bluuebunny/crossref_metadata_2025 huggingface dataset:
Anal phyllodes tumor in a male patient: a unique case presentation and literature review
Authors: Ho Szu-pei , Tseng Hui-hwa , King TM , Chow Philip-C
Published: March 2013

Lesions of anogenital mammary-like glands are rare, and only 44 female cases have been reported. Herein, we describe a particularly rare case of phyllodes tumor of anogenital mammary-like glands in a 41-year-old male presenting anal bleeding. Papillectomy was performed. The excised tumor was circumscribed in shape, and after it was sliced into sections, it was noted that there were leaf-like slits on the surface of cut side. Under the microscope, the tumor was found to be biphasic, with a bland glandular epithelium and low-to-intermediate cellular stroma, which together created the leaf-like slits. Gynecomastoid hyperplasia was evident at the periphery. The epithelium showed immuno-activity for ER, PR(focal), AR, and GCDFP-15. The stromal cells showed positive staining for CD34 and vimentin. The morphology and immunophenotype were similar to benign phyllodes tumors of breast. To the best of our knowledge, this case report represents the first case of phyllodes tumor of anogenital mammary-like glands with gynecomastoid hyperplasia at the periphery in a male patient. To make a diagnosis, we had to differentiate this lesion from hidradenoma papilliferum of skin appendage, phyllodes tumor of ectopic prostatic tissue, and other tumors of anogenital mammary-like glands analogous to the breast tumor (e.g., fibroadenoma phyllodes, periductal stromal sarcoma, and spindle cell carcinoma). While gynecomastia of male breast is usually a result of hormone imbalance, our patient’s tumor did not seem to be related to peripheral hormone status in the anogenital mammary-like glands. Nevertheless, because hormone imbalance has been strongly related to male breast cancer, hormone levels may need to be followed in male patients who have this rare malady.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1509145815899177
Magnetic resonance imaging and genetic investigation of a case of rottweiler leukoencephalomyelopathy
Authors: Hirschvogel Katrin , Matiasek Kaspar , Flatz Katharina , Drögemüller Michaela , Drögemüller Cord , Reiner Bärbel , Fischer Andrea
Published: March 2013

Background

Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement.

Case presentation

A two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any disease-associated variants in the DNA sequence.

Conclusion

It was concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy with brain stem and spinal cord involvement.
Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients
Authors: Galas Filomena RBG , Almeida Juliano P , Fukushima Julia T , Osawa Eduardo A , Nakamura Rosana E , Silva Carolina MPDC , de Almeida Elisângela Pinto Marinho , Auler Jose Otavio Costa , Vincent Jean-Louis , Hajjar Ludhmila A
Published: March 2013

Background

Allogeneic red blood cell (RBC) transfusion has been proposed as a negative indicator of quality in cardiac surgery. Hospital length of stay (LOS) may be a surrogate of poor outcome in transfused patients.

Methods

Data from 502 patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study were analyzed to assess the relationship between RBC transfusion and hospital LOS in patients undergoing cardiac surgery and enrolled in the TRACS study.

Results

According to the status of RBC transfusion, patients were categorized into the following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241 patients (48%) who received 3 RBC units or fewer (low transfusion requirement group), and 3) 62 patients (12%) who received more than 3 RBC units (high transfusion requirement group). In a multivariable Cox proportional hazards model, the following factors were predictive of a prolonged hospital length of stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure, LVEF lower than 40% and RBC transfusion of > 3 units.

Conclusion

RBC transfusion is an independent risk factor for increased LOS in patients undergoing cardiac surgery. This finding highlights the adequacy of a restrictive transfusion therapy in patients undergoing cardiac surgery.

Trial registration

Clinicaltrials.gov identifier: NCT01021631.
The hCMEC/D3 cell line as a model of the human blood brain barrier
Authors: Weksler Babette , Romero Ignacio A , Couraud Pierre-Olivier
Published: March 2013

Since the first attempts in the 1970s to isolate cerebral microvessel endothelial cells (CECs) in order to model the blood–brain barrier (BBB) in vitro, the need for a human BBB model that closely mimics the in vivo phenotype and is reproducible and easy to grow, has been widely recognized by cerebrovascular researchers in both academia and industry. While primary human CECs would ideally be the model of choice, the paucity of available fresh human cerebral tissue makes wide-scale studies impractical. The brain microvascular endothelial cell line hCMEC/D3 represents one such model of the human BBB that can be easily grown and is amenable to cellular and molecular studies on pathological and drug transport mechanisms with relevance to the central nervous system (CNS). Indeed, since the development of this cell line in 2005 over 100 studies on different aspects of cerebral endothelial biology and pharmacology have been published. Here we review the suitability of this cell line as a human BBB model for pathogenic and drug transport studies and we critically consider its advantages and limitations.
Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care
Authors: Llewelyn Martin J , Berger Mario , Gregory Mark , Ramaiah Ravi , Taylor Amanda L , Curdt Ingo , Lajaunias Frédéric , Graf Rolf , Blincko Stuart J , Drage Stephen , Cohen Jonathan
Published: March 2013

Introduction

Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness.

