bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus
Authors: Harris Kira B. , McCarty Delilah J.
Published: November 2014

Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first- and second-line diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin. Greater glycemic control was seen with liraglutide compared with the other GLP-1 treatment options; however, the two long-acting agents were superior to exenatide twice daily. All agents were well tolerated with most adverse events being mild or moderate in nature. The most common adverse event was transient nausea which typically resolved 4–8 weeks after treatment initiation. Long-acting agents had lower rates of nausea but an increased incidence of injection site reactions. Trials have suggested GLP-1 RAs may improve cardiovascular risk factors including blood pressure, lipid parameters and inflammatory markers. Future trials are needed to confirm the clinical outcomes of these agents. Overall, GLP-1 RAs will provide benefit for patients with T2DM intolerable to or not reaching glycemic goals with first-line agents, especially in patients in need of weight loss.
Development of a measure of knowledge use by stakeholders in rehabilitation technology
Authors: Stone Vathsala I , Nobrega Amanda R , Lane Joseph P , Tomita Machiko R , Usiak Douglas J , Lockett Michelle M
Published: November 2014

Objectives:

Uptake of new knowledge by diverse and diffuse stakeholders of health-care technology innovations has been a persistent challenge, as has been measurement of this uptake. This article describes the development of the Level of Knowledge Use Survey instrument, a web-based measure of self-reported knowledge use.

Methods:

The Level of Knowledge Use Survey instrument was developed in the context of assessing effectiveness of knowledge communication strategies in rehabilitation technology. It was validated on samples representing five stakeholder types: researchers, manufacturers, clinician–practitioners, knowledge brokers, and consumers. Its structure is broadly based on Rogers’ stages of innovation adoption. Its item generation was initially guided by Hall et al’s Levels of Use framework. Item selection was based on content validity indices computed from expert ratings ( n1 = 4; n2 = 3). Five representative stakeholders established usability of the web version. The version included 47 items (content validity index for individual items >0.78; content validity index for a scale or set of items >0.90) in self-reporting format. Psychometrics were then established for the version.

Results:

Analyses of data from small ( n = 69) and large ( n = 215) samples using the Level of Knowledge Use Survey instrument suggested a conceptual model of four levels of knowledge use—Non-awareness, Awareness, Interest, and Use. The levels covered eight dimensions and six user action categories. The sequential nature of levels was inconclusive due to low cell frequencies. The Level of Knowledge Use Survey instrument showed adequate content validity (≈ 0.88; n = 3) and excellent test–retest reliability (1.0; n = 69). It also demonstrated good construct validity ( n = 215) for differentiating among new knowledge outputs ( p < 0.001) and among stakeholder types (0.001 <  p ≤ 0.013). It showed strong responsiveness to change between baseline and follow-up testing (0.001 <  p ≤ 0.002; n = 215).

Conclusion:

The Level of Knowledge Use Survey instrument is valid and reliable for measuring uptake of innovations across diffuse stakeholders of rehabilitation technologies and therefore also for tracking changes in knowledge use.
Does educational intervention improve doctors’ knowledge and perceptions of generic medicines and their generic prescribing rate? A study from Malaysia
Authors: Hassali Mohamed Azmi , Wong Zhi Yen , Alrasheedy Alian A. , Saleem Fahad , Mohamad Yahaya Abdul Haniff , Aljadhey Hisham
Published: November 2014

Objectives:

To investigate the impact of an educational intervention on doctors’ knowledge and perceptions towards generic medicines and their generic (international non-proprietary name) prescribing practice.

Methods:

This is a single-cohort pre-/post-intervention pilot study. The study was conducted in a tertiary care hospital in Perak, Malaysia. All doctors from the internal medicine department were invited to participate in the educational intervention. The intervention consisted of an interactive lecture, an educational booklet and a drug list. Doctors’ knowledge and perceptions were assessed by using a validated questionnaire, while the international non-proprietary name prescribing practice was assessed by screening the prescription before and after the intervention.

