bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors that Influence Midwives to Serve as Preceptors: An American College of Nurse‐Midwives Survey
Authors: Germano Elaine , Schorn Mavis N. , Phillippi Julia C. , Schuiling Kerri
Published: March 2014

Introduction

Projected shortages in the primary care workforce underlie a need for more women's health care providers. In order to prepare more midwives to address this deficit, educators require additional clinical placement sites for students. The purpose of this study was to determine factors that influence practicing midwives to serve as preceptors.

Methods

An e‐mail invitation to participate in an online survey was sent to 7658 current and lapsed members of the American College of Nurse‐ Midwives (ACNM), who provided ACNM with a valid e‐mail address. The survey assessed factors that enabled or were barriers for midwifery preceptors. Forced‐choice questions were analyzed using descriptive statistics. Participant comments were analyzed using qualitative descriptive methods.

Results

There were a total of 1517 surveys completed, for a response rate of 19.8%. Participants were primarily certified nurse‐midwives (96.0%) who were in clinical practice (83.9%), with 78.0% in full‐scope clinical practice. Participants represented all geographic regions of the United States. The majority of the participants indicated they or someone in their practice could precept a midwifery student. A commitment to the midwifery profession was the most commonly identified motivating factor (58.5%). Larger practices were more likely to precept midwifery students and to accept more than one student at a time. The most frequently identified barrier to precepting was the need to maintain a high patient volume (6.9%). Write‐in comments were provided by approximately 500 participants and coded into 9 themes: payment, barriers to precepting, incentives, student characteristics, mechanisms for placement, communication, giving back, preceptor qualifications, and professional issues.

Discussion

There is a strong commitment from preceptors to give back to the profession through the teaching of the future generation of midwives. Many of the barriers to precepting could be addressed by ACNM, the Accreditation Commission for Midwifery Education, and individual midwifery education programs.
Carbon recycling goes full circle: fatty acids to excitatory amino acids and now excitatory amino acids to fatty acids
Authors: Murphy Eric J.
Published: March 2014

Read the full article ‘Fatty acid biosynthesis fromglutamate and glutamine is specifically induced in neuronal cells under hypoxia’ on doi: 10.1111/jnc.12617
17α‐Oestradiol‐Induced Neuroprotection in the Brain of Spontaneously Hypertensive Rats
Authors: Pietranera L. , Brocca M. E. , Roig P. , Lima A. , Garcia‐Segura L. M. , De Nicola A. F.
Published: March 2014

17β‐oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17α‐Oestradiol, a nonfeminising isomer showing low affinity for oestrogen receptors, is also endowed with neuroprotective effects in vivo and in vitro. We therefore investigated whether treatment with 17α‐oestradiol prevented pathological changes of the hippocampus and hypothalamus of SHR. We used 20‐week‐old male SHR with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 μg pellet of 17α‐oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar–Kyoto (WKY) rats were used as controls. 17α‐Oestradiol did not modify blood pressure, serum prolactin, 17β‐oestradiol levels or the weight of the testis and pituitary of SHR. In the brain, we analysed steroid effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase immunostaining and brain‐derived neurotrophic factor (BDNF) mRNA. In the hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR with 17α‐oestradiol enhanced the number of Ki67+ in the subgranular zone and DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to 17α‐oestradiol. These data indicate a role for 17α‐oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17α‐oestradiol is weakly oestrogenic in the periphery and can be used in males.
Influence of experimental oesophageal acidification on masseter muscle activity, cervicofacial behaviour and autonomic nervous activity in wakefulness
Authors: Ohmure H. , Sakoguchi Y. , Nagayama K. , Numata M. , Tsubouchi H. , Miyawaki S.
Published: March 2014

Recent studies have been revealing the relationship between the stomatognathic system and the gastrointestinal tract. However, the effect of oesophageal acid stimulation on masticatory muscle activity during wakefulness has not been fully elucidated. To examine whether intra‐oesophageal acidification induces masticatory muscle activity, a randomised trial was conducted investigating the effect of oesophageal acid infusion on masseter muscle activity, autonomic nervous system (ANS) activity and subjective symptoms. Polygraphic monitoring consisting of electromyography of the masseter muscle, electrocardiography and audio–video recording was performed in 15 healthy adult men, using three different 30‐min interventions: (i) no infusion, (ii) intra‐oesophageal saline infusion and (iii) intra‐oesophageal infusion of acidic solution (0·1 N HCl; pH 1·2). This study was registered with the UMIN Clinical Trials Registry, UMIN000005350. Oesophageal acid stimulation significantly increased masseter muscle activity during wakefulness, especially when no behaviour was performed in the oro‐facial region. Chest discomfort, including heartburn, also increased significantly after oesophageal acid stimulation; however, no significant correlation was observed between increased subjective symptoms and masseter muscle activity. Oesophageal acid infusion also altered ANS activity; a significant correlation was observed between masticatory muscle changes and parasympathetic nervous system activity. These findings suggest that oesophageal‐derived ANS modulation induces masseter muscle activity, irrespective of the presence or absence of subjective gastrointestinal symptoms.
The effect of oral appliances that advanced the mandible forward and limited mouth opening in patients with obstructive sleep apnea: A systematic review and meta‐analysis of randomised controlled trials
Authors: Okuno K. , Sato K. , Arisaka T. , Hosohama K. , Gotoh M. , Taga H. , Sasao Y. , Hamada S.
Published: March 2014

Oral appliances (OAs) have demonstrated efficacy in treating obstructive sleep apnea (OSA), but many different OA devices are available. The Japanese Academy of Dental Sleep Medicine supported the use of OAs that advanced the mandible forward and limited mouth opening and suggested an evaluation of their effects in comparison with untreated or CPAP. A systematic search was undertaken in 16 April 2012. The outcome measures of interest were as follows: Apnea Hypopnea Index (AHI), lowest SpO2, arousal index, Epworth Sleepiness Scale (ESS), the SF‐36 Health Survey. We performed this meta‐analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Five studies remained eligible after applying the exclusion criteria. Comparing OA and control appliance, OA significantly reduced the weighted mean difference (WMD) in both AHI and the arousal index (favouring OA, AHI: −7·05 events h−1; 95% CI, −12·07 to −2·03; P = 0·006, arousal index: −6·95 events h−1; 95% CI, −11·75 to −2·15; P = 0·005). OAs were significantly less effective at reducing the WMD in AHI and improving lowest SpO2 and SF‐36 than CPAP, (favouring OA, AHI: 6·11 events h−1; 95% CI, 3·24 to 8·98; P = 0·0001, lowest SpO2: −2·52%; 95% CI, −4·81 to −0·23; P = 0·03, SF‐36: −1·80; 95% CI, −3·17 to −042; P = 0·01). Apnea Hypopnea Index and arousal index were significantly improved by OA relative to the untreated disease. Apnea Hypopnea Index, lowest SpO2 and SF‐36 were significantly better with CPAP than with OA. The results of this study suggested that OAs improve OSA compared with untreated. CPAP appears to be more effective in improving OSA than OAs.
Melatonin, energy metabolism, and obesity: a review
Authors: Cipolla‐Neto J. , Amaral F. G. , Afeche S. C. , Tan D. X. , Reiter R. J.
Published: March 2014

Melatonin is an old and ubiquitous molecule in nature showing multiple mechanisms of action and functions in practically every living organism. In mammals, pineal melatonin functions as a hormone and a chronobiotic, playing a major role in the regulation of the circadian temporal internal order. The anti‐obesogen and the weight‐reducing effects of melatonin depend on several mechanisms and actions. Experimental evidence demonstrates that melatonin is necessary for the proper synthesis, secretion, and action of insulin. Melatonin acts by regulating GLUT4 expression and/or triggering, via its G‐protein‐coupled membrane receptors, the phosphorylation of the insulin receptor and its intracellular substrates mobilizing the insulin‐signaling pathway. Melatonin is a powerful chronobiotic being responsible, in part, by the daily distribution of metabolic processes so that the activity/feeding phase of the day is associated with high insulin sensitivity, and the rest/fasting is synchronized to the insulin‐resistant metabolic phase of the day. Furthermore, melatonin is responsible for the establishment of an adequate energy balance mainly by regulating energy flow to and from the stores and directly regulating the energy expenditure through the activation of brown adipose tissue and participating in the browning process of white adipose tissue. The reduction in melatonin production, as during aging, shift‐work or illuminated environments during the night, induces insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chronodisruption leading to obesity. The available evidence supports the suggestion that melatonin replacement therapy might contribute to restore a more healthy state of the organism.
Mental health nursing staff's attitudes towards mental illness: an analysis of related factors
Authors: Mårtensson G. , Jacobsson J. W. , Engström M.
Published: March 2014

Accessible summary

Employer/workplaces have an impact on mental health nursing staff's general attitudes towards persons with mental illness.

Staff have more positive attitudes if their knowledge about mental illness is less stigmatized and currently have or have once had a close friend with mental problem.

More favourable attitudes among staff towards persons with mental illness could be developed and transmitted in the subculture at work places.

