bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia‐inducible factors as neuroprotective agent in Alzheimer's disease
Authors: Ashok Ben Sundra , Ajith Thekkuttuparambil Ananthanarayanan , Sivanesan Senthilkumar
Published: December 2016

Beta amyloid (Aβ)‐42 peptide and phosphorylated tau protein have been demonstrated as the pathological hallmarks of Alzheimer's disease (AD). A gradual decline of oxygen and glucose supply to the brain during aging or hypoxia was manifested as a contributing factor to hypometabolism. The brain regions susceptible to hypometabolism are the hippocampus, entorhinal cortex and cognition‐associated neocortical regions like parietal, temporal and frontal cortex. In AD patients, the brain regions with hypometabolism can trigger overexpression of amyloid precursor protein and decrease the clearance of Aβ. Aβ and hypoxia can evoke inflammation, oxidative stress and finally neuronal cell death. Among the transcription factors involved in the compensatory mechanism, hypoxia‐inducible factor‐1 alpha (HIF‐1α) has a major role in the cellular adaptation by inducing the expression of several proteins, including vascular endothelial growth factor, erythropoietin and inducible nitric oxide synthase. Therefore, maintaining the HIF‐1α level by inhibiting the prolyl 4‐hydroxylase was effective to attenuate the nerve damage during hypoxia and postpone the incidence of AD. Agents such as iron chelators, and heavy metals like cobalt and nickel were demonstrated to be effective in maintaining the HIF‐1α level in the nerve. This review article discusses the possible role of HIF‐1α as a neuroprotector in AD and the future perspectives.
Waging War for the Righteous: William Eaton on Enlightenment, Empire, and Coup d'état in the First Barbary War, 1801–1805
Authors: BOW C. B.
Published: December 2016

The Ottoman provinces of Tripoli, Algiers, Tunis, and the independent sultanate of Morocco, known as Barbary States, terrorized merchant ships with piracy of cargoes and enslavement of their sailors throughout the early modern period. Barbary privateers, known as corsairs, justified their selective targeting of ‘kafir’ or ‘infidel’ merchant ships as waging ‘sea jihad’. Agents of empire struggled to reconcile principles of ‘just war’ in the natural law tradition with the negotiated payment of Barbary tributes for unobstructed passage through the Mediterranean. Resolving this Barbary threat by way of war or tribute involved American interests after 1783. This article examines the ways in which William Eaton, as the United States Consul for Tunis, intervened between Enlightenment and imperial responses to Barbary piracy. Eaton defied Thomas Jefferson's foreign policies by engineering the first American attempt at coup d’état in a foreign government. In doing so, Eaton's strategy of military interventionism offered an alternative to perennial Enlightenment and imperial designs for war and peace in the Islamic world.
The Rhinoceros and the Chatham Railway: Taxidermy and the Production of Animal Presence in the ‘Great Indoors’
Authors: JONES KAREN
Published: December 2016

This article considers the practice of taxidermy and its relationship to the ‘golden age’ of big game hunting, the science of natural history and the dramaturgical codes of empire by looking at the collecting exploits of one man, Major Percy Powell‐Cotton (1866–1940), and his attempts to preserve the spoils of the hunt in the ‘great indoors’. As various scholars have pointed out, taxidermy offers up a vivid and striking ‘afterlife’ of the animal with a unique (and some might say unsavoury) ability to elucidate our environmental and cultural relations with other species. As such, the reanimated animals of empire, posed on the walls of the country estate or arrested in museum cases, represent valuable historical artefacts ripe for unstitching. Drawing on the work of Garry Marvin, Sam Alberti and Merle Patchett, this article stalks Powell‐Cotton's taxidermic project across various sites of capture, production and display (what I call necrogeographies) to illuminate the sinuous contours of imperial natural history and the stories of pursuit, production and performance lurking beneath the skin of the reanimated animal.
Awareness of diabetes, hypertension, and hypercholesterolemia in Malaysia
Authors: Yen Steven T. , Tan Andrew K.G. , Mustapha Feisul I.
Published: December 2016

Background

Policy interventions for cardiovascular diseases require individual awareness of ailments. Such awareness is also key to individuals making changes to their lifestyle and dietary habits. The present study investigated the association of sociodemographic, health, and lifestyle factors with the awareness and prevalence of three ailments: diabetes, hypertension, and hypercholesterolemia.

Methods

Data were obtained from the Malaysia Non‐Communicable Disease Surveillance‐1. Logistic regressions were estimated and odds ratios of exposure variables calculated.

Results

Diabetes awareness was associated with work hours, age, family history of illnesses, and ethnicity. Individuals with diminished hypertension awareness included those who were younger, without family history of illnesses, not obese, working more hours, and not adhering to a healthy diet. Low awareness of hypercholesterolemia was associated with younger age, lower education level, living in rural areas, female gender, no family history of illnesses, non‐obesity, and minority ethnic background. Prevalence generally had the same pattern of association with the exposure variables.