Results:

The intervention was effective in improving doctors’ knowledge towards bioequivalence, similarity of generic medicines and safety standards required for generic medicine registration (p = 0.034, p = 0.034 and p = 0.022, respectively). In terms of perceptions towards generic medicines, no significant changes were noted (p > 0.05). Similarly, no impact on international non-proprietary name prescribing practice was observed after the intervention (p > 0.05).

Conclusion:

Doctors had inadequate knowledge and misconceptions about generic medicines before the intervention. Moreover, international non-proprietary name prescribing was not a common practice. However, the educational intervention was only effective in improving doctors’ knowledge of generic medicines.
Heart rate variability evaluation in the assessment and management of in-utero drug-exposed infants
Authors: Nagiub Mohamed , Alton Karen , Avula Varun , Hagglund Karen , Anne Premchand
Published: November 2014

Aim:

To determine whether heart rate variability parameters vary between in-utero drug-exposed infants and controls. To determine correlations between Finnegan score and heart rate variability parameters. To differentiate those drug-exposed infants who require treatment from those infants who do not.

Methods:

A total of 24 jaundiced control subjects and 25 in-utero drug-exposed infants were enrolled. The Finnegan score and an electrocardiographic rhythm strip were obtained at 4-h intervals. RR intervals (time between consecutive R waves) were manually tabulated from the rhythm strip and analyzed. Time-domain heart rate variability parameters were calculated and analyzed for both groups.

Results:

Heart rate variability parameters were cumulatively lower over 3 days in in-utero drug-exposed infants compared with controls (p < 0.05). Root mean square of differences of standard deviation of RR intervals on first day of life, and standard deviation of RR intervals, percentage of consecutive RR intervals greater than 50 ms, and root mean square of differences of standard deviation of RR intervals on the second day of life were significantly lower between in-utero drug-exposed infants and control infants. Three out of five parameters were significantly lower in in-utero drug-exposed infants pre-treatment versus post-treatment (p = 0.001, p = 0.0001, and p = 0.021, respectively). Root mean square of differences of standard deviation of RR intervals was able to differentiate in-utero drug-exposed infants requiring opiate therapy and in-utero drug-exposed infants that did not (p = 0.02).

Conclusion:

Heart rate variability analysis can contribute to the management of in-utero drug-exposed infants. Heart rate variability could be used in dose titration.
Efficacy of chemotherapy after hormone therapy for hormone receptor–positive metastatic breast cancer
Authors: Mori Ryutaro , Nagao Yasuko
Published: November 2014

Objective:

According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases.

Methods:

Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated.

Results:

A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy.

Conclusion:

The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of hormone receptor–positive metastatic breast cancer, if needed.
Atrial myxoma masquerading as Takayasu’s arteritis
Authors: Fung Kenneth , Edmondson Stephen , Wald David S
Published: November 2014

Lesson

We describe the case of a 48-year-old woman whose atrial myxoma was mistaken for vasculitis. The case report highlights the reasons why these two disorders may become confused, the dangers of initiating the wrong treatment and a simple means of avoiding misdiagnosis.
Should magnetic resonance imaging or computed tomography be the primary brain imaging modality in the transient ischemic attack clinic?
Authors: Ganesalingam Jeban , Jenkins I Harri
Published: November 2014

Objective

The Royal College of Physicians and National Institute of Clinical Excellence have recommended that magnetic resonance imaging should be the modality of choice for cerebral imaging in transient ischemic attack patients. However, implementation of this is often difficult. Therefore, it is important to know whether magnetic resonance imaging contributes significantly to early clinical management in transient ischemic attack patients.

Design

A retrospective case-notes review of 65 consecutive patients seen by one neurology trainee (with consultant review), in a neurovascular service where computed tomography has been the primary cerebral imaging modality.