There is growing awareness that mental illness is surrounded by negative attitudes and stigmas. The aim of the present study was to investigate factors associated with mental health nursing staff's attitudes towards persons with mental illness. Data were collected from 256 mental health nursing staff employed by one county council and 10 municipalities. The findings show that staff have more positive attitudes towards persons with mental illness if their knowledge about mental illness is less stigmatized, their work places are in the county council, and they currently have or have once had a close friend with mental health problems. The multiple regression model explained 16% of the variance; stigma‐related knowledge and employer had significant Beta‐coefficients. To account for unknown correlations in data, a linear generalized estimating equation was performed. In this model, stigma‐related knowledge and employer remained significant, but a new significant factor also emerged: personal contact, i.e. currently having or having once had a close friend with mental health problems. This indicates correlations at unit level in the county council and in the municipalities. The conclusion is that more favourable attitudes among staff towards persons with mental illness could be developed and transmitted in the subculture at work places.
Dementia care: using empathic curiosity to establish the common ground that is necessary for meaningful communication
Authors: McEvoy P. , Plant R.
Published: March 2014

Accessible summary

Empathic curiosity is a standpoint that we adopt when we focus our attention on the perceptual experiences of people with dementia, as they are experiencing them in the here and now.

Adopting an empathic and curious stance may help to establish the common ground for meaningful communication and help to cultivate relationships that are based upon equality and common understanding, rather than power and dependency.

Four key sets of communication skills can support this approach: (1) asking short open questions in the present tense; (2) picking up on emotional cues; (3) giving time and space for the person with dementia to find their words and share responsibility for steering the course of a conversation; and (4) exploring the use of metaphors.

Providing access to training and supervision that supports these communication skills may be an essential element of building an informed and effective dementia care workforce.

Over the past two decades the advocates of person‐centred approaches to dementia care have consistently argued that some of the negative impacts of dementia can be ameliorated in supportive social environments and they have given lie to the common but unfounded, nihilistic belief that meaningful engagement with people with dementia is impossible. This discussion paper contributes to this welcome trend by exploring how carers can use empathic curiosity to establish the common ground that is necessary to sustain meaningful engagement with people who have mild to moderate dementia. The first section of the paper gives a brief theoretical introduction to the concept of empathic curiosity, which is informed by perceptual control theory and applied linguistics. Three case examples taken from the literature on dementia care are then used to illustrate what empathic curiosity may look like in practice and to explore the potential impact that adopting an empathic and curious approach may have.
IV‐BASED COINTEGRATION TESTING IN DEPENDENT PANELS WITH TIME‐VARYING VARIANCE
Authors: Demetrescu Matei , Hanck Christoph , Tarcolea Adina I.
Published: March 2014

The distributions of cointegration tests are affected when the innovation variance varies over time. In panels, one must also pay attention to dependence among units. To obtain a panel cointegration test robust to both heteroskedasticity and dependence, we adapt the nonlinear instruments method proposed for the Dickey–Fuller test by Chang (2002, J Econometrics 110, 261–292) to an error‐correction framework. We show that IV‐based testing of the no error‐correction null in individual equations yields standard normal test statistics when computed with heteroskedasticity‐robust standard errors. The result holds under endogenous regressors, irrespective of the number of integrated covariates and for any variance profile. A non‐cointegration test combining single‐equation tests retains these nice properties. In panels of fixed cross‐sectional dimension, such test statistics from individual units are shown to be asymptotically independent even under dependence, leading to panel tests robust to dependence and heteroskedasticity. The tests perform well in finite panels.
Hemodynamic and Biochemical Alterations in Dogs with Lymphoma after Induction of Chemotherapy
Authors: Fine D.M. , Selting K. , Backus R.C. , Rossi N.F. , Harmon M.W. , Durham H.E. , Spier A.W.
Published: March 2014

Background

Doxorubicin is a common antineoplastic agent with dose‐dependent cardiotoxic adverse effects, and pre‐existing myocardial dysfunction is a contraindication to its use.

Objectives

To systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration.

Animals

Twenty‐one client‐owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age‐ and weight‐matched dogs were used as controls.

Methods

Physical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively.

Results

Baseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls.

Conclusion and Clinical Importance

Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.
A Review of the Studies Using Buprenorphine in Cats
Authors: Steagall P.V.M. , Monteiro‐Steagall B.P. , Taylor P.M.
Published: March 2014

Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic‐pharmacodynamic (PK‐PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association‐dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clinicians should not expect to observe pain relief immediately after drug administration. In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported. The route of administration influences the onset, duration, and magnitude of antinociception and analgesia when using this drug in cats. At clinical dosages, the SC route of administration does not appear to provide adequate antinociception and analgesia whereas the buccal route has produced inconsistent results. Intravenous or IM administration at a dosage of 0.02–0.04 mg/kg is the preferred for treatment of pain in the acute setting. A literature search found 14 clinical trials evaluating buprenorphine sedation, analgesia, or both in cats. There were 22 original research studies reporting the antinociceptive effects of buprenorphine by means of thermal threshold, mechanical threshold, or both, minimal alveolar concentration, or PK‐PD. Individual variability in response to buprenorphine administration has been reported, indicating that buprenorphine may not provide sufficient analgesia in some cats. Pain assessment is important when evaluating the efficacy of buprenorphine and determining whether additional analgesic treatment is needed.
Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture‐adjusted quantitative structure permeability relationship
Authors: Riviere J. E. , Brooks J. D. , Collard W. T. , Deng J. , de Rose G. , Mahabir S. P. , Merritt D. A. , Marchiondo A. A.
Published: March 2014

Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of 14C‐labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4–5 replicates per treatment) nonoccluded to 0.64 cm2 disks of dermatomed pig or dog skin mounted in flow‐through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four‐term Abrahams and Martin (hydrogen‐bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r2, cross‐validation coefficient, coefficients (q2s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r2 = 0.86, q2s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r2 = 0.91, q2s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical–chemical properties of the penetrant and formulation components.
Congruent phylogeographical patterns of eight tree species in Atlantic Central Africa provide insights into the past dynamics of forest cover
Authors: Dauby G. , Duminil J. , Heuertz M. , Koffi G. K. , Stévart T. , Hardy O. J.
Published: March 2014

Cycles of Quaternary climatic change are assumed to be major drivers of African rainforest dynamics and evolution. However, most hypotheses on past vegetation dynamics relied on palaeobotanical records, an approach lacking spatial resolution, and on current patterns of species diversity and endemism, an approach confounding history and environmental determinism. In this context, a comparative phylogeographical study of rainforest species represents a complementary approach because Pleistocene climatic fluctuations may have left interpretable signatures in the patterns of genetic diversity within species. Using 1274 plastid DNA sequences from eight tree species (Afrostyrax kamerunensis, A. lepidophyllus, Erythrophleum suaveolens, Greenwayodendron suaveolens, Milicia excelsa, Santiria trimera, Scorodophloeus zenkeri and Symphonia globulifera) sampled in 50 populations of Atlantic Central Africa (ACA), we averaged divergence across species to produce the first map of the region synthesizing genetic distinctiveness and standardized divergence within and among localities. Significant congruence in divergence was detected mostly among five of the eight species and was stronger in the northern ACA. This pattern is compatible with a scenario of past forest fragmentation and recolonization whereby forests from eastern Cameroon and northeastern Gabon would have been more affected by past climatic change than those of western Cameroon (where one or more refugia would have occurred). By contrast, southern ACA (Gabon) displayed low congruence among species that may reflect less drastic past forest fragmentation or a more complex history of vegetation changes. Finally, we also highlight the potential impact of current environmental barriers on spatial genetic structures.
Spatial patterns of neutral and functional genetic variations reveal patterns of local adaptation in raccoon (Procyon lotor) populations exposed to raccoon rabies
Authors: Kyle Christopher J. , Rico Yessica , Castillo Sarrah , Srithayakumar Vythegi , Cullingham Catherine I. , White Bradley N. , Pond Bruce A.
Published: March 2014

Local adaptation is necessary for population survival and depends on the interplay between responses to selective forces and demographic processes that introduce or retain adaptive and maladaptive attributes. Host–parasite systems are dynamic, varying in space and time, where both host and parasites must adapt to their ever‐changing environment in order to survive. We investigated patterns of local adaptation in raccoon populations with varying temporal exposure to the raccoon rabies virus (RRV).RRVinfects approximately 85% of the population when epizootic and has been presumed to be completely lethal once contracted; however, disease challenge experiments and varying spatial patterns ofRRVspread suggest some level of immunity may exist. We first assessed patterns of local adaptation in raccoon populations along the eastern seaboard ofNorthAmerica by contrasting spatial patterns of neutral (microsatellite loci) and functional, major histocompatibility complex (MHC) genetic diversity and structure. We explored variation ofMHCallele frequencies in the light of temporal population exposure toRRV(0–60 years) and specificRRVstrains in infected raccoons. Our results revealed high levels ofMHCvariation (66DRBexon 2 alleles) and pronounced genetic structure relative to neutral microsatellite loci, indicative of local adaptation. We found a positive association linkingMHCgenetic diversity and temporalRRVexposure, but no association with susceptibility and resistance toRRVstrains. These results have implications for landscape epidemiology studies seeking to predict the spread ofRRVand present an example of how population demographics influence the degree to which populations adapt to local selective pressures.
Elevated levels of the second messenger c‐di‐GMP contribute to antimicrobial resistance of Pseudomonas aeruginosa
Authors: Gupta Kajal , Liao Julie , Petrova Olga E. , Cherny K. E. , Sauer Karin
Published: March 2014

Biofilms are highly structured, surface‐associated communities. A hallmark of biofilms is their extraordinary resistance to antimicrobial agents that is activated during early biofilm development of Pseudomonas aeruginosa and requires the regulatory hybrid SagS and BrlR, a member of the MerR family of multidrug efflux pump activators. However, little is known about the mechanism by which SagS contributes to BrlR activation or drug resistance. Here, we demonstrate that ΔsagS biofilm cells harbour the secondary messenger c‐di‐GMP at reduced levels similar to those observed in wild‐type cells grown planktonically rather than as biofilms. Restoring c‐di‐GMP levels to wild‐type biofilm‐like levels restored brlR expression, DNA binding by BrlR, and recalcitrance to killing by antimicrobial agents of ΔsagS biofilm cells. We likewise found that increasing c‐di‐GMP levels present in planktonic cells to biofilm‐like levels (≥ 55 pmol mg−1) resulted in planktonic cells being significantly more resistant to antimicrobial agents, with increased resistance correlating with increased brlR, mexA, and mexE expression and BrlR production. In contrast, reducing cellular c‐di‐GMP levels of biofilm cells to ≤ 40 pmol mg−1 correlated with increased susceptibility and reduced brlR expression. Our findings suggest that a signalling pathway involving a specific c‐di‐GMP pool regulated by SagS contributes to the resistance of P. aeruginosa biofilms.
Streptococcus pneumoniae PBP2x mid‐cell localization requires the C‐terminal PASTA domains and is essential for cell shape maintenance
Authors: Peters Katharina , Schweizer Inga , Beilharz Katrin , Stahlmann Christoph , Veening Jan‐Willem , Hakenbeck Regine , Denapaite Dalia
Published: March 2014

The transpeptidase activity of the essential penicillin‐binding protein 2x (PBP2x) of Streptococcus pneumoniae is believed to be important for murein biosynthesis required for cell division. To study the molecular mechanism driving localization of PBP2x in live cells, we constructed a set of N‐terminal GFP–PBP2x fusions under the control of a zinc‐inducible promoter. The ectopic fusion protein localized at mid‐cell. Cells showed no growth defects even in the absence of the genomic pbp2x, demonstrating that GFP–PBP2x is functional. Depletion of GFP–PBP2x resulted in severe morphological alterations, confirming the essentiality of PBP2x and demonstrating that PBP2x is required for cell division and not for cell elongation. A genetically or antibiotic inactivated GFP–PBP2x still localized at septal sites. Remarkably, the same was true for a GFP–PBP2x derivative containing a deletion of the central transpeptidase domain, although only in the absence of the protease/chaperone HtrA. Thus localization is independent of the catalytic transpeptidase domain but requires the C‐terminal PASTA domains, identifying HtrA as targeting GFP–PBP2x derivatives. Finally, PBP2x was positioned at the septum similar to PBP1a and the PASTA domain containing StkP protein, confirming that PBP2x is a key element of the divisome complex.
Association of Malassezia species with psoriatic lesions
Authors: Rudramurthy Shivaprakash M. , Honnavar Prasanna , Chakrabarti Arunaloke , Dogra Sunil , Singh Pankaj , Handa Sanjeev
Published: March 2014

The aetiology of psoriasis remains elusive. Among multiple factors hypothesised, association of Malassezia spp. is supported by response to topical antifungals. The objective of this study was to evaluate the association of Malassezia spp. with psoriatic lesion. The subjects included 50 consecutive patients with psoriasis, and 50 age‐ and sex‐matched healthy controls. Samples were collected using scotch tape over one square inch area from the lesional and non‐lesional sites. The isolated Malassezia spp. were identified by phenotypic methods and confirmed by ITS2 PCR‐RFLP and sequencing of D1/D2 region of 26S rDNA. Psoriatic lesions were seen commonly on scalp (28%, 14), chest (22%, 11) and arms (16%, 8). Majority of cases presented with chronic plaque form (76%, 38; P < 0.05). From psoriatic lesions, most frequently isolated Malassezia species was M. furfur (70.6%, 24), followed by M. japonica (11.8%, 4) and M. globosa (8.8%, 3). From healthy individuals M. furfur, M. sympodialis, mixture of M. furfur and M. globosa was isolated in 73.3%, 10% and 16.7% (22, 3 and 5) of cases respectively. The average number of colonies isolated from scalp lesions of the patients was significantly higher (P = 0.03) than healthy areas. Although no strong association of Malassezia species was formed with psoriatic lesion in general, the fungi may play a role in exacerbation of scalp psoriasis.
Dissecting impulsivity and its relationships to drug addictions
Authors: Jentsch J. David , Ashenhurst James R. , Cervantes M. Catalina , Groman Stephanie M. , James Alexander S. , Pennington Zachary T.
Published: March 2014

Addictions are often characterized as forms of impulsive behavior. That said, it is often noted that impulsivity is a multidimensional construct, spanning several psychological domains. This review describes the relationship between varieties of impulsivity and addiction‐related behaviors, the nature of the causal relationship between the two, and the underlying neurobiological mechanisms that promote impulsive behaviors. We conclude that the available data strongly support the notion that impulsivity is both a risk factor for, and a consequence of, drug and alcohol consumption. While the evidence indicating that subtypes of impulsive behavior are uniquely informative—either biologically or with respect to their relationships to addictions—is convincing, multiple lines of study link distinct subtypes of impulsivity to low dopamine D2 receptor function and perturbed serotonergic transmission, revealing shared mechanisms between the subtypes. Therefore, a common biological framework involving monoaminergic transmitters in key frontostriatal circuits may link multiple forms of impulsivity to drug self‐administration and addiction‐related behaviors. Further dissection of these relationships is needed before the next phase of genetic and genomic discovery will be able to reveal the biological sources of the vulnerability for addiction indexed by impulsivity.
Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa: A Consensus‐Generated Clinical Research Tool
Authors: Schwieger‐Briel Agnes , Chakkittakandiyil Ajith , Lara‐Corrales Irene , Aujla Nimrita , Lane Alfred T. , Lucky Anne W. , Bruckner Anna L. , Pope Elena
Published: March 2014

Epidermolysis bullosa (EB) is a genetic condition characterized by skin fragility and blistering. There is no instrument available for clinical outcome research measurements. Our aim was to develop a comprehensive instrument that is easy to use in the context of interventional studies. Item collection was accomplished using a two‐step Delphi Internet survey process for practitioners and qualitative content analysis of patient and family interviews. Items were reduced based on frequency and importance using a 4‐point Likert scale and were subject to consensus (>80% agreement) using the nominal group technique. Pilot data testing was performed in 21 consecutive patients attending an EB clinic. The final score, Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa (iscorEB), is a combined score that contains clinician items grouped in five domains (skin, mucosa, organ involvement, laboratory abnormalities, and complications and procedures; maximum score 114) and patient‐derived items (pain, itch, functional limitations, sleep, mood, and effect on daily and leisurely activities; maximum score 120). Pilot testing revealed that combined (see below) and subscores were able to differentiate between EB subtypes and degrees of clinical severity (EB simplex 21.7 ± 16.5, junctional EB 28.0 ± 20.7, dystrophic EB 57.3 ± 24.6, p = 0.007; mild 17.3 ± 9.6, moderate 41.0 ± 19.4, and severe 64.5 ± 22.6, p < 0.001). There was high correlation between clinician and patient subscores (correlation coefficient = 0.79, p < 0.001). iscorEB seems to be a sensitive tool in differentiating between EB types and across the clinical spectrum of severity. Further validation studies are needed.
“You make me a better/worse person”: A two‐dimensional model of relationship self‐change
Authors: MATTINGLY BRENT A. , LEWANDOWSKI GARY W. , McINTYRE KEVIN P.
Published: March 2014

For better or worse, relationships have the potential to affect individuals' self‐concepts; however, currently no integrative model exists to explain the variety of these self‐concept changes. We propose that self‐concept changes occur along two independent dimensions: direction (increase vs. decrease in content) and valence (positivity vs. negativity of content). These two dimensions combine to create four processes of relationship‐induced self‐concept change: self‐expansion (increasing positive content), self‐contraction (decreasing positive content), self‐pruning (decreasing negative content), and self‐adulteration (increasing negative content). Using community and university samples, we developed a measure of self‐concept change (Study 1) and examined how the four self‐processes were associated with love (Study 1), relationship quality (Studies 2 and 3), and infidelity (Study 3). The self‐concept improvement processes (i.e., self‐expansion and self‐pruning) were associated with greater love and relationship quality, whereas in Study 3 self‐concept degradation processes (i.e., self‐contraction and self‐adulteration) predicted infidelity.
Defining Public Will
Authors: Raile Eric D. , Raile Amber N. W. , Salmon Charles T. , Post Lori Ann
Published: March 2014

Scientific elaboration of “public will” would enhance the concept's analytical usefulness and contribute to improved understanding in various fields, including political science and public policy. Previous work has utilized the term but has jumped the crucial stage of formally defining public will as a conceptual variable. This project constructs a definitional system that breaks the concept into components and offers operationalizations and assessment targets. Analysis begins with consideration of social systems and their direct ties with other definitional components like shared recognition of the problem and of proposed means of addressing the problem. Resolve to address the situation and to sustain collective action are also essential components. The project then applies the definitional system through a brief case study of firearm control and considers various scholarly implications. The definitional system emphasizes the simultaneous existence of multiple “publics” and argues against using public will synonymously with majority public opinion.
The Early Modern Kidney—Nephrology in and about the Nineteenth Century (Part 2)
Authors: Eknoyan Garabed
Published: March 2014

Two basic science specialties that matured in the nineteenth century were instrumental in the transformation of medicine into a scientific discipline and in the process of establishing the evidentiary basis of the fundamental role of the kidney in maintaining homeostasis, whose continued exploration would lead to the emergence of nephrology in the following century. The first specialty was that of chemistry, which progressed from a descriptive to an analytical, organic, biological, and physical science that progressively eroded the animism of the “vital” forces of old and replaced it with the physicochemical forces and laws of chemical reactions that govern the “matters of life”. The second specialty was that of cell biology, which established the cell as the structural and functional unit of living organisms, be they plant or animal. Refined microscopic technologies then helped to identify the structural components of the cell, amongst which the plasma membrane emerged as the most important in regulating the separation of the intracellular machinery from its external environment and thereby maintaining the internal milieu of cells. The interaction of these two specialties (chemistry, cell biology) clarified the functions of the cell in health and disease and extended it to the study of epithelial cell transport. This transforming turn of events established the role of the renal tubules in the vital function of the kidney of maintaining body homeostasis, a function well beyond that of the passive excretory filter of wastes and excess fluids it had been considered theretofore.
Identification of a novel HLA‐C*01 allele, C*01:73, by sequence‐based typing
Authors: Zeng D.‐F. , Chang C. , Zhang X. , Kong P.‐Y.
Published: March 2014

The new allele HLA‐C*01:73 differs from C*01:02:01 by 10 nucleotide changes.
Genetic variants of 17q21 are associated with childhood‐onset asthma and related phenotypes in a northeastern Han Chinese population: a case–control study
Authors: Yu X. , Yu C. , Ren Z. , Deng Y. , Song J. , Zhang H. , Zhou H.
Published: March 2014

A genome‐wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood‐onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood‐onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12–1.65, P = 0.002] and an OR of 1.36 (95% CI 1.07–1.74, P = 0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR = 1.57, 95% CI 1.04–2.36, P = 0.032; recessive OR = 1.41, 95% CI 1.09–1.83, P = 0.009; additive OR = 1.97, 95% CI 1.24–3.14, P = 0.004; recessive OR = 1.50, 95% CI 1.13–1.98, P = 0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10‐transformed immunoglobulin E (IgE) level (IU/ml) and log10‐transformed eosinophil percentage (dominant, P = 0.04; additive, P = 0.01; recessive, P = 0.04; recessive, P = 0.03; additive, P = 0.02). Collectively, our findings suggest that orosomucoid 1‐like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood‐onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood‐onset asthma.
Development of a simple microarray for genotyping HIV‐1 drug resistance mutations in the reverse transcriptase gene in rural Tanzania
Authors: Masimba Pax , Gare Janet , Klimkait Thomas , Tanner Marcel , Felger Ingrid
Published: March 2014

Objective

Aiming at a simple, inexpensive and robust tool for HIV‐1 drug resistance genotyping during antiretroviral therapy (ART) we developed and validated a microarray‐based detection of 25 drug resistance mutations most relevant for the Tanzanian ART regimen.

Methods

A reverse transcriptase gene fragment was reverse‐transcribed and amplified by reverse transcription–polymerase chain reaction (RT–PCR). Primers for mini‐sequencing were designed based on alignments of the most prevalent local HIV‐1 variants. Tagged primers were extended by fluorochrome‐labelled dideoxynuclotide triphosphate (ddNTPs) to indicate the single‐nucleotide polymorphism (SNP) allele of the sample tested, followed by hybridisation on treated microarray slides. Images were analysed with a laser scanner and genotype calling was performed using in‐house developed software.

Results

The microarray was validated with four cloned HIV‐1 genome fragments from a Swiss HIV‐1 cohort and 102 HIV‐1 sequences amplified from the Tanzanian target population (field samples). Results were concordant with the Sanger sequencing SNP profile in 92.7% of 2550 SNP data points compared. Lack of signals in small number of SNPs was due to either failure in the extension reaction or hybridisation owing to mismatches between PCR product and extension primer.

Conclusion

Our study demonstrates the feasibility of hybridisation‐based genotyping of drug resistance mutations of HIV, even though our microarray, which was designed for population studies, achieved only correct assignment of 92% of all SNPs in the tested samples.
Taenia solium metacestode fasciclin‐like protein is reactive with sera of chronic neurocysticercosis
Authors: Bae Young‐An , Yeom Joon‐Sup , Wang Hu , Kim Seon‐Hee , Ahn Chun‐Seob , Kim Jin‐Taek , Yang Hyun‐Jong , Kong Yoon
Published: March 2014

Objectives

Neurocysticercosis (NC), an infection of the central nervous system with Taenia solium metacestodes (TsM), invokes a formidable neurological disease. A bundle of antigens is applicable for serodiagnosis of active cases, while they demonstrate fairly low reactivity against sera of chronic NC. Identification of sensitive biomarkers for chronic NC is critical for appropriate management of patients.