Methods

Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria.

Results

Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone.

Conclusions

PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population.
Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer
Authors: Bower Julienne E. , Ganz Patricia A. , Irwin Michael R. , Castellon Steven , Arevalo Jesusa , Cole Steven W.
Published: March 2013

Purpose

Fatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors.

Patients and Methods

Women diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB −511 C>T (rs16944), IL6 −174 G>C (rs1800795), and TNF −308 G>A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms.

Results

The genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF −308 and IL6 −174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016).

Conclusion

These findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes.
Physician and Stakeholder Perceptions of Conflict of Interest Policies in Oncology
Authors: Lockhart A. Craig , Brose Marcia S. , Kim Edward S. , Johnson David H. , Peppercorn Jeffrey M. , Michels Dina L. , Storm Courtney D. , Schuchter Lynn M. , Rathmell W. Kimryn
Published: March 2013

Purpose

The landscape of managing potential conflicts of interest (COIs) has evolved substantially across many disciplines in recent years, but rarely are the issues more intertwined with financial and ethical implications than in the health care setting. Cancer care is a highly technologic arena, with numerous physician-industry interactions. The American Society of Clinical Oncology (ASCO) recognizes the role of a professional organization to facilitate management of these interactions and the need for periodic review of its COI policy (Policy).

Methods

To gauge the sentiments of ASCO members and nonphysician stakeholders, two surveys were performed. The first asked ASCO members to estimate opinions of the Policy as it relates to presentation of industry-sponsored research. Respondents were classified as consumers or producers of research material based on demographic responses. A similar survey solicited opinions of nonphysician stakeholders, including patients with cancer, survivors, family members, and advocates.

Results

The ASCO survey was responded to by 1,967 members (1% of those solicited); 80% were producers, and 20% were consumers. Most respondents (93% of producers; 66% of consumers) reported familiarity with the Policy. Only a small proportion regularly evaluated COIs for presented research. Members favored increased transparency about relationships over restrictions on presentations of research. Stakeholders (n = 264) indicated that disclosure was “very important” to “extremely important” and preferred written disclosure (77%) over other methods.

Conclusion

COI policies are an important and relevant topic among physicians and patient advocates. Methods to simplify the disclosure process, improve transparency, and facilitate responsiveness are critical for COI management.
Morphogen transport
Authors: Müller Patrick , Rogers Katherine W. , Yu Shuizi R. , Brand Michael , Schier Alexander F.
Published: March 2013

The graded distribution of morphogens underlies many of the tissue patterns that form during development. How morphogens disperse from a localized source and how gradients in the target tissue form has been under debate for decades. Recent imaging studies and biophysical measurements have provided evidence for various morphogen transport models ranging from passive mechanisms, such as free or hindered extracellular diffusion, to cell-based dispersal by transcytosis or cytonemes. Here, we analyze these transport models using the morphogens Nodal, fibroblast growth factor and Decapentaplegic as case studies. We propose that most of the available data support the idea that morphogen gradients form by diffusion that is hindered by tortuosity and binding to extracellular molecules.
Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization
Authors: Sipe Conor W. , Liu Lixia , Lee Jianyi , Grimsley-Myers Cynthia , Lu Xiaowei
Published: March 2013

The V-shaped hair bundles atop auditory hair cells and their uniform orientation are manifestations of epithelial planar cell polarity (PCP) required for proper perception of sound. PCP is regulated at the tissue level by a conserved core Wnt/PCP pathway. However, the hair cell-intrinsic polarity machinery is poorly understood. Recent findings implicate hair cell microtubules in planar polarization of hair cells. To elucidate the microtubule-mediated polarity pathway, we analyzed Lis1 function in the auditory sensory epithelium in the mouse. We show that conditional deletion of Lis1 in developing hair cells causes defects in cytoplasmic dynein and microtubule organization, resulting in planar polarity defects without overt effects on the core PCP pathway. Lis1 ablation during embryonic development results in defects in hair bundle morphology and orientation, cellular organization and junctional nectin localization. We present evidence that Lis1 regulates localized Rac-PAK signaling in embryonic hair cells, probably through microtubule-associated Tiam1, a guanine nucleotide exchange factor for Rac. Lis1 ablation in postnatal hair cells significantly disrupts centrosome anchoring and the normal V-shape of hair bundles, accompanied by defects in the pericentriolar matrix and microtubule organization. Lis1 is also required for proper positioning of the Golgi complex and mitochondria as well as for hair cell survival. Together, our results demonstrate that Lis1 mediates the planar polarity of hair cells through regulation of microtubule organization downstream of the tissue polarity pathway.
UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development
Authors: Hegarty Jeffrey M. , Yang Hongbo , Chi Neil C.
Published: March 2013