Setting

Outpatient TIA/Neurovascular clinic at Imperial College hospital.

Participants

65 consecutive patients seen by one neurology trainee (with consultant review).

Main outcome measure

We recorded the preliminary clinical diagnosis, details of investigations performed and whether or not patients had a magnetic resonance imaging brain scan subsequently, the number followed up in clinic and the final diagnosis.

Results

Of the 65 cases seen, 55% were classified initially as transient ischemic attack/stroke mimics. Of the 29 cases (45%) that were classified as transient ischemic attack, all had computed tomography scans, 12 had magnetic resonance imaging scans subsequently and 14 were followed up several weeks later. Of the 36 cases classified as stroke mimics, 27 had computed tomography scans immediately and 31 had carotid Dopplers, six subsequently had magnetic resonance imaging scans and 14 were followed up in clinic. Only two patients had their diagnosis revised on the basis of the magnetic resonance imaging.

Conclusions

Our study suggests that magnetic resonance imaging brain changes the diagnosis in a relatively small percentage of cases. A good history and examination remain paramount in the assessment of patients presenting to the transient ischemic attack clinic, particularly when more than 50% of cases referred are transient ischemic attack/stroke mimics.
Hypochondriacal attitudes and beliefs, attitudes towards complementary and alternative medicine and modern health worries predict patient satisfaction
Authors: Fionda Sofia , Furnham Adrian
Published: November 2014

Summary

Objective

To investigate how hypochondriacal attitudes and beliefs, attitudes towards complementary and alternative medicine (CAM) and modern health worries (MHWs) related to patient satisfaction with their general practitioner.

Design

Participants completed a five-part questionnaire anonymously which measured satisfaction with one’s doctor, hypochondriacal beliefs, attitudes to CAM, MHWs and personality.

Setting

England

Participants

Included 215 adults from a variety of cultural backgrounds.

Main outcome measure

The Illness Attitudes Scales measuring the attitudes, fears and beliefs associated with hypochondriasis; Worry about Illness; Concerns about Pain, Health Habits, Hypochondriacal beliefs; Thanatophobia, Disease phobia, Bodily preoccupations; Treatment experience and Effects of symptoms.

Results

Correlations (around r = .10 to .25) and Regressions (R square from .06 to .09) showed demographic and personality variables only modestly related to patient satisfaction. Hypochondriasis, CAM and MHWs were associated with greater patient dissatisfaction as predicted with the former as the most powerful correlate.

Conclusion

The study indicates the different needs of potential patients in a typical medical consultation. It is important to ascertain patients’ health beliefs and practices with regard to medical history, attitudes to CAM and MHWs to increase consultation satisfaction.
Views of senior UK doctors about working in medicine: questionnaire survey
Authors: Lambert Trevor W , Smith Fay , Goldacre Michael J
Published: November 2014

Summary

Objectives

We surveyed the UK medical qualifiers of 1993. We asked closed questions about their careers; and invited them to give us comments, if they wished, about any aspect of their work. Our aim in this paper is to report on the topics that this senior cohort of UK-trained doctors who work in UK medicine raised with us.

Design

Questionnaire survey

Participants

3479 contactable UK-trained medical graduates of 1993.

Setting

UK.

Main outcome measures

Comments made by doctors about their work, and their views about medical careers and training in the UK.

Method

Postal and email questionnaires.

Results

Response rate was 72% (2507); 2252 were working in UK medicine, 816 (36%) of whom provided comments. Positive comments outweighed negative in the areas of their own job satisfaction and satisfaction with their training. However, 23% of doctors who commented expressed dissatisfaction with aspects of junior doctors’ training, the impact of working time regulations, and with the requirement for doctors to make earlier career decisions than in the past about their choice of specialty. Some doctors were concerned about government health service policy; others were dissatisfied with the availability of family-friendly/part-time work, and we are concerned about attitudes to gender and work-life balance.