Conclusions

Various sociodemographic and health and lifestyle characteristics were associated with diabetes, hypertension, and hypercholesterolemia awareness in Malaysia, albeit with varying outcomes. Therefore, programs focusing on lifestyle improvements should be targeted at high‐risk subgroups, such as individuals working longer hours and young adults, who are less likely to be aware of their health risk factors.
Soviet Women Collaborators in Occupied Ukraine 1941–1945
Authors: Rudakova Daria
Published: December 2016

Despite the recent growth in scholarship on collaboration in the occupied Soviet territories during the Second World War, there appears to be a gap in the historiography concerning civilian women and their experiences under occupation. Soviet post‐war war crimes trials reveal that women made up a small but important number of local collaborators with the Nazi occupation regime in Ukraine. The crimes these women committed during the German occupation ranged from denunciation, to helping the occupation regime through administrative work, to actively being an agent provocateur and a spy. Some had little participation in the Nazi atrocities while others had first‐hand involvement in interrogations and beatings of victims. A few of the women even denounced fellow neighbors, friends and family members to the occupiers. This article argues that there was no one stereotypical female collaborator nor was there one dominant motivating factor for collaboration among the women in this study. Their age, nationality, educational and socio‐economic background varied significantly, and so did their motivations and degrees of involvement in the Nazi murder of Jews and Soviet partisans. The reasons for the women collaborators’ actions during the occupation were as individual and varied as the women themselves.
Validation of International Classification of Disease Ninth Revision codes for atopic dermatitis
Authors: Hsu D. Y. , Dalal P. , Sable K. A. , Voruganti N. , Nardone B. , West D. P. , Silverberg J. I.
Published: December 2016

Background

Evaluation of large‐scale data sets is needed to better understand the epidemiology, cost, and burden of atopic dermatitis (AD). We sought to validate the use of ICD‐9‐CM codes for identifying AD.

Methods

Patients from a large metropolitan quaternary care medical center with a diagnostic code of either 691.8 (AD) or 692.9 (eczema and contact dermatitis) were queried. Medical records were reviewed for demographics, Hanifin & Rajka (H&R) and United Kingdom Working Party (UKWP) criteria. Sensitivity, specificity, and positive predictive values (PPV) of the codes were calculated.

Results

Of 43 278 patients identified with associated ICD‐9 codes of 691.8 or 692.9, 519 and 253 with 691.8 and 692.9 were randomly selected for chart review. There was extensive overlap: 34.3% had ≥1 occurrences of 691.8 and 692.9 and 25.6% had multiple occurrences of both codes. Among patients with ≥1 occurrence of 691.8, 29.9% and 30.8% met the H&R and UKWP criteria, respectively. Similarly, among patients with ≥1 occurrence of 692.9, 33.7% and 32.2% met the H&R and UKWP criteria. Increased PPV was associated with concomitant diagnoses of asthma, hay fever, and food allergy and increased disease severity.

Conclusions

In the outpatient setting, the ICD‐9‐CM codes 691.8 and 692.9 alone have poor PPV. Incorporation of diagnoses of asthma, hay fever, and food allergy improves PPV and specificity. In the inpatient setting, a primary discharge diagnosis of 691.8 had excellent PPV. Although ICD‐10 has been adopted in Europe and more recently in the USA, the same systematic errors would likely occur unless providers standardize their coding.
Cholesterol metabolism: a potential therapeutic target in Mycobacteria
Authors: Abuhammad Areej
Published: December 2016

Tuberculosis (TB), although a curable disease, is still one of the most difficult infections to treat. Mycobacterium tuberculosis infects 10 million people worldwide and kills 1.5 million people each year. Reactivation of a latent infection is the major cause of TB. Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl‐CoA, a precursor that is incorporated into lipid virulence factors. The M. tuberculosis genome contains a large regulon of cholesterol catabolic genes suggesting that the microorganism can utilize host sterol for infection and persistence. The protein products of these genes present ideal targets for rational drug discovery programmes. This review summarizes the development of enzyme inhibitors targeting the cholesterol pathway in M. tuberculosis. This knowledge is essential for the discovery of novel agents to treat M. tuberculosis infection.

Linked Articles

This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro‐organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc
Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung adenocarcinoma
Authors: Kusumoto Hidenori , Shintani Yasushi , Kanzaki Ryu , Kawamura Tomohiro , Funaki Soichiro , Minami Masato , Nagatomo Izumi , Morii Eiichi , Okumura Meinoshin
Published: December 2016

Epithelial–mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL‐knockdown (KD) or PODXL‐overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL‐KD cells were epithelial in shape, whereas PODXL‐OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL‐KD cells and downregulated in PODXL‐OE cells, whereas mesenchymal markers were downregulated in the former and upregulated in the latter. A highly selective inhibitor of phosphatidylinositol 3‐kinase‐Akt signaling attenuated EMT of PODXL‐OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3‐kinase pathway. In lung adenocarcinoma clinical specimens, PODXL expression was detected in minimally invasive and invasive adenocarcinoma, but not in non‐invasive adenocarcinoma. Disease free survival and cancer‐specific survival were significantly worse for patients whose tumors overexpressed PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression.
Chronic airway inflammation provides a unique environment for B cell activation and antibody production
Authors: Feldman S. , Kasjanski R. , Poposki J. , Hernandez D. , Chen J. N. , Norton J. E. , Suh L. , Carter R. G. , Stevens W. W. , Peters A. T. , Kern R. C. , Conley D. B. , Tan B. K. , Shintani‐Smith S. , Welch K. C. , Grammer L. C. , Harris K. E. , Kato A. , Schleimer R. P. , Hulse K. E.
Published: December 2016

Background

B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways.

Objective

We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation.

Methods

We analysed B cells from NP or tonsil, or after ILC2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody‐secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT‐PCR.

Results

NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein–Barr virus‐induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with tonsil. Antibody production and the frequency of antibody‐secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro.

Conclusions and Clinical Relevance

Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC‐mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell‐targeted therapies may provide new treatment options for CRSwNP.
Is the reproducibility of shear wave elastography of thyroid nodules high enough for clinical use? A methodological study
Authors: Swan Kristine Zøylner , Nielsen Viveque Egsgaard , Bibby Bo Martin , Bonnema Steen Joop
Published: December 2016

Objective

To systematically assess the reproducibility of thyroid ultrasonographic shear wave elastography (SWE).

Context

SWE has been suggested as a potential tool for thyroid nodule evaluation, but assessment of its reproducibility has been insufficiently addressed.

Design

SWE examinations were performed prospectively by two investigators.

Patients

Seventy‐two patients (male/female: 19/53; mean age: 53 ± 14 years; malignant/benign 17/55) undergoing thyroid surgery were enrolled in the study.

Measurements

Repeated and blinded measurements of elasticity index (EI) in predefined regions of interest (ROI) were collected. The inter‐ and intrarater agreement, along with the day‐to‐day agreement, was evaluated in terms of the 95% limits of agreement (LOA). Results are presented as a ratio, by which 1·0 indicates perfect agreement.

Results

The interrater, intrarater and day‐to‐day LOA showed ratios between repeated measurements of 1·7–3·6, 1·8–3·7 and 2·2–2·9, respectively. These values reflect a low to moderate degree of agreement for all EI outcomes. The interrater LOA was higher for malignant nodules compared with benign nodules for six of seven EI outcomes (P < 0·001–0·03). The proportion of agreement calculated from the optimum cutoff point for differentiating malignant from benign nodules was 63–88% for the investigated EI outcomes.

Conclusions

In this methodological study, EI measured by thyroid SWE seems suboptimal for clinical use, due to a low inter‐ and intrarater agreement. That EI varies from day to day furthermore jeopardizes the validity of the method. Although the proportion of agreement was acceptable for some EI parameters, it is questionable whether EI assessments can reliably differentiate malignant from benign nodules in the individual patient.
Effects of pupil dilation on MAIA microperimetry
Authors: Han Ruofan C , Jolly Jasleen K , Xue Kanmin , MacLaren Robert E
Published: December 2016

Background

Macular Integrity Assessment microperimetry assesses macular sensitivity to projected point light sources and maps eye movements to assess fixation stability. Although microperimetry is gaining prominence as an assessment tool in clinical and research settings, there is no consensus on whether it should be performed before or after pupil dilation. No studies to date have examined the effect of pupil dilation on results. The aim of this project was to elucidate the effect of pupil dilation on microperimetry outcomes.

Design

Prospective audit.

Participants

Twenty healthy patients from postoperative cataract clinic and 10 patients with choroideremia to simulate a disease with peripheral visual field loss.

Methods

Subjects underwent 10–2 68‐point field testing using the Macular Integrity Assessment microperimeter on each eye. Subjects then underwent randomized dilation of one eye, and the test was repeated in both eyes.

Main Outcome Measures

We compared changes in threshold sensitivity and fixation stability pre‐pupil and post‐pupil dilation. The undilated eye was analysed for any learning or fatigue effect caused by test repetition.

Results

Dilation produced no significant effect on threshold sensitivity (dilation effect: −0.29 decibels, P = 0.23) or fixation stability in healthy controls or in choroideremia patients (dilation effect: +0.08log bivariate contour ellipse area, P = 0.14). There was also no significant learning effect seen in the undilated eye, with no improvement in threshold sensitivity (order of eye testing: +0.03log bivariate contour ellipse area, P = 0.71).