Multi-organ animals, such as vertebrates, require the development of a closed vascular system to ensure the delivery of nutrients to, and the transport of waste from, their organs. As a result, an organized vascular network that is optimal for tissue perfusion is created through not only the generation of new blood vessels but also the remodeling and maintenance of endothelial cells via apoptotic and cell survival pathways. Here, we show that UBIAD1, a vitamin K2/menaquinone-4 biosynthetic enzyme, functions cell-autonomously to regulate endothelial cell survival and maintain vascular homeostasis. From a recent vascular transgene-assisted zebrafish forward genetic screen, we have identified a ubiad1 mutant, reddish/reh, which exhibits cardiac edema as well as cranial hemorrhages and vascular degeneration owing to defects in endothelial cell survival. These findings are further bolstered by the expression of UBIAD1 in human umbilical vein endothelial cells and human heart tissue, as well as the rescue of the reh cardiac and vascular phenotypes with either zebrafish or human UBIAD1. Furthermore, we have discovered that vitamin K2, which is synthesized by UBIAD1, can also rescue the reh vascular phenotype but not the reh cardiac phenotype. Additionally, warfarin-treated zebrafish, which have decreased active vitamin K, display similar vascular degeneration as reh mutants, but exhibit normal cardiac function. Overall, these findings reveal an essential role for UBIAD1-generated vitamin K2 to maintain endothelial cell survival and overall vascular homeostasis; however, an alternative UBIAD1/vitamin K-independent pathway may regulate cardiac function.
Activation of Dioxygen in an Aqueous System of [FeIIITMPyP]–MBTH–O2 to Form Peroxide and Azine from MBTH: Reactivity of Superoxohemin ([FeIIITMPyP–OO]•) and Peroxohemin ([FeIIITMPyP–OO]−)
Authors: Nakano Taku , Kakuda Hiroko , Shinoda Hiroyuki , Moriyama Hiroshi
Published: March 2013

Activation of dioxygen in the heme system is observed in an artificial aqueous model system. It has been demonstrated that in the system of a water-soluble hemin, tetrakis(N-methylpyridyl)porphinatoiron(III) pentachloride ([FeIIITMPyP]Cl5), and a mild reducing reagent, 3-methyl-2-benzothiazolinonehydrazone (MBTH), a superoxide anion radical and hydrogen peroxide have been produced in air at pH 7.0 that degrades hemin. In this complex system with a reductant and an oxidant, we have found the reaction products derived from MBTH: a bridging peroxide, 2,2′-peroxybis(3-methyl-2,3-dihydrobenzothiazole) (MBTPO), adding to a previously observed azine, 1,2-bis(3-methyl-2,3-dihydrobenzothiazole-2-ylidene)hydrazine (MBTA), and also a small amount of ketone, 3-methyl-2(3H)-benzothiazolone (MBTZ). We suggest that dioxygen is activated to the intermediates, superoxohemin ([FeIII–OO]•) and peroxohemin ([FeIII–OO]−). Because the addition of reactive oxygen species quenchers such as superoxide dismutase (SOD) and catalase allows reaction that prevents the degradation of heme, the roles of liberated superoxide or hydrogen peroxide are excluded from the mechanism. On the other hand, another possible intermediate, a high-valent oxoiron species ([Fe+=O]), is suggested to form the ketone, MBTZ, while under anaerobic conditions organic hydroperoxide (t-BuOOH) instead of O2 solely reacts to form the ketone. The system is discussed in relation to NADPH oxidase, cytochrome P450, NO synthase (NOS), and heme oxidase (HO).
Alkali-Metal Ion Catalysis and Inhibition in Nucleophilic Displacement Reaction of O-Ethyl O-4-Nitrophenyl Phenylphosphonothioate with Alkali-Metal Ethoxides
Authors: Um Ik-Hwan , Kang Ji-Sun , Shin Minah
Published: March 2013

A kinetic study on nucleophilic displacement reactions of O-ethyl O-4-nitrophenyl phenylphosphonothioate (an insecticide called EPN) with alkali-metal ethoxides (EtOM; M = Li, Na, K, and K/18-crown-6-ether) is reported. Dissection of pseudo-first-order rate constant (kobsd) into the second-order rate constants for the reaction of EPN with the dissociated EtO− (kEtO-) and ion-paired EtOM (kEtOM) has revealed that the reactivity increases in the order kEtOLi < kEtO- < kEtONa < kEtOK < kEtOK/18-crown-6-ether, indicating that Li+ inhibits the reaction while the other M+ ions behave as a Lewis acid catalyst in the order Na+ < K+ < 18C6-complexed K+. The contrasting M+ ion effects have been explained in terms of the hard and soft acids and bases (HSAB) principle, since EPN, as a polarizable P=S centered electrophile, would exert a weak interaction with Li+ (a hard acid) but a strong interaction with the 18C6-complexed K+ ion (a soft acid). M+ ions catalyze the current reaction by increasing the electrophilicity of the reaction center. EPN is less reactive than O-4-nitrophenyl diphenylphosphinothioate but is more reactive than O-4-nitrophenyl O,O-diethyl thiophosphate. Factors governing the reactivity of these P=S centered electrophiles are discussed.
A New Facile Two-Step Synthetic Procedure of 1,1′-Diaminoferrocene
Authors: Abdulmalic Mohammad A , Rüffer Tobias
Published: March 2013

1,1′-Diaminoferrocene (3) was conveniently synthesized by employing a Gabriel synthesis in two steps starting from 1,1′-dibromoferrocene (1). Compound 1 was reacted with 2.5 equivalents of phthalimide in the presence of Cu2O using 4-picoline as a solvent to give 1,1′-diphthalimidoferrocene (2) in a moderate yield. Hydrazinolysis of 2 in EtOH afforded 3 in good yields of ca. 70%. The subsequent reaction of 3 with two equivalents of ethyloxalyl chloride in THF gave the diethyl ester of N,N′-ferrocenylene bis(oxamic acid) (1,1′-fcbaH2Et2, 4). The solution obtained by treating 4 with two equivalents of n-Bu4NOH in H2O was added to a solution of Pd(AcO)2 in THF to give the palladium complex [n-Bu4N]2[Pd(1,1′-fcba)] (5) in ca. 80% yield. The compounds 2–4 were characterized by 1H, 13C NMR and IR spectroscopy as well as elemental analysis and the heterobinuclear complex 5 by 1H NMR and IR spectroscopy, elemental analysis and by a single-crystal X-ray diffraction study.
Development Effects of Electrification: Evidence from the Topographic Placement of Hydropower Plants in Brazil
Authors: Lipscomb Molly , Mobarak A. Mushfiq , Barham Tania
Published: March 2013

We estimate the development effects of electrification across Brazil over the period 1960–2000. We simulate a time series of hypothetical electricity grids for Brazil for the period 1960–2000 that show how the grid would have evolved had infrastructure investments been made based solely on geography-based cost considerations. Using the model as an instrument, we document large positive effects of electrification on development that are underestimated when one fails to account for endogenous targeting. Broad-based improvement in labor productivity across sectors and regions rather than general equilibrium re-sorting appears to be the likely mechanism by which these development gains are realized. (JEL H54, L94, O11, O13, Q41, Q43)
Starting Right: Using “Biophilia,” Organism Cards, & Key Themes in Biology to Introduce Student-Centered Active-Learning Strategies at the Beginning of a Course
Authors: Metzger Kelsey
Published: March 2013

To create rich learning experiences, it is important to engage students from the very beginning of a course and lay the foundation for constructing a community of active learners. The activities described here using “organism cards” connect students’ previous knowledge to course goals and address key themes in biology while initiating student-centered and active learning. Using these approaches from the very first day of class can contribute to creating a positive learning environment in which students engage with each other and instructors, resulting in significant learning experiences.
Aliens in the Classroom: Fantastical Creatures as Tools in Teaching Biology
Authors: Cruz Ronald Allan L.
Published: March 2013

Creatures from science fiction and fantasy can be used to illustrate key concepts and principles in biology. This article describes a project for a university-level general zoology course wherein the students classify, down to at least the phylum level, “animals” from the Alien Species Wiki (2013). This is an online database of creatures from television, film, literature, and games. The primary challenges that the students faced were overly fantastical hybridizations and assigning reality-based classification mechanisms to fictional beings, but the project is a useful exercise in creativity, knowledge of diagnostic characteristics, and the wonder of discovery of new, previously unexplainable physio-morphologies.
Integrating Quantitative Skills in Introductory Ecology: Investigations of Wild Bird Feeding Preferences
Authors: Small Christine J. , Newtoff Kiersten N.
Published: March 2013

