopsies of lesions confirmed to be intramucosal carcinomas (IMC). For validation of the results, an independent cohort consisting of 616 gastric biopsies confirmed as EGC were analyzed. For statistical analyses, χ-square test, Fisher’s exact test and multiple logistic progression tests were used.

Results

In the biopsy specimens of patients with SMiGCs, differentiated histology, poorly differentiated component, wisps of muscularis mucosa, tumor cribriforming, papillary architecture, desmoplasia and intraglandular eosinophilic necrotic debris (IEND) were observed in 96.7%, 36.7%, 16.7%, 16.7%, 23.3%, 40%, and 46.7% of cases, respectively, while the same features were observed in 100%, 5.2%, 0%, 1.7%, 5.2%, 19%, and 22.4% of biopsies with IMC. In multivariate analyses, poorly differentiated component [odds ratio (OR), 9.59, p = 0.002], IEND [OR, 6.23, p = 0.012], tumor cribriforming [OR, 4.66, p = 0.03] and papillary architecture [OR, 5.52, p = 0.018] were significantly associated with the detection of SM invasion. In the validation cohort, poorly differentiated component (p = 0.003) and papillary architecture (p = 0.008) remained significant.

Conclusion

Poorly differentiated component and papillary architecture are significant histopathologic predictors of SM invasion in pretreatment gastric biopsies of lesions considered for endoscopic therapy. Additional prospective studies are warranted to confirm our findings.

Virtual slide

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1588557731103084
Contaminants in human nail dust: an occupational hazard in podiatry?
Authors: Tinley Paul D , Eddy Karen , Collier Peter
Published: February 2014

Background

There has been limited literature indicating that podiatrists' health may be at risk from exposure to human nail dust. Previous studies carried out in the UK have shown that large amounts of dust become airborne during the human nail drilling procedure and are present in the air up to 10 hours after a clinical session. This increases the risk of Respiratory Tract (RT) infection for the practitioner.

Methods

This study used a nasal swabbing technique and fungal culture to determine whether podiatrists (n = 50) had the same microbes present in their nasal cavities as non‐podiatry health professional control group (n = 45). All swabs were cultured, counted and identified for each subject. Survey data of use and type of nail drill, type of mask used and frequency of change over a two week period.

Results

The results showed podiatrists had a greater range of microbes in their nasal cavities although the controls had greater overall numbers of organisms. The known pathogen and common mould, Aspergillus fumigatus was ost commonly found fungus within the podiatric group with 44% of the group having the fungus present. All nail drills used by the podiatrists had some form of dust extraction (except one). Of concern was 17% (n = 8) of the podiatrists did not use a mask at all whilst drilling and seemed unaware of any infection control issues. Simple disposable masks were the most frequently worn with only half being changed after each patient further increasing the cross infection risk

Conclusion

The high levels of Aspergilus contamination is a significant finding in the podiatry group as this fungus is small enough to enter the tissue of the nasal cavity and as a small particle will stay airborne in the room for up to 16 hours. Aspergilus has been shown to cause brain and soft tissue tumours in extreme cases. The high levels of upper respiratory track problems reported in the literature may well be caused by this fungal agent. The non use and use of inappropriate masks by podiatrists is clearly an occupational hazard to their health and well being.
Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes
Authors: Udpa Nitin , Ronen Roy , Zhou Dan , Liang Junbin , Stobdan Tsering , Appenzeller Otto , Yin Ye , Du Yuanping , Guo Lixia , Cao Rui , Wang Yu , Jin Xin , Huang Chen , Jia Wenlong , Cao Dandan , Guo Guangwu , Claydon Victoria E , Hainsworth Roger , Gamboa Jorge L , Zibenigus Mehila , Zenebe Guta , Xue Jin , Liu Siqi , Frazer Kelly A , Li Yingrui , Bafna Vineet , Haddad Gabriel G
Published: February 2014

Background

Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited.

Results

We report here the results of the first whole genome resequencing-based analysis identifying genes that likely modulate high altitude adaptation in native Ethiopians residing at 3,500 m above sea level on Bale Plateau or Chennek field in Ethiopia. Using cross-population tests of selection, we identify regions with a significant loss of diversity, indicative of a selective sweep. We focus on a 208 kbp gene-rich region on chromosome 19, which is significant in both of the Ethiopian subpopulations sampled. This region contains eight protein-coding genes and spans 135 SNPs. To elucidate its potential role in hypoxia tolerance, we experimentally tested whether individual genes from the region affect hypoxia tolerance in Drosophila. Three genes significantly impact survival rates in low oxygen: cic, an ortholog of human CIC, Hsl, an ortholog of human LIPE, and Paf-AHα, an ortholog of human PAFAH1B3.

Conclusions

Our study reveals evolutionarily conserved genes that modulate hypoxia tolerance. In addition, we show that many of our results would likely be unattainable using data from exome sequencing or microarray studies. This highlights the importance of whole genome sequencing for investigating adaptation by natural selection.
TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η
Authors: Wallace Heather A. , Merkle Julie A. , Yu Michael C. , Berg Taloa G. , Lee Ethan , Bosco Giovanni , Lee Laura A.
Published: February 2014

We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of the Y-family of DNA polymerases that facilitate replicative bypass of damaged DNA (translesion synthesis) as TRIP interactors. We show that TRIP and NOPO co-immunoprecipitate with human and Drosophila Polη, respectively, from cultured cells. We generated a null mutation in Drosophila Polη (dPolη) and found that dPolη-derived embryos have increased sensitivity to ultraviolet irradiation and exhibit nopo-like mitotic spindle defects. dPolη and nopo interact genetically in that overexpression of dPolη in hypomorphic nopo-derived embryos suppresses nopo phenotypes. We observed enhanced ubiquitylation of Polη by TRIP and NOPO E3 ligases in human cells and Drosophila embryos, respectively, and show that TRIP promotes hPolη localization to nuclear foci in human cells. We present a model in which TRIP/NOPO ubiquitylates Polη to positively regulate its activity in translesion synthesis.