bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries
Authors: Khedr Naglaa Fathi
Published: March 2015

Cyclophosphamide (CP) causes infertility due to ovarian toxicity. The toxicity mechanism suggests oxidative stress. We assessed whether mirtazapine (MTZ) and hesperidin (HSP) could promote ovarian protection against damage due to CP chemotherapy. Female Wistar rats aged 14 weeks were used. Animals were divided into four groups: control vehicle group ( n = 8); CP group ( n = 8, rats received 150 mg/kg of CP, single intraperitoneal [i.p.] injection); CP + MTZ group ( n = 8, rats received same dose of CP + 30 mg/kg of MTZ, orally, daily); and HSP + CP group ( n = 8, rats received same dose of CP + 100 mg/kg of HSP, orally, daily). After eight days of medication, ovaries were removed and ovarian toxicity was assessed by counting follicles and corpora lutea. Nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were estimated in ovarian tissue. NO level, MDA level, and MPO activity were increased ( P < 0.001), while, GPx and SOD activities were lowered significantly ( P < 0.001) in CP-treated group compared with control vehicle. In addition, ovulation, number of follicles, and ovarian weight were reduced by CP treatment. On the contrary, rats pretreated with MTZ and HSP showed significant decrease in NO, MDA levels, and MPO activity, while, activities of SOD and GPx were increased ( P < 0.001). Oxidative stress induced by CP in the rat ovary causes infertility in the female rats. HSP and MTZ could reverse this effect and provide protection of fertility against CP-induced toxicity.
Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders
Authors: Brown Shan-Estelle , Vagenas Panagiotis , Konda Kelika A. , Clark Jesse L. , Lama Javier R. , Gonzales Pedro , Sanchez Jorge , Duerr Ann C. , Altice Frederick L.
Published: March 2015

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW ( n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves “social” drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs.
Early report: The use of Cytosorb™ haemabsorption column as an adjunct in managing severe sepsis: initial experiences, review and recommendations
Authors: Morris Craig , Gray Lewis , Giovannelli Marco
Published: March 2015

A novel synthetic haemabsorption column (Cytosorb™) has recently become commercially available. We describe its use in patients with overwhelming sepsis and consider the experience and evidence supporting its use. While Cytosorb haemabsorption is mechanistically distinct from other extracorporeal therapies in sepsis and appears effective in reducing inflammatory cytokines during sepsis, much of the basic science and clinical benefits remain unclear. Significant interactions including removal of antibiotics may be harmful and require further study. Suggestions for future research and how Cytosorb™ could be incorporated into practice are provided.
N-acetylcysteine infusion in preventing hepatotoxicity secondary to intravenous injection of household bleach
Authors: Eidan Anthony H , Sira James , Bellamy Mark
Published: March 2015

We present a case of non-accidental injection of 40 ml of domestic bleach through a long-term central venous catheter (CVC) with subsequent AKI, and for the first time in the literature severe coagulopathy and acute liver injury. We detail the clinical course of events and our management plan which adds to the body of evidence for prognosis and treatment in these unusual cases.
Michael Oakeshott’s political philosophy of civil association and constructivism in International Relations
Authors: Orsi Davide
Published: March 2015

This article shows the relevance of Oakeshott’s political philosophy for the contemporary constructivist debate in International Relations. First, the article argues that Oakeshott’s perspective stresses that political institutions are based on norms and relationships which result from human understanding. Second, it elaborates on Nicholas Rengger’s recent work and reveals that Oakeshott’s On Human Conduct presents considerations pertaining to international politics that are consistent with his broader political philosophy. These observations concern the nature of war, the historical role of colonialism and the evolution of international society. Third, this article discusses Terry Nardin’s notion of ‘practical association’ and Christian Reus-Smit’s criticism of it. It contends that international civil association is a relationship between states based on understood and socially constructed moral values and practices. Finally, the article claims that customary international law declares and reflects these values and practices. As such, it reveals that Oakeshott’s notion of authority and his theory of civil association illuminate the possibility of an international legal order without a legislative office. This is of particular relevance also because of the Hobbesian influence on Oakeshott. Overall, this article illustrates how Michael Oakeshott’s theory of civil association sheds light on the nature of international society and law.
Monitoring the Progression of Spontaneous Articular Cartilage Healing with Infrared Spectroscopy
Authors: O’Brien Megan P. , Penmatsa Madhuri , Palukuru Uday , West Paul , Yang Xu , Bostrom Mathias P. G. , Freeman Theresa , Pleshko Nancy
Published: March 2015

Objective

Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design

Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and IFOP data obtained from defect and adjacent regions at 2, 4, 6, 8, 12, and 16 weeks postsurgery. Tissues were assessed histologically using the modified O’Driscoll score, by FT-IRIS, and by partial least squares (PLS) modeling of IFOP spectra.