Undergraduate biology education is undergoing dramatic changes, emphasizing student training in the “tools and practices” of science, particularly quantitative and problem-solving skills. We redesigned a freshman ecology lab to emphasize the importance of scientific inquiry and quantitative reasoning in biology. This multi-week investigation uses observations of avian form and function and an extensive student-generated data set to introduce hypothesis testing, experimental design, and biological statistics. Research groups compare feeding preferences (location and seed selection) between selected species of wild birds, evaluating their findings quantitatively through descriptive statistics, graphing, and data analysis, and ecologically through comparisons of species biology and natural history.
And So It Grows: Using a Computer-Based Simulation of a Population Growth Model to Integrate Biology & Mathematics
Authors: Street Garrett M. , Laubach Timothy A.
Published: March 2013

We provide a 5E structured-inquiry lesson so that students can learn more of the mathematics behind the logistic model of population biology. By using models and mathematics, students understand how population dynamics can be influenced by relatively simple changes in the environment.
Beyond the male sex hormone: deciphering the metabolic and vascular actions of testosterone
Authors: Kang Hong-Yo
Published: March 2013

Among all the androgens that stimulate or control the development and maintenance of body composition, testosterone could be the most well known and important due to its linkage to many diseases, including the metabolic syndrome, type 2 diabetes, and cardiovascular disease. The detailed mechanisms of how testosterone functions in health and disease, however, remain unclear. During the past several decades, the successful cloning of the androgen receptor (AR) and its coregulators and establishment of AR transgenic and knockout animal models have led to rapid development in this field of study. The two thematic reviews in this issue of the Journal of Endocrinology provide a timely and useful guide and source of information to discuss the current knowledge of the metabolic and vascular actions of testosterone involvement in these androgen-related disorders. They described the mechanisms of relationships between testosterone and metabolic disease and how testosterone regulates vascular function and inflammation with a comprehensive summary of updated androgen-AR findings. As more research and clinical trials have put efforts into the study of how testosterone functions in these diseases, it is expected that the roles of testosterone and its actions will become clearer in the near future.
Large-Scale Use of the Modified Checklist for Autism in Low-Risk Toddlers
Authors: Chlebowski Colby , Robins Diana L. , Barton Marianne L. , Fein Deborah
Published: March 2013

OBJECTIVE:

The purpose of the study was to examine use of the Modified Checklist for Autism in Toddlers (M-CHAT) as an autism-specific screening instrument in a large, geographically diverse pediatrics-based sample.

METHODS:

The M-CHAT and the M-CHAT Follow-Up (M-CHAT/F) were used to screen 18 989 toddlers at pediatric well-child visits in 2 US geographic regions. Pediatricians directly referred children to ascertain potential missed screening cases. Screen-positive children received the M-CHAT/F; children who continued to screen positive after the M-CHAT/F received a diagnostic evaluation.

RESULTS:

Results indicated that 54% of children who screened positive on the M-CHAT and M-CHAT/F presented with an autism spectrum disorder (ASD), and 98% presented with clinically significant developmental concerns warranting intervention. An M-CHAT total score cutoff of ≥3 identifies nearly all screen-positive cases, and for ease of scoring the use of only the M-CHAT total score cutoff is recommended. An M-CHAT total score of 7 serves as an appropriate clinical cutoff, and providers can bypass the M-CHAT/F and refer immediately to evaluation and intervention if a child obtains a score of ≥7.

CONCLUSIONS:

This study provides empirical support for the utility of population screening for ASD with the use of the M-CHAT in a primary care setting. Results suggest that the M-CHAT continues to be an effective screening instrument for ASD when the 2-step screening process is used. The M-CHAT is widely used at pediatric offices, and this study provides updated results to facilitate use and scoring of the M-CHAT by clinical providers.
Mutation in the SLC29A3 Gene: A New Cause of a Monogenic, Autoinflammatory Condition
Authors: Melki Isabelle , Lambot Karen , Jonard Laurence , Couloigner Vincent , Quartier Pierre , Neven Bénédicte , Bader-Meunier Brigitte
Published: March 2013

Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a Rosai-Dorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor α antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G>A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis).
Neuropsychological Effects of Konzo: A Neuromotor Disease Associated With Poorly Processed Cassava
Authors: Boivin Michael J. , Okitundu Daniel , Makila-Mabe Bumoko Guy , Sombo Marie-Therese , Mumba Dieudonne , Tylleskar Thorkild , Page Connie F. , Tamfum Muyembe Jean-Jacques , Tshala-Katumbay Desire
Published: March 2013

BACKGROUND:

Konzo is an irreversible upper-motor neuron disorder affecting children dependent on bitter cassava for food. Although the neuroepidemiology of konzo is well characterized, we report the first neuropsychological findings.

METHOD:

Children with konzo in the Democratic Republic of Congo (mean age 8.7 years) were compared with children without konzo (mean age 9.1 years) on the Kaufman Assessment Battery for Children, second edition (KABC-II), and the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2). Both groups were also compared with normative KABC measures from earlier studies in a nearby nonkonzo region.

RESULTS:

Using a Kruskal-Wallis test, children with konzo did worse on the KABC-II simultaneous processing (visual-spatial analysis) (K [1] = 8.78, P = .003) and mental processing index (MPI) (K [1] = 4.56, P = .03) than children without konzo. Both konzo and nonkonzo groups had poorer KABC sequential processing (memory) and MPI relative to the normative group from a nonkonzo region (K [2] = 75.55, P < .001). Children with konzo were lower on BOT-2 total (K [1] = 83.26, P < .001). KABC-II MPI and BOT-2 total were predictive of konzo status in a binary logistic regression model: odds ratio = 1.41, P < .013; 95% confidence interval 1.13–1.69.

CONCLUSIONS:

Motor proficiency is dramatically affected, and both children with and without konzo have impaired neurocognition compared with control children from a nonoutbreak area. This may evidence a subclinical neurocognitive form of the disease, extending the human burden of konzo with dramatic public health implications.
Prenatal Maternal Bereavement and Congenital Heart Defects in Offspring: A Registry-Based Study
Authors: Zhu Jin Liang , Olsen Jørn , Sørensen Henrik Toft , Li Jiong , Nohr Ellen A. , Obel Carsten , Vestergaard Mogens , Olsen Morten Smærup
Published: March 2013

OBJECTIVES:

It has been suggested that maternal emotional stress during cardiogenesis may be a risk factor for congenital heart defects (CHD). We examined this association using bereavement around the time of conception as an indicator of maternal exposure to stress in a large registry-based study.

METHODS:

We identified 1 770 878 singletons born in Denmark from January 1, 1978, to December 31, 2008. Of these, 44 820 children were born to mothers who had lost a first-degree relative during the time period from 1 year before their last menstrual period until delivery (6080 mothers lost a child or partner, and 38 740 mothers lost a parent or sibling). CHD diagnoses were identified from the Danish Registry of Congenital Heart Disease. We used logistic regression models to calculate prevalence odds ratios (ORs) of CHD for exposed children compared with unexposed children.

RESULTS:

Exposed children had a slightly higher prevalence of CHD than unexposed children (0.94% vs 0.82%; adjusted OR = 1.11, 95% confidence interval 1.00–1.22). The association was most marked for children of mothers who had lost a child or partner (1.15% vs 0.82%; adjusted OR = 1.32, 1.04–1.67).

CONCLUSIONS:

Prenatal exposure to severe emotional stress may slightly increase the prevalence of CHD in offspring.
Trends in the Management of Viral Meningitis at United States Children’s Hospitals
Authors: Nigrovic Lise E. , Fine Andrew M. , Monuteaux Michael C. , Shah Samir S. , Neuman Mark I.
Published: March 2013

OBJECTIVE:

To determine trends in the diagnosis and management of children with viral meningitis at US children’s hospitals.

METHODS:

We performed a multicenter cross sectional study of children presenting to the emergency department (ED) across the 41 pediatric tertiary-care hospitals participating in the Pediatric Health Information System between January 1, 2005, and December 31, 2011. A case of viral meningitis was defined by International Classification of Diseases, Ninth Revision, discharge diagnosis, and required performance of a lumbar puncture. We examined trends in diagnosis, antibiotic use, and resource utilization for children with viral meningitis over the study period.

RESULTS:

We identified 7618 children with viral meningitis (0.05% of ED visits during the study period). Fifty-two percent of patients were <1 year of age, and 43% were female. The absolute number and the proportion of ED visits for children with viral meningitis declined from 0.98 cases per 1000 ED visits in 2005 to 0.25 cases in 2011 (P < .001). Most children with viral meningitis received a parenteral antibiotic (85%), and were hospitalized (91%). Overall costs for children for children with viral meningitis remain substantial (median cost per case $5056, interquartile range $3572–$7141).

CONCLUSIONS:

Between 2005 and 2011, viral meningitis diagnoses at US children’s hospitals declined. However, most of these children are hospitalized, and the cost for caring for these children remains considerable.
Electronic Prescribing in Pediatrics: Toward Safer and More Effective Medication Management
Authors:   COUNCIL ON CLINICAL INFORMATION TECHNOLOGY EXECUTIVE COMMITTEE, 2011–2012, Lehmann Christoph U. , Johnson Kevin B. , Del Beccaro Mark A. , Alexander Gregg , Drummond Willa H. , Francis Anne B. , Handler Eric G. , Johnson Timothy D. , Kim George R. , Leu Michael , Tham Eric , Weinberg Stuart T. , Zuckerman Alan E.
Published: March 2013

This Policy Statement was retired.

This policy statement identifies the potential value of electronic prescribing (e-prescribing) systems in improving quality and reducing harm in pediatric health care. On the basis of limited but positive pediatric data and on the basis of federal statutes that provide incentives for the use of e-prescribing systems, the American Academy of Pediatrics recommends the adoption of e-prescribing systems with pediatric functionality. The American Academy of Pediatrics also recommends a set of functions that technology vendors should provide when e-prescribing systems are used in environments in which children receive care.
Evaluation for Bleeding Disorders in Suspected Child Abuse
Authors: Anderst James D. , Carpenter Shannon L. , Abshire Thomas C. ,   the SECTION ON HEMATOLOGY/ONCOLOGY and COMMITTEE ON CHILD ABUSE AND NEGLECT, Anderst James D. , Carpenter Shannon L. , Abshire Thomas C. , Hord Jeffrey , Crouch Gary , Hale Gregory , Mueller Brigitta , Rogers Zora , Shearer Patricia , Werner Eric , Feig Stephen , Kodish Eric , Gamis Alan
Published: March 2013

Bruising or bleeding in a child can raise the concern for child abuse. Assessing whether the findings are the result of trauma and/or whether the child has a bleeding disorder is critical. Many bleeding disorders are rare, and not every child with bruising/bleeding concerning for abuse requires an evaluation for bleeding disorders. In some instances, however, bleeding disorders can present in a manner similar to child abuse. The history and clinical evaluation can be used to determine the necessity of an evaluation for a possible bleeding disorder, and prevalence and known clinical presentations of individual bleeding disorders can be used to guide the extent of the laboratory testing. This clinical report provides guidance to pediatricians and other clinicians regarding the evaluation for bleeding disorders when child abuse is suspected.
The Effects of Immigration on Social Trust in the United Kingdom
Authors: Hodosi Anett
Published: March 2013

Egy korábbi kutatás megmutatta, hogy a magas minőségű formális intézményi háttérhez alacsony szintű társadalmi bizalom társul az Egyesült Királyságban. Jelen cikk célja ennek a paradoxonnak a feloldása, melyet a királyság heterogén társadalmi jellegében keresünk. Az elemzés az etnikai, vallási és jövedelmi alapú különbségekre összpontosít, amiket a közösségen kívüli hálózatnak, a közösségen belüli bizalomnak, a bizalom körének és a külső, formális kikényszeríthetőség szükségességének mátrixában vizsgál. Három tényező – koncentrált, nagyon diverz területek, korlátozott közösségen kívüli kapcsolattal rendelkező, szoros közösségek egymás mellett élése és a kisebbségi csoportok nélkülözésnek való nagy mértékű kitettsége – adja a puzzle megoldását. Mindezek tovagyűrűző, bizalomromboló hatását tovább erősíti az alacsony jövedelmű népességcsoport igazságszolgáltatáshoz való hozzáférésének korlátozottsága, aminek eredményeként olyan környezet jön érte, ahol a külső kikényszeríthetőség sem informális, sem formális intézményeken keresztül nem érhető el.
Faith and Traditional Capitals
Authors: Baker Chris , Miles-Watson Jonathan
Published: March 2013

This discursive literature review was originally produced for the Leverhulme Trust in 2007 by the William Temple Foundation as a part of a research project to test the concept of religious capital (along with associated ideas of spiritual, faithful and religious social capital) with new empirical research. The research project aims also to explore emerging alternative paradigms to “capital” as a way of describing and evaluating the role and contribution of faiths to civil society. To that end, the article traces the historical development of the concept of social capital and its use by three influential thinkers in the field, namely Pierre Bourdieu, James Coleman and Robert Putnam. It then proceeds to map emerging

developments in the construction of definitions of religious and spiritual capital (and including ideas of religious social and faithful capital). It concludes with an extended discussion concerning some of the public policy implications of this research field, including the emerging concept of secular spiritual capital and its contribution to discerning common core values within the public domain.
New Environmental Movements and Implicit Religion
Authors: Reader John
Published: March 2013

The paper revisits an earlier article which drew parallels between New Social Movements and developing contextual theologies. It argues that a contemporary form of this debate is to be found in an examination of links between the Transition Initiatives Movement and Implicit Religion. It then employs three frameworks, the first two of which come from within the academic study of Implicit Religion, those of Professor Edward Bailey and Dr Karen Lord, and then a third framework developed by the author, to determine the extent to which the Transition movement can be identified with the motivations to be found within a religious setting. It concludes that there are indeed common themes at work, as well as areas where faith can learn from the ideas and practices of this environmental discussion, but also significant differences that are to be acknowledged as those of faith engage with the Transition movement.
The Personality Cult of Prince
Authors: Till Rupert
Published: March 2013

Prince is an artist who uses popular iconography to present himself as an icon of consumer culture, as a deified “rock god” worshipped by his fans, analogous to a preacher leading his audience like a congregation. His personality cult mixes spirituality and sexuality freely, and deals with issues of ecstasy and liberation, a transgressional approach that draws both controversy and public interest. This paper looks at the traditions that inform Prince’s work and at what it means to call a pop star an icon within contemporary culture. It also investigates the roles of physicality and sexuality in this process and discusses to what extent popular musical culture has taken the place of religious practice within contemporary western culture. The paper investigates Prince’s semi-fictional character development, his manipulation of the star system, and how he uses popular iconography to blur the distinctions between spirituality and sexuality, the idealized performer and the real world, the sacred and the secular, and the human and the divine. It explores how he possesses and is possessed by the audience, who enter into the hollow vessel he offers up to his fans. It suggests that personality cults such as that of Prince, are a form of implicit religion, that they are breaking down the traditional distinctions between the secular and the sacred, and are part of the impact of postmodernity on religion.
Cultural Uniqueness and Implicit Religion
Authors: Dutton Edward
Published: March 2013

This article will argue that “uniqueness” can be understood as a form of Implicit Religion. This will be demonstrated through an analysis of the word and the use of fieldwork in two cultures in which “uniqueness” is a strong component of the nationalist discourse. In doing so, it will respond to serious and superficially persuasive criticisms of the idea that uniqueness relates to religion and, implicitly, to Implicit Religion as a concept. It will highlight the logically unsustainable philosophical presuppositions underlying Implicit Religion, and the false rationalist and

unsustainable philosophical presuppositions underlying the critique. It will conclude that the critique itself would be fruitful pasture for Implicit Religion analysis.
On Creation Myths
Authors: Badertscher John
Published: March 2013

Some of the methodological assumptions operative in this essay are: all faiths express themselves through a variety of forms; one can never

observe a faith directly, but only through its expressions; a religion is a shared faith, expressing itself through particular manifestations that have sufficiently shared meanings; one of the forms through which any religion manifests itself is myth. By “myth” is meant a narrative told for the purpose of inculcating a particular sense of the meaning and purpose of life.
Prayer, Poetry, and Politics
Authors: Johnson Stephen M.
Published: March 2013

Review article focussing on Science as Sacred Metaphor: An Evolving Revelation, by Elizabeth Michael Boyle. Liturgical Press, 2006. 160pp., pb. $14.95. ISBN-13: 9780814624043.
Culture Shock as Implicit Religion in the Romantic Tradition
Authors: Dutton Edward
Published: March 2013

This article will examine the religious dimensions to the phenomenon of Culture Shock. Drawing upon a functionalist definition of religion, it will argue, with some nuances, that Culture Shock sits in the Romantic tradition of Cultural Relativism and that this is best understood in religious terms. It will also compare Culture Shock to Religious Experience and Conversion Experience, further demonstrating its implicit religiosity. It will recommend changes in the way it is taught at many universities, as part of the burgeoning field of Intercultural Education.
Professional’s Calling
Authors: Parkes Madeleine , Gilbert Peter
Published: March 2013

Mental health professionals enter the service with a desire to work to provide better outcomes for service users and carers. However sometimes the system gets in the way and produces unintended consequences. Recently service users have requested that the spiritual dimension of their lives be given greater attention, and this fits strongly with the recovery approach and its accent on service users being able to take control of their own lives. Research undertaken at Birmingham and Solihull Mental Health Foundation Trust has found that staff across all professional groups have recognised the importance of spirituality and spiritual care and wish to receive greater guidance and education in how to respond to services user needs.
Playing Games with Death
Authors: Grainger Roger
Published: March 2013

The symbolism of chaos which emerges from the “amusements” around which traditional Irish funerals were organized brings home an essential truth about corporate rituals: that they serve to focus our awareness of a global truth embodied within an articulated gesture of human meaning. In the act which signifies a specific dying, a message about all human life is encapsulated. The funeral is seen as a communication about survival. Examples of this are given, and it is argued that the structure of such ceremonies reveals the underlying function of ritual itself. Corporate rites present us with a paradigm of the use of chaos to clear a way for new kinds of order. In their three-fold configuration, rites of passage reveal the need for genuine beginnings to be preceded by actual endings.