bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation
Authors: Deniz R , Ozen G , Yilmaz-Oner S , Alibaz-Oner F , Erzik C , Aydin S Z , Inanc N , Eren F , Bayalan F , Direskeneli H , Atagunduz P
Published: November 2014

Objective

Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients.

Material and method

The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis.

Results

None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis ( p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04–16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69–197.13).

Conclusions

Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.
Lupus erythematosus tumidus: a clinical and histological study of 25 cases
Authors: Rodriguez-Caruncho C , Bielsa I , Fernández-Figueras M T , Roca J , Carrascosa J M , Ferrándiz C
Published: November 2014

Background

Lupus erythematosus tumidus (LET) is a subtype of cutaneous lupus erythematosus (CLE) that has been well characterized in recent years. However, some controversy still remains concerning the histological features of epidermal involvement.

Objectives

The objective of this report is to describe the clinical and microscopic features of LET in patients diagnosed at Hospital Universitari Germans Trias i Pujol, Spain.

Methods

We conducted a retrospective study of 25 patients with a diagnosis of LET.

Results

All patients presented with typical LET lesions (smooth, erythematous plaques without macroscopic epidermal changes, such as follicular plugs or scale, that resolved without residual scarring or hypopigmentation). None of the patients fulfilled the criteria for systemic lupus erythematosus during follow-up. Test results for antinuclear antibodies were positive in five patients (20%), with titres below one of 320 in all cases. Twenty-two patients (88%) required antimalarial therapy; response was good in 70% and moderate response in 30%. Minor epidermal alterations were observed in 52% of biopsy specimens, with focal basal vacuolization being the most frequent.

Conclusions

LET is a variant of CLE that has distinctive clinical, histologic and prognostic features. Unlike the patients in the case series previously described in the literature, most of our patients required treatment with antimalarials. Histology revealed mild epidermal alterations in a significant percentage of patients. Thus, in our opinion, the absence of microscopic epidermal alterations is not constant in LET.
Widen NomoGram for multinomial logistic regression: an application to staging liver fibrosis in chronic hepatitis C patients
Authors: Ardoino Ilaria , Lanzoni Monica , Marano Giuseppe , Boracchi Patrizia , Sagrini Elisabetta , Gianstefani Alice , Piscaglia Fabio , Biganzoli Elia M
Published: November 2014

The interpretation of regression models results can often benefit from the generation of nomograms, ‘user friendly’ graphical devices especially useful for assisting the decision-making processes. However, in the case of multinomial regression models, whenever categorical responses with more than two classes are involved, nomograms cannot be drawn in the conventional way. Such a difficulty in managing and interpreting the outcome could often result in a limitation of the use of multinomial regression in decision-making support. In the present paper, we illustrate the derivation of a non-conventional nomogram for multinomial regression models, intended to overcome this issue. Although it may appear less straightforward at first sight, the proposed methodology allows an easy interpretation of the results of multinomial regression models and makes them more accessible for clinicians and general practitioners too. Development of prediction model based on multinomial logistic regression and of the pertinent graphical tool is illustrated by means of an example involving the prediction of the extent of liver fibrosis in hepatitis C patients by routinely available markers.
Potential and Emerging Treatment Options for Ebola Virus Disease
Authors: Bishop Bryan M.
Published: November 2014

Objective: To describe the current Ebola virus epidemic and the potential options for treatment and prevention of Ebola virus disease. Data Sources: A PubMed literature search (1976 through October 20, 2014) was conducted using the search term Ebola. Study Selection and Data Extraction: Animal and human studies published in English were selected. Studies published within the past 5 years were the primary focus of this review. Data Synthesis: The current Ebola virus epidemic has primarily been contained in West Africa though it has subsequently spread to other areas, including the United States. The first patient in the United States infected with Ebola virus was diagnosed, treated, and expired in Texas. Two nurses caring for this patient also were diagnosed with Ebola virus and have been successfully treated. Treatment options for patients infected with Ebola virus are limited. Supportive therapy is centered on fluid resuscitation, electrolyte imbalance correction, treating complicating infections, and preventing complications of shock. Experimental therapies (ZMapp, brincidofovir, TKM-Ebola, and favipiravir) have been used during this current outbreak. Several medications such as amiodarone, chloroquine, and clomiphene may prevent the transmission of or treat Ebola virus. Different vaccine therapies are also in early-stage development. One of the vaccine strategies using recombinant vesicular stomatitis virus as a delivery vector has demonstrated efficacy when used for preexposure and postexposure prophylaxis. Conclusion: Ebola virus is highly virulent and fatal, and treatment options are limited. Several experimental and existing therapies may be options for preventing and treating Ebola virus disease.
Officers and School Settings
Authors: Rhodes Trisha N.
Published: November 2014

Despite growing numbers of school police personnel, little research has examined how school environments influence officers assigned to school resource officer (SRO) programs. This study explored officers’ perceptions of their roles and job satisfaction. Fifty-two SROs from a statewide Midwestern region were matched to 320 patrol officers at a Midwestern agency. Propensity score matching analyses revealed, compared with patrol officers, SROs performed fewer law enforcement and order maintenance tasks, reported lower levels of role ambiguity and conflict, and were more satisfied along one dimension of job satisfaction. Findings indicated officers in a specialized position were protected from sources of role ambiguity and conflict resulting in greater job satisfaction, which poses implications for improving job performance and officer wellbeing.
Theorizing healthy settings: a critical discussion with reference to Healthy Universities
Authors: Dooris Mark , Wills Jane , Newton Joanne
Published: November 2014

The settings approach appreciates that health determinants operate in settings of everyday life. Whilst subject to conceptual development, we argue that the approach lacks a clear and coherent theoretical framework to steer policy, practice and research. Aims: To identify what theories and conceptual models have been used in relation to the implementation and evaluation of Healthy Universities. Methods: A scoping literature review was undertaken between 2010 and 2013, identifying 26 papers that met inclusion criteria. Findings: Seven theoretical perspectives or conceptual frameworks were identified: the Ottawa Charter; a socio-ecological approach (which implicitly drew on sociological theories concerning structure and agency); salutogenesis; systems thinking; whole system change; organizational development; and a framework proposed by Dooris. These were used to address interrelated questions on the nature of a setting, how health is created in a setting, why the settings approach is a useful means of promoting health, and how health promotion can be introduced into and embedded within a setting. Conclusions: Although distinctive, the example of Healthy Universities drew on common theoretical perspectives that have infused the settings discourse more generally. This engagement with theory was at times well-developed and at other times a passing reference. The paper concludes by pointing to other theories that offer value to healthy settings practice and research and by arguing that theorization has a key role to play in understanding the complexity of settings and guiding the planning, implementation and evaluation of programmes.
Development, implementation and evaluation of a process to prevent and combat workplace bullying
Authors: Strandmark Margaretha , Rahm Gullbritt
Published: November 2014

Aim: Our objective was to develop and implement an intervention program in collaboration with workplace personnel, to evaluate the process as a vehicle to prevent and combat bullying. Methods: The project emanates from a community-based participatory approach. We obtained data from individual and focus group interviews. We used grounded theory methodology, and made a comparative analysis before and after the intervention. Results: Focus group interviews at the three first meetings indicated that those best positioned to prevent and combat bullying were the immediate supervisors, in collaboration with co-workers and upper management. The goal of zero tolerance toward bullying can be achieved if all concerned work together, using a humanistic value system, an open workplace atmosphere, group collaboration and conflict resolution. We developed an intervention, including lecturers and reflection groups, which ultimately resulted in an action plan. Focus group interviews at the fourth meeting, after the implementation, showed that employees were then more aware of bullying problems; the atmosphere at the workplace improved; the collaboration between and within the group was stronger; and the supervisor worked continuously to prevent and combat bullying, using the humanistic values suggested. We propose additional systematic work to implement our action plan and a conflict resolution system. Conclusions: The anti-bullying program implementation in the workplace achieved some success, but the intervention process is ongoing.
Stories of pain and health by elderly Pakistani women in Norway
Authors: Sverre Beate Lie , Solbrække Kari Nyheim , Eilertsen Grethe
Published: November 2014

Background: This ethnographic study investigates the stories of elderly Pakistani women living in Norway. Migration studies indicate that elderly migrant women are passive, ill victims caught in a marginalized position due to age, ethnicity and gender, and thus have little access to opposition and agency. To broaden the picture it is necessary to develop an innovative approach to understand what is implicated in the process of migration. The importance of considering life conditions that surrounds potential health promotion behaviors of immigrants is stressed by several researchers. However, up to now limited research guided by this perspective has been done in Norway. Therefore, this study explored how elderly Pakistani women in Norway promote their health and well-being through some distinct social interactions. The intention is to bring awareness to how health, even by so-called disadvantaged social groups, may take place. These practices are important to take into consideration when developing health-promoting policies for elderly immigrants. Methods: An ethnographic study of 15 Pakistani women, aged 53-75, was carried out in a multisided fieldwork in Oslo using participant observation and ethnographic interviews. The analytical approach was inspired by the constructivist theoretical framework of narrative ethnography. Results: The elderly Pakistani women in Norway construct stories of living in-between cultures and experiences of acculturative stress caused by being elderly, immigrants and women. However, this analysis also suggests that through distinct social relationships, primarily in the context of a voluntary organization, elderly Pakistani women do health by the way they interact and construct a repertoire of social identities. Conclusions: The healing practices taking place among elderly Pakistani women may counteract the negative health outcomes associated with age, migration and gender. Implications for immigrant health-promoting policy in Norway may be to increase the establishment and allocate funds to sustain voluntary organizations run by and for immigrants.
Research that empowers responsibility: Reconciling human agency with materiality
Authors: Domingo David
Published: November 2014

Despite the virtues of an emphasis on materiality in Journalism Studies, such an approach risks dis-empowering journalists as agents of change in the evolution of their profession. The principles of actor-network theory offer an opportunity to reconnect studies that are sensitive to the role of technology in the newsroom with the agency of the human actors that use it. By exposing the contingent nature of news practices, researchers can encourage journalists to take responsibility on the configuration of their work and the technical tools they use. The article proposes as well a collective discussion about the normative position of researchers and their engagement with fostering social change in the media industry.
A rare combination of atypical cerebral vascular anatomy
Authors: Koleilat Issam , Eidt John
Published: November 2014

A 57-year-old woman presented with neurologic deficits consistent with a cerebrovascular accident. Her workup demonstrated the simultaneous occurrence of three uncommon cerebrovascular congenital anomalies in a single patient: (1) persistent trigeminal artery, (2) persistent fetal origin of the posterior cerebral artery and (3) bilateral occurrence of the vertebral arteries terminating in the posterior inferior cerebellar arteries. These persistent fetal cerebrovascular anatomic variants are reviewed and the clinical relevance discussed.
Clinical impact of hypogastric artery occlusion in endovascular aneurysm repair
Authors: Kalteis Manfred , Gangl Odo , Huber Florian , Adelsgruber Peter , Kastner Manfred , Lugmayr Herbert
Published: November 2014

Purpose

To report the long-term results for patients treated with endovascular aneurysm repair and additional embolization and coverage of the hypogastric artery compared with patients treated with simple endovascular aneurysm repair.

Methods

A database of our endovascular aneurysm repair patient cohort was reviewed to find patients with iliac artery aneurysms. The baseline characteristics, the procedural data and the results for patients treated with endovascular aneurysm repair and concomitant hypogastric artery embolization were compared with those for patients treated with simple endovascular aneurysm repair. The results were analyzed for significant differences.

Results

Of 106 endovascular aneurysm repair patients treated at our vascular unit from 2001 to 2010, 24 had undergone additional hypogastric artery embolization. The complication rate was significantly increased in this group (12.5% vs. 2.4%; p = 0.041), and the long-term results were significantly poorer. Additional hypogastric artery embolization resulted in late rupture (1.2% vs. 12.5%; p = 0.036), buttock claudication (8.6% vs. 43.8%; p = 0.001) and new onset erectile dysfunction (17.3% vs. 42.9%; p = 0.043).

Conclusion

Endovascular aneurysm repair with extension of the stent graft to the external iliac artery and embolization of the hypogastric artery was associated with more complications and worse long-term results compared with simple endovascular aneurysm repair.
Jordanian stakeholder attitudes toward generic substitution
Authors: Alabbadi Ibrahim , Abbott Ryan , Jaber Deema
Published: November 2014

About 10% of Jordan’s gross domestic product is spent on health care, almost one-third of which is spent on pharmaceuticals. Jordan’s pharmaceutical spending is a substantially higher percentage of gross domestic product than that of other developed countries. Generic substitution is a mechanism that could lower pharmaceutical spending costs in Jordan, but Jordan’s domestic law currently forbids pharmacists in the private market from dispensing generic equivalents to branded medicines without a physician’s approval. This article provides the results of a study that surveyed prominent organizational stakeholders (n = 17, RR 100%) in Jordan’s health care system and evaluates their opinions about generic substitution. The study finds there is a broad base of support for allowing and encouraging generic substitution in the private sector, and for mandating generic substitution in the public sector. Given that generic substitution may help to reduce health care costs and improve access to medicines, policymakers should consider legal and policy changes to facilitate generic substitution. The research suggests that key players in Jordan’s health care system will support such proposals.
Bearing fault diagnosis based on a new acoustic emission sensor technique
Authors: Van Hecke Brandon , Qu Yongzhi , He David
Published: November 2014

The diagnosis of bearing health by quantifying acoustic emission data has been an area of interest for recent years due to the numerous advantages over vibration-based techniques. However, most acoustic emission–based methodologies to date are data-driven technologies. This research takes a novel approach combining a heterodyne-based frequency reduction technique, time synchronous resampling, and spectral averaging to process acoustic emission signals and extract condition indicators for bearing fault diagnosis. The heterodyne technique allows the acoustic emission signal frequency to be shifted from several megahertz to less than 50 kHz, which is comparable to that of vibration-based techniques. Then, the digitized signal is band-pass filtered to retain the information associated with the bearing defects. Finally, the tachometer signal is used to time synchronously resample the acoustic emission data, allowing the computation of a spectral average which in turn enables the extraction and evaluation of condition indicators for bearing fault diagnosis. The presented technique is validated using the acoustic emission signals of seeded fault steel bearings on a bearing test rig. The result is an effective acoustic emission–based approach validated to diagnose all four fault types: inner race, outer race, ball, and cage.
Big Data ethics
Authors: Zwitter Andrej
Published: November 2014

The speed of development in Big Data and associated phenomena, such as social media, has surpassed the capacity of the average consumer to understand his or her actions and their knock-on effects. We are moving towards changes in how ethics has to be perceived: away from individual decisions with specific and knowable outcomes, towards actions by many unaware that they may have taken actions with unintended consequences for anyone. Responses will require a rethinking of ethical choices, the lack thereof and how this will guide scientists, governments, and corporate agencies in handling Big Data. This essay elaborates on the ways Big Data impacts on ethical conceptions.
Development of a continuous cooling transformation diagram for Eglin steel
Authors: Leister B. M. , DuPont J. N.
Published: November 2014

Eglin steel is a new ultrahigh strength steel that has been developed at Eglin Air Force Base in the early 2000s. This steel could be subjected to a variety of processing steps during fabrication, each with its own thermal history. This article presents a continuous cooling transformation diagram developed for Eglin steel to be used as a guideline during processing. Dilatometry techniques performed on a Gleeble thermomechanical simulator were combined with microhardness results and microstructural characterisation to develop the diagram. The results show that four distinct microstructures form within Eglin steel depending on the cooling rate. At cooling rates above ∼1°C s−1, a predominately martensitic microstructure is formed with hardness of ∼520 HV. Intermediate cooling rates of 1 to 0.2°C s−1 produce a mixed martensitic/bainitic microstructure with a hardness that ranges from 520 to 420 HV. Slower cooling rates of 0.1 to 0.03°C s−1 lead to the formation of a bainitic microstructure with a hardness of ∼420 HV. The slowest cooling rate of 0.01°C s−1 formed a bainitic microstructure with an apparent carbide constituent at the prior austenite grain boundaries.
Red cells from ferrochelatase-deficient erythropoietic protoporphyria patients are resistant to growth of malarial parasites
Authors: Smith Clare M. , Jerkovic Ante , Puy Hervé , Winship Ingrid , Deybach Jean-Charles , Gouya Laurent , van Dooren Giel , Goodman Christopher Dean , Sturm Angelika , Manceau Hana , McFadden Geoffrey Ian , David Peter , Mercereau-Puijalon Odile , Burgio Gaétan , McMorran Brendan J. , Foote Simon J.
Published: November 2014

Key Points

Malarial parasite growth is impeded in erythropoietic protoporphyric erythrocytes because of decreased host cell ferrochelatase activity. A ferrochelatase competitive inhibitor prevents the growth of malarial parasites in normal red cells.
Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency
Authors: Stepensky Polina , Rensing-Ehl Anne , Gather Ruth , Revel-Vilk Shoshana , Fischer Ute , Nabhani Schafiq , Beier Fabian , Brümmendorf Tim H. , Fuchs Sebastian , Zenke Simon , Firat Elke , Pessach Vered Molho , Borkhardt Arndt , Rakhmanov Mirzokhid , Keller Bärbel , Warnatz Klaus , Eibel Hermann , Niedermann Gabriele , Elpeleg Orly , Ehl Stephan
Published: November 2014

Key Points

Deficiency of TPP2 is associated with Evans syndrome and viral infection susceptibility. TPP2 deficiency links premature immunosenescence of T and B cells with severe autoimmunity.
Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study
Authors: Zilberberg Marya D , Shorr Andrew F , Micek Scott T , Vazquez-Guillamet Cristina , Kollef Marin H
Published: November 2014

Introduction

The impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS).

Methods

We conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous.

Results

Out of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P <0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P <0.001) and receive non-IAAT (43.4% versus 14.6%, P <0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31).

Conclusions

MDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical.
Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease
Authors: Hoang Long Truong , Shimizu Chisato , Ling Ling , Naim Ahmad Nazri Mohamed , Khor Chiea Chuen , Tremoulet Adriana H , Wright Victoria , Levin Michael , Hibberd Martin L , Burns Jane C
Published: November 2014

Background

Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD.

Methods

To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.

Results

The overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target.

Conclusion

Our study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.
The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology
Authors: Grässel Susanne
Published: November 2014

The peripheral nervous system is critically involved in bone metabolism, osteogenesis, and bone remodeling. Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diathrodial joints. They modulate vascularization and matrix differentiation during endochondral ossification in embryonic limb development, indicating a distinct role in skeletal growth and limb regeneration processes. In pathophysiological situations, the innervation pattern of sympathetic and sensory nerve fibers is altered in adult joint tissues and bone. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters. Osteoblasts, osteoclasts, mesenchymal stem cells, synovial fibroblasts, and different types of chondrocytes produce distinct subtypes of adrenoceptors, receptors for vasointestinal peptide, for substance P and calcitonin gene-related peptide. Many of these cells even synthesize neuropeptides such as substance P and calcitonin gene-related peptide and are positive for tyrosine-hydroxylase, the rate-limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells during endochondral ossification in limb development. In adults, sensory and sympathetic neurotransmitters are critical for bone regeneration after fracture and are involved in the pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints. Possibly, they might also play a role in pathogenesis of degenerative joint disorders, such as osteoarthritis. All together, accumulating data imply that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth. In adults, they modulate bone regeneration, bone remodeling, and articular cartilage homeostasis in addition to their classic neurological actions.
A potential scavenger of carbon radicals for ancient carbonized silk fabrics: Superoxide Dismutase (SOD)
Authors: Bai Xiaojian , Gong Yuxuan , Yang Haiyan , Gong Decai
Published: November 2014

Superoxide Dismutase (SOD) was proposed as a potential scavenger of carbon radicals in ancient carbonized silk fabrics. Ancient and artificially carbonized silk samples were treated using this method. The optimal experimental conditions of the treatment were determined by variance analysis. The effects of the scavenging on carbonized silks were investigated by electron paramagnetic resonance (EPR). The results showed that the carbon radicals in both ancient and artificially carbonized silks were cleared to a great extent. The ageing resistance of the treated samples and scanning electron microscope (SEM) images of samples before and after treatment ensured that the treatment would not aggravate the deterioration of silk. Thus, the potential of SOD to scavenge carbon radicals in historic silk was demonstrated. Our research may help to alleviate further degradation which could occur during preservation of silk.
A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties
Authors: Kasus-Jacobi Anne , Noor-Mohammadi Samaneh , Griffith Gina L , Hinsley Heather , Mathias Lauren , Pereira H Anne
Published: November 2014

CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120–146 QR, 120–146 QH, 120–146 WR, and 120–146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120–146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo.
Joint interpretation and uncertainty analysis of petrophysical properties in unconventional shale reservoirs
Authors: Yang Qinshan , Torres-Verdín Carlos
Published: November 2014

Interpretation of hydrocarbon-bearing shale is subject to great uncertainty because of pervasive heterogeneity, thin beds, and incomplete and uncertain knowledge of saturation-porosity-resistivity models. We developed a stochastic joint-inversion method specifically developed to address the quantitative petrophysical interpretation of hydrocarbon-bearing shale. The method was based on the rapid and interactive numerical simulation of resistivity and nuclear logs. Instead of property values themselves, the estimation method delivered the a posteriori probability of each property. The Markov-chain Monte Carlo algorithm was used to sample the model space to quantify the a posteriori distribution of formation properties. Additionally, the new interpretation method allows the use of fit-for-purpose statistical correlations between water saturation, salt concentration, porosity, and electrical resistivity to implement uncertain, non-Archie resistivity models derived from core data, including those affected by total organic carbon (TOC). In the case of underdetermined estimation problems, i.e., when the number of measurements was lower than the number of unknowns, the use of a priori information enabled plausible results within prespecified petrophysical and compositional bounds. The developed stochastic interpretation technique was successfully verified with data acquired in the Barnett and Haynesville Shales. Core data (including X-ray diffraction data) were combined into a priori information for interpretation of nuclear and resistivity logs. Results consisted of mineral concentrations, TOC, and porosity together with their uncertainty. Eighty percent of the core data was located within the 95% credible interval of estimated mineral/fluid concentrations.
Prenatal Influence of an Androgen Agonist and Antagonist on the Differentiation of the Ovine Sexually Dimorphic Nucleus in Male and Female Lamb Fetuses
Authors: Roselli Charles E. , Reddy Radhika C. , Estill Charles T. , Scheldrup Melissa , Meaker Mary , Stormshak Fred , Montilla Hernán J.
Published: November 2014

The ovine sexually dimorphic nucleus (oSDN) is 2 times larger in rams than in ewes. Sexual differentiation of the oSDN is produced by testosterone exposure during the critical period occurring between gestational day (GD)60 and GD90 (term, 147 d). We tested the hypothesis that testosterone acts through the androgen receptor to control development of the male-typical oSDN. In experiment 1, pregnant ewes received injections of vehicle, androgen receptor antagonist flutamide, or nonaromatizable androgen dihydrotestosterone (DHT) propionate during the critical period. Fetuses were delivered at GD135. Both antagonist and agonist treatments significantly reduced mean oSDN volume in males but had no effects in females. Experiment 2, we analyzed the effect of treatments on the fetal hypothalamic-pituitary-gonadal axis to determine whether compensatory changes in hormone secretion occurred that could explain the effect of DHT. Pregnant ewes were injected with vehicle, flutamide, or DHT propionate from GD60 to GD84, and fetuses were delivered on GD85. Flutamide significantly increased LH and testosterone in males, whereas DHT significantly decreased both hormones. In females, LH was unaffected by flutamide but significantly reduced by DHT exposure. DHT significantly decreased pituitary gonadotropin and hypothalamic kisspeptin mRNA expression in males and females. These results suggest that androgen receptor mediates the effect of testosterone on oSDN masculinization, because this process was blocked by the androgen receptor antagonist flutamide in eugonadal males. In contrast, the reduction of oSDN volume observed after DHT exposure appears to be mediated by a negative feedback mechanism exerted on the hypothalamus to reduce LH and testosterone secretion. The reduced androgen exposure most likely accounted for the decreased oSDN volume. We conclude that, during the critical period, the male reproductive axis in long gestation species, such as sheep, is sufficiently developed to react to perturbations in serum androgens and mitigate disruptions in brain masculinization.
Systemic, Cerebral and Skeletal Muscle Ketone Body and Energy Metabolism During Acute Hyper-D-β-Hydroxybutyratemia in Post-Absorptive Healthy Males
Authors: Mikkelsen Kristian H. , Seifert Thomas , Secher Niels H. , Grøndal Thomas , van Hall Gerrit
Published: November 2014

Context:

Ketone bodies are substrates during fasting and when on a ketogenic diet not the least for the brain and implicated in the management of epileptic seizures and dementia. Moreover, D-β-hydroxybutyrate (HOB) is suggested to reduce blood glucose and fatty acid levels.

Objectives:

The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism.

Design:

Single trial.

Setting:

Hospital.

Participant:

Healthy post-absorptive males (n = 6).

Interventions:

Subjects were studied under basal condition and three consecutive 1-hour periods with a 3-, 6-, and 12-fold increased HOB concentration via HOB infusion.

Main Outcome Measures:

Systemic, cerebral, and skeletal muscle HOB kinetics, oxidation, glucose turnover, and lipolysis via arterial, jugular, and femoral venous differences in combination with stable isotopically labeled HOB, glucose, and glycerol, infusion.

Results:

An increase in HOB from the basal 160–450 μmol/L elicited 14 ± 2% reduction (P = .03) in glucose appearance and 37 ± 4% decrease (P = .03) in lipolytic rate while insulin and glucagon were unchanged. Endogenous HOB appearance was reduced in a dose-dependent manner with complete inhibition at the highest HOB concentration (1.7 mmol/L). Cerebral HOB uptake and subsequent oxidation was linearly related to the arterial HOB concentration. Resting skeletal muscle HOB uptake showed saturation kinetics.

Conclusion:

A small increase in the HOB concentration decreases glucose production and lipolysis in post-absorptive healthy males. Moreover, cerebral HOB uptake and oxidation rates are linearly related to the arterial HOB concentration of importance for modifying brain energy utilization, potentially of relevance for patients with epileptic seizures and dementia.
Oxidative Desulfurization of Coal Tar Pitch Using a Urea–Hydrogen Peroxide Complex/Carboxylic Anhydride System in THF
Authors: Yazu Kazumasa , Takanohashi Toshimasa
Published: November 2014

Oxidative desulfurization of coal tar pitch (CTP) using a urea–hydrogen peroxide complex with a carboxylic anhydride in THF was investigated. The sulfur content in CTP was reduced by more than 15% through the process.
Preparation of Thermoresponsive Nanosheets Exhibiting Phase Transitions in Water via Surface Modification of Layered Perovskite Nanosheets with Poly(N-isopropylacrylamide) (PNIPAAm)
Authors: Idota Naokazu , Fukuda Satoshi , Tsukahara Takehiko , Sugahara Yoshiyuki
Published: November 2014

Thermoresponsive inorganic–organic hybrid nanosheets were prepared by surface modification of layered perovskite HLaNb2O7·xH2O (HLaNb) with poly(N-isopropylacrylamide) (PNIPAAm) through surface-initiated atom transfer radical polymerization (SI-ATRP). The PNIPAAm-modified HLaNb could be exfoliated into nanosheets, which had a plate-like morphology with a thickness of ca. 25 nm. The aqueous suspension of the PNIPAAm-modified nanosheets in water exhibited phase transitions with increases in temperature to above 34 °C. The nanosheets did not form precipitates when dispersed in water, even though the modified polymer chains became hydrophobic at high temperatures.
Fission yeast RNA triphosphatase reads an Spt5 CTD code
Authors: Doamekpor Selom K. , Schwer Beate , Sanchez Ana M. , Shuman Stewart , Lima Christopher D.
Published: November 2014

mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1·Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The bound CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an “Spt5 CTD code” in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on–off switch that is read by diverse CTD receptors, each in its own distinctive manner.
UV-independent induction of beta defensin 3 in neonatal human skin explants
Authors: Wolf Horrell Erin , D'Orazio John
Published: November 2014

In order to determine the effect of UV radiation on β-defensin 3 (BD3) expression in human skin, freshly-isolated UV-naïve skin was obtained from newborn male infants undergoing planned circumcision.  Skin explants sustained ex vivo dermis side down on RPMI media were exposed to 0.5 kJ/m2UVB, and biopsies were taken from the explant through 72 hours after radiation.  mRNA expression was measured by qRTPCR and normalized to TATA-binding protein.  BD3 expression at each time point was compared with an untreated control taken at time 0 within each skin sample.  Extensive variability in both the timing and magnitude of BD3 induction across individuals was noted and was not predicted by skin pigment phenotype, suggesting that BD3 induction was not influenced by epidermal melanization.  However, a mock-irradiated time course demonstrated UV-independent BD3 mRNA increases across multiple donors which was not further augmented by treatment with UV radiation, suggesting that factors other than UV damage promoted increased BD3 expression in the skin explants.  We conclude that BD3 expression is induced in a UV-independent manner in human skin explants processed and maintained in standard culture conditions, and that neonatal skin explants are an inappropriate model with which to study the effects of UV on BD3 induction in whole human skin.
The two souls of social work: exploring the roots of ‘popular social work’ – popular or radical social work?
Authors: McDermott Des
Published: November 2014

This commentary is a response to the article ‘The two souls of social work: exploring the roots of “popular social work”’ by Chris Jones and Michael Lavalette (2013), which raised a number of important insights and questions about the state of social work under conditions of neoliberalism. The commentary raises concerns about the concept ‘popular social work’ and in particular some of the formulations that the authors have adopted.
Costuming as subculture: The multiple bodies of cosplay
Authors: Lamerichs Nicolle
Published: November 2014

This article explores the subculture of cosplay, short for ‘costume play’. In this particular practice, fans create and wear costumes that allow them to re-enact existing fictional characters from popular culture. These outfits and subsequent performances are a physical manifestation of their immersion into the fictional realms of television, games and movies, among others. Cosplay can be understood as the culture of costuming that occurs beyond the institutional remit of the theatre. Especially in western countries, cosplay is intimately connected to the carnivalesque space of the fan convention, where fans gather and re-enact their favourite characters. I argue that embodiment plays a unique role in cosplay that should be interrogated closely. The fan performer relies on multiple bodies and repertoires that are intimately connected to the fan’s identity and the performed character.
Biological variation database: structure and criteria used for generation and update
Authors: Perich Carmen , Minchinela Joana , Ricós Carmen , Fernández-Calle Pilar , Alvarez Virtudes , Doménech María Vicenta , Simón Margarita , Biosca Carmen , Boned Beatriz , García-Lario José Vicente , Cava Fernando , Fernández-Fernández Pilar , Fraser Callum G.
Published: November 2014

Numerical data on the components of biological variation (BV) have many uses in laboratory medicine, including in the setting of analytical quality specifications, generation of reference change values and assessment of the utility of conventional reference values.

Generation of a series of up-to-date comprehensive database of components of BV was initiated in 1997, integrating the more relevant information found in publications concerning BV. A scoring system was designed to evaluate the robustness of the data included. The database has been updated every 2 years, made available on the Internet and derived analytical quality specifications for imprecision, bias and total allowable error included in the tabulation of data.

Our aim here is to document, in detail, the methodology we used to evaluate the reliability of the included data compiled from the published literature. To date, our approach has not been explicitly documented, although the principles have been presented at many symposia, courses and conferences.
Perspective switching as event affordance: The ontogeny of abductive reasoning
Authors: West Donna E.
Published: November 2014

The present model identifies Index as the representational component driving children’s advances in abductive reasoning, capitalizing upon the means to subjunctivize within constructed events. As such, an essential semiotic device underlies the recognition of shifting perspectives to operationalize abductive reasoning within event profiles. Beyond using Index to establish the point of orientation (Origo), one “tries on” that Origo’s covert and overt orientation via deictic terms that encode Origo’s role as a conversational on-looker of an episode. This subjunctive competence entails taking note of cause-effect relations to anticipate the affective, social, cognitive, and physical viewpoints likely to be assumed by that Origo. Hypothesis-making then entails going beyond grounded experience to represent intermediate and final states of affairs for other Origos. Abductions require dynamically imaging how distinctive agents affect action schemes together with their relied-upon judgments to effectuate resultative states. The use of indexically grounded cognitions (given their role in preempting event relations) rivets the onlooker to the “why” of unexpected events and increases the likelihood that the guess of another within novel contexts is plausible. Shifting perspectives underlie abductions because they trigger defeasible but plausible explanations for puzzling events.