Results

The FT-IRIS parameters of collagen content, proteoglycan content, and collagen index correlated significantly with modified O’Driscoll score ( P = 0.05, 0.002, and 0.02, respectively), indicative of their sensitivity to tissue healing. Repair tissue IFOP spectra were distinguished from normal tissue IFOP spectra in all samples by PLS analysis. However, the PLS model for prediction of histological score had a high prediction error, which was attributed to the spectral information being acquired from the tissue surface only.

Conclusion

The strong correlations between FT-IRIS data and histological score support further development of the IFOP technique for clinical applications, although further studies to optimize data collection from the full sample depths are required.
Availability of Alcoholic Beverages During the Brazilian Navy Working Hours
Authors: Halpern Elizabeth Espindola , Leite Ligia Costa
Published: March 2015

This article presents and discusses one of the five main categories that emerged from the narratives of patients treated in a military outpatient clinic of the Brazilian Navy: the availability of drinks on board. A dense ethnography was conducted at this clinic from 2005 to 2009, and, in 2010, a participant observation was carried out in two treatment groups, during 24 sessions. Sampling, data collection, analysis, and interpretation occurred in an interactive way, rather than in a stepwise sequence. Data interpretation was possible by using the Peircean abduction reasoning of the peculiar categories that emerged in the participants’ discourse. A templum-synthesis was built according to the Boudon diagram to analyze and discuss the information. In conclusion, the institution seems to contribute to the production of the alcoholic habitus, unaware that alcohol availability may influence the emergence of alcoholism, leading to harmful impacts on the health of its contingent.
Young Women With Anorexia Nervosa
Authors: Dahlborg Lyckhage Elisabeth , Gardvik Anna , Karlsson Helena , Törner Mulari Jenny , Berndtsson Ina
Published: March 2015

The aim of this study was to describe how young women living with self-identified anorexia narrate about their lives by blogging. Thirteen Swedish blogs were chosen and analyzed by means of qualitative content analysis. The results described falling ill, the illness itself, and the path to recovery. Low self-esteem, depressed state of mind, and self-destructive behavior were typical signs at the start of the illness. The women’s lives were characterized by a need for controlling their body by tormenting it and by the illness demanding all their concentration and energy. The women suffered from the feeling of being a disappointment to their family members. The illness was like an enemy that had to be defeated with the help of family members, health care professionals, and by means of therapy. A turning point occurred when the women felt at their worst or had tired of the illness and could concentrate on something other than their body and the eating disorder. Suffering from self-identified anorexia was described as experiencing low self-esteem. The illness took all of the women’s time and energy. For a turning point to be reached, the women needed support from family, friends, and health care professionals, including the use of distractions.
Where Have We Been and Where Are We Going? A Conceptual Framework for Child Advocacy
Authors: Cascardi Michele , Brown Cathy , Shpiegel Svetlana , Alvarez Ariel
Published: March 2015

The primary goal of this article is to chart the development of child advocacy as an interdisciplinary field of study and conclude with a conceptual framework for research and higher education in child advocacy. Historically, child advocacy has justifiably focused on protection needs. Values and assumptions about children’s best interest have also governed child advocacy, in part because evidence to inform decisions was lacking and in part because of its history as an activist movement. Against this historical backdrop, we describe contemporary trends in child advocacy that reconcile children’s protection with their inherent rights to personhood. We rely on the principles and articles of the United Nations Convention on the Rights of the Child, most notably children’s rights to participation and self-expression. At the same time, we demonstrate how values and ideology are being integrated with empiricism and objective analysis to inform policy and practice in child advocacy. The future of child advocacy depends on continued synthesis of rights and protection as well as values and rigorous analysis. From this perspective, we offer a conceptual framework for research and education in child advocacy.
Pivoting Health Promotional Efforts Among Fathers
Authors: Rovito Michael J. , Rovito Kathy E.
Published: March 2015

