bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol‐binding globulin concentrations
Authors: Chung T.T. , Gunganah K. , Monson J.P. , Drake W.M.
Published: November 2015

Background

Patients taking hydrocortisone (HC) replacement for primary or secondary adrenal failure require individual adjustment of their dose. In addition to modifying the administered doses of HC for each patient, physicians are increasingly interested in variations in the bioavailability of glucocorticoid replacement. One potential determinant of the bioavailability of replaced HC is a variation in serum cortisol‐binding globulin (CBG) concentration, which may, in turn, affect interpretation of cortisol profiles and individual dose selection for patients on hydrocortisone replacement therapy.

Aim

To investigate the hypothesis that there is a circadian variation in CBG levels.

Methods and results

A total of 34 male patients divided into 3 groups (10 patients with non‐somatotroph structural pituitary disease on HC replacement, 11 patients with treated acromegaly on HC replacement and 13 patients with treated acromegaly not on HC replacement) and 10 healthy volunteers were included. Cortisol and CBG levels were measured at 6 time points (0800, 1100, 1300, 1500, 1700 and 1900). No significant circadian variation in CBG concentration was found in any of the 4 groups.

Conclusion

Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol‐binding globulin concentration. Changes in serum cortisol levels may thus be explained by other factors including 11 β‐hydroxysteroid dehydrogenase type 1 activity or circadian changes in the binding properties of CBG.
Additional transbronchial needle aspiration through a guide sheath for peripheral pulmonary lesions that cannot be detected by radial EBUS
Authors: Hayama Manabu , Izumo Takehiro , Chavez Christine , Matsumoto Yuji , Tsuchida Takaaki , Sasada Shinji
Published: November 2015

Background

Endobronchial ultrasound with a guide sheath (EBUS‐GS) has resulted to better diagnostic outcome for peripheral pulmonary lesions (PPLs), although the yield is not satisfactory for lesions that cannot be located by EBUS. We aimed to evaluate whether the addition of a new technique, transbronchial needle aspiration through a guide sheath (GS‐TBNA), can increase the yield for these cases.

Methods

This was a retrospective review of cases that were not located by EBUS during EBUS‐GS for PPL diagnosis. From September 2012 to August 2014, 67 PPLs had ‘invisible’ EBUS‐GS location prior to transbronchial sampling. The patients were divided into two groups according to the use of additional GS‐TBNA: GS‐TBNA group (n=22) and non‐GS‐TBNA group (n=45). Diagnostic yields were compared and multivariate analysis was performed to determine the factors associated with increased diagnostic yield.

Results

The diagnostic yield was significantly higher in the GS‐TBNA group than in the non‐GS‐TBNA group (54.5% vs 17.8%, P<0.01). The complication rate was not significantly different between the GS‐TBNA group and the non‐GS‐TBNA group (0% vs 4.4%, P=1.0). Multivariate analysis showed that only performing GS‐TBNA was significantly associated with increased diagnostic yield (odds ratio 3.99, P=0.03).

Conclusion

GS‐TBNA is a safe technique for PPL diagnosis and may be useful when the EBUS probe cannot reach the lesion.
Clinical characteristics and outcomes of patients with community‐acquired, health‐care‐associated and hospital‐acquired empyema
Authors: Koma Yasuko , Inoue Sayaka , Oda Nao , Yokota Naoya , Tamai Koji , Matsumoto Yusuke , Okada Nobuhiko , Otsuka Akiko , Nakashima Nariyasu , Masuya Daiki , Matsuoka Hirofumi , Yoshimatsu Harukazu , Suzuki Yujiro
Published: November 2015

Background and Aims

Patients with pneumonia, a common cause of empyema, are stratified based on their risk factors, and the treatment of empyema might benefit from this risk stratification.

Methods

The etiology, bacteriologic profile and outcome of patients diagnosed with empyema in Shinko Hospital between May 2005 and October 2013 were retrospectively studied. The patients were stratified according to whether they had community‐acquired empyema (CAE), health‐care‐associated empyema (HCAE) or hospital‐acquired empyema (HAE).

Results

The study included 81 patients, 25 CAE, 40 HCAE and 16 HAE. The comorbidity rate was highest among HAE patients (100%), followed by 95% of HCAE and 72% of CAE patients (P = 0.005). The rates of cancer and central nervous system (CNS) disease were higher in patients with HCAE and HAE than in patients with CAE (P = 0.030, P = 0.018, respectively). Pleural fluid cultures were positive in 58/81 patients. Streptococcus species were the most common organisms cultured from CAE (12/15) and HCAE patients (17/30), but not from HAE patients (3/13). Anaerobic organisms were cultured from 3 CAE, 5 HCAE and 3 HAE patients. Methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa were only cultured from HCAE and HAE patients. The mortality rates were higher in HCAE (18%) and HAE (50%) than in CAE (4%) patients (log‐rank test: P = 0.0012).

Conclusions

Half of patients with empyema were HCAE patients, who had comorbidities, bacteriological profile and outcome different from CAE patients. The patient with HCAE should be differentiated from CAE patient, and the stratification of patients based on risk factors may be useful for treatment strategy.
Efficacy of three therapy approaches in preschool children with cerebral palsy: a randomized controlled trial
Authors: Kruijsen‐Terpstra Anne J A , Ketelaar Marjolijn , Verschuren Olaf , Gorter Jan Willem , Vos Rimke C , Verheijden Johannes , Jongmans Marian J , Visser‐Meily Anne
Published: November 2015

Aim

To examine the efficacy of child‐focused, context‐focused, and regular care approaches, delivered in a rehabilitation setting by physical or occupational therapists to preschool children with cerebral palsy (CP), in optimizing the child's self‐care and mobility capabilities.

Method

A multicentre randomized controlled trial clustered at therapist level was conducted in 13 rehabilitation centres. It included 68 children with CP (38 males, 30 females; mean age 3y, SD 6mo, range 1y 11mo–4y), classified as Gross Motor Function Classification System levels I to IV, who were already receiving therapy. Children received a child‐focused, context‐focused, or regular care approach during a 6‐month period. Self‐care and mobility capabilities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory.

Results

The child‐focused, context‐focused, and regular care approaches all resulted in significant but similar improvements in self‐care (regular: reference; child‐focused: β=−0.11, 95% confidence interval [CI] −0.68 to 0.46; context‐focused: β=0.13, CI −0.38 to 0.64) and mobility (regular: reference; child‐focused: β=−0.09, CI=−0.93 to 0.75; and context‐focused: β=0.14, CI −0.65 to 0.94) capabilities.

Interpretation

The results suggest that the three therapy approaches were equally efficacious for preschool children with CP. Depending on a child's individual situation each approach can be selected.
Therapy for young children with cerebral palsy: what, when, where, and how?
Authors: Harvey Adrienne
Published: November 2015

This commentary is on the original article by Kruijsen‐Terpstra et al. on pages 758–766 of this issue.
Efficacy and safety of live varicella zoster vaccine in diabetes: a randomized, double‐blind, placebo‐controlled trial
Authors: Hata A. , Inoue F. , Hamamoto Y. , Yamasaki M. , Fujikawa J. , Kawahara H. , Kawasaki Y. , Honjo S. , Koshiyama H. , Moriishi E. , Mori Y. , Ohkubo T.
Published: November 2015

Aims

To elucidate varicella zoster virus (VZV)‐specific cell‐mediated immunity and humoral immunogenicity against live attenuated Oka varicella zoster vaccine concurrently vaccinated with 23‐valent pneumococcal polysaccharide vaccine (PPSV23) in elderly people with diabetes mellitus.

Methods

This double‐blind randomized controlled single‐centre study of 60–70‐year‐old people with diabetes compared immunity and safety profiles 3 months after one dose of varicella zoster vaccine or placebo. PPSV23 was immunized simultaneously. Primary analysis evaluated cell‐mediated immunity using the VZV skin test. Secondary analyses were a VZV interferon–γ enzyme‐linked immunospot (ELISPOT) assay and immunoadherence haemagglutination test. Adverse experiences were recorded using diary questionnaires.

Results

By intent‐to‐treat analysis, 27 participants with diabetes who had been administered the vaccine were compared with 27 participants who were given a placebo. Changes in skin test scores were 0.41 ± 0.80 and 0.11 ± 0.93 (P = 0.2155), and geometric mean fold rises of the ELISPOT counts were 1.2 [95% confidence interval (CI) 0.2, 7.9] and 1.2 (95% CI 0.2, 7.3) (P = 0.989) in the vaccine and placebo groups, respectively. The geometric mean titre did not increase 3 months after vaccination in either group. No vaccination‐related severe adverse experience was reported and no participant developed herpes zoster.

Discussion

Our previous results demonstrated that varicella zoster vaccine safely enhanced VZV‐specific immunity in elderly people with or without diabetes. The results of this study showed that varicella zoster vaccine can be used safely, but it cannot boost virus‐specific immunity in elderly people with diabetes when administered with concurrent PPSV23. Alternative strategies are needed to prevent VZV‐associated diseases in this population.
ECONOMIC STRUCTURE AND SEIGNIORAGE: A DYNAMIC PANEL DATA ANALYSIS
Authors: Elbahnasawy Nasr G. , Ellis Michael A.
Published: November 2015

Controlling for a more comprehensive set of economic structure variables and using system generalized method of moment (GMM) dynamic panel estimation, we consider the determinants of seigniorage. While we confirm some results found in previous literature, including an inverse relationship of financial development and exchange rate management to seigniorage, we find little evidence that political instability and polarization lead to greater reliance on seigniorage. We also find robust evidence that the size of the shadow economy and natural resource rents are directly related to seigniorage, the latter result likely a result of exchange rate management. Thus, an effective strategy to reduce reliance on seigniorage is to lower the incentives to operate in the shadow economy, while exchange rate management may be counter‐productive in countries with considerable natural resource rents. (JEL E5, O50)
Novel echocardiographic indicator for potential cardioembolic stroke
Authors: Kim Y. , Kim T. J. , Park J.‐B. , Lee S. , Kim Y.‐J. , Lee J. S. , Lee S.‐H.
Published: November 2015

Background and purpose

In many cardioembolic strokes (CSs), the specific embolic source is uncertain. Despite the high mortality of CS, not enough attention is paid to its potential source. Although atrial fibrillation (AF) is the most common source of embolism, more complex and dynamic multiplicities may influence CS. The aim of this study was to evaluate novel indicators of transthoracic echocardiography (TTE) that have additional value for detecting CS.

Methods

In total, 1878 patients with acute ischaemic stroke who had TTE during admission were identified. Of the patients with undetermined etiology, 93 patients with incomplete evaluations were excluded. Thereafter, two stroke neurologists reviewed all of the magnetic resonance images to assess cardioembolic lesion patterns. The patients were classified into two groups: potential cardioembolic stroke (PCS) and non‐PCS.

Results

Amongst a total of 1601 patients, 518 (32.4%) had PCS. About half of the patients with PCS had AF. Patients with PCS were more likely to have larger left ventricular (LV) end‐diastolic diameters, larger LV end‐systolic diameters, larger left atrial sizes, increased E/A ratios and reduced LV ejection fractions. After adjusting for multiple clinical and TTE variables including AF, an E/A ratio ≥1.5 had a significant predictive value for PCS (odds ratio 2.89, 95% confidence interval 1.57–5.31, P < 0.01).

Conclusion

An E/A ratio ≥1.5 is independently associated with PCS after adjusting for multiple covariates including AF and provides incremental prognostic information for detecting PCS.
Tumor necrosis factor inhibitors added to nonbiological immunosuppressants vs. nonbiological immunosuppressants alone: a different signal of cancer risk according to the condition. A disproportionality analysis in a nationwide pharmacovigilance database
Authors: Saliba Layla , Moulis Guillaume , Abou Taam Malak , Rousseau Vanessa , Chebane Leila , Petitpain Nadine , Baldin Bernadette , Pugnet Grégory , Montastruc Jean‐Louis , Bagheri Haleh
Published: November 2015

We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF inhibitor (TNFi) and nonbiological immunosuppressant (NBIS), compared with NBIS alone for autoimmune diseases. Secondly, we aimed at comparing this risk between the different TNFis. We conducted a disproportionality analysis (case/noncase study) from the French National PharmacoVigilance Database. We selected all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal 3‐month exposure to NBIS. Noncases were all the other reports. We searched for exposure to TNFi and calculated reporting odds ratios (RORs), stratified by condition and type of cancer and adjusted by age, gender, history of cancer, type of NBIS and year of reporting. Of the 1918 reports included in the study population, 217 were cases (135 solid and 82 blood cancers). A safety signal was found in rheumatoid arthritis (RA) (ROR: 5.43, 95% CI[3.52–8.38]) particularly for nonmelanoma skin cancer (NMSC) (20.17[2.49–163.36]), and in psoriasis/psoriatic arthritis (3.45[1.09–10.92]). No signal was found in inflammatory bowel diseases (IBD) and ankylosing spondylitis, whatever the type of cancer. There was no difference between TNFis. This study puts the argument of an increased risk of cancer (particularly NMSC) in patients with rheumatoid arthritis exposed to TNFi and NBIS compared with NBIS alone, but not in IBD and ankylosing spondylitis patients. No signal was detected for melanoma potentially related to the lack of power. The signal seems similar whatever the TNFi.
A comparison of methods for predicting the fatigue life of gray cast iron at elevated temperatures
Authors: Lee Keum‐Oh , Lee Soon‐Bok
Published: November 2015

High temperature fatigue life tests were compared with various life assessment methods for gray cast iron in the cylinder liners of marine engines. The plastic strain range‐based methods such as the universal slopes method, Mitchell's method, Bäumel and Seeger's method, and Ong's method were not predicted well. A method employing tensile energy density, which is defined as the sum of the tensile area of the plastic energy and the elastic energy in the hysteresis loop, was suggested as an improved alternative to the plastic strain range‐based methods. The life estimation equation using tensile energy density predicted well within the 3X scatter band at various temperature ranges of the gray cast iron.
Anti‐inflammatory role of glucose‐dependent insulinotropic polypeptide in periodontitis
Authors: Suzuki Yuki , Nakamura Nobuhisa , Miyabe Megumi , Nishikawa Toru , Miyajima Shin‐ichi , Adachi Kei , Mizutani Makoto , Kikuchi Takeshi , Miyazawa Ken , Goto Shigemi , Tsukiyama Katsushi , Yamada Yuichiro , Ohno Norikazu , Noguchi Toshihide , Mitani Akio , Matsubara Tatsuaki , Naruse Keiko
Published: November 2015

Aims/Introduction

The involvement of glucose‐dependent insulinotropic polypeptide (GIP) on inflammation was explored in atherosclerosis and adipose tissue. Periodontal disease is a chronic inflammatory disease, and is considered one of the diabetic complications. In the present study, to examine the effect of GIP on periodontitis, we induced experimental periodontitis in glucose‐dependent insulinotropic polypeptide receptor‐knockout mice (GIPRKO). We also investigated the anti‐inflammatory effect of GIP in a culture system.

Materials and Methods

Experimental periodontitis was induced by ligature wire in GIPRKO and C57BL/C mice. Two weeks after the ligature, immunohistological evaluation and inflammatory messenger ribonucleic acid expression in the gingiva was examined. To elucidate the role of GIP in inflammation, the effects of GIP on lipopolysaccharide‐induced gene expressions in THP‐1 cells were evaluated.

Results

Periodontitis increased inflammatory cell infiltration, macrophage accumulation and tumor necrosis factor‐α and nitric oxide synthase gene expressions in the gingiva. Periodontitis in GIPRKO showed a marked increase of inflammatory cells in the gingivomucosal tissue. Mac‐1‐positive macrophages and the inflammatory gene expressions were significantly increased in periodontitis in GIPRKO compared with C57BL/C mice periodontitis. Immunohistochemical staining confirmed that GIP receptors were expressed in residual and infiltrated Mac‐1‐positive macrophages. The in vitro study showed that GIP suppressed lipopolysaccharide‐induced tumor necrosis factor‐α and nitric oxide synthase gene expression in a dose‐dependent manner. Furthermore, the inhibitory effect of GIP on lipopolysaccharide‐induced inflammatory gene expressions was at least partially through cyclic adenosine monophosphate/protein kinase A pathway.

Conclusions

These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti‐inflammatory effect on periodontitis in addition to its glucose‐lowering effect.
Design and setup of intermittent‐flow respirometry system for aquatic organisms
Authors: Svendsen M. B. S. , Bushnell P. G. , Steffensen J. F.
Published: November 2015

Intermittent‐flow respirometry is an experimental protocol for measuring oxygen consumption in aquatic organisms that utilizes the best features of closed (stop‐flow) and flow‐through respirometry while eliminating (or at least reducing) some of their inherent problems. By interspersing short periods of closed‐chamber oxygen consumption measurements with regular flush periods, accurate oxygen uptake rate measurements can be made without the accumulation of waste products, particularly carbon dioxide, which may confound results. Automating the procedure with easily available hardware and software further reduces error by allowing many measurements to be made over long periods thereby minimizing animal stress due to acclimation issues. This paper describes some of the fundamental principles that need to be considered when designing and carrying out automated intermittent‐flow respirometry (e.g. chamber size, flush rate, flush time, chamber mixing, measurement periods and temperature control). Finally, recent advances in oxygen probe technology and open source automation software will be discussed in the context of assembling relatively low cost and reliable measurement systems.
Activation of microglial Toll‐like receptor 3 promotes neuronal survival against cerebral ischemia
Authors: Jeong Si‐Yeon , Jeon Raok , Choi Yoon Kyung , Jung Joo Eun , Liang Anna , Xing Changhong , Wang Xiaoying , Lo Eng H. , Song Yun Seon
Published: November 2015

Emerging experimental evidence suggests that activation of Toll‐like receptor 3 (TLR3) by its agonist polyinosinic polycytidylic acid (poly‐ICLC) protects neurons against cerebral ischemia, but the underlying mechanisms remain largely unknown. In the brain, TLR3 is mostly expressed in glial cells. Therefore, we assess the hypothesis that TLR3 activation in microglia is required for neuroprotection against ischemia. After transient focal cerebral ischemia, microglia/macrophages (MMs) demonstrate a significant reduction in TLR3 and its downstream cytokine interleukin 6 (IL‐6). Subsequently, activation of TLR3 by poly‐ICLC restored TLR3 expression and decreased infarction. To further investigate these mechanisms, we turned to a primary cell culture system. Consistent with the in vivo findings, oxygen–glucose deprivation (OGD) significantly reduced TLR3 and IL‐6 mRNA expression in microglia, but poly‐ICLC significantly rescued TLR3 and IL‐6 expression. Importantly, conditioned media from OGD‐treated microglia increased neuronal death after OGD. In contrast, the conditioned media from microglia treated with poly‐ICLC after OGD significantly protected against OGD‐induced neuron death. Taken together, our findings provide proof‐of‐concept that activation of TLR3 in microglia may promote neuron survival after ischemia.

image

We assessed the hypothesis that Toll‐like receptor 3 (TLR3) activation in microglia is required for neuroprotection against ischemia. After transient focal cerebral ischemia, microglia/macrophage demonstrates a reduction in TLR3 and Interleukin 6 (IL‐6). Also, oxygen–glucose deprivation (OGD) reduces TLR3 and IL‐6 expression in microglia, but polyinosinic polycytidylic acid (poly‐ICLC) rescues TLR3 and IL‐6. Importantly, conditioned media from microglia treated with poly‐ICLC protects against OGD‐induced neuron death. We propose that activation of TLR3 in microglia may promote neuron survival after ischemia.
Myositis‐specific autoantibodies: an important tool to support diagnosis of myositis
Authors: Betteridge Z. , McHugh N.
Published: November 2015

The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis‐specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti‐TIF1, anti‐NXP2, anti‐MDA5, anti‐SAE, anti‐HMGCRand anti‐cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin‐induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis‐specific and myositis‐associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.
PI3K is required for both basal and LPA‐induced DNA synthesis in oral carcinoma cells
Authors: Aasrum Monica , Tjomsland Vegard , Thoresen G. Hege , De Angelis Paula M. , Christoffersen Thoralf , Brusevold Ingvild J.
Published: November 2015

Background

The glycerophospholipid lysophosphatidic acid (LPA), which is present in most tissues and in high concentrations in saliva, may exert profound effects on oral cancer cells. We have investigated mitogenic signalling induced by LPA in the two oral carcinoma cell lines, D2 and E10, focusing on the role of EGFR transactivation and downstream pathways.

Methods

Two oral squamous carcinoma cell lines, D2 and E10, were analysed for effects of LPA on signalling pathways and induction of DNA synthesis. Pathway activation was investigated by examining phosphorylation of signalling proteins and by the use of specific pathway inhibitors.

Results

The D2 cells had higher levels of activated signalling proteins and higher DNA synthesis activity in the basal condition than E10 cells. EGF did not induce proliferation in D2 cells, whereas LPA induced proliferation in both cell lines, by mechanisms depending on EGFR transactivation. Release of EGFR ligands was involved in basal and LPA‐induced proliferation in both D2 and E10 cells. The proliferation in D2 cells was dependent on the PI3K/Akt pathway, but not the MEK/ERK pathway. In E10 cells, the PI3K/Akt, MEK/ERK and p38 pathways were all involved in the proliferation.

Conclusion

Transactivation of EGFR is required for LPA‐induced DNA synthesis in D2 and E10 cells. Our results also show that although proliferation of oral carcinoma cells is regulated by several pathways, and differentially in E10 and D2 cells, the PI3K pathway has a crucial role in both cell lines.
The story of HCC in NAFLD: from epidemiology, across pathogenesis, to prevention and treatment
Authors: Margini Cristina , Dufour Jean F.
Published: November 2015

Background & Aims

Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death worldwide. An increasing number of reports describe HCC in the setting of obesity and diabetes, two major risk factors for non‐alcoholic fatty liver disease (NAFLD). The increasing incidence of these conditions and the emerging evidence of HCC in non‐cirrhotic NAFLD prioritize a better understanding of NAFLD‐related HCC epidemiology and pathogenesis in order to target screening policies and develop preventive‐therapeutic strategies. In this review, we focus on the epidemiological impact of this condition, suggesting a possible link between HCC in cryptogenic cirrhosis and NAFLD. Furthermore, we analyse the suggested pathogenic mechanisms and the possible preventive‐therapeutic strategies.
CONFLICTS OF INTEREST IN INTERNATIONAL ORGANIZATIONS: EVIDENCE FROM TWO UNITED NATIONS HUMANITARIAN AGENCIES
Authors: MELE VALENTINA , ANDERFUHREN‐BIGET SIMON , VARONE FRÉDÉRIC
Published: November 2015

The independence of international civil servants (ICSs) from their country of origin is often presumed but rarely accounted for empirically. In order to address this gap, we investigate whether ICSs face conflicts between national and international interests and which conditions are more conducive to the manifestation of this conflict in international organizations. We adopt a mixed‐methods design, including a survey with 1,400 respondents working in two United Nations humanitarian organizations, followed by semi‐structured interviews with a purposive sample of respondents. The findings show that such conflicts matter for ICSs, hierarchical grade has stronger explanatory power than the other factors, and the higher the level in the international organization, the less frequently ICSs face conflict. The qualitative analysis explains these results by pointing to the effects of socialization among ICSs but also by shedding light on a related effect: dilution of national identity, as well as on the implications of locally recruiting lower‐level staff.
Some Non‐FDA Approved Uses for Neuromodulation: A Review of the Evidence
Authors: Lee Samuel , Abd‐Elsayed Alaa
Published: November 2015

Introduction

Neuromodulation, including spinal cord stimulation and peripheral nerve field stimulation, has been used with success in treating several painful conditions. The FDA approved the use of neuromodulation for a few indications. We review evidence for neuromodulation in treating some important painful conditions that are not currently FDA approved.

Methods

This review included an online web search for only clinical trials testing the efficacy of neuromodulation in treating coronary artery disease, peripheral vascular disease (PVD), headache, and peripheral field stimulation.

Results

Our systematic literature search found 10, 6, and 3 controlled studies relating to coronary artery disease, PVD, and headache, respectively. Our review also included 5 noncontrolled studies relating to peripheral field stimulation, as no controlled studies had been completed.

Conclusion

This review article shows compelling evidence based on clinical trials that neuromodulation can be of benefit for patients with serious painful conditions that are not currently approved by the FDA.
Wittgenstein and Objectivity in Ethics: A Reply toBrandhorst
Authors: De Mesel Benjamin
Published: November 2015

In “Correspondence toReality inEthics”,MarioBrandhorst examines the view of ethics thatWittgenstein took in his later years. According toBrandhorst,Wittgenstein leaves room for truth and falsity, facts, correspondence and reality in ethics.Wittgenstein's target, arguesBrandhorst, is objectivity. I argue (i) thatBrandhorst's arguments in favour of truth, facts, reality and correspondence in ethics invite similar arguments in favour of objectivity, (ii) thatBrandhorst does not recognise this because his conception of objectivity is distorted by aPlatonist picture and (iii) that he misinterprets the passage which he takes to support aWittgensteinian case against objectivity.
Mechanisms of resistance in Brassica carinata, B. napus and B. juncea to Pseudocercosporella capsellae
Authors: Gunasinghe N. , You M. P. , Clode P. L. , Barbetti M. J.
Published: November 2015

Studies were undertaken to compare susceptible and resistant host responses to Pseudocercosporella capsellae in cotyledons of Brassica carinata, B. juncea and B. napus in order to define the mechanisms of resistance in these three species. On both resistant and susceptible hosts, hyphal penetration was always through stomatal openings and without infection pegs or appressoria. On resistant B. carinata ATC94129P, up to 72% of spores disintegrated and, generally, germination (<22%) and germ tube lengths (<25 μm) were comparatively low. Resistant B. napus Hyola 42 had the lowest germination (8%) and susceptible B. carinata UWA#012 had the highest (51%). On resistant B. carinata ATC94129P, germ tube extension was impeded across 24–60 h post‐inoculation (hpi) and percentage stomatal penetration lower (4%) at 60 hpi compared with susceptible B. carinata UWA#012 (26%). Stomatal densities (stomata/14 757 μm2) on resistant B. juncea Dune (2·12) and B. napus Hyola 42 (1·62) were lower than for susceptible B. juncea Vardan (2·40) and B. napus Trilogy (2·03). Resistant B. carinata ATC94129P had greater stomatal density (1·89) than susceptible B. carinata UWA#012 (1·58). Overall, B. juncea had greater stomatal density (2·26) compared with B. napus (1·83) and B. carinata (1·74). In resistant B. carinata ATC94129P, P. capsellae induced 28% stomata to close, while in susceptible B. carinata UWA#012 no such closure was induced. Epicuticular wax crystalloids were present only on resistant B. carinata ATC94129P and probably also contribute towards resistance.
Influence of Post‐Mortem Sperm Recovery Method and Extender on Unstored and Refrigerated Rooster Sperm Variables
Authors: Villaverde‐Morcillo S , Esteso MC , Castaño C , Santiago‐Moreno J
Published: November 2015

Contents

Many post‐mortem sperm collection techniques have been described for mammalian species, but their use in birds is scarce. This paper compares the efficacy of two post‐mortem sperm retrieval techniques ‐ the flushing and float‐out methods ‐ in the collection of rooster sperm, in conjunction with the use of two extenders, i.e., L&R‐84 medium and Lake 7.1 medium. To determine whether the protective effects of these extenders against refrigeration are different for post‐mortem and ejaculated sperm, pooled ejaculated samples (procured via the massage technique) were also diluted in the above extenders. Post‐mortem and ejaculated sperm variables were assessed immediately at room temperature (0 h), and after refrigeration at 5°C for 24 and 48 h. The flushing method retrieved more sperm than the float‐out method (596.5 ± 75.4 million sperm vs 341.0 ± 87.6 million sperm; p < 0.05); indeed, the number retrieved by the former method was similar to that obtained by massage‐induced ejaculation (630.3 ± 78.2 million sperm). For sperm collected by all methods, the L&R‐84 medium provided an advantage in terms of sperm motility variables at 0 h. In the refrigerated sperm samples, however, the Lake 7.1 medium was associated with higher percentages of viable sperm, and had a greater protective effect (p < 0.05) with respect to most motility variables. In conclusion, the flushing method is recommended for collecting sperm from dead birds. If this sperm needs to be refrigerated at 5°C until analysis, Lake 7.1 medium is recommended as an extender.
Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals
Authors: Abdel Aziz N. , Tallima H. , Hafez E. A. , El Ridi R.
Published: November 2015

We have previously shown that immunization of outbred rodents with cysteine peptidases‐based vaccine elicited type 2‐biased immune responses associated with consistent and reproducible protection against challenge Schistosoma mansoni. We herein start to elucidate the molecular basis of C57BL/6 mouse resistance to S. mansoni following treatment with the cysteine peptidase, papain. We evaluated the early cytokine signals delivered by epidermal, dermal, and draining lymph node cells of naïve, and S. mansoni ‐infected mice treated 1 day earlier with 0 or 50 μg papain, or immunized twice with papain only (10 μg/mouse), papain‐free recombinant S. mansoni glyceraldehyde 3‐phosphate dehydrogenase and 2‐Cys peroxiredoxin peptide (10 and 15 μg/mouse, respectively = antigen Mix), or papain‐adjuvanted antigen Mix. Schistosoma mansoni infection induced epidermal and lymph node cells to release type 1, type 2 and type 17 cytokines, known to counteract each other. Expectedly, humoral immune responses were negligible until patency. Papain pretreatment or papain‐based vaccination diminished or shut off S. mansoni infection early induction of type 1, type 17 and type 2 cytokines except for thymic stromal lymphopoietin and programmed the immune system towards a polarized type 2 immune milieu, associated with highly significant (P < 0.005 – <0.0001) resistance to S. mansoni infection.
Exploring the Downside of Social Embeddedness: Evidence from a Cross‐National Study*
Authors: Hyun‐soo Kim Harris
Published: November 2015

Objective

The interdisciplinary literature on social capital has given relatively little attention to the potential downside of social embeddedness. Based on a cross‐national data set (International Social Survey Programme), this study examines how and to what extent social ties and organizational membership are associated with experiencing “too many demands” from close contacts.

Methods

Hierarchical general linear models are estimated to analyze the linkage between several social capital indicators and the precarious nature of being connected.

Results

Findings from multilevel analysis indicate that frequency of interaction with friends and relatives, as well as level of involvement in voluntary organizations, are significantly related to feeling burdened because of network‐mediated demands.

Conclusion

This study suggests that network ties may be viewed as a double‐edged sword. Interpersonal and organizational embeddedness not only produces benefits of social capital but also requires from individual members the necessary obligations and responsibilities associated with it.
Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation
Authors: Diri R. , Anwer F. , Yeager A. , Krishnadasan R. , McBride A.
Published: November 2015

Background

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life‐threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim‐sulfamethoxazole (TMP‐SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients.

Methods

A single‐institution retrospective review of electronic medical records was conducted for patients who underwent allo‐HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre‐transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes.

Results

A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1–23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second‐line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP‐SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis.

Conclusion

This retrospective study showed that IV PEN is very effective and well‐tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients.
Adsorption kinetics of benzene on graphene: An ultrahigh vacuum study
Authors: Chakradhar Ashish , Sivapragasam Nilushni , Nayakasinghe Mindika T. , Burghaus Uwe
Published: November 2015

Experimental data for benzene adsorption on chemical vapor deposited graphene/Cu and graphene/SiO2 studied at ultrahigh vacuum conditions are discussed and compared with prior work on physical vapor deposited graphene/Ru(0001). Two widely considered topics, namely, the transparency of graphene and support effects of epitaxial graphene are investigated. Graphene is nearly transparent for benzene adsorption on both copper and silica supports opposed to Ru(0001). In addition, the desorption energy for benzene on epitaxial graphene depends on the reactivity of the support.
Investigation of breakdown mechanism during field emission process of AlN thin film microscopic cold cathode
Authors: Liang Feng , Chen Ping , Zhao Degang , Jiang Desheng , Liu Zongshun , Zhu Jianjun , Yang Jing , Le Lingcong , Liu Wei , He Xiaoguang , Li Xiaojing , Li Xiang , Zhang Liqun , Liu Jianping , Yang Hui
Published: November 2015

The breakdown mechanism of a 100 nm-thick AlN thin film cold cathode structure was investigated during the field emission process, where the AlN film was synthesized by metalorganic chemical vapor deposition under low pressure on an n-type SiC substrate. The microdevice structure formed by a Si-doped AlN film (NSi = 1.0 × 1018–1.0 × 1019 cm−3) and by an unintentionally doped AlN film were first characterized by a field emission (FE) system in a vacuum chamber. During the measurement, the FE current of those two samples presented an discontinuous increase with increasing voltage, and ultimately a breakdown of current with an abrupt drop-down (around 1 × 10−6 A). Scanning electron microscopy coupled with energy dispersive spectral analysis was applied to characterize the surface morphology and chemical elements of the Si-doped AlN film surface after the FE measurement. Nonuniform local field enhancement factors of the AlN film was proposed to explain the fluctuation increase in the FE current with increasing electric field. It was believed that both heat accumulation in the cathode and the bombardment of Au ions sputtered from the anode are responsible for the breakdown of the FE characteristics of the AlN cold cathode.
Comparison of tungsten films grown by CVD and hot-wire assisted atomic layer deposition in a cold-wall reactor
Authors: Yang Mengdi , Aarnink Antonius A. I. , Kovalgin Alexey Y. , Gravesteijn Dirk. J. , Wolters Rob A. M. , Schmitz Jurriaan
Published: November 2015

In this work, the authors developed hot-wire assisted atomic layer deposition (HWALD) to deposit tungsten (W) with a tungsten filament heated up to 1700–2000 °C. Atomic hydrogen (at-H) was generated by dissociation of molecular hydrogen (H2), which reacted with WF6 at the substrate to deposit W. The growth behavior was monitored in real time by an in situ spectroscopic ellipsometer. In this work, the authors compare samples with tungsten grown by either HWALD or chemical vapor deposition (CVD) in terms of growth kinetics and properties. For CVD, the samples were made in a mixture of WF6 and molecular or atomic hydrogen. Resistivity of the WF6-H2 CVD layers was 20 μΩ·cm, whereas for the WF6-at-H-CVD layers, it was 28 μΩ·cm. Interestingly, the resistivity was as high as 100 μΩ·cm for the HWALD films, although the tungsten films were 99% pure according to x-ray photoelectron spectroscopy. X-ray diffraction reveals that the HWALD W was crystallized as β-W, whereas both CVD films were in the α-W phase.
Better treatment for dyskinesia
Authors: Gough Nancy R.
Published: November 2015

Enhancing cholinergic signaling reduces a major side effect of ʟ-DOPA therapy in Parkinson’s disease models.
Evolutionary Selection on Barrier Activity: Bar1 Is an Aspartyl Protease with Novel Substrate Specificity
Authors: Jones Stephen K. , Clarke Starlynn C. , Craik Charles S. , Bennett Richard J.
Published: November 2015

Peptide-based pheromones are used throughout the fungal kingdom for coordinating sexual responses between mating partners. Here, we address the properties and function of Bar1, an aspartyl protease that acts as a “barrier” and antagonist to pheromone signaling in multiple species.
Candida albicans
Bar1 was purified and shown to exhibit preferential cleavage of native α pheromone over pheromones from related fungal species. This result establishes that protease substrate specificity coevolved along with changes in its pheromone target. Pheromone cleavage by Bar1 occurred between residues Thr-5 and Asn-6 in the middle of the tridecapeptide sequence. Surprisingly, proteolytic activity was independent of the amino acid residues present at the scissile bond and instead relied on residues at the C terminus of α pheromone. Unlike most aspartyl proteases, Bar1 also exhibited a near-neutral pH optimum and was resistant to the class-wide inhibitor pepstatin A. In addition, genetic analysis was performed on
C. albicans
BAR1
and demonstrated that the protease not only regulates endogenous pheromone signaling but also can limit interspecies pheromone signaling. We discuss these findings and propose that the unusual substrate specificity of Bar1 is a consequence of its coevolution with the α pheromone receptor Ste2 for their shared peptide target.

IMPORTANCE
Pheromones are important for intraspecies communication across the tree of life. In the fungal kingdom, extracellular proteases play a key role in antagonizing pheromone signaling in multiple species. This study examines the properties and function of
Candida albicans
Bar1, an aspartyl protease that cleaves and thereby inactivates α pheromone. We demonstrate that Bar1 plays important roles in regulating both intra- and interspecies pheromone signaling. The fungal protease shows preferential activity on the endogenous pheromone, but, surprisingly, cleavage activity is dependent on amino acid residues distal to the scissile bond. We propose that the unusual substrate specificity of Bar1 is a direct result of coevolution with Ste2, the receptor for α pheromone, for recognition of the same peptide target. The novel specificity of Bar1 reveals the complex forces shaping the evolution of mating pathways in fungi and uncovers a protease with potentially important applications in the biotechnology industry.
Thymic carcinoma presenting as atypical chest pain
Authors: Siddiqui Sadiq , Connelly Tara , Keita Luther , Blazkova Sylvie , Veerasingam Dave
Published: November 2015

A 58-year-old woman with a 2-month history of atypical chest pain was referred to the chest pain clinic by the general practitioner. Exercise stress test was positive and subsequent coronary angiogram revealed significant triple vessel disease with left ventricular impairment requiring a coronary artery bypass graft (CABG). The patient had a chest X-ray as part of the preoperative work up. Chest X-ray revealed a large anterior mediastinal mass. Subsequent thorax CT revealed a 7.2  cm anterior mediastinal mass. CT-guided biopsy of the mass revealed the diagnosis of a poorly differentiated thymic basaloid carcinoma. The patient was successfully treated with concomitant surgery involving complete resection of the mass and a CABG procedure.
A young woman with a jejuno-jejunal intussusception
Authors: van Dijk Louisa J D , Noordman Bo Jan , Scheepers Joris J , Hartholt Klaas A
Published: November 2015

A 27-year-old woman presented at the emergency department, with pain in the epigastric region. Because physical examination, blood results, urine tests and an X-ray of the thorax showed no abnormalities, she was discharged. Twelve hours later, she presented again at the emergency department, with intense abdominal pain. The blood results, an X-ray and ultrasound of the abdomen were now aberrant. A CT of the abdomen showed an extensive intussusception. During an emergency laparotomy, the intussusception of the proximal jejunum was confirmed. Owing to gangrene of the proximal jejunum, a resection was inevitable. A polyp in the resected part of the jejunum was the lead point of the intussusception. This case report shows the challenges of diagnosing an ‘intussusception’ and gives a short overview of this condition in adults.
The unexpected finding of a splenic infarction in a patient with infectious mononucleosis due to Epstein-Barr virus
Authors: Machado Catarina , Melo Salgado Joana , Monjardino Leonor
Published: November 2015

The authors present a case of a 24-year-old man with infectious mononucleosis (IM) due to Epstein-Barr virus (EBV). Among his symptoms, he reported abdominal pain in the upper left quadrant. An abdominal ultrasound and CT revealed an extensive splenic infarction. During the acute stage of this disease, the thrombophilic screening revealed reduced free protein S and elevated factor VIII, with normalisation on re-evaluation 6 weeks later. Splenic infarction is a very rare complication of IM due to EBV but should be considered in patients presenting abdominal pain. A hypercoagulability state should be investigated. To our knowledge, this is the first described case of a splenic infarction in a patient with IM due to EBV associated with a transient reduction of protein S and elevation of factor VIII. Thus, this work promotes the importance of including these factors in the thrombophilic screening conducted during the investigation of similar cases.
Continuous use of enzalutamide in a patient who developed enzalutamide-induced thrombocytopenia
Authors: Sato Atsuko , Kosaka Takeo , Oya Mototsugu
Published: November 2015

Drug-induced thrombocytopenia (DIT) is known to be caused by many drugs. In daily clinical practice, it is not uncommon to observe cases of thrombocytopenia related to enzalutamide. We report the case of a 69-year-old patient with metastatic castration-resistant prostate cancer (CRPC) who was started on enzalutamide at a dose of 160 mg/day. Two weeks after starting enzalutamide, asymptomatic thrombocytopenia (platelet count 14 000/µL) occurred. Enzalutamide was withdrawn and the patient received platelet transfusions. The platelet count recovered immediately. Because the prostate-specific antigen (PSA) level had started to fall during treatment with enzalutamide, the patient was restarted on enzalutamide, but at a dose of 80 mg/day. He has continued to use enzalutamide without developing thrombocytopenia and the PSA level has kept falling. This case suggests that it is possible to again use enzalutamide in patients who have developed enzalutamide-induced thrombocytopenia.