Conclusions

In the clinical setting, patients may be tested for 10 degree microperimetry with or without pupil dilation, as both scenarios yield consistent and interchangeable results.
The Generalized Quantum Episodic Memory Model
Authors: Trueblood Jennifer S. , Hemmer Pernille
Published: December 2016

Recent evidence suggests that experienced events are often mapped to too many episodic states, including those that are logically or experimentally incompatible with one another. For example, episodic over‐distribution patterns show that the probability of accepting an item under different mutually exclusive conditions violates the disjunction rule. A related example, called subadditivity, occurs when the probability of accepting an item under mutually exclusive and exhaustive instruction conditions sums to a number >1. Both the over‐distribution effect and subadditivity have been widely observed in item and source‐memory paradigms. These phenomena are difficult to explain using standard memory frameworks, such as signal‐detection theory. A dual‐trace model called the over‐distribution (OD) model (Brainerd & Reyna, 2008) can explain the episodic over‐distribution effect, but not subadditivity. Our goal is to develop a model that can explain both effects. In this paper, we propose the Generalized Quantum Episodic Memory (GQEM) model, which extends the Quantum Episodic Memory (QEM) model developed by Brainerd, Wang, and Reyna (2013). We test GQEM by comparing it to the OD model using data from a novel item‐memory experiment and a previously published source‐memory experiment (Kellen, Singmann, & Klauer, 2014) examining the over‐distribution effect. Using the best‐fit parameters from the over‐distribution experiments, we conclude by showing that the GQEM model can also account for subadditivity. Overall these results add to a growing body of evidence suggesting that quantum probability theory is a valuable tool in modeling recognition memory.
Subcutaneous dirofilariasis: a masquerade of a palisaded granulomatous dermatitis
Authors: Muller Kristen E. , Schwartzman Joseph D. , Seidel Gregory D.
Published: December 2016

Dirofilaria species are roundworms responsible for “heartworm” in canines. On occasion, humans are an accidental host, resulting in pulmonary (Dirofilaria immitis) or extrapulmonary (Dirofilaria repens) manifestations. Of the extrapulmonary sites of involvement, subcutaneous involvement is particularly common. We report a case of a 49‐year‐old female who presented with an erythematous nodule on her shin, which closely resembled necrobiosis lipoidica on histopathologic examination. On closer examination, there were foci of necrosis that harbored segments of the nematode, diagnostic of dirofiliarisis. We present this case to highlight the histopathologic similarities and differences between palisaded necrobiotic conditions and this potentially underrecognized entity.
Primary cutaneous histiocytoid carcinoma with distant metastasis
Authors: Philips Rebecca , Langston Leila , Hwang Helena , Vandergriff Travis , Trynosky Tanya , Berlingeri‐Ramos Alma C.
Published: December 2016

Distinguishing primary cutaneous adnexal carcinoma from metastatic carcinoma of unknown primary can be a diagnostic challenge due to the frequent overlap of histologic and immunohistochemical features. A 58‐year‐old man presented with a tender, indurated plaque on axillary skin. Biopsy revealed infiltrating atypical cells throughout the dermis, without connection to the epidermis. Tumor cells had a histiocytoid appearance and displayed mild pleomorphism. The tumor was discohesive and had areas with a single file pattern. Signet ring cells were also present. Cells were reactive with CK7, CK5/6, p63, GATA3, GCDFP‐15 and Her 2‐neu. Additional studies were negative, including TTF‐1, CDX2, E‐cadherin, mammaglobin, estrogen receptor and progesterone receptor. Thorough clinical and radiologic evaluation failed to identify an occult primary extracutaneous malignancy; however, regional lymphadenopathy, widespread osteoblastic lesions and multiple subcentimeter liver hypodensities were noted. Considering the clinical and histopathologic features, the diagnosis of primary cutaneous histiocytoid carcinoma with distant metastasis was favored.
Eruptive xanthogranuloma in a healthy adult male
Authors: Ederle Ashley , Kim Kevin H. , Gardner Jerad M.
Published: December 2016

Xanthogranuloma is a benign, non‐Langerhans cell histiocytosis primarily diagnosed in infants and children, although a subset occurs in adults. Multifocal eruptive presentation of xanthogranuloma is very rare with only 4 previous cases reported in the literature to our knowledge. We describe a case of eruptive xanthogranuloma in a 49‐year‐old man who presented with sudden onset of numerous asymptomatic, red‐yellow to orange papules on the face, scalp, axilla, flank and scrotum. Histologic features were consistent with xanthogranuloma with diffuse mixed infiltrate of foamy histiocytes, Touton giant cells and lymphocytes. Other than temporarily elevated non‐fasting triglycerides, lab values have been unremarkable including serum plasma electrophoresis; however, the patient will continue to be monitored for ocular and other extracutaneous involvement and hematologic malignancies.
Income Inequality and Wealth Concentration in the Recent Crisis
Authors: Goda Thomas , Onaran Özlem , Stockhammer Engelbert
Published: December 2016

This article shows that the increase of income inequality and global wealth concentration was an important driver for the financial and Eurozone crisis. The high levels of income inequality resulted in balance of payment imbalances and growing debt levels. Rising wealth concentration contributed to the crisis because the increasing asset demand from the rich played a key role in the growth of the structured credit market and enabled poor and middle‐income households to accumulate increasing amounts of debt. This analysis thereby puts both income and wealth inequality at the epicentre of the recent crisis, and as crucial for social scientists analysing the causes of the crisis. The authors’ findings suggest that the policy response to the crisis should not be limited to financial regulation but must involve policies to address inequality by increasing the bargaining power of labour as well as redistributive tax policies.
Biogeographic patterns in major marine realms: function not taxonomy unites fish assemblages in reef, seagrass and mangrove systems
Authors: Hemingson Christopher R. , Bellwood David R.
Published: December 2016

We examine the effects of different biogeographic histories on assemblage composition in three major marine habitats in two biogeographically distinct marine realms. Specifically, we quantify the taxonomic and functional composition of fish assemblages that characterise coral reef, seagrass and mangrove habitats, to explore the potential effects of biogeographic history and environment on assemblage composition. The three habitats were surveyed in the Caribbean and on the Great Barrier Reef using a standardised underwater visual census method to record fish size and abundance data. The taxonomic composition of assemblages followed biogeographic expectations, with realm‐specific family‐level compositions. In marked contrast, the functional composition of assemblages separated habitats regardless of their biogeographic locations. In essence, taxonomy characterises biogeographic realms while functional groups characterise habitats. The Caribbean and Indo‐West Pacific have been separated for approximately 15 million years. The two realms have different taxonomic structures which reflect this extended separation, however, the three dominant shallow‐water marine habitats all retain distinct functional characteristics: seagrass fishes are functionally similar regardless of their taxonomic composition or biogeographic location. Likewise, for coral reefs and mangroves. The results emphasise the advantages and limitations of taxonomic vs. functional metrics in evaluating patterns. Taxonomy primarily reflects biogeographic and evolutionary history while functional characteristics may better reflect ecological constraints.
Activation of galanin and cholecystokinin receptors in the lumbosacral spinal cord is required for ejaculation in male rats
Authors: Kozyrev Natalie , Coolen Lique M.
Published: December 2016

The spinal ejaculation generator is comprised of lumbar spinothalamic (LSt) cells and their axonal projections to autonomic and motor neurons in the lumbosacral spinal cord. LSt cells regulate ejaculatory reflexes by release of neuropeptides that are co‐expressed in their axons, as previously demonstrated for gastrin‐releasing peptide and enkephalin. Here, the role of two other neuropeptides co‐expressed in LSt cells for ejaculatory reflexes is demonstrated: galanin and cholecystokinin (CCK). Adult male rats were anesthetized, spinalized, and received intrathecal infusions of galanin receptor antagonist Galantide (1 or 10 nmol) or CCK receptor antagonist proglumide (71 or 714 nmol). The dorsal penile nerve (DPN) was electrically stimulated to trigger ejaculatory reflexes and seminal vesicle pressure (SVP) and rhythmic contractions of the bulbocavernosus muscle (BCM) were analyzed as parameters of emission and expulsion respectively. Treatment with galanin or CCK antagonists significantly reduced SVP increases and BCM bursting, demonstrating that galanin and CCK are required for ejaculation. Next, anesthetized, spinalized males received intrathecal infusions of galanin (0.15 or 0.3 nmol) or CCK(26–33) (4.35 nmol) and effects on subthreshold DPN stimulations were determined. Intrathecal infusions of galanin or CCK facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals, but did not trigger ejaculatory reflexes in the absence of DPN stimulation. Together, these results demonstrate that galanin and CCK both act in the spinal ejaculation generator to regulate ejaculation. However, effects of galanin and CCK were dependent on DPN stimulation, suggesting that these neuropeptides may act in concert with other LSt co‐expressed neuropeptides.
Is the early course of multiple sclerosis the same in adults and children?
Authors: Brownlee W. J. , Ciccarelli O.
Published: December 2016

Click here to view the accompanying paper in this issue.
Firm Opacity Lies in the Eye of the Beholder
Authors: Dahiya Sandeep , Iannotta Giuliano , Navone Marco
Published: December 2016

We classify and test empirical measures of firm opacity and document theoretical and empirical inconsistencies across these proxies by testing the relative opacity of banks versus non‐banks. We evaluate the effectiveness of these proxies by observing the effect of two cleanly identified shocks to firm‐specific information: credit rating initiation and inclusion in the S&P 500 index. Using a difference‐in‐difference approach, we compare firms that are newly rated and firms that are included in the S&P 500 index with a propensity matched sample of “unchanged” firms. We find that only the number of analysts and Amihud's illiquidity ratio provide consistent patterns across different estimation specifications and different econometric settings. These two proxies show that banks are more opaque than non‐banks. Based on our tests, we recommend that these proxies be used as the primary measures of firm opacity.
Occipital Condyle Syndrome: A Red Flag for Malignancy. Comprehensive Literature Review and New Case Report
Authors: Rodríguez‐Pardo Jorge , Lara‐Lara Manuel , Sanz‐Cuesta Borja E. , Fuentes Blanca , Díez‐Tejedor Exuperio
Published: December 2016

Objective

To perform a literature review of the epidemiology, clinical presentation, diagnostic evaluation, and clinical course of occipital condyle syndrome, including a new case report.

Background

Occipital condyle syndrome (OCS) is a rare clinical syndrome, consisting of unilateral occipital headache accompanied by ipsilateral hypoglossal palsy. This headache typically radiates to the temporal region, and is triggered by contralateral head rotation. It is usually associated with skull base metastasis, often unrevealed in basic neuroimaging studies. OCS might be the first manifestation of malignancy, and its unfamiliarity can lead to a delay in the diagnosis.

Methods

We performed a systematic literature review using PubMed and Embase for OCS, along with a new case report.

Results

A total of 35 cases (mean age 59 years, range 25‐77), 24 (70%) men, presented typical unilateral headache followed by ipsilateral hypoglossal palsy from 0 to 150 days after headache presentation. In 16 patients (46%), initial neuroimaging studies were normal. OCS was due to skull base metastasis in 32 cases (91%). In 18 patients (51%), OCS was the first symptom of disease.

Conclusions

OCS represents a warning sign and requires an exhaustive search for underlying neoplasm. An appropriate clinical evaluation can lead to an earlier diagnosis in patients with consistent headache.
Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours
Authors: Yuan Chang‐Tsu , Huang Wen‐Chih , Lee Cheng‐Han , Lin Ming‐Chieh , Lee Chen‐Hui , Kao Yu‐Chien , Huang Hsuan‐Ying , Kuo Kuan‐Ting , Lee Jen‐Chieh
Published: December 2016

Aims

MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours.

Methods and results

Sixty‐eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 Müllerian adenosarcomas (including three tentatively diagnosed as ‘variant adenosarcomas’), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in‐situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three ‘variant adenosarcomas’ harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1–SUZ12 or JAZF1–PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild‐type. The three MED12‐mutated ‘variant adenosarcomas’ showed distinctive morphological features, including ‘fibromyomatous’ cytomorphology, a close association with adenomyosis, clustered thick‐walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes‐like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course.

Conclusions

These MED12‐mutated adenosarcoma‐like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.
Opt‐out screening strategy for HIV infection among patients attending emergency departments: systematic review and meta‐analysis
Authors: Henriquez‐Camacho C , Villafuerte‐Gutierrez P , Pérez‐Molina JA , Losa J , Gotuzzo E , Cheyne N
Published: December 2016

Objectives

International health agencies have promoted nontargeted universal (opt‐out) HIV screening tests in different settings, including emergency departments (EDs). We performed a systematic review and meta‐analysis to assess the testing uptake of strategies (opt‐in targeted, opt‐in nontargeted and opt‐out) to detect new cases of HIV infection in EDs.

Methods

We searched the Pubmed and Embase databases, from 1984 to April 2015, for opt‐in and opt‐out HIV diagnostic strategies used in EDs. Randomized controlled or quasi experimental studies were included. We assessed the percentage of positive individuals tested for HIV infection in each programme (opt‐in and opt‐out strategies). The mean percentage was estimated by combining studies in a random‐effect meta‐analysis. The percentages of individuals tested in the programmes were compared in a random‐effect meta‐regression model. Data were analysed using stata version 12. Quality assessments were performed using the Newcastle−Ottawa Scale.

Results

Of the 90 papers identified, 28 were eligible for inclusion. Eight trials used opt‐out, 18 trials used opt‐in, and two trials used both to detect new cases of HIV infection. The test was accepted and taken by 75 155 of 172 237 patients (44%) in the opt‐out strategy, and 73 581 of 382 992 patients (19%) in the opt‐in strategy. The prevalence of HIV infection detected by the opt‐out strategy was 0.40% (373 cases), that detected by the opt‐in nontargeted strategy was 0.52% (419 cases), and that detected by the opt‐in targeted strategy was 1.06% (52 cases).

Conclusions

In this meta‐analysis, the testing uptake of the opt‐out strategy was not different from that of the opt‐in strategy to detect new cases of HIV infection in EDs.
An oral formulation of efavirenz‐loaded lactoferrin nanoparticles with improved biodistribution and pharmacokinetic profile
Authors: Kumar P , Lakshmi YS , Kondapi AK
Published: December 2016

Objectives

Efavirenz (EFV), a non‐nucleoside reverse transcriptase inhibitor, is a drug that is frequently included in highly active antiretroviral therapy for treatment of HIV infection. Decreased bioavailability and increased toxicity limit its use. We report a formulation of efavirenz‐loaded lactoferrin nanoparticles (lacto‐EFV‐nano) for oral delivery which exhibited significantly improved pharmacological properties coupled with reduced toxicity compared with its free form.

Methods

Lacto‐EFV‐nano was prepared using the Sol‐oil protocol and characterized using various sources of characterization. In vitro and in vivo studies were performed to test the stability, safety, efficacy, biodistribution and pharmacokinetics of lacto‐EFV‐nano.

Results

The nanoparticles prepared for the present study had an average size of 45−60 nm as revealed by field emission scanning electron microscope measurements. Further, dynamic light scattering data showed a hydrodynamic radius of 103 ± 5.3 nm, a zeta potential of −23 ± 1.2 mV and a polydispersity index of < 0.341. Lacto‐EFV‐nano was found to be stable as assessed using differential scanning calorimetry and Fourier‐transform infrared spectroscopy. Cell viability studies showed that lacto‐EFV‐nano was at least 2‐fold less toxic to peripheral blood mononuclear cells, Jurkat T cell and B16‐F10 cell lines than free EFV. Furthermore, lacto‐EFV‐nano [50% inhibitory concentration (IC50) < 1.1 nM] showed > 2‐fold enhanced anti‐HIV‐1 activity compared with free EFV (IC50 = 2.56 nM). Lacto‐EFV‐nano exhibited improved oral bioavailability and an improved in vivo pharmacokinetic profile, with a > 3−4‐fold increase in the area under the plasma concentration−time curve (AUC), a 6−7‐fold increase in the area under the first moment curve (AUMC), a > 30% increase in the peak plasma concentration of the drug after oral administration (Cmax) and a 2‐fold increase in the time to reach Cmax (Tmax) and the time required for the concentration of the drug to reach half of its original value (t1/2). Furthermore, lacto‐EFV‐nano did not show any organ‐related toxicity. A significant decrease in the concentrations of various parameters, elevated concentrations of which are markers of reduced safety, were also observed in rats treated with lacto‐EFV‐nano.

Conclusions

Compared with free EFV, lacto‐EFV‐nano is a promising oral nanoformulation with enhanced bioavailability and efficacy of EFV and improved safety.
Qualitative study of peer workers within the ‘Partners in Recovery’ programme in regional Australia
Authors: Hurley John , Cashin Andrew , Mills Jem , Hutchinson Marie , Kozlowski Desiree , Graham Iain
Published: December 2016

In Australia and internationally, Peer Workers are increasingly being incorporated into the mental health workforce. Underpinning this trend is the conviction that the inclusion of workers with lived experience in overcoming mental health challenges is central to transforming service delivery. Given there are few identified Australian studies into the experiences of Peer Workers, this paper reports findings from qualitative interviews conducted in a Partners In Recovery programme in one regional area in Australia. The interviews formed part of a larger mixed‐method study evaluating Peer Worker roles in the programme. Thematic analysis of interview transcripts with Peer Workers and other staff employed in the programme (n = 22) was undertaken. Central to the five themes that emerged was the concept of lived experience expertise in overcoming mental health challenges. The themes were: (i) role variance, (ii) the challenges and opportunities for Peer Worker, (iii) the processes Peer Workers employed as they attempted to shape an identify and language, (iv) the inconsistencies and challenges of employing lived experience as a defining feature of the peer worker role, and (v) the nature of trust arising from lived experience relationships. From this study, it is evident that the Peer Worker role remains underdeveloped. The difficulties experienced by Peer Workers in establishing a homogenous identity and role is not unique. The process and lack of clarity around role identity revealed from the narratives, parallels the experiences of Mental Health Nursing.
Observation of ceramic cracking during quenching
Authors: Shao Yingfeng , Song Fan , Liu Boyang , Li Wei , Li Long , Jiang Chiping
Published: December 2016

It is difficult to observe the thermal shock cracking in real time, so the measurement of the crack after thermal shock is considered as an alternative method. This paper proposes a new experimental method which can exhibit the thermal shock cracking in real time by water quenching of translucent ceramic and high‐speed imaging. The crack propagation is captured, and the crack growth rate is calculated. The results confirm the previous theoretical predictions of crack propagation under thermal shock. This paper expands the research on understanding the failure mechanisms of ceramic materials in thermal shock.
Goals of care: a concept clarification
Authors: Stanek Susan
Published: December 2016

Aim

To report an analysis and clarification of the concept of goals of care.

Background

Goals of care have been used by healthcare providers since 1978, but no operationalized, consensual definition exists.

Design

Norris's method of concept clarification was used to create an operational definition, conceptual model and testable hypotheses of goals of care from the healthcare provider's perspective.

Data sources

Data came from current research reports, interviews with experts and web sites of professional organizations. Research reports were published between 2003–2013.

Methods

Antecedents, definitions and consequences were systematized and organized into coherent and more abstract groups to define goals of care. A conceptual model and testable hypotheses were created from this process.

Results

Goals of care are desired health expectations that are formulated through the thoughtful interaction between a human being seeking medical care and the healthcare team in the healthcare system and are appropriate, agreed on, documented and communicated.

Conclusions

Development of clear goals of care can increase patient satisfaction and quality of care while decreasing costs, hospital length of stay and hospital readmission. Goals of care are dynamic and should be reassessed regularly. How and when goals of care transition from implicit to explicit should be explored further, and what prompts this transition. Nurses, physicians and healthcare providers need education on how to best fill their roles in the development of goals of care.
“Falls prevention among older people and care providers: protocol for an integrative review”
Authors: de la Cuesta‐Benjumea Carmen , Henriques Maria Adriana , Abad‐Corpa Eva , Roe Brenda , Orts‐Cortés María Isabel , Lidón‐Cerezuela Beatriz , Avendaño‐Céspedes Almudena , Oliver‐Carbonell José Luís , Sánchez‐Ardila Carmen
Published: December 2016

Aim

To review the evidence about the role of care providers in fall prevention in older adults aged ≥ 65 years, this includes their views, strategies, and approaches on falls prevention and effectiveness of nursing interventions.

Background

Some fall prevention programmes are successfully implemented and led by nurses and it is acknowledged the vital role they play in developing plans for fall prevention. Nevertheless, there has not been a systematic review of the literature that describes this role and care providers' views on fall's prevention initiatives.

Design

A convergent synthesis of qualitative, quantitative, and mixed methods studies. The eligibility criteria will be based on participants, interventions/exposure, comparisons, and outcomes for quantitative studies and on population, the phenomena of interest and the context, for qualitative studies. To extract data and assess study qualities members of the research team will work in pairs according to their expertise. The review will follow the guidelines for integrative reviews and the proposed methods will adhere to the PRISMA statement checklist complemented by the ENTREQ framework. As qualitative synthesis are emergent, all procedures and changes in procedure will be documented.

Discussion

The review has a constructivist drive as studies that combine methods ought to be paradigmatic driven. Review questions are broad to allow issues emerge and have purposefully left the design flexible to allow for adjustments as the review progresses. The review seeks to highlight the roles that care providers play in fall prevention and their views on fall's prevention initiatives.
The geographical diversification of Furnariides: the role of forest versus open habitats in driving species richness gradients
Authors: Pinto‐Ledezma Jesús N. , Simon Lorena Mendes , Diniz‐Filho José Alexandre F. , Villalobos Fabricio
Published: December 2016

Aim

Explaining species richness gradients in space and time requires understanding the evolutionary processes that ultimately alter the number of species. Here we examine species richness differences between primary habitats (forest versus open) for Furnariides birds, a Neotropical endemic bird clade, to test three major historical hypotheses – diversification rate, out of the tropics and tropical niche conservatism – and assess the role of evolutionary processes in driving the Furnariides species richness gradient.

Location

Neotropics.

Methods

We used phylogenetic and spatial data to tests the historical hypotheses. First, we used GeoSSEand Bayesian Analysis of Macroevolutionary Mixture models to evaluate differential diversification and dispersal rates between habitats. Second, we quantify the root distance of each species and examined the phylogenetic structure of the richness gradient and the correlation between total species richness and the richness of early‐diverged and recently originated species.

Results

Furnariides species richness is higher in forest than in open habitats. However, we found higher speciation, extinction, and dispersal rates in open when compared to forest habitats, resulting in a higher diversification rate in open habitats and higher dispersal rate out of open habitats than into them. The phylogenetic structure of the richness gradient showed strong spatial pattern, with early diverged species richness peaking in forest habitats and driving the overall Furnariides gradient.

Main conclusions

The Furnariides species richness gradient results from the joint effect of differential rates of macroevolutionary processes. Our findings highlight dispersal and extinction as dominant forces driving richness differences between habitats, through the addition and extirpation of species from open to forest habitats. Differences in species richness between habitats support niche conservatism of forest habitat preferences of Furnariides species. We suggest that open habitats are effective evolutionary arenas and a key to the maintenance of bird diversity in forest habitats over evolutionary time.