The ideas of “father” and “family” as they are traditionally defined may possibly limit the effectiveness of parenting interventions among certain groups of contemporary fathers. Strongly held normative beliefs portraying men as daft caregivers and/or characterizing most families as traditional with mother serving as primary caregiver may not be appropriately addressing the needs of many modern American families. Each father has his unique needs and sets of skills that must be taken into consideration when developing health outreach programs. Essentially, effective parenting curriculum should be tailored to specific types of fathers. Health promotion and health education professionals need to become aware of these newly emerging fathers in order to create more relevant and effective educational programs. This discussion is an attempt to bring awareness to this issue and help facilitate a transition from a singular approach to fatherhood outreach rooted in traditional characterizations of “family” and “father” to a more diverse, multifactorial approach addressing more unique populations of fathers, hereby called Generation F. A pedagogical guideline to assist in developing more effective interventions targeting fathers is presented.
WellnessRx Education Initiative
Authors: Bistritz Lana , Kovacs-Burns Katharina , Avdagovska Melita , McCargar Linda , Olson Karin , Gramlich Leah
Published: March 2015

Background. Health profession students require knowledge and skills in nutrition and physical activity for patient/client care and for their own wellness. This is generally lacking in their preprofessional didactic education. Method. Based on an environmental scan of health profession student education programs at our university and a conceptual framework based on adult learning theory and Kolb’s cycle, interprofessional stakeholders developed online learning modules on nutrition and physical activity for incorporation into course curricula by health science faculties. This process included articulating goals and objectives, with an outcome of enhancing student knowledge, skills, and attitudes (KSAs). Pilots of the modules included student KSA assessment and interviews/focus groups. Results. Designing learning modules on nutrition and physical activity for individualized implementation in different faculties was a priority. Two learning modules were developed and pilot-tested within one faculty. Pre- and posttests of student knowledge were used to assess effectiveness. Knowledge scores improved from pretest (54.7%) to posttest (68.2%, p < .001) for the module “Nutrition and Physical Activity Across the Life Cycle” but did not change significantly (pretest 76.3%, posttest 77.0%; p = .70) for the “Self-Health” module. Interviews/focus groups showed students perceived the two modules as influencing their learning of KSAs. Conclusions. This process addressed a curricular gap across health science faculties. The consensus-building design process helped focus curriculum priorities and develop a shared curriculum vision. Students demonstrated KSA learning as shown in their pre–post assessments and comments. Further module development and larger scale implementation and evaluation studies are proposed.
Effectiveness of cold metal transfer process for welding 7075 aluminium alloys
Authors: Elrefaey A.
Published: March 2015

Cold metal transfer (CMT) welding is a promising process to improve the mechanical characteristics of the hard to weld 7075-T6 aluminium alloy owing to its unique advantages in contrast to conventional metal inert gas welding process. The welded joints, using ER5356, were identified and characterised by means of optical microscopy, scanning electron microscopy and energy dispersive spectroscopy. Mechanical properties were measured by tensile and hardness tests. Results indicate that CMT provides better joint tensile strength and ductility compared to metal inert gas welding. The softness in the heat affected zone was very low, but a big hardness gap was recognised in the welded metal compared to base metal. The joint had mechanical property coefficients of 77%, 60% and 69% for yield strength, ultimate tensile strength and elongation respectively.
NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT
Authors: Karimi Mobin A. , Bryson Jerrod L. , Richman Lee P. , Fesnak Andrew D. , Leichner Theresa M. , Satake Atsushi , Vonderheide Robert H. , Raulet David H. , Reshef Ran , Kambayashi Taku
Published: March 2015

Key Points

NKG2D enhances cytotoxicity and survival of CD8+ T cells, which contributes to GVHD and GVT effects after allogeneic HSCT. The temporally distinct expression pattern of NKG2D ligands may allow separation of GVHD and GVT effects by transient NKG2D blockade.
Sensitization of P2Χ3 Receptors by Cystathionine β-Synthetase Mediates Persistent Pain Hypersensitivity in a Rat Model of Lumbar Disc Herniation
Authors: Wang Qianliang , Zhu Hongyan , Zou Kang , Yuan Bo , Zhou You-Lang , Jiang Xinghong , Yan Jun , Xu Guang-Yin
Published: March 2015

Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2Χ3Rs and P2Χ2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2Χ3Rs, but not P2Χ1Rs and P2Χ2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2Χ3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced-persistent pain hypersensitivity. Our results suggest that sensitization of P2Χ3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2Χ3R signaling may represent a potential treatment for neuropathic pain caused by LDH.
Functional outcomes in ICU – what should we be using? - an observational study
Authors: Parry Selina M , Denehy Linda , Beach Lisa J , Berney Sue , Williamson Hannah C , Granger Catherine L
Published: March 2015

Introduction

With growing awareness of the importance of rehabilitation, new measures are being developed specifically for use in the intensive care unit (ICU). There are currently 26 measures reported to assess function in ICU survivors. The Physical Function in Intensive care Test scored (PFIT-s) has established clinimetric properties. It is unknown how other functional measures perform in comparison to the PFIT-s or which functional measure may be the most clinically applicable for use within the ICU. The aims of this study were to determine (1) the criterion validity of the Functional Status Score for the ICU (FSS-ICU), ICU Mobility Scale (IMS) and Short Physical Performance Battery (SPPB) against the PFIT-s; (2) the construct validity of these tests against muscle strength; (3) predictive utility of these tests to predict discharge to home; and (4) the clinical applicability. This was a nested study within an ongoing controlled study and an observational study.

Methods

Sixty-six individuals were assessed at awakening and ICU discharge. Measures included: PFIT-s, FSS-ICU, IMS and SPPB. Bivariate relationships (Spearman’s rank correlation coefficient) and predictive validity (logistic regression) were determined. Responsiveness (effect sizes); floor and ceiling effects; and minimal important differences were calculated.

Results

Mean ± SD PFIT-s at awakening was 4.7 ± 2.3 out of 10. On awakening a large positive relationship existed between PFIT-s and the other functional measures: FSS-ICU (rho = 0.87, p < 0.005), IMS (rho = 0.81, p < 0.005) and SPPB (rho = 0.70, p < 0.005). The PFIT-s had excellent construct validity (rho = 0.8, p < 0.005) and FSS-ICU (rho = 0.69, p < 0.005) and IMS (rho = 0.57, p < 0.005) had moderate construct validity with muscle strength. The PFIT-s and FSS-ICU had small floor/ceiling effects <11% at awakening and ICU discharge. The SPPB had a large floor effect at awakening (78%) and ICU discharge (56%). All tests demonstrated responsiveness; however highest effect size was seen in the PFIT-s (Cohen’s d = 0.71).

Conclusions

There is high criterion validity for other functional measures against the PFIT-s. The PFIT-s and FSS-ICU are promising functional measures and are recommended to measure function within the ICU.

Trial registration

Clinicaltrials.gov NCT02214823. Registered 7 August 2014).
Validity of administrative data in recording sepsis: a systematic review
Authors: Jolley Rachel J , Sawka Keri Jo , Yergens Dean W , Quan Hude , Jetté Nathalie , Doig Christopher J
Published: March 2015

Introduction

Administrative health data have been used to study sepsis in large population-based studies. The validity of these study findings depends largely on the quality of the administrative data source and the validity of the case definition used. We systematically reviewed the literature to assess the validity of case definitions of sepsis used with administrative data.

Methods

Embase and MEDLINE were searched for published articles with International Classification of Diseases (ICD) coded data used to define sepsis. Abstracts and full-text articles were reviewed in duplicate. Data were abstracted from all eligible full-text articles, including ICD-9- and/or ICD-10-based case definitions, sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV).

Results

Of 2,317 individual studies identified, 12 full-text articles met all eligibility criteria. A total of 38 sepsis case definitions were tested, which included over 130 different ICD codes. The most common ICD-9 codes were 038.x, 790.7 and 995.92, and the most common ICD-10 codes were A40.x and A41.x. The PPV was reported in ten studies and ranged from 5.6% to 100%, with a median of 50%. Other tests of diagnostic accuracy were reported only in some studies. Sn ranged from 5.9% to 82.3%; Sp ranged from 78.3% to 100%; and NPV ranged from 62.1% to 99.7%.

Conclusions

The validity of administrative data in recording sepsis varied substantially across individual studies and ICD definitions. Our work may serve as a reference point for consensus towards an improved and harmonized ICD-coded definition of sepsis.
Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia
Authors: Lyon Richard M , Perkins Zane B , Chatterjee Debamoy , Lockey David J , Russell Malcolm Q ,   on behalf of Kent, Surrey & Sussex Air Ambulance Trust
Published: March 2015

Introduction

Rapid Sequence Induction of anaesthesia (RSI) is the recommended method to facilitate emergency tracheal intubation in trauma patients. In emergency situations, a simple and standardised RSI protocol may improve the safety and effectiveness of the procedure. A crucial component of developing a standardised protocol is the selection of induction agents. The aim of this study is to compare the safety and effectiveness of a traditional RSI protocol using etomidate and suxamethonium with a modified RSI protocol using fentanyl, ketamine and rocuronium.

Methods

We performed a comparative cohort study of major trauma patients undergoing pre-hospital RSI by a physician-led Helicopter Emergency Medical Service. Group 1 underwent RSI using etomidate and suxamethonium and Group 2 underwent RSI using fentanyl, ketamine and rocuronium. Apart from the induction agents, the RSI protocol was identical in both groups. Outcomes measured included laryngoscopy view, intubation success, haemodynamic response to laryngoscopy and tracheal intubation, and mortality.

Results

Compared to Group 1 (n = 116), Group 2 RSI (n = 145) produced significantly better laryngoscopy views (p = 0.013) and resulted in significantly higher first-pass intubation success (95% versus 100%; p = 0.007). A hypertensive response to laryngoscopy and tracheal intubation was less frequent following Group 2 RSI (79% versus 37%; p < 0.0001). A hypotensive response was uncommon in both groups (1% versus 6%; p = 0.05). Only one patient in each group developed true hypotension (SBP < 90 mmHg) on induction.

Conclusions

In a comparative, cohort study, pre-hospital RSI using fentanyl, ketamine and rocuronium produced superior intubating conditions and a more favourable haemodynamic response to laryngoscopy and tracheal intubation. An RSI protocol using fixed ratios of these agents delivers effective pre-hospital trauma anaesthesia.
Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials
Authors: Ruan Sheng-Yuan , Huang Tao-Min , Wu Hon-Yen , Wu Huey-Dong , Yu Chong-Jen , Lai Mei-Shu
Published: March 2015

Introduction

Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS.

Methods

A systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model.

Results

Ten RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75).

Conclusions

The available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.
Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model
Authors: Lacerda Lara , Debeb Bisrat G , Smith Daniel , Larson Richard , Solley Travis , Xu Wei , Krishnamurthy Savitri , Gong Yun , Levy Lawrence B , Buchholz Thomas , Ueno Naoto T , Klopp Ann , Woodward Wendy A
Published: March 2015

Introduction

Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d’orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth.

Methods

Hypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs).

Results

MSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors.

Conclusions

Our findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers.
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response
Authors: Jézéquel Pascal , Loussouarn Delphine , Guérin-Charbonnel Catherine , Campion Loïc , Vanier Antoine , Gouraud Wilfried , Lasla Hamza , Guette Catherine , Valo Isabelle , Verrièle Véronique , Campone Mario
Published: March 2015

Introduction

Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients.

Methods

We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n = 87) was used for validation.

Results

Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P < 0.0001 for both comparisons). Significant event-free survival (P = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 (P = 0.01) and C2 (P = 0.02). Event-free survival analysis results were confirmed when our cohort was pooled with the external cohort (n = 194; P = 0.01). Functional annotation showed that 22% of triple-negative patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response and low M2-like macrophages were a hallmark of C3, and that these patients had a better event-free survival than C2 patients, characterized by low immune response and high M2-like macrophages: P = 0.02 for our cohort, and P = 0.03 for pooled cohorts.