Conclusions

Though satisfied with their own training and their current position, many senior doctors felt that changes to working hours and postgraduate training had reduced the level of experience gained by newer graduates. They were also concerned about government policy interventions.
The Effects of Reiki Therapy and Companionship on Quality of Life, Mood, and Symptom Distress During Chemotherapy
Authors: Orsak Gabriela , Stevens Arlene M. , Brufsky Adam , Kajumba Mayanja , Dougall Angela Liegey
Published: November 2014

This pilot study examined the effects of Reiki therapy and companionship on improvements in quality of life, mood, and symptom distress during chemotherapy. Thirty-six breast cancer patients received usual care, Reiki, or a companion during chemotherapy. First, data were collected from patients receiving usual care. Second, patients were randomized to either receive Reiki or a companion during chemotherapy. Questionnaires assessing quality of life, mood, symptom distress, and Reiki acceptability were completed at baseline and chemotherapy sessions 1, 2, and 4. Reiki was rated relaxing with no side effects. Reiki and companion groups reported improvements in quality of life and mood that were greater than those seen in the usual care group. Interventions during chemotherapy, such as Reiki or companionship, are feasible, acceptable, and may reduce side effects.
Dental Provider Attitudes Are a Barrier to Expanded Oral Health Care for Children ≤3 Years of Age
Authors: Clark Sarah J. , Duong Sophia , Fontana Margherita
Published: November 2014

Purpose. To describe the perspectives of general dentists regarding oral health care for children ≤3 years. Methods. Mailed survey of 444 general dentists in Michigan. Results. Although most dentists were aware of recommendations for early dental visits, only 36% recommended their own patients begin dental visits by 1 year of age. Only 37% dentists felt that screening for oral health problems can be done by medical providers, whereas 34% agreed administration of fluoride varnish by medical providers would be effective in preventing dental problems in young children. Conclusions. Dentists’ failure to recommend 1-year dental visits is due neither to lack of awareness nor to capacity problems. The limited enthusiasm for involving children’s medical providers in oral health promotion signals attitudinal barriers that must be overcome to improve children’s oral health. Primary care providers should identify and refer to dentists in their community who are willing to see young children.
HGAL localization to cell membrane regulates B-cell receptor signaling
Authors: Lu Xiaoqing , Sicard Renaud , Jiang Xiaoyu , Stockus Jessica N. , McNamara George , Abdulreda Midhat , Moy Vincent T. , Landgraf Ralf , Lossos Izidore S.
Published: November 2014

Key Points

HGAL protein can be myristoylated and palmitoylated, and these modifications localize HGAL to lipid rafts. Raft localization of HGAL protein facilitates interaction with Syk, and modulation of BCR activation and signaling.
Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways
Authors: Gröschel Stefan , Sanders Mathijs A. , Hoogenboezem Remco , Zeilemaker Annelieke , Havermans Marije , Erpelinck Claudia , Bindels Eric M. J. , Beverloo H. Berna , Döhner Hartmut , Löwenberg Bob , Döhner Konstanze , Delwel Ruud , Valk Peter J. M.
Published: November 2014

Key Points

inv(3)/t(3;3) disease exhibits high rates of activated RAS/RTK signaling, epigenetic modifier, splice, and transcription factor mutations. AML and MDS with inv(3)/t(3;3) display similar mutational and gene expression profiles and should be considered a single molecular entity.
Plasmonic molecules via glass annealing in hydrogen
Authors: Redkov Alexey , Chervinskii Semen , Baklanov Alexander , Reduto Igor , Zhurikhina Valentina , Lipovskii Andrey
Published: November 2014

Growth of self-assembled metal nanoislands on the surface of silver ion-exchanged glasses via their thermal processing in hydrogen followed by out-diffusion of neutral silver is studied. The combination of thermal poling of the ion-exchanged glass with structured electrode and silver out-diffusion was used for simple formation of separated groups of several metal nanoislands presenting plasmonic molecules. The kinetics of nanoisland formation and temporal evolution of their size distribution on the surface of poled and unpoled glass are modeled.

PACS

78.67.Sc (nanoaggregates; nanocomposites); 81.16.Dn (self-assembly); 68.35.bj (surface structure of glasses); 64.60.Qb (Nucleation); 81.16.Nd (micro- and nanolithography)
IL-10 regulates Aicda expression through miR-155
Authors: Fairfax Kirsten A , Gantier Michael P , Mackay Fabienne , Williams Bryan R G , McCoy Claire E
Published: November 2014

Aicda is a critical component of antibody class-switching in B cells. In this work, we study the impact of TLR4 activation and IL-10 stimulation on Aicda expression in B cells. Through the global analysis of miRNAs in response to TLR4 activation, in combination with IL-10 stimulation, we identified that IL-10 can suppress TLR4-induced miR-155 expression, an effect that resulted in enhanced Aicda expression. Furthermore, when preventing miR-155 control of Aicda expression, by genetic mutation of its target site in the Aicda mRNA, IL-10 could further potentiate Aicda expression. Given that miR-155 expression is lost, and expression levels of both Aicda and IL-10 are high in diseases, such as Burkitt’s lymphoma, our results suggest a stringent and sophisticated control of Aicda by a novel IL-10/miR-155 axis, where the imbalance of IL-10 and/or miR-155 may contribute to disease pathogenesis.
Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia
Authors: Wallace Alison E , Whitley Guy S , Thilaganathan Baskaran , Cartwright Judith E
Published: November 2014

During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-α, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.
Down-regulation of survivin alleviates experimental arthritis
Authors: Andersson K M E , Svensson M N D , Erlandsson M C , Jonsson I-M , Bokarewa M I
Published: November 2014

Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a molecular marker of cancer. Recently, survivin has emerged as a feature of RA, associated with severe joint damage and poor treatment response. The present study examined if inhibition of survivin affects experimental arthritis, which was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or developed spontaneously in collagen type II-immunized mice. The inhibition of survivin transcription by a lentivirus shRNA construct alleviated joint inflammation and reduced bone damage. The inhibition of survivin reduced the levels of metalloproteinases, β-catenin, and vimentin, limiting the invasive capacity of synovia, while no inhibition of osteoclastogenesis could be found. The inhibition of survivin led to a p53-independent reduction of T cell proliferation and favored the transcription and activity of Blimp-1, which limited IL-2 production and facilitated formation of regulatory Foxp3+CD4+ and effector CD8+ T cells. The study shows that the inhibition of survivin is sufficient to reduce joint inflammation and bone damage in preclinical models of arthritis. Antiarthritic effects of survivin inhibition are related to p53-independent control of lymphocyte proliferation.
The immunophenotype of mast cells and its utility in the diagnostic work-up of systemic mastocytosis
Authors: Teodosio Cristina , Mayado Andrea , Sa´nchez-Mun~oz Laura , Morgado Jose´ M , Jara-Acevedo Mari´a , A´lvarez-Twose Ivan , Garci´a-Montero Andre´s C , Matito Almudena , Caldas Caldas , Escribano Luis , Orfao Alberto
Published: November 2014

SM comprises a heterogeneous group of disorders, characterized by an abnormal accumulation of clonal MCs in 1 or more tissues, frequently involving the skin and BM. Despite the fact that most adult patients (>90%) carry the same genetic lesion (D816V KIT mutation), the disease presents with multiple variants with very distinct clinical and biologic features, a diverse prognosis, and different therapeutic requirements. Recent advances in the standardization of the study of BM MC by MFC allowed reproducible identification and characterization of normal/reactive MCs and their precursors, as well as the establishment of the normal MC maturational profiles. Analysis of large groups of patients versus normal/reactive samples has highlighted the existence of aberrant MC phenotypes in SM, which are essential for the diagnosis of the disease. In turn, 3 clearly distinct and altered maturation-associated immunophenotypic profiles have been reported recently in SM, which provide criteria for the distinction between ISM patients with MC-restricted and multilineage KIT mutation; thus, immunphenotyping also contributes to prognostic stratification of ISM, particularly when analysis of the KIT mutation on highly purified BM cells is not routinely available in the diagnostic work-up of the disease.
CREM/ICERs up-regulation suppresses sponge endothelial CRE-HIF-1α-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes
Authors: Bitar Milad S. , Al-Mulla Fahd
Published: November 2014

Impaired angiogenesis and endothelial dysfunction in type 2 diabetes constitute a dominant risk factor for non-healing wounds and most forms of cardiovascular disease. We propose that diabetes shifts the “angiogenic balance” in favor of excessive antiangiogenic phenotype. Herein, we report that diabetes impairs in vivo sponge angiogenic capacity by decreasing VEGF expression/fibrovascular invasion and reciprocally enhances the formation of angiostatic molecules such as thrombospondins, NFκB and FasL. Defective in vivo angiogenesis prompted cellular studies in cultured endothelial cells derived from subcutaneous sponge implants (SIECs) of control and Goto-Kakizaki rats. Ensuing data in diabetic SIECs, demonstrated a marked up-regulation in cAMP-PKA-CREB signaling, possibly stemming from increased and decreased expression of adenylyl cyclase isoforms 3/8 and PDE3, respectively. Mechanistically, we found that oxidative stress and PKA activation in diabetes enhanced CREM/ICERs expression. This reduces IRS2 cellular content by inhibiting CRE transcriptional activity. Consequently, a decrease in the activity of Akt-mTOR is ensued with a concomitant reduction in total and nuclear protein levels of HIF-1α. Limiting HIF-1α availability for the specific HREs in diabetic SIECs elicited a marked reduction in VEGF expression, both at the mRNA and protein levels. These molecular abnormalities were illustrated functionally by a defect in various proangiogenic properties including cell proliferation, migration and tube formation. A genetic-based strategy in diabetic SIECs using CREM/ICER siRNA significantly augmented the PKA-dependent VEGF expression. To this end, the current data identify the criticality of CREM/ICER as a negative regulator of endothelial function and establish a link between CREM/ICER overexpression and impaired angiogenesis during the course of diabetes. Moreover, it may also offer CREM/ICERs as a potential therapeutic target in the treatment of pathological angiogenesis in diseases such as diabetes and cancer.
The exocyst is required for trypanosome invasion and the repair of mechanical plasma membrane wounds
Authors: Fernandes Maria Cecilia , Corrotte Matthias , Miguel Danilo C. , Tam Christina , Andrews Norma W.
Published: November 2014

Host cell invasion by Trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. Both processes require Ca2+-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase, and formation of ceramide-enriched endocytic compartments. T. cruzi invades at peripheral sites, suggesting a need for spatial regulation of membrane traffic. Here we show that Exo70 and Sec8, components of the exocyst complex, accumulate in nascent T. cruzi vacuoles and at sites of mechanical wounding. Exo70 or Sec8 depletion inhibits T. cruzi invasion and Ca2+-dependent resealing of mechanical wounds, but does not affect repair of smaller lesions caused by pore-forming toxins. Thus, T. cruzi invasion and mechanical lesion repair share a unique requirement for the exocyst, consistent with a dependence on targeted membrane delivery.
Proteasome dysfunction induces muscle growth defects and protein aggregation
Authors: Kitajima Yasuo , Tashiro Yoshitaka , Suzuki Naoki , Warita Hitoshi , Kato Masaaki , Tateyama Maki , Ando Risa , Izumi Rumiko , Yamazaki Maya , Abe Manabu , Sakimura Kenji , Ito Hidefumi , Urushitani Makoto , Nagatomi Ryoichi , Takahashi Ryosuke , Aoki Masashi
Published: November 2014

The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3, resulted in profound muscle growth defects and a decrease in force production in mice. Specifically, developing muscles in conditional Rpt3-knockout animals showed dysregulated proteasomal activity. The autophagy pathway was upregulated, but the process of autophagosome formation was impaired. A microscopic analysis revealed the accumulation of basophilic inclusions and disorganization of the sarcomeres in young adult mice. Our results suggest that appropriate proteasomal activity is important for muscle growth and for maintaining myofiber integrity in collaboration with autophagy pathways. The deletion of a component of the proteasome complex contributed to myofiber degeneration and weakness in muscle disorders that are characterized by the accumulation of abnormal inclusions.
Reactivation of inactive X chromosome and post-transcriptional reprogramming of Xist in induced pluripotent stem cells
Authors: Kim Jong Soo , Choi Hyun Woo , Araúzo-Bravo Marcos J. , Schöler Hans R. , Do Jeong Tae
Published: November 2014

Direct reprogramming of somatic cells to pluripotent stem cells entails the obliteration of somatic cell memory and the reestablishment of epigenetic events. Induced pluripotent stem (iPS) cells have been created by reprogramming somatic cells through the transduction of reprogramming factors. During cell reprogramming, female somatic cells must overcome at least one more barrier than male somatic cells in order to enter a pluripotent state, as they must reactivate an inactive X chromosome (Xi). In this study, we investigated whether the sex of somatic cells affects reprogramming efficiency, differentiation potential, and the post-transcriptional processing of Xist RNA after reprogramming. There were no differences between male and female iPS cells with respect to reprogramming efficiency or their differentiation potential in vivo. However, reactivating Xi took longer than reactivating pluripotency-related genes. We also found that direct reprogramming leads to gender appropriate posttranscriptional reprogramming: like male embryonic stem (ES) cells, male iPS cells expressed only the long Xist isoform, whereas female iPS cells, like female ES cells, expressed both the long and short isoforms.
CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase
Authors: Viera Alberto , Alsheimer Manfred , Gómez Rocío , Berenguer Inés , Ortega Sagrario , Symonds Catherine E. , Santamaría David , Benavente Ricardo , Suja José A.
Published: November 2014

In most organisms telomeres attach to the nuclear envelope at the onset of meiosis to promote the crucial processes of pairing, recombination and synapsis during prophase I. This attachment of meiotic telomeres is mediated by the specific distribution of several nuclear envelope components, which interact with the attachment plates of the synaptonemal complex. We have determined by immunofluorescence and electron microscopy that the ablation of the kinase CDK2 alters the nuclear envelope in mouse spermatocytes, and that the proteins SUN1, KASH5 and lamin C2 show an abnormal cap-like distribution facing the centrosome. Strikingly, some telomeres are not attached to the nuclear envelope but remain at the nuclear interior associated with SUN1 and with nuclear envelope-detached vesicles. We also demonstrate that mouse testis CDK2 phosphorylates SUN1 in vitro. We propose that during mammalian prophase I the kinase CDK2 is a key factor governing the integrity of the nuclear envelope and the telomere-led chromosome movements essential for homologue pairing.
DAPK-HSF1 interaction as a new positive feedback loop for TNF-induced apoptosis in colorectal cancer cells
Authors: Benderska Natalya , Ivanovska Jelena , Rau Tilman T. , Schulze-Luehrmann Jan , Mohan Suma , Chakilam Saritha , Gandesiri Muktheshwar , Ziesché Elisabeth , Fischer Thomas , Söder Stephan , Agaimy Abbas , Distel Luitpold , Sticht Heinrich , Mahadevan Vijayalakshmi , Schneider-Stock Regine
Published: November 2014

Death-associated protein kinase (DAPK) is a serine-threonine kinase with tumor suppressor function. Previously we demonstrated that TNF induced DAPK-mediated apoptