bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Kim-1 is a sensitive biomarker for the early stage of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats
Authors: Hosohata Keiko , Ando Hitoshi , Takeshita Yumie , Misu Hirofumi , Takamura Toshinari , Kaneko Shuichi , Fujimura Akio
Published: May 2014

Although urinary albumin is the well-known non-invasive marker for diabetic nephropathy, its sensitivity is relatively low. To select more adequate marker, we examined whether urinary tubular markers were more sensitive than albumin using spontaneous type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The OLETF rats exhibited histopathological alterations in glomeruli and tubules at 14 weeks of age, but there were no significant differences in the urinary albumin between OLETF and control, Long-Evans Tokushima Otsuka (LETO), rats at 10–16 weeks of age. In the OLETF rats, urinary excretions of N-acetyl-β-d-glucosaminidase and neutrophil gelatinase–associated lipocalin did not increase at least until 20 weeks of age, and urinary vanin-1 transiently increased at 18 weeks of age. On the other hand, urinary kidney injury molecule-1 (Kim-1) in the OLETF rats significantly increased at 14 weeks of age, and the elevation continued up to 22 weeks of age. In a clinical study, urinary KIM-1 levels tended to be higher in type 2 diabetic patients with and without albuminuria than in control subjects. These results suggest that compared to urinary albumin, urinary Kim-1 is a more sensitive biomarker for the detection of early stage of nephropathy in these type 2 diabetic animals. Merit of urinary KIM-1 in diabetic patients remains to be determined.
Transatlantic Peer-to-Peer Learning
Authors: Lynch Noel Patrick , Cil Tulin , Lehane Elaine , Reardon Michelle , Corrigan Mark
Published: May 2014

Introduction. Peer-to-peer learning is a well-established learning modality, which has been shown to improve learning outcomes, with positive implications for clinical practice. The purpose of this pilot study was to explore the feasibility of linking students from North America and Europe with a peer-to-peer learning approach. Methods. Face and content validity studies were completed on the previously designed and validated online repository http://www.pilgrimshospital.com . Four medical students from the University of Toronto, Canada, were paired with four students from University College Cork, Ireland. Each student was invited to upload two pieces of information learned from a senior colleague that day. Each student was asked to review the information uploaded by their partner, editing with references if needed. Quantitative and qualitative evaluations of the e-peer system were conducted. Results. Over the study period, the system recorded a total of 10 079 individual page views. Questionnaires completed by participants demonstrated that 6/8 found the system either “very easy” or “easy” to use, whereas all found that the system promoted evidenced-based and self-directed learning. Structured interviews revealed 3 main themes: The Peer Connection, Trust in Data Veracity, and Aid to Clinical Learning. Conclusion. This pilot study demonstrates it is feasible to link students from separate continents in a community of peer-to-peer learning. This is viewed positively by students and enhances evidenced-based learning, and the aspect of peer connectivity was important to participating students. Such an approach encourages peer cooperation and has the potential to disseminate key clinical learning experiences widely.
A rare case of large isolated internal iliac artery aneurysm with ureteral obstruction and hydronephrosis: Compression symptoms are limitation for endovascular procedures
Authors: Nenezic Dragoslav , Tanaskovic Slobodan , Gajin Predrag , Ilijevski Nenad , Novakovic Aleksandra , Radak Djordje
Published: May 2014

Introduction

In this report, we aim to present a rare case of isolated internal iliac artery aneurysm with associated left ureteric obstruction and consequent hydronephrosis.

Case report

A 66-year-old male patient was admitted for occasional pain in the lower back that appeared one month earlier. CT arteriography revealed isolated internal iliac artery (diameter 99 mm) with ureteral obstruction, hydroureter and left kidney hydronephrosis occurrence. Aneurysm was resected, after six months the patient was doing well. Bearing in mind that 77% of the patients with isolated internal iliac artery have symptoms caused by aneurysmal compression on adjacent organs, we wanted to highlight that despite the amazing expansion of endovascular procedures in the last decades, its therapeutic effect in isolated internal iliac artery’s treatment is to a great extent limited since compression symptoms cannot be solved.

Conclusion

Open surgery remains the gold standard for isolated internal iliac artery’s treatment considering significant limitations of endovascular procedures due to the inability to eliminate problems caused by compression.
Trapped cerebral thrombectomy device: A case report of a rare complication
Authors: Geuzebroek Guillaume SC , Wille Jan , Vries Jean-Paul de , Schonewille Wouter , Vos Jan-Albert
Published: May 2014

Intravenous thrombolysis with recombinant tissue plasminogen activator is currently the standard therapy for acute ischaemic stroke when started within 4.5 h of symptom onset. Systemic thrombolytic therapy can, however, lead to potentially lethal bleeding complications and is contra-indicated in several circumstances. Intra-arterial thrombolysis and/or intra-arterial thrombectomy can overcome these drawbacks and even increase the rate of recanalization. While intravenous thrombolysis is a relatively non-complex treatment, intra-arterial therapy in acute ischaemic stroke patients requires a dedicated intervention team which has to be available at all times. In this case report, we describe the multidisciplinary approach of a rare complication of a trapped mechanical thrombectomy device.
Understanding the local
Authors: Woods Philip , Simkins Tim
Published: May 2014

The structure of the English school system has been the subject of almost continuous change since the late-1980s. The most recent was commenced by the Conservative–Liberal Democrat Coalition government, which was elected in May 2010. This policy set in train, very quickly, processes through which all schools have been encouraged, and in some cases required, to become independent of local authorities (LAs) and funded directly by central government, the government’s vision being to create a complete system of publicly funded ‘independent’ schools. This article considers some of the implications of these aspirations and the ways in which they have been translated into policy and implemented. It begins by setting the policies of the Coalition government within a context of trends in education policy since 1988, showing how these can be related to three dominant themes: school autonomy, central control and diversity of provision. It then proceeds to consider how these developments can be theorized, suggesting that diversity of governance, legitimacy and agency provide a suitable framework for analysing the emerging English experience. These ideas are then used to examine this experience and draw conclusions about key issues for the future.
Exploring governance in two chains of academy schools
Authors: Salokangas Maija , Chapman Christopher
Published: May 2014

Although the number and size of academy chains in England is still increasing, the implications of these arrangements at a local level remain under-researched. This article reports findings from a comparative case study focusing on governance arrangements and sponsor involvement in two chains of academies. The findings suggest that the policy and practice of these multi-academy sponsors define the autonomy of the individual academies within the chains, so that the level of autonomy individual academies experience varies significantly between, as well as within, chains.
Re-making the middle
Authors: Lubienski Christopher
Published: May 2014

Recent reforms in England’s education system have been justified on the grounds that other countries have pursued similar approaches to education reform. Many such policies that by-pass or otherwise diminish meso-level institutions demonstrate a commitment to the idea of devolving authority to local actors. The current reforms in England and elsewhere reconfigure governance structures to diminish intermediate-level institutions on the grounds that these reforms lead to more effective and equitable educational systems. But in lieu of compelling evidence of such an impact, it appears that such policies are often instead simply a political attack on meso-level authorities, and may in fact represent an opportunity for new policy players to occupy the space left by receding meso-level institutions. This article surveys some of the specific policies that have emerged from recent policy trends, particularly those that have undercut established intermediate-level institutions in the USA and New Zealand. Reviewing the empirical record from these cases, I argue that, rather than simply devolving power away from intermediate authorities to local actors in order to produce more effective or equitable outcomes, many of these reforms have been more successful instead in creating the conditions in which new, non-state actors are able to accrue policy power for themselves.
A simplified training method for soft tissue foreign body detection using ultrasound in emergency medicine residency program
Authors: Farahmand Shervin , Bagheri-Hariri Shahram , Mehran Sadjad , Arbab Mona , Khazaeipour Zahra , Basir-Ghafouri Hamed , Saeedi Morteza
Published: May 2014

Using ultrasound for detecting soft tissue foreign bodies seems to be the preferred choice with minimum invasion and easy availability at the bedside in emergency departments. In this study, a workshop (1 hour of lecture presentation and 3 hours of interactive hands-on) was designed to evaluate the efficacy of a short course of simple interactive training to improve the ability of emergency medicine residents to detect foreign bodies with ultrasound. Eight pieces of fresh full thickness (10 × 10 × 10 cm) lamb leg muscle were used in this study. Five different types of foreign bodies, including: a piece of glass (5 × 5 × 4 mm), wood (5 × 5 × 4 mm), gravel (5 mm diameter), plastic (5 × 5 × 2 mm) and a nail (25 mm in length) were placed deep inside each lamb leg. An ultrasound machine with a 7.5 MHz linear probe was used in this study. 35 emergency medicine residents (12 PGY1, 11 PGY2 and 12 PGY3) were enrolled in this study. Pretest and post-test results were compared and analyzed. Among all 35 participants in the training session, foreign body detection was significantly improved after the workshop ( p < 0.001). Overall sensitivity and specificity for differentiating the presence and absence of a foreign body with 95% confidence were 60% (75% for PGY3) and 85.7% (91.7% for PGY3), respectively. The overall accuracy increased from 20.2% to 72.8% due to this session. This study supported the possibility of using ultrasound to detect foreign bodies by emergency physicians with a very short training course. This is highly beneficial for overcrowded emergency departments.
An observational study of hand hygiene adherence following the introduction of an education intervention
Authors: Randle Jacqueline , Arthur Antony , Vaughan Natalie , Wharrad Heather , Windle Richard
Published: May 2014

Hand hygiene adherence needs to be increased and sustained in order to prevent and reduce healthcare associated infections. We implemented an educational intervention and observed the adherence of healthcare workers, patients and visitors over 24 hour periods at four observation points. For healthcare workers a total of 2,294 opportunities were observed and for patients and visitors, a total of 597 opportunities were observed. Healthcare worker adherence increased following the introduction of the educational intervention, with 53.0% (282/532) adherence at baseline (observation point 1), and was sustained varying between 67.7% and 70.8% in the post-intervention points ( p=0.0007). The greatest increase in adherence was observed between baseline and the observation point 2. Adherence varied according to type of opportunity ( p<0.0001) with the lowest level of adherence observed after contact with patient surroundings, however there was no obvious trend across the observation points. There was an interaction between point of study and ward ( p=0.0001). For patients and visitors, adherence did differ according to the point of study ( p=0.0074) with adherence prior to the intervention being 49.1% and then ranging from 43.5–61.8%. We suggest that future educational interventions should be implemented as this study implies that there is potential for increased and sustained adherence to hand hygiene protocols.
An unusual case of primary hepatic lymphoma mimicking sarcoidosis in MRI
Authors: Do Thuy D , Neurohr Claus , Michl Marlies , Reiser Maximilian F , Zech Christoph J
Published: May 2014

Sarcoidosis is a granulomatous disease, in which liver affection is common, contrary to a primary hepatic lymphoma that is very rarely seen. On MRI both present with almost the same imaging features: hypointense in T1-weighted and hyperintense in T2-weighted sequences. Our patient with a histologically confirmed sarcoidosis in the lungs showed liver lesions that were similar to sarcoidosis manifestations of the liver. Due to size, progression and overlapping features with secondary malignant liver lesions within an interval of 5 months, a biopsy was conducted and confirmed a primary hepatic lymphoma with diffuse large b-cells. Thus, we would recommend performing a biopsy in ambiguous lesions with indistinguishable characteristics and progression within a short follow-up interval.
Outcomes following primary percutaneous coronary intervention in the setting of cardiac arrest: A registry database study
Authors: Kunadian Vijay , Bawamia Bilal , Maznyczka Annette , Zaman Azfar , Qiu Weiliang
Published: May 2014

Background:

The mortality rate among patients undergoing primary percutaneous coronary intervention (PPCI) in the setting of cardiac arrest (CA) and whether the location where the patient sustains CA influences the outcome is not known in the contemporary era.

Methods:

Prospectively collected data at a tertiary cardiac centre on all patients undergoing PPCI for ST elevation myocardial infarction (STEMI) in the setting of CA was analysed.

Results:

In total, 484/4118 (11.8%) patients sustained CA during the study period. Of these, 91/484 (18.8%) sustained CA prior to ambulance arrival, the remainder occurred either after ambulance arrival or in hospital. The overall in-hospital mortality was 20.5% in this cohort. Those sustaining CA before ambulance arrival experienced the highest unadjusted mortality compared to those that had CA after ambulance arrival, in hospital and in the catheterisation laboratory (29.7% versus 12.0%, 16.1% and 23.8% respectively, p=0.03). Multiple logistic regression analysis showed that the following parameters are independent predictors of in-hospital mortality: age (odds ratio (OR) for each year increment of age 1.05; 95% confidence interval (CI) 1.02–1.08, p=0.0009); female gender (OR 2.42; 95% CI 1.17–4.99, p=0.0173); previous PCI (OR 7.59; 95% CI 1.72–33.53, p=0.0075); asystole/ electromechanical dissociation (EMD) (OR 13.43; 95% CI 5.34–33.80, p<0.0001); and patient location at arrest (OR 5.77 for before ambulance arrival; 95% CI 2.55–13.07, p<0.0001).

Conclusions:

In conclusion, in-hospital mortality remains high among patients undergoing PPCI in the context of CA, particularly among those that arrest prior to ambulance arrival.
Perception without awareness of supraliminal stimuli: A critical review and a proposition for an integrated model
Authors: Derbaix Christian , Herrmann Jean-Luc , Kacha Mathieu
Published: May 2014

This article offers a critical review of marketing research focused on the effects of supraliminal stimuli perceived in the absence of awareness. On the basis of findings emerging from the literature related to memory accessibility, likelihood of inclusion in the consideration set, evaluation and likelihood of consumer choice, we progressively derive 10 research proposals. Finally, we propose an integrated model and outline priority avenues for future research.
Immigrant threat and national salience: Understanding the “English official” movement in the United States
Authors: Liu Amy H , Sokhey Anand Edward , Kennedy Joshua B , Miller Annie
Published: May 2014

The passage of (and debate over) immigration laws in Arizona highlights the increasing linguistic diversity of the US. To date, 31 states have passed an English-official bill. In this paper, we test several hypotheses concerning the adoption of such legislation across the states. Using data spanning the past three decades, we present event history models on the timing of adoption since the start of the modern movement in 1980. Like previous works, we find that the timing of adoption in states is structured by immigrant population and the initiative process. However, we find a conditional story that has been overlooked to date: the effects of immigrant threat only increase the likelihood of English-official legislation adoption when the issue of immigration is nationally salient.
Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer
Authors: van den Eijnde Wilbert A.J. , Peppelman Malou , Lamers Edwin A.D. , van de Kerkhof Peter C.M. , van Erp Piet E.J.
Published: May 2014

Background:

Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports.

Purpose:

To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact.

Results:

The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries.

Conclusion:

The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin.
Arthroscopic Removal of Chronic Symptomatic Calcifications of the Supraspinatus Tendon Without Acromioplasty
Authors: Maier Dirk , Jaeger Martin , Izadpanah Kaywan , Köstler Wolfgang , Bischofberger Anne K. , Südkamp Norbert P. , Ogon Peter
Published: May 2014

Background:

Little knowledge exists on postoperative recovery of pain and shoulder function following arthroscopic removal of calcific deposits of the supraspinatus tendon (ACDSSP). Certain factors may influence outcome, including acromial morphology.

Purpose:

To examine postoperative recovery following ACDSSP without acromioplasty and to analyze influential outcome factors.

Study Design:

Case series; Level of evidence, 4.

Methods:

This prospective study evaluated 82 patients (105 shoulders) after ACDSSP without acromioplasty. Time periods for postoperative recovery of pain and subjective shoulder function were recorded. The absolute and normalized Constant scores (CSabs and CSnorm, respectively), Oxford Shoulder Score (OSS), DASH score (DS), and subjective shoulder value (SSV) were measured after a mean follow-up of 33.9 months. Analyzed outcome factors included localization of the calcific deposit (CD), acromial morphology, radiographic extent of CD removal, type of nonoperative treatment, and preoperative duration of symptoms.

Results:

Mean duration of postoperative pain was 2.2 weeks. Recovery of subjective shoulder function required 11.1 weeks on average. Mean ± standard deviation follow-up values were 91.1 ± 8.3 for CSabs, 104.2% ± 8.2% for CSnorm, 13.1 ± 2.6 for OSS, 1.81 ± 4.59 for DS, and 93.8% ± 10.7% for SSV. Abduction was significantly ( P = .008) lower in patients with type III (170° ± 17.5°) compared with type I (174° ± 20.7°) and type II (179° ± 4.5°) acromions. Also, abduction was significantly ( P = .001) lower in patients with long-standing symptoms (>72 months). Minor calcific remnants were found in 19 of 105 shoulders (18.1%), but affected neither postoperative recovery nor outcome.

Conclusion:

ACDSSP without acromioplasty yielded favorable outcomes and effected fast remission of pain regardless of acromial morphology. However, recovery of subjective shoulder function required almost 3 months on average. Minimal restriction of abduction occurred in patients with hook-shaped acromions and long-standing preoperative symptoms. The present data do not support routine performance of acromioplasty.
Hypertension in an Adolescent Secondary to Performance-Enhancement Supplement Use
Authors: Milton Robin M. , Kelly-Rehm Merry , Brahm Nancy , Fox Mark D.
Published: May 2014

Objective: To describe the effects of performance-enhancing supplements and caffeine on the blood pressure (BP) of an adolescent male. Case Summary: An adolescent male presented to his primary care provider for a preseason athletic physical. On physical exam, his BP was 162/90, exceeding the 99th percentile for his age. It had been elevated during the previous 2 yearly physicals. He was referred to the Pediatric Preventive Cardiology Clinic for follow-up. Illegal substance use and renal trauma were ruled out. During the evaluation, the patient acknowledged using energy drinks and performance-enhancing supplements, the majority of which were caffeine-based. His intention was to continue the use of supplements, so lisinopril was initiated. On follow-up, however, the patient reported supplement discontinuation, intermittent medication adherence, and lower home-based BP readings. He was subsequently lost to follow-up. An objective causality assessment revealed that the adverse drug event was probable. Discussion: When working with adolescent patients, it is particularly important to conduct an in-depth interview reflecting lifestyle choices. Use of performance-enhancing supplements and caffeine for adolescent athletes has been well reported in the literature. Adolescent use of supplements may be driven by misguided beliefs and lack of knowledge about potentially detrimental health effects, such as altered heart rate and elevated BP. Little evidence-based research is available to provide treatment guidance for clinicians regarding potential effects. Conclusions: A thorough patient history, including specific questions probing for any recent or chronic use of nutritional supplements, including energy drinks, will help identify substances that may contribute to BP variations. Even mild BP elevations in adolescents should lead clinicians to further investigate supplement use and include specific questions on any product use within the past 24 hours, several days, or longer. Adolescents may not consider the potential for adverse health effects when ingesting performance-enhancing supplements or energy drinks.
Microstructure and mechanical properties of tungsten inert gas welded–brazed Mg/Ti lap joints
Authors: Xu C. , Sheng G. M. , Deng Y. Q. , Yuan X. J. , Tang K. L.
Published: May 2014

The tungsten inert gas (TIG) welding–brazing technology using Mg based filler was developed to join AZ31B Mg alloy to TA2 pure Ti in a lap configuration. The results indicate that robust joints can be obtained with welding current in the range of 60–70 A and welding speed of 0·2 m min−1. The joints were found to be composed of the coarse grained fusion zone accompanied with the precipitated phase of Mg17Al12, and a distributed Mg–Ti solid solution zone at the interface of Mg/Ti, indicating that metallurgical bonding was achieved. The maximum tensile–shear strength of 193·5 N mm−1, representing 82·3% joint efficiency relative to the Mg alloy base metal, was attained. The optimised Mg/Ti joint fractured at Mg fusion zone upon tensile–shear loading, mainly caused by grain coarsening. Moreover, the fracture surface practically consisted of scraggly areas, which was characterised by equiaxed dimple patterns accompanied with a few lamellar tearing.
Reactive friction stir processing of AA 5052–TiO2 nanocomposite: process–microstructure–mechanical characteristics
Authors: Khodabakhshi F. , Simchi A. , Kokabi A. H. , Sadeghahmadi M. , Gerlich A. P.
Published: May 2014

Friction stir processing (FSP) is a solid state route with a capacity of preparing fine grained nanocomposites from metal sheets. In this work, we employed this process to finely distribute TiO2 nanoparticles throughout an Al–Mg alloy, aiming to enhance mechanical properties. Titanium dioxide particles (30 nm) were preplaced into grooves machined in the middle of the aluminium alloy sheet and multipass FSP was afforded. This process refined the grain structure of the aluminium alloy, distributed the hard nanoparticles in the matrix and promoted solid state chemical reactions at the interfaces of the metal/ceramic particles. Detailed optical and electron microscopic studies showed that the microstructural homogeneity was improved with repetition of FSP up to four passes. The average grain size of the nanocomposite was ∼2 μm, while nanometric MgO and Al3Ti particles were formed in situ and homogenously distributed in the metal matrix. Mechanical characterisations showed that the yield strength and elongation were increased from 93±5 MPa and 13·8 to 117±3 MPa and 25·3 after employing four-pass FSP. Fractographic studies also revealed that agglomerated TiO2 particles could operate as sites of crack initiation and propagation, which led to brittle fracture. By increasing the number of FSP passes, the agglomerates were disappeared and the ductility was enhanced remarkably.
Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans
Authors: Flynn Ryan , Du Jing , Veenstra Rachelle G. , Reichenbach Dawn K. , Panoskaltsis-Mortari Angela , Taylor Patricia A. , Freeman Gordon J. , Serody Jonathan S. , Murphy William J. , Munn David H. , Sarantopoulos Stefanie , Luznik Leo , Maillard Ivan , Koreth John , Cutler Corey , Soiffer Robert J. , Antin Joseph H. , Ritz Jerome , Dubovsky Jason A. , Byrd John C. , MacDonald Kelli P. , Hill Geoff R. , Blazar Bruce R.
Published: May 2014

Key Points

T follicular helper cells and germinal center B cells are increased and strongly correlate with the development of cGVHD in a murine model. Blocking mAbs for IL-21, ICOS, and CD40L are potential novel therapeutics for cGVHD.
Minkowski-type inequalities involving Hardy function and symmetric functions
Authors: Wen JiaJin , Wu ShanHe , Han TianYong
Published: May 2014

The Hardy matrix

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, the Hardy function

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and the generalized Vandermonde determinant

det

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are defined in this paper. By means of algebra and analysis theories together with proper hypotheses, we establish the following Minkowski-type inequality involving Hardy function:

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+
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]

1

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+

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.

As applications, our inequality is used to estimate the lower bounds of the increment of a symmetric function.

MSC:26D15, 15A15.
Acid suppressive agents and risk of Mycobacterium Tuberculosis: case–control study
Authors: Hsu Wen-Hung , Kuo Chao-Hung , Wang Sophie SW , Lu Chien-Yu , Liu Chung-Jung , Chuah Seng-Kee , Kuo Fu-Chen , Chen Yen-Hsu , Huang Yaw-Bin , Hou Ming-Feng , Wu Deng-Chyang , Hu Huang-Ming
Published: May 2014

Background

The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported.

Methods

We conducted a case–control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed.

Results

TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended.

Conclusions

Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.
Site-selective substitutional doping with atomic precision on stepped Al (111) surface by single-atom manipulation
Authors: Chen Chang , Zhang Jinhu , Dong Guofeng , Shao Hezhu , Ning Bo-yuan , Zhao Li , Ning Xi-jing , Zhuang Jun
Published: May 2014

In fabrication of nano- and quantum devices, it is sometimes critical to position individual dopants at certain sites precisely to obtain the specific or enhanced functionalities. With first-principles simulations, we propose a method for substitutional doping of individual atom at a certain position on a stepped metal surface by single-atom manipulation. A selected atom at the step of Al (111) surface could be extracted vertically with an Al trimer-apex tip, and then the dopant atom will be positioned to this site. The details of the entire process including potential energy curves are given, which suggests the reliability of the proposed single-atom doping method.
Reference values for toe grip strength among Japanese adults aged 20 to 79 years: a cross‐sectional study
Authors: Uritani Daisuke , Fukumoto Takahiko , Matsumoto Daisuke , Shima Masayuki
Published: May 2014

Background

No standardised method has been adopted for measuring toe‐grip strength (TGS), and no reference values have been established for evaluating it. The present study investigated age‐related changes in TGS and the association of TGS with various descriptive characteristics.

Methods

TGS was measured in both feet of 1842 community‐dwelling individuals aged 20–79 years using a toe‐grip dynamometer. The participants were classified by decade into six age groups: 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years. Correlations for TGS between the dominant and non‐dominant sides were analysed according to decade and sex using Pearson's correlation coefficient. The mean TGS and TGS‐to‐weight ratio (TGS/Wt%) were compared between sexes by each decade and among all decades by sex using two‐way analysis of variance with post‐hoc tests. To assess relationships between mean TGS and various descriptive characteristics, we determined Pearson's correlation coefficient by sex and performed a stepwise multiple‐regression analysis. Significance was set at 5%.

Results

Correlations for TGS between the dominant and non‐dominant sides were significant in all decades by sex, ranging from 0.73 for men in their 70s to 0.91 for women in their 50s. Mean TGS and TGS/Wt% significantly differed between the sexes in all decades and in all decades except the 40s, respectively. In men, the mean TGS and TGS/Wt% significantly decreased with aging after the 50s and 60s, respectively. In women, both the mean TGS and TGS/Wt% significantly decreased between the 40s and 50s and between the 60s and 70s. TGS significantly correlated with age, height, and weight in both sexes. The stepwise multiple‐regression analysis revealed TGS was significantly associated with sex, age, height, and weight (adjusted R2 = 0.31).

Conclusions

TGS was closely correlated between the dominant and non‐dominant sides. TGS and TGS/Wt were significantly reduced with aging after the 50s in men and significantly reduced between the 40s and 50s and between the 60s and 70s in women. Age, sex, height, and weight accounted for only 30.8% of the variance in TGS. Therefore, other factors (e.g. toe flexibility, structural characteristics) should be considered for improving the accuracy of predicting TGS.
Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology
Authors: Bhansing Kavish J , Lammens Martin , Knaapen Hanneke KA , van Riel Piet LCM , van Engelen Baziel GM , Vonk Madelon C
Published: May 2014

Introduction

The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM).

Methods

A three-way comparison of patients with SSc-PM overlap (n = 25) with patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic features and causes of death. One neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and immunohistochemical staining. Clinical or myopathologic characteristics were compared by using the χ2 test or one-way analysis of variance (ANOVA).

Results

The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality was 32% (eight of 25) in SSc-PM, of which half was related to cardiac diseases. The prevalence of pulmonary fibrosis was significantly increased in SSc-PM (83%) (P = 0.04) compared with SSc (49%) and PM (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers were present, which was significantly increased compared with PM patients (P = 0.02).

Conclusions

Patients with SSc-PM have increased prevalence of pulmonary fibrosis and cardiac disease as the cause of death compared with patients with SSc and PM . In addition, we found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relation to pulmonary involvement and mortality in patients with SSc-PM overlap.
Using procalcitonin to guide antimicrobial duration in sepsis: asking the same questions will not bring different answers
Authors: Salluh Jorge IF , Nobre Vandack , Povoa Pedro
Published: May 2014

Severe sepsis is a major healthcare problem and the early initiation of antimicrobials is one of the few measures associated with improved outcomes. However, antibiotic overuse is an increasing problem in critical care. Of several potential biomarkers for antibiotic stewardship, procalcitonin represents the most widely studied and validated. In this commentary we address the current literature on the use of biomarkers to guide antimicrobial therapy in the critically ill and discuss its limitations and future directions.
Comparison of Subcutaneous Versus Intravenous Administration of Rituximab As Maintenance Treatment for Follicular Lymphoma: Results From a Two-Stage, Phase IB Study
Authors: Salar Antonio , Avivi Irit , Bittner Beate , Bouabdallah Reda , Brewster Mike , Catalani Olivier , Follows George , Haynes Andrew , Hourcade-Potelleret Florence , Janikova Andrea , Larouche Jean-François , McIntyre Christine , Pedersen Michael , Pereira Juliana , Sayyed Pakeeza , Shpilberg Ofer , Tumyan Gayane
Published: May 2014

Purpose

This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma.

Patients and Methods

In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m
2
, 625 mg/m
2
, or an additional group at 800 mg/m
2
) or IV rituximab (375 mg/m
2
). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (C
trough
) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1:1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m
2
) given at 2- or 3-month intervals. The objective was to demonstrate noninferior rituximab C
trough
of SC rituximab relative to IV rituximab 375 mg/m
2
.

Results

Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum C
trough
in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean C
trough SC
:C
trough
IV
ratios for the 2- and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration.

Conclusion

The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior C
trough
levels relative to IV rituximab 375 mg/m
2
dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.
Human Papillomavirus Genotyping and p16 Expression As Prognostic Factors for Patients With American Joint Committee on Cancer Stages I to III Carcinoma of the Anal Canal
Authors: Serup-Hansen Eva , Linnemann Dorte , Skovrider-Ruminski Wojciech , Høgdall Estrid , Geertsen Poul Flemming , Havsteen Hanne
Published: May 2014

Purpose

Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease-specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal.

Patients and Methods

HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone.

Results

HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved OS (74% v 52%; P = .036) and DSS (84% v 52%; P = .002), and p16 positivity was significantly correlated with improved OS (76% v 30%; P < .001) and DSS (85% v 30%; P < .001). In multivariable COX analysis that included HPV status, p16 status, sex, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for OS (hazard ratio [HR], 0.07; 95% CI, 0.01 to 0.61; P = .016) and DSS (HR, 0.07; 95% CI, 0.01 to 0.53; P = .011).

Conclusion

p16 positivity is an independent prognostic factor for OS and DSS in patients with AJCC stages I to III carcinoma of the anal canal.
Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Is Safe, Effective, and Efficient Neoadjuvant Treatment for Muscle-Invasive Bladder Cancer: Results of a Multicenter Phase II Study With Molecular Correlates of Response and Toxicity
Authors: Plimack Elizabeth R. , Hoffman-Censits Jean H. , Viterbo Rosalia , Trabulsi Edouard J. , Ross Eric A. , Greenberg Richard E. , Chen David Y.T. , Lallas Costas D. , Wong Yu-Ning , Lin Jianqing , Kutikov Alexander , Dotan Efrat , Brennan Timothy A. , Palma Norma , Dulaimi Essel , Mehrazin Reza , Boorjian Stephen A. , Kelly William Kevin , Uzzo Robert G. , Hudes Gary R.
Published: May 2014

Purpose

Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls.

Patients and Methods

Patients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity.

Results

Forty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non–muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity.

Conclusion

AMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy.
Novel Ligands Balance Estrogen Receptor β and α Agonism for Safe and Effective Suppression of the Vasomotor Response in the Ovariectomized Female Rat Model of Menopause
Authors: McGregor Chelsea , Sau Andrea , Ruddy Samantha C. , Leung Dan , Webb Murray , Durst Tony , Wright James S. , Lagace Diane , Pratt M.A. Christine
Published: May 2014

Vasomotor thermo-dysregulation (hot flashes) are an often debilitating symptom of menopause. Effective treatment is achieved primarily through activation of the estrogen receptor (ER)α with estrogens but is also associated with increased risk for breast and uterine cancer. In this study, we have tested novel compounds lacking the B ring of 17-hydroxy-β-estradiol (E2) (A-CD compounds) with differing ratios of ERα:ERβ binding affinities for the ability to reduce diurnal/nocturnal tail-skin temperatures (TSTs) in the ovariectomized female rat menopausal hot flash model. Normal mammary tissue expresses the predominantly antiproliferative ERβ. Therefore, we hypothesized that a preferential ERβ agonist with fractional ERα activity would safely reduce TSTs. The A-CD compound, L17, is a preferential ERβ agonist that has a ratio of ERβ:ERα binding affinity relative to E2 of 9.3 (where ERβ:ERα for E2, 1.0). In the ovariectomized rat, daily administration of low doses (1 mg/kg) of the A-CD compound TD81 (ERα:ERβ relative affinity, 15.2) was ineffective in temperature regulation, whereas L17 showed a trend toward TST reduction. Both E2 and the A-CD compound, TD3 (ERβ:ERα relative affinity, 5.0), also reduced TSTs but had marked proliferative effects on mammary and uterine tissues. At 2 mg/kg, L17 strongly reduced TSTs even more effectively than E2 but, importantly, had only minimal effect on uterine weight and mammary tissues. Both E2- and L17-treated rats showed similar weight reduction over the treatment period. E2 is rapidly metabolized to highly reactive quinones, and we show that L17 has 2-fold greater metabolic stability than E2. Finally, L17 and E2 similarly mediated induction of c-fos expression in neurons within the rat thermoregulatory hypothalamic median preoptic nucleus. Thus, the A-CD compound, L17, may represent a safe and effective approach to the treatment of menopausal hot flashes.
Dopamine-2 Receptor Activation Suppresses PACAP Expression in Gonadotrophs
Authors: Winters Stephen J. , Ghooray Dushan T. , Yang Rong Q , Holmes Joshua B. , O’Brien Andrew RW , Morgan Jay , Moore Joseph P.
Published: May 2014

Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed at a high level in the fetal pituitary and decreases profoundly between embryonic day 19 and postnatal day 1 (PN1), with a further decrease from PN1 to PN4. In this series of experiments, we investigated the hypothesis that dopamine 2 receptor (Drd2) activation interrupts a cAMP-dependent feed-forward loop that maintains PACAP expression at a high level in the fetal pituitary. Using single-cell RT-PCR of pituitary cell cultures from newborn rats, Drd2 mRNA was identified in gonadotrophs that were also positive for PACAP mRNA. PACAP expression in pituitary cultures from embryonic day 19 rats was suppressed by the PACAP6–38 antagonist and by the Drd2 agonist bromocriptine. Increasing concentrations of bromocriptine inhibited cAMP production as well as cAMP signaling based on cAMP response element-luciferase activity, decreased PACAP promoter activity, and decreased PACAP mRNA levels in αT3–1 gonadotroph cells. Furthermore, blockade of dopamine receptors by injecting haloperidol into newborn rat pups partially reversed the developmental decline in pituitary PACAP mRNA that occurs between PN1 and PN4. These results provide evidence that dopamine receptor signaling regulates PACAP expression under physiological conditions and lend support to the hypothesis that a rise in hypothalamic dopamine at birth abrogates cAMP signaling in fetal gonadotrophs to interrupt a feed-forward mechanism that maintains PACAP expression at a high level in the fetal pituitary. We propose that this perinatal decline in pituitary PACAP reduces pituitary follistatin which permits GnRH receptors and FSH-β to increase to facilitate activation of the neonatal gonad.