bluuebunny/crossref_metadata_2025 huggingface dataset:
Early multimodal rehabilitation following lumbar disc surgery: a randomised clinical trial comparing the effects of two exercise programmes on clinical outcome and lumbar multifidus muscle function
Authors: Hebert Jeffrey J , Fritz Julie M , Thackeray Anne , Koppenhaver Shane L , Teyhen Deydre
Published: September 2013

Background

The optimal components of postoperative exercise programmes following single-level lumbar discectomy have not been identified. Facilitating lumbar multifidus (LM) function after discectomy may improve postoperative recovery. The aim of this study was to compare the clinical and muscle function outcomes of patients randomised to receive early multimodal rehabilitation following lumbar discectomy consisting of exercises targeting specific trunk muscles including the LM or general trunk exercises.

Methods

We included participants aged 18 to 60 years who were scheduled to undergo single-level lumbar discectomy. After two postoperative weeks, participants were randomly assigned to receive an 8-week multimodal exercise programme including either general or specific trunk exercises. The primary outcome was pain-related disability (Oswestry Index). Secondary outcomes included low back and leg pain intensity (0–10 numeric pain rating scale), global change, sciatica frequency, sciatica bothersomeness and LM function measured with real-time ultrasound imaging. Treatment effects 10 weeks and 6 months after surgery were estimated with linear mixed models.

Results

61 participants were randomised to receive a general trunk (n=32) or specific (n=29) exercise programme. There were no between-group differences in clinical or muscle function outcomes. Participants in both groups experienced improvements in most outcome measures.

Conclusions

Following lumbar discectomy, multimodal rehabilitation programmes comprising specific or general trunk exercises have similar effects on clinical and muscle function outcomes. Local factors such as the individual patient characteristics identified by specific assessment findings, clinician expertise and patient preferences should direct therapy selection when considering the types of exercises tested in this trial for inclusion in rehabilitation programmes following lumbar disc surgery.
Stakeholder experiences with general practice pharmacist services: a qualitative study
Authors: Tan Edwin C K , Stewart Kay , Elliott Rohan A , George Johnson
Published: September 2013

Objectives

To explore general practice staff, pharmacist and patient experiences with pharmacist services in Australian general practice clinics within the Pharmacists in Practice Study.

Design

Qualitative study.

Setting

Two general practice clinics in Melbourne, Australia, in which pharmacists provided medication reviews, patient and staff education, medicines information and quality assurance services over a 6-month period.

Participants

Patients, practice staff and pharmacists.

Method

Semi-structured telephone interviews with patients, focus groups with practice staff and semi-structured interviews and periodic narrative reports with practice pharmacists. Data were analysed thematically and theoretical frameworks used to explain the findings.

Results

34 participants were recruited: 18 patients, 14 practice staff (9 general practitioners, 4 practice nurses, 1 practice manager) and 2 practice pharmacists. Five main themes emerged: environment; professional relationships and integration; pharmacist attributes; staff and patient benefits and logistical challenges. Participants reported that colocation and the interdisciplinary environment of general practice enabled better communication and collaboration compared to traditional community and consultant pharmacy services. Participants felt that pharmacists needed to possess certain attributes to ensure successful integration, including being personable and proactive. Attitudinal, professional and logistical barriers were identified but were able to be overcome. The findings were explained using D'Amour's structuration model of collaboration and Roger's diffusion of innovation theory.

Conclusions

This is the first qualitative study to explore the experiences of general practice staff, pharmacists and patients on their interactions within the Australian general practice environment. Participants were receptive of colocated pharmacist services, and various barriers and facilitators to integration were identified. Future research should investigate the feasibility and sustainability of general practice pharmacist roles.
Development of hospital disaster resilience: conceptual framework and potential measurement
Authors: Zhong Shuang , Clark Michele , Hou Xiang-Yu , Zang Yu-Li , Fitzgerald Gerard
Published: September 2013

Objective

Despite ‘hospital resilience’ gaining prominence in recent years, it remains poorly defined. This article aims to define hospital resilience, build a preliminary conceptual framework and highlight possible approaches to measurement.

Methods

Searches were conducted of the commonly used health databases to identify relevant literature and reports. Search terms included ‘resilience and framework or model’ or ‘evaluation or assess or measure and hospital and disaster or emergency or mass casualty and resilience or capacity or preparedness or response or safety’. Articles were retrieved that focussed on disaster resilience frameworks and the evaluation of various hospital capacities.

Result

A total of 1480 potentially eligible publications were retrieved initially but the final analysis was conducted on 47 articles, which appeared to contribute to the study objectives. Four disaster resilience frameworks and 11 evaluation instruments of hospital disaster capacity were included.

Discussion and conclusion

Hospital resilience is a comprehensive concept derived from existing disaster resilience frameworks. It has four key domains: hospital safety; disaster preparedness and resources; continuity of essential medical services; recovery and adaptation. These domains were categorised according to four criteria, namely, robustness, redundancy, resourcefulness and rapidity. A conceptual understanding of hospital resilience is essential for an intellectual basis for an integrated approach to system development. This article (1) defines hospital resilience; (2) constructs conceptual framework (including key domains); (3) proposes comprehensive measures for possible inclusion in an evaluation instrument; and (4) develops a matrix of critical issues to enhance hospital resilience to cope with future disasters.
DNA detection and seroprevalence of human papillomavirus in a cohort of adolescent women
Authors: Ermel Aaron C , Shew Marcia L , Weaver Bree A , Qadadri Brahim , Denski Cheryl , Tu Wanzhu , Tong Yan , Fortenberry J D , Brown Darron R
Published: September 2013

Objectives

Human papillomavirus (HPV) infections are common in adolescent women, while the rare cancerous sequelae of HPV infections do not generally occur until the 4th or 5th decades of life. This prospective study of a cohort of adolescent women was performed to further our knowledge of the natural history of incident and prevalent HPV infections.

Methods

Self-vaginal swabs collected from high-risk, unvaccinated adolescent women in a longitudinal study were analysed for HPV DNA. Sera were collected at enrolment and later tested for HPV antibodies. Statistical analysis was performed to determine the HPV genotype distribution and duration of detection, and to determine rates of seropositivity and seroconversion for HPV types represented in the assays.

Results

146 subjects (mean enrolment age=15.4 years; mean duration of follow-up=5.8 years) had samples adequate for analysis of HPV detection, and 95 of these subjects had paired sera available. The cumulative prevalence for high-risk and low-risk HPV types was 95.9% and 91.1%, respectively. HPV types 6, 11, 16 and 18 (HPV types represented in the quadrivalent vaccine) were found at some point in 40.4%, 6.2%, 48% and 24% of participants, respectively. Serological data confirmed exposure to these vaccine-covered types, as well as to other high-risk HPV types.

Conclusions

In this cohort of adolescent women, high- and low-risk HPV types were frequently detected, and serological data confirmed exposure in most subjects. The high-prevalence HPV types represented in the quadrivalent HPV vaccine further support vaccination of women at an age well before sexual debut.
External quality assurance with dried tube specimens (DTS) for point-of-care syphilis and HIV tests: experience in an indigenous populations screening programme in the Brazilian Amazon
Authors: Benzaken Adele Schwartz , Bazzo Maria Luiza , Galban Enrique , Pinto Ione Conceição Pereira , Nogueira Christiane Lourenço , Golfetto Lisléia , Benzaken Nina Schwartz , Sollis Kimberly A , Mabey David , Peeling Rosanna W
Published: September 2013

Objectives

The availability of point-of-care (POC) tests for infectious diseases has revolutionised the provision of healthcare for remote rural populations without access to laboratories. However, quality assurance for POC tests has been largely overlooked. We have evaluated the use and stability of dry tube specimens (DTS) for External Quality Assurance (EQA) for HIV and syphilis screening in remote indigenous populations in the Amazon region of Brazil.

Methods

All healthcare workers (HCWs) participating in the community-screening were trained. We used HIV and syphilis DTS panels developed by the reference laboratory, containing samples with negative and positive results at different antibody concentrations, for both infections. DTS panels were distributed to HCWs in the communities for reconstitution and testing using POC HIV and syphilis tests. The results of testing were sent to the reference laboratory for marking and remedial action taken where necessary.

Results

In total 268 HCWs tested 1607 samples for syphilis and 1608 samples for HIV. Results from HCWs showed a concordance rate of 90% for syphilis and 93% for HIV (κ coefficients of 0.74 and 0.78, respectively) with reference laboratories. Most false negatives were in samples of very low antibody concentration. DTS syphilis specimens produced the expected results after storage at 2–8°C or at 18–24°C for up to 3 weeks.

Conclusions

The results show that POC tests for syphilis and HIV give valid results in environments where traditional tests do not work, but errors in the interpretation of POC test results were identified by the EQA programme using DTS. EQA using DTS can help to improve the quality of screening programmes using POC tests in remote regions.
Pointing the way to improved welfare for companion animals
Authors: O'Neill D.
Published: September 2013

In May this year, the VetCompass small animal surveillance project passed a notable milestone and celebrated the half‐millionth animal being added to its database. To date, 190 veterinary practices across the UK have shared data on 2,890,973 episodes of clinical care covering 502,712 animals, including 251,771 dogs and 201,802 cats as well as a wide range of other companion animal species. Dan O'Neill describes the project and explains how the data gathered are being used.
Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo
Authors: Wang Lanlan , Wang Changjun , Su Bingnan , Song Quansheng , Zhang Yingmei , Luo Yang , Li Qi , Tan Weifeng , Ma Dalong , Wang Lu
Published: September 2013

Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA-MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells.
Winter and summer leaves of Cistus incanus: differences in leaf morphofunctional traits, photosynthetic energy partitioning, and poly(ADP-ribose) polymerase (PARP) activity
Authors: Arena Carmen , De Micco Veronica , De Maio Anna , Mistretta Carmela , Aronne Giovanna , Vitale Luca
Published: September 2013

Leaf anatomy, photosynthetic performance, and the role of poly(ADP-ribosyl)ation in maintaining genomic stability in winter and summer leaves of Cistus incanus L. were investigated to evaluate the strategies allowing this species to grow in a Mediterranean climate. Measurements on summer leaves (SL) were conducted at midday and on the following morning to assess the reversibility of changes induced by high temperatures and irradiances reached at midday. Winter leaves (WL) were thicker with a lower leaf density and higher intercellular spaces compared with SL, which showed reduced net photosynthesis (Pn) and a decrease in Rubisco activity. Compared with WL, SL showed a higher thermal dissipation (ΦNPQ) in compensating for the reduced Pn. This allowed minimization of ROS production (low ΦNO) and hence prevented photo-oxidative damage. In SL, poly(ADP-ribose) polymerase (PARP) activity was down-regulated, probably allowing leaves to become tolerant to high temperatures and irradiances. SL are also characterised by chloroplasts occupying larger cell volume and well exposed to intercellular spaces. This may well favour better liquid-phase CO2 diffusion towards carboxylation sites, contributing to reducing the negative influence of high leaf density and the low percentage of intercellular spaces on photosynthesis.
Musalmah Sauce: Opt for the Best
Authors: Dardak Rozhan Abu , Quoquab Farzana
Published: September 2013

This case illustrates how a processed food firm can strategize its business to increase its product sales in a competitive domestic market. Musalmah Food Industries Sdn Bhd (MFI), the manufacturer of Musalmah, a premium quality ready-to-eat sauce, had been facing fierce competition from other manufacturers of domestic and imported products in Malaysia. The intense competition led to a lower domestic sales growth. Musalmah had been retailed mostly at the supermarkets, hypermarkets and big grocery shops with the target to serve mainly the ethnic Malay consumers who traveled overseas and the outdoor types for camping or fishing activities. The sales performance for the past five years (2003 to 2008) showed a continuous increase but on a diminishing growth. Datuk Ibrahim Mohammad, the company's CEO directed his management team to prepare a business proposal to understand how they could increase their domestic sales based on the year 2008 performance. He wanted the business proposal to be ready by 30 April as he had to present it to the company's shareholders during the Musalmah Holding Berhad annual general meeting which had been scheduled for 25 May 2009.
DISTINCT ELEMENT METHOD SIMULATION ON DEFORMATION MODE AND STRESS STATE FOR SPECIMEN SHAPE IN DIRECT SHEAR TEST
Authors: KIM BYEONG-SU , PARK SEONG-WAN , KATO SHOJI
Published: September 2013

In order to examine the deformation mode and the stress state according to the specimen shape in the direct shear test (DST), a series of the three-dimensional DEM (distinct element method) simulations of the DST for sandy soils were carried out with the circular and the rectangular specimens. From the obtained results, the deformation mode of the rectangular specimen was under the plane strain condition, while the deformation mode of the circular specimen could not be explained as a plane strain condition. In addition, the principal stress states around the potential shear plane were analyzed and discussed by means of the analysis of the soil particle level.
The Shuilikeng fault in the central Taiwan mountain belt
Authors: Camanni Giovanni , Brown Dennis , Alvarez-Marron Joaquina , Wu Yih-Min , Chen Hsi-An
Published: September 2013

For over 200 km along strike the Shuilikeng fault of Taiwan separates Miocene rocks of the Western Foothills from the largely Eocene and Oligocene rocks of the Hsuehshan Range to the east. Despite its importance in the Taiwan mountain belt, the structure and kinematics of the Shuilikeng fault are not well known. Here, we present results from new geological mapping along 100 km of its strike length. At the surface, the Shuilikeng fault is a steeply east-dipping brittle fault with a series of splays and bifurcations. Along its southern part, it cuts an earlier fold and fault system. Outcrop kinematic data vary widely, from thrusting to strike-slip. The surface data are integrated with a relocated and collapsed seismicity database to interpret the fault location at depth. These data indicate that the Shuilikeng fault can be traced to greater than 20 km depth. Some 260 focal mechanisms from this dataset indicate that its kinematics is overall transpressive. From a regional perspective, we interpret the Shuilikeng fault to reactivate a pre-existing rift-related basin-bounding fault to the east of which rocks in the Hsuehshan Range are being exhumed.
Physiography of the NE margin of the Permian Salt Basin: new insights from 3D seismic reflection data
Authors: Jackson Christopher A-L. , Lewis Matthew M.
Published: September 2013

Three-dimensional seismic reflection data from the Egersund Basin, offshore Norway image geomorphological features that record mid-Permian footwall degradation of basin-bounding fault systems. This ancient landscape was subsequently flooded during the pan-European, Late Permian transgression of the North Permian Salt Basin and was fossilized beneath Zechstein Supergroup evaporites. We provide the first conclusive evidence for pre-Zechstein normal faulting in the Egersund Basin, indicating that extensional strain was shared between Permian and Late Jurassic–Early Cretaceous rift events.

Supplementary materials:

Uninterpreted versions of the seismic sections shown in Figure 2 are available are available at
www.geolsoc.org.uk/SUP18678
.
Preferential eruption of andesitic magmas: Implications for volcanic magma fluxes at convergent margins
Authors: Kent Adam J. R.
Published: September 2013

Andesitic magmas (herein defined as having
c.
55–65 wt% SiO
2
) are abundant in convergent margin volcanoes. Although andesites and other intermediate magmas can plausibly be produced by a number of mechanisms, a lack of evidence for andesitic liquids relative to the abundance of andesite volcanic rocks, together with widespread evidence for hybridization and recharge, suggests that many erupted andesites form by mixing between relatively mafic magmas that ultimately derive from the mantle wedge, and more felsic magmas or mush zones derived from differentiation and crustal melting.

A model of
recharge filtering
accounts for the high abundance of andesitic volcanic rocks and reflects the simple idea that the processes that create hybridized andesitic magmas in the shallow crust can also initiate volcanic activity, resulting in preferential eruption of andesitic magmas relative to the parental magmas that mix to produce them. This occurs via mafic recharge – intrusion of a mafic magma into a silicic magma or mush within the shallow crust. The overall abundance and variability from volcano to volcano of andesitic volcanism at convergent margins also suggests important roles for hydrous mafic magma in promoting mixing and eruption during mafic recharge, and the crust for modulating the compositions of volcanic outputs.
Effects of acute exercise on flow-mediated dilatation in healthy humans
Authors: Dawson Ellen A. , Green Daniel J. , Timothy Cable N. , Thijssen Dick H. J.
Published: September 2013

Although the effects of exercise training on vascular function have been well studied, less is known about the effects of acute exercise bouts. This synthesis summarizes and integrates knowledge derived from papers relating acute impacts of exercise on artery function, specifically endothelial function assessed by flow-mediated dilatation (FMD). We propose that an immediate decrease in FMD (“nadir”) occurs soon after exercise cessation and that this is followed by a (supra)normalization response. The magnitude of the nadir and (supra)normalization and duration of this biphasic pattern of response appears to be influenced by numerous factors, including the nature of the exercise stimulus (e.g., type, duration, intensity), the subject population (e.g., trained vs. untrained), and various methodological factors. The impact of these factors on the biphasic pattern are most likely mediated through stimuli that underpin altered FMD postexercise, including shear and oxidative stress, changes in arterial diameter, and antioxidant status. We propose that a combination of these stimuli act synergistically to balance the vasomotor responses postexercise. Finally, we discuss the potential (clinical) relevance of the biphasic response after acute exercise, as the immediate nadir may represent an essential response for subsequent training-induced adaptations but may also represent a transient period of increased cardiovascular risk leading to the “exercise paradox.”
Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia
Authors: Petousi Nayia , Croft Quentin P. P. , Cavalleri Gianpiero L. , Cheng Hung-Yuan , Formenti Federico , Ishida Koji , Lunn Daniel , McCormack Mark , Shianna Kevin V. , Talbot Nick P. , Ratcliffe Peter J. , Robbins Peter A.
Published: September 2013

Tibetan natives have lived on the Tibetan plateau (altitude ∼4,000 m) for at least 25,000 years, and as such they are adapted to life and reproduction in a hypoxic environment. Recent studies have identified two genetic loci, EGLN1 and EPAS1, that have undergone natural selection in Tibetans, and further demonstrated an association of EGLN1/ EPAS1 genotype with hemoglobin concentration. Both genes encode major components of the hypoxia-inducible factor (HIF) transcriptional pathway, which coordinates an organism's response to hypoxia. Patients living at sea level with genetic disease of the HIF pathway have characteristic phenotypes at both the integrative-physiology and cellular level. We sought to test the hypothesis that natural selection to hypoxia within Tibetans results in related phenotypic differences. We compared Tibetans living at sea level with Han Chinese, who are Tibetans' most closely related major ethnic group. We found that Tibetans had a lower hemoglobin concentration, a higher pulmonary ventilation relative to metabolism, and blunted pulmonary vascular responses to both acute (minutes) and sustained (8 h) hypoxia. At the cellular level, the relative expression and hypoxic induction of HIF-regulated genes were significantly lower in peripheral blood lymphocytes from Tibetans compared with Han Chinese. Within the Tibetans, we found a significant correlation between both EPAS1 and EGLN1 genotype and the induction of erythropoietin by hypoxia. In conclusion, this study provides further evidence that Tibetans respond less vigorously to hypoxic challenge. This is evident at sea level and, at least in part, appears to arise from a hyporesponsive HIF transcriptional system.
Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer
Authors: Garcia-Recio Susana , Fuster Gemma , Fernandez-Nogueira Patricia , Pastor-Arroyo Eva M. , Park So Yeon , Mayordomo Cristina , Ametller Elisabet , Mancino Mario , Gonzalez-Farre Xavier , Russnes Hege G. , Engel Pablo , Costamagna Domiziana , Fernandez Pedro L. , Gascón Pedro , Almendro Vanessa
Published: September 2013

ERBB receptor transmodulation by heterologous G-protein–coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2+ primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored. Cancer Res; 73(21); 6424–34. ©2013 AACR.
PRIMA-1Met/APR-246 Displays High Antitumor Activity in Multiple Myeloma By Induction of p73 and Noxa
Authors: Saha Manujendra N. , Jiang Hua , Yang Yijun , Reece Donna , Chang Hong
Published: September 2013

Targeting p53 by the small-molecule PRIMA-1Met/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1Met–induced apoptosis is not completely understood and its effect on multiple myeloma cells is unknown. In this study, we evaluated antitumor effect of PRIMA-1Met alone or its combination with current antimyeloma agents in multiple myeloma cell lines, patient samples, and a mouse xenograft model. Results of our study showed that PRIMA-1Met decreased the viability of multiple myeloma cells irrespective of p53 status, with limited cytotoxicity toward normal hematopoietic cells. Treatment of multiple myeloma cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of colony formation, and migration. PRIMA-1Met restored wild-type conformation of mutant p53 and induced activation of p73 upregulating Noxa and downregulating Mcl-1 without significant modulation of p53 level. siRNA-mediated silencing of p53 showed a little effect on apoptotic response of PRIMA-1Met, whereas knockdown of p73 led to substantial attenuation of apoptotic activity in multiple myeloma cells, indicating that PRIMA-1Met–induced apoptosis is, at least in part, p73–dependent. Importantly, PRIMA-1Met delayed tumor growth and prolonged survival of mice bearing multiple myeloma tumor. Furthermore, combined treatment of PRIMA-1Met with dexamethasone or doxorubicin displayed synergistic effects in both multiple myeloma cell lines and primary multiple myeloma samples. Consistent with our in vitro observations, cotreatment with PRIMA-1Met and dexamethasone resulted in enhanced antitumor activity in vivo. Our study for the first time shows antimyeloma activity of PRIMA-1Met and provides the rationale for its clinical evaluation in patients with multiple myeloma, including the high-risk group with p53 mutation/deletion. Mol Cancer Ther; 12(11); 2331–41. ©2013 AACR.
177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy
Authors: Reber Josefine , Haller Stephanie , Leamon Christopher P. , Müller Cristina
Published: September 2013

Targeted radionuclide therapy has shown impressive results for the palliative treatment of several types of cancer diseases. The folate receptor has been identified as specifically associated with a variety of frequent tumor types. Therefore, it is an attractive target for the development of new radionuclide therapies using folate-based radioconjugates. Previously, we found that pemetrexed (PMX) has a favorable effect in reducing undesired renal uptake of radiofolates. Moreover, PMX also acts as a chemotherapeutic and radiosensitizing agent on tumors. Thus, the aim of our study was to investigate the combined application of PMX and the therapeutic radiofolate 177Lu-EC0800. Determination of the combination index (CI) revealed a synergistic inhibitory effect of 177Lu-EC0800 and PMX on the viability of folate receptor–positive cervical (KB) and ovarian (IGROV-1) cancer cells in vitro (CI < 0.8). In an in vivo study, tumor-bearing mice were treated with 177Lu-EC0800 (20 MBq) and a subtherapeutic (0.4 mg) or therapeutic amount (1.6 mg) of PMX. Application of 177Lu-EC0800 with PMXther resulted in a two- to four-fold enhanced tumor growth delay and a prolonged survival of KB and IGROV-1 tumor-bearing mice, as compared to the combination with PMXsubther or untreated control mice. PMXsubther protected the kidneys from undesired side effects of 177Lu-EC0800 (20 MBq) by reducing the absorbed radiation dose. Intact kidney function was shown by determination of plasma parameters and quantitative single-photon emission computed tomography using 99mTc-DMSA. Our results confirmed the anticipated dual role of PMX. Its unique features resulted in an improved antitumor effect of folate-based radionuclide therapy and prevented undesired radio-nephrotoxicity. Mol Cancer Ther; 12(11); 2436–45. ©2013 AACR.
Facial Affect Recognition Performance and Event-Related Potentials in Violent and Non-Violent Schizophrenia Patients
Authors: Frommann Nicole , Stroth Sanna , Brinkmeyer Jürgen , Wölwer Wolfgang , Luckhaus Christian
Published: September 2013

We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) are more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become apparent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and fear stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly larger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces are more salient and evoke higher arousal. Larger impairment in AR performance combined with higher salience and arousal may contribute to the occurrence of violent acts in schizophrenia patients.
Serum Brain-Derived Neurotrophic Factor Levels and Cocaine-Induced Transient Psychotic Symptoms
Authors: Corominas-Roso Margarida , Roncero Carlos , Eiroa-Orosa Francisco-Jose , Ribasés Marta , Barral Carmen , Daigre Constanza , Martínez-Luna Nieves , Sánchez-Mora Cristina , Ramos-Quiroga Josep Antoni , Casas Miguel
Published: September 2013

Background: Cocaine-induced psychosis (CIP) is among the most serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the involvement of BDNF in CIP are lacking. Methods: A total of 22 cocaine-dependent patients (aged 33.65 ± 6.85) who had never experienced psychotic symptoms under the influence of cocaine (non-CIP) and 18 patients (aged 34.18 ± 8.54) with a history of CIP completed a 2-week detoxification program in an inpatient facility. Two serum samples were collected from each patient at baseline and at the end of the protocol. Demographic, consumption and clinical data were recorded for all patients. A paired group of healthy controls was also included. Results: At the beginning of the detoxification treatment, serum BDNF levels were similar in both the non-CIP and the CIP groups. During early abstinence, the non-CIP group exhibited a significant increase in serum BDNF levels (p = 0.030), whereas the CIP group exhibited a decrease. Improvements in depression (Beck Depression Inventory, BDI, p = 0.003) and withdrawal symptoms (Cocaine Selective Severity Assessment, CSSA, p = 0.013) show a significant positive correlation with serum BDNF levels in the non-CIP group, whereas no correlation between the same variables was found in the CIP group. Conclusions: This study suggests that BDNF plays a role in the transient psychotic symptoms associated with cocaine consumption. In the non-CIP group, the increase in serum BDNF appears to be driven by the effects of chronic cocaine consumption and withdrawal. In contrast, patients with CIP share some of the neurotrophic deficiencies that characterize schizophrenia and psychosis.
Differences in Geographical Distribution and Risk Factors for Urinary Incontinence in Turkey: Analysis of 6,473 Women
Authors: Dursun Polat , Dogan Nasuh Utku , Kolusari Ali , Dogan Selen , Ugur Mete Gurol , Komurcu Ozge , Altuntas Baris , Gultekin Murat , Celik Nilufer Yigit , Karaca Mehmet , Guzel Ahmet Baris , Cim Numan , Ege Serhat , Koc Onder , Yigit Filiz Altinok
Published: September 2013

Objective: To assess the prevalence, types and risk factors for urinary incontinence (UI) and to evaluate the impact of incontinence on quality of life by using validated and objective questionnaires in the western and eastern parts of Turkey. Methods: In this multicenter observational study, 6,473 women from 38 cities in the western and eastern parts of Turkey were included. UI was assessed by ICIQ-SF (International Consultation on Incontinence Questionnaire Short Form) and IIQ-7 (Incontinence Impact Questionnaire). Results: The UI rate was 20.9% (10% for stress, 8.3% overactive bladder and 2.6% for mixed type). In all, stress incontinence was the most common type. The rate of UI in women residing in the west was higher than in women living in the east (p < 0.001). ICIQ scores were comparable in the two groups but women in the west scored higher in each item of the IIQ. Age >40 years (p < 0.001), number of siblings >5 (p < 0.001) and low educational status (p < 0.001) increased the rate of incontinence. In binary logistic regression analysis menopausal status, age >40 years, number of siblings >5, being overweight, region of residence, and educational status were associated with UI. Conclusion: The rate of UI in women residing in the western part of Turkey was higher than women living in the east. Residing in a different geographical region (in our case living either in the western or eastern part of Turkey) seemed to be an independent risk factor for UI. Moreover, UI deteriorates quality of life and more attention should be paid to this vulnerable population.
Community-Acquired Methicillin-Resistant Staphylococcus aureus: The New Face of an Old Foe?
Authors: Udo Edet E.
Published: September 2013

The burden of infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing among different patient populations globally. As CA-MRSA has become established in healthcare facilities, the range of infections caused by them has also increased. Molecular characterization of CA-MRSA isolates obtained from different centers has revealed significant diversity in their genetic backgrounds. Although many CA-MRSA strains are still susceptible to non-β-lactam antibiotics, multiresistance to non-β-lactam agents has emerged in some clones, posing substantial problems for empirical and directed therapy of infections caused by these strains. Some CA-MRSA clones have acquired the capacity to spread locally and internationally. CA-MRSA belonging to ST80-MRSA-IV and ST30-MRSA-IV appear to be the dominant clones in the countries of the Gulf Cooperation Council (GCC). The emergence of pandemic CA-MRSA clones not only limits therapeutic options but also presents significant challenges for infection control. Continued monitoring of global epidemiology and emerging drug resistance data is critical for the effective management of these infections.
Sperm Parameters: Paradigmatic Index of Good Health and Longevity
Authors: Omu Alexander E.
Published: September 2013

Since the discovery of spermatozoon by Anton van Leeuwenhoek in 1677, there has been an ever increasing understanding of its role in reproduction. Many factors adversely affect sperm quality, including varicocele, accessory gland infection, immunological factors, congenital abnormalities, and iatrogenic systemic and endocrine causes, such as diabetes mellitus, obesity, metabolic syndrome, and smoking. The mechanisms responsible for the association between poor sperm parameters and ill health may include oxidative stress, low-grade inflammation, low testosterone, and low sex-hormone-binding globulin. Oxidative stress in the testicular microenvironment may result in decreased spermatogenesis and sperm DNA damage, loss of sperm motility, and abnormal sperm morphology. Low testosterone caused by advanced age, visceral obesity, and inflammation is associated with the development of cardiovascular disease. Hence, semen analysis has an important role in the routine evaluation of idiopathic male infertility, usually manifested as low sperm counts, impaired sperm motility, or absence of sperm, and remains the most common single diagnostic tool. Several studies have shown an inverse relationship between semen quality and medical disorders. This review elucidates the effect of medical disorders and social habits on sperm quality, the mechanisms that are involved in the impairment of sperm quality, and whether or not sperm quality can be used as an index of good health and longevity in a man.
Primary Cytomegalovirus Infection in Pregnant Egyptian Women Confirmed by Cytomegalovirus IgG Avidity Testing
Authors: Kamel N. , Metwally L. , Gomaa N. , Sayed Ahmed W.A. , Lotfi M. , Younis S.
Published: September 2013

Objective: To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. Subjects and Methods: A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. Results: All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Conclusion: Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing.
Serum Endostatin and Risk of Mortality in the Elderly
Authors: Ärnlöv Johan , Ruge Toralph , Ingelsson Erik , Larsson Anders , Sundström Johan , Lind Lars
Published: September 2013

Objective—

Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk.

Approach and Results—

Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25–1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10–1.66]).

Conclusions—

High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.
Apolipoprotein A-IV Expression in Mouse Liver Enhances Triglyceride Secretion and Reduces Hepatic Lipid Content by Promoting Very Low Density Lipoprotein Particle Expansion
Authors: VerHague Melissa A. , Cheng Dongmei , Weinberg Richard B. , Shelness Gregory S.
Published: September 2013

Objective—

Previous studies demonstrated that apolipoprotein A-IV (apoA-IV) promotes apoB lipoprotein–mediated triglyceride (TG) secretion in transfected enterocytes and hepatoma cells; however, evidence for a role in lipid transport in vivo is lacking. Using mouse models, we explored the role of apoA-IV in hepatic very low density lipoprotein–mediated lipid efflux under conditions that promote hepatic steatosis.

Approach and Results—

Hepatic steatosis, induced by either high-fat diet or enhanced de novo lipogenesis caused by transgenic overexpression of SREBP-1a (SREBP-1a
Tg
), was associated with up to a 43-fold induction of hepatic apoA-IV mRNA and protein levels. In both models, a positive linear correlation between hepatic TG content and apoA-IV mRNA abundance was observed (
r
2
=0.8965). To examine whether induction of apoA-IV affected hepatic TG secretion, SREBP-1a
Tg
mice were crossed with
Apoa4
knockout mice. With Triton blockade of peripheral lipolysis, SREBP-1a
Tg
/
Apoa4
knockout mice demonstrated a 24% reduction in hepatic TG secretion rate, relative to SREBP-1a
Tg
controls, but no change in apoB production. Negative stain electron microscopy revealed a 33% decrease in the abundance of secreted very low density lipoprotein particles with diameters ≥120 nm. Conversely, mice infected with a recombinant human apoA-IV adenovirus demonstrated a 52% increase in the hepatic TG secretion rate, relative to controls, a 38% reduction in liver TG content, and a 43% increase in large diameter (≥120 nm) very low density lipoprotein particles, with no change in apoB secretion.

Conclusions—

Hepatic steatosis in mice induces hepatic apoA-IV expression, which in turn promotes lipoprotein particle expansion and reduces hepatic lipid burden without increasing the number of secreted atherogenic apoB-containing lipoprotein particles.
Vascular Endothelial Growth Factor Blockade Prevents the Beneficial Effects of β-Blocker Therapy on Cardiac Function, Angiogenesis, and Remodeling in Heart Failure
Authors: Rengo Giuseppe , Cannavo Alessandro , Liccardo Daniela , Zincarelli Carmela , de Lucia Claudio , Pagano Gennaro , Komici Klara , Parisi Valentina , Scala Oriana , Agresta Alessia , Rapacciuolo Antonio , Perrone Filardi Pasquale , Ferrara Nicola , Koch Walter J. , Trimarco Bruno , Femminella Grazia Daniela , Leosco Dario
Published: September 2013

Background—

Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, β-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart.

Methods and Results—

Eight weeks from surgically induced myocardial infarction, heart failure rats were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week treatment period, echocardiography revealed reduced cardiac diameters and improved cardiac function in B-treated compared with vehicle-treated rats. Moreover, B treatment was associated with increased cardiac angiogenesis and in vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after B treatment was started, increased cardiac VEGF expression and Akt and endothelial NO synthase activation were observed by comparing B-treated with drug-untreated failing hearts. To test whether the proangiogenic effects of B act via activation of VEGF pathway, rats were intravenously injected with adenoviral vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at the start of the treatment with B. After 10 weeks, histological analysis revealed reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the positive effects of B on cardiac function and remodeling.

Conclusions—

β-Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF signaling pathway. β-Blocker–induced enhancement of cardiac angiogenesis is essential for the favorable effects of this therapy on cardiac function and remodeling.
Oxidized Ca
2+
/Calmodulin-Dependent Protein Kinase II Triggers Atrial Fibrillation
Authors: Purohit Anil , Rokita Adam G. , Guan Xiaoqun , Chen Biyi , Koval Olha M. , Voigt Niels , Neef Stefan , Sowa Thomas , Gao Zhan , Luczak Elizabeth D. , Stefansdottir Hrafnhildur , Behunin Andrew C. , Li Na , El-Accaoui Ramzi N. , Yang Baoli , Swaminathan Paari Dominic , Weiss Robert M. , Wehrens Xander H.T. , Song Long-Sheng , Dobrev Dobromir , Maier Lars S. , Anderson Mark E.
Published: September 2013

Background—

Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting reactive oxygen species and AF are unknown. The Ca
2+
/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a reactive oxygen species–activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF.

Methods and Results—

We found that oxidized CaMKII was increased in atria from AF patients compared with patients in sinus rhythm and from mice infused with angiotensin II compared with mice infused with saline. Angiotensin II–treated mice had increased susceptibility to AF compared with saline-treated wild-type mice, establishing angiotensin II as a risk factor for AF in mice. Knock-in mice lacking critical oxidation sites in CaMKIIδ (MM-VV) and mice with myocardium-restricted transgenic overexpression of methionine sulfoxide reductase A, an enzyme that reduces oxidized CaMKII, were resistant to AF induction after angiotensin II infusion.

Conclusions—

Our studies suggest that CaMKII is a molecular signal that couples increased reactive oxygen species with AF and that therapeutic strategies to decrease oxidized CaMKII may prevent or reduce AF.