Conclusions

We identified three subtypes of triple-negative patients: luminal androgen receptor (22%), basal-like with low immune response and high M2-like macrophages (45%), and basal-enriched with high immune response and low M2-like macrophages (33%). We noted out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in triple-negative basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype triple-negative patients.
PCAC: Power- and Connectivity-Aware Clustering for Wireless Sensor Networks
Authors: Butun Ismail , Ra In-ho , Sankar Ravi
Published: March 2015

In this article, we investigate clustering algorithms that are proposed for wireless sensor networks (WSNs). Then, we propose a clustering algorithm for WSNs called PCAC, that is both power and connectivity aware. Our proposed Power- and Connectivity-Aware Clustering (PCAC) algorithm provides higher energy efficiency and increases the total life time (TLT) of the network. We evaluate our proposed PCAC algorithm in a simulation environment and compare its performance to previously proposed algorithms. According to the simulation results, our proposed PCAC algorithm is energy efficient and also provides longer TLT (in worst-case, up to 85% improvement for a 15-node network with one-hop connectivity) to the network, compared to the previously proposed algorithms.
Application of Reverse Transcriptase –PCR (RT-PCR) for rapid detection of viable Escherichia coli in drinking water samples
Authors: Molaee Neda , Abtahi Hamid , Ghannadzadeh Mohammad Javad , Karimi Masoude , Ghaznavi-Rad Ehsanollah
Published: March 2015

Background

Polymerase chain reaction (PCR) is preferred to other methods for detecting Escherichia coli (E. coli) in water in terms of speed, accuracy and efficiency. False positive result is considered as the major disadvantages of PCR. For this reason, reverse transcriptase-polymerase chain reaction (RT-PCR) can be used to solve this problem. The aim of present study was to determine the efficiency of RT-PCR for rapid detection of viable Escherichia coli in drinking water samples and enhance its sensitivity through application of different filter membranes.

Materials and methods

Specific primers were designed for 16S rRNA and elongation Factor II genes. Different concentrations of bacteria were passed through FHLP and HAWP filters. Then, RT-PCR was performed using 16srRNA and EF –Tu primers. Contamination of 10 wells was determined by RT-PCR in Arak city. To evaluate RT-PCR efficiency, the results were compared with most probable number (MPN) method.

Results

RT-PCR is able to detect bacteria in different concentrations. Application of EF II primers reduced false positive results compared to 16S rRNA primers. The FHLP hydrophobic filters have higher ability to absorb bacteria compared with HAWB hydrophilic filters. So the use of hydrophobic filters will increase the sensitivity of RT-PCR.

Conclusion

RT-PCR shows a higher sensitivity compared to conventional water contamination detection method. Unlike PCR, RT-PCR does not lead to false positive results. The use of EF-Tu primers can reduce the incidence of false positive results. Furthermore, hydrophobic filters have a higher ability to absorb bacteria compared to hydrophilic filters.
A Modified Delphi Process to Identify Process of Care Indicators for the Identification, Prevention and Management of Acute Kidney Injury after Major Surgery
Authors: James Matthew T , Pannu Neesh , Barry Rebecca , Karsanji Divya , Tonelli Marcello , Hemmelgarn Brenda R , Manns Braden J , Bagshaw Sean M , Stelfox H Tom , Dixon Elijah
Published: March 2015

Background:

The outcomes of acute kidney injury (AKI) are well appreciated. However, valid indicators of high quality processes of care for AKI after major surgery are lacking.

Objectives:

To identify indicators of high quality processes of care related to AKI prevention, identification, and management after major surgery.

Design:

A three stage modified Delphi process.

Setting:

The study was conducted in Alberta, Canada using an online format.

Participants:

A panel of care providers from surgery, critical care, and nephrology.

Measurements:

The degree of validity of candidate indicators were rated by panelists on a 7-point Likert scale that ranged from “strongly disagree” to “strongly agree”.

Methods:

A focused literature review was performed to identify candidate indicators. A modified Delphi process, with three rounds, was used to obtain expert consensus on the validity of potential process of care quality indicators.

Results:

Thirty-three physicians participated (6 from surgery, 10 from critical care, and 17 from nephrology). A list of 58 potential process of care quality indicators for AKI after surgery was generated including 28 indicators from the initial literature review and 30 indicators suggested by panelists. Following the third round of questioning, 40 process of care indicators were identified with a high level of agreement for face validity; 16 of these reached high consensus among all panelists.

Limitations:

The consensus of panelists from Alberta, Canada may not be generalizable to other settings. The modified Delphi process did not focus on the feasibility of measuring these process indicators.

Conclusions:

These indicators can be used to measure and improve the quality of care for AKI after major surgery.
Biased assembly of the nuclear pore complex is required for somatic and germline nuclear differentiation in Tetrahymena
Authors: Iwamoto Masaaki , Koujin Takako , Osakada Hiroko , Mori Chie , Kojidani Tomoko , Matsuda Atsushi , Asakawa Haruhiko , Hiraoka Yasushi , Haraguchi Tokuko
Published: March 2015

Ciliates have two functionally distinct nuclei, a somatic macronucleus (MAC) and a germline micronucleus (MIC) that develop from daughter nuclei of the last postzygotic division (PZD) during the sexual process of conjugation. Understanding this nuclear dimorphism is a central issue in ciliate biology. We show, by live-cell imaging of Tetrahymena, that biased assembly of the nuclear pore complex (NPC) occurs immediately after the last PZD, which generates anterior-posterior polarized nuclei: MAC-specific NPCs assemble in anterior presumptive MACs, but not in posterior presumptive MICs. MAC-specific NPC assembly in the anterior nuclei occurs much earlier than transport of Twi1p, which is required for MAC genome rearrangement. Correlative light-electron microscopy shows that addition of new nuclear envelope (NE) precursors occurs through the formation of domains of redundant NE, where the outer double membrane contains the newly assembled NPCs. Nocodazole inhibition of the second PZD results in assembly of MAC-specific NPCs in the division-failed zygotic nuclei, leading to failure of MIC differentiation. Our findings demonstrate that NPC type switching has a critical role in the establishment of nuclear differentiation in ciliates.
Weak and contradictory effects of self-medication with nectar nicotine by parasitized bumblebees
Authors: Baracchi David , Brown Mark J. F. , Chittka Lars
Published: March 2015

The presence of antimicrobial secondary metabolites in nectar suggests that pollinators, which are threatened globally by emergent disease, may benefit from the consumption of nectars rich in these metabolites. We tested whether nicotine, a nectar secondary metabolite common inSolenaceaeandTiliaspecies, is used by parasitized bumblebees as a source of self-medication,using a series of toxicological, microbiological and behavioural experiments. Caged bees infected withCrithidia bombi[TI1] had a slight preference for sucrose solution laced with the alkaloid and behavioural tests showed that the parasite infection induced an increased consumption of nicotine during foraging activity. When ingested, nicotine delayed the progression of a gut infection in bumblebees by a few days, but dietary nicotine did not clear the infection, and after 10 days the parasite load approached that of control bees. Moreover, when pathogens were exposed to the alkaloid prior to host ingestion the protozoan’s viability was not directly affected, suggesting that anti-parasite effects were relatively weak. Nicotine consumption in a single dose did not impose any cost even in food-stressed bees (starved) but the alkaloid had detrimental effects on healthy bees if consistently consumed for weeks. These toxic effects disappeared in infected bees suggesting that detoxification costs might have been counterbalanced by the advantages in slowing the progression of the infection. Nonetheless we did not find a benefit of nicotine consumption in terms of life expectancy of infected bees, making these findings difficult to interpret. Our results indicate that caution is warranted in interpreting impacts of plant metabolites on insect parasites and suggest that the conditions under which nicotine consumption provides benefits to either bees or plants remain to be identified. The contention that secondary metabolites in nectar may be under selection from pollinators, or used by plants to enhance their own reproductive success, remains to be confirmed.
Yakutia’s Mining Science Contribution to the Republic’s Ecological Security Problems Solution
Authors: Киселев  , Kiselev V. , Каймонов  , Kaimonov Mikhail , Хохолов  , Khokholov Yu.
Published: March 2015

Created by unutilized waste a potential radiation hazard for a biota has been noted in this paper. The radiation and

ecological situation in Yakutia’s certain regions have been considered. Developed by institute a concept and solid highly

toxic waste disposal processes have been submitted.
Ice-Jam Floods in the Irkutsk Region and Possibility of Their Elimination by Combined Methods
Authors: Тимофеева  , Timofeeva Svetlana , Морозова  , Morozova O.
Published: March 2015

A retrospective analysis of floods in the Irkutsk region territory caused by ice-jam phenomena has been performed. The

region’s most dangerous sites and areas have been revealed. Prediction estimates for a possible number of the floods

caused by ice-jam formation in the Irkutsk region territory have been carried out based on statistical information analysis

for the last 20 years. Methods of fight against ice-jams have been considered, and a combined technology of ice weakening

has been offered. Field trial results have been presented. It has been recommended to apply an entering of brine from

Znamensky industrial water field into ice kerfs or ice’s blackened surface irrigation.
Staff Training on Work Safety Within a Framework of “Technosphere Safety” Direction
Authors: Девисилов  , Devisilov Vladimir
Published: March 2015

The problem related to staff training on work safety – what and how specialists for labor protection services should learn —

is considered. An offered structure of educational program for “Work Safety” profile within a framework of "Technosphere

safety" higher education direction has been presented. Tasks related to improvement of education system in the specified

area have been defined.
Online Content Pricing: Purchase and Rental Markets
Authors: Rao Anita
Published: March 2015

Digitization of content is changing how consumers and firms use purchase and rental markets. Low transaction costs make accessing content easier for consumers. Digital technology enables firms to create nondurable “rental” versions of their content and to restrict content to the purchasing consumer, effectively shutting down resale markets. To empirically analyze the interaction of purchase and rental markets, I design a preference measurement tool to recover consumers’ intertemporal preferences through current-period choices alone. I then use these preferences to solve for a dynamic equilibrium between consumers and the firm. In the context of the online home video market, I find that when the firm is able to commit to holding prices fixed forever, providing content through the purchase market alone is sufficient. However, when the firm is unable to commit, it should serve both purchase and rental markets. Canonical theory models would predict exclusive rentals, but the purchase option enables indirect price discrimination in practice. I also find that when consumers place a premium on accessing new content, they are less likely to intertemporally substitute, thereby increasing the firm’s pricing power. Consistent with theory, commitment to future prices increases profits considerably. This finding supports the rigid pricing structure of such retailers as Apple, despite studios’ push toward more pricing flexibility.
No Unlabeled Containers Anywhere, Ever! Where Did this Come From?
Authors: Cohen Michael R. , Smetzer Judy L.
Published: March 2015

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Retrospective Review of Critically Ill Patients Experiencing Alcohol withdrawal: Dexmedetomidine versus Propofol and/or Lorazepam Continuous Infusions
Authors: Ludtke Kimberly A. , Stanley Kevin S. , Yount Natalie L. , Gerkin Richard D.
Published: March 2015

Background

Alcohol withdrawal symptoms can be difficult to manage and may lead to an intensive care unit (ICU) admission. Patients experiencing severe alcohol withdrawal often require high doses of sedatives, which can lead to respiratory depression and the need for endotracheal intubation. Dexmedetomidine, an alpha-2 adrenoreceptor agonist, provides adequate sedation with little effect on respiratory function when compared to other sedatives.

Objective

To evaluate sedation with a continuous infusion of dexmedetomidine versus propofol and/or lorazepam in critically ill patients experiencing alcohol withdrawal.

Methods

A retrospective chart review was conducted on ICU admissions between March 2002 and April 2009 for alcohol withdrawal patients who necessitated treatment with a continuous infusion of dexmedetomidine, propofol, and/or lorazepam. Primary outcomes included the incidence of mechanical ventilation, length of mechanical ventilation (if applicable), and ICU and hospital length of stay.

Results

Fifteen patients were treated with a continuous infusion of dexmedetomidine, and 17 were treated with an infusion of propofol and/or lorazepam. Two patients (13.3%) required intubation and mechanical ventilation in the dexmedetomidine group versus 10 (58.8%) in the propofol and/or lorazepam group ( P = .006). Length of stay in the ICU was 53 hours for patients treated with dexmedetomidine versus 114.9 hours in the propofol and/or lorazepam group ( P = .016). Hospital length of stay was less for the dexmedetomidine group, 135.8 hours versus 241.1 hours in the propofol and/or lorazepam group ( P = .008).

Conclusions

Dexmedetomidine use was associated with a decrease in the incidence of endotracheal intubation when used to sedate patients experiencing alcohol withdrawal. Patients transferred to a lower level of care faster and were discharged from the hospital sooner when treated with dexmedetomidine.