Methods

Proteome analysis revealed several isoforms of 65‐ and 83‐kDa TsM fasciclin‐like proteins (TsMFas) to be highly reactive with sera of chronic NC. A cDNA encoding one of the 83‐kDa TsMFas (TsMFas1) was isolated from a cDNA library. We expressed a recombinant protein (rTsMFas1) and evaluated its diagnostic potential employing sera from chronic NC (n = 80), tissue‐invasive cestodiases (n = 169) and trematodiases (n = 80) and those of normal controls (n = 50).

Results

Secretory TsMFas1 was composed of 766 amino acid polypeptide and harboured fasciclin and fasciclin‐superfamily domains. The protein was constitutively expressed in metacestode and adult stages, with preferential locality in the scolex. Bacterially expressed rTsMFas1 exhibited 78.8% sensitivity (63/80 cases) and 93% specificity (278/299 samples) in diagnosing chronic NC. Some cross‐reactivity was observed with sera of cystic echinococcosis (10/56, 17.8%) and sparganosis (4/50, 8%). Positive and negative predictive values were 75% and 95.5%, respectively.

Conclusion

TsM fasciclin‐like protein may be useful for differential diagnosis of chronic NC in clinical settings, especially where both NC and other infectious cerebral granulomatoses are prevalent.
Adjusting the HIV prevalence for non‐respondents using mortality rates in an open cohort in northwest Tanzania
Authors: Tenu Filemon , Isingo Raphael , Zaba Basia , Urassa Mark , Todd Jim
Published: March 2014

Objective

To estimate HIV prevalence in adults who have not tested for HIV using age‐specific mortality rates and to adjust the overall population HIV prevalence to include both tested and untested adults.

Methods

An open cohort study was established since 1994 with demographic surveillance system (DSS) and five serological surveys conducted. Deaths from Kisesa DSS were used to estimate mortality rates and 95% confidence intervals by HIV status for 3‐ 5‐year periods (1995–1999, 2000–2004, and 2005–2009). Assuming that mortality rates in individuals who did not test for HIV are similar to those in tested individuals, and dependent on age, sex and HIV status and HIV, prevalence was estimated.

Results

In 1995–1999, mortality rates (per 1000 person years) were 43.7 (95% CI 35.7–53.4) for HIV positive, 2.6 (95% CI 2.1–3.2) in HIV negative and 16.4 (95% CI 14.4–18.7) in untested. In 2000–2004, mortality rates were 43.3 (95% CI 36.2–51.9) in HIV positive, 3.3 (95% CI 2.8–4.0) in HIV negative and 11.9 (95% CI 10.5–13.6) in untested. In 2005–2009, mortality rates were 30.7 (95% CI 24.8–38.0) in HIV positive, 4.1 (95% CI 3.5–4.9) in HIV negative and 5.7 (95% CI 5.0–6.6) in untested residents. In the three survey periods (1995–1999, 2000–2004, 2005–2009), the adjusted period prevalences of HIV, including the untested, were 13.5%, 11.6% and 7.1%, compared with the observed prevalence in the tested of 6.0%, 6.8 and 8.0%. The estimated prevalence in the untested was 33.4%, 21.6% and 6.1% in the three survey periods.

Conclusion

The simple model was able to estimate HIV prevalence where a DSS provided mortality data for untested residents.
Rhabdomyosarcoma associated with the lead wire of a pacemaker generator implant
Authors: Thieman Mankin Kelley M. , Dunbar Mark D. , Toplon David , Ginn Pamela , Maisenbacher Herbert W. , Risselada Marije
Published: March 2014

An 11‐year‐old female spayed Labrador Retriever was presented for a draining, painful subcutaneous mass palpated over a previously implanted pacemaker generator. Infection was suspected and the mass was removed surgically. On cut surface, the mass was friable and mottled tan to brown with firm pale tan nodules, surrounding the pacemaker lead wire adjacent to the pacemaker generator. Cytologic interpretation of impression smears was consistent with a sarcoma, and suggestive of a rhabdomyosarcoma due to the presence of strap‐like cells. On histopathologic examination, a highly invasive nodular mass surrounded the pacemaker lead, composed of pleomorphic round, spindle and strap cells, and multinucleated giant cells. The population exhibited microscopic invasion into the deep portion of the fibrous capsule surrounding the pacemaker generator. There were tumor emboli within small to medium subcutaneous veins adjacent to the mass. Immunohistochemically, the neoplastic cells stained positive for α‐sarcomeric actin and vimentin, and negative for α‐smooth muscle actin, consistent with a rhabdomyosarcoma arising at the site of the pacemaker generator. To our knowledge, this is the first report of a rhabdomyosarcoma associated with the lead wire of a pacemaker generator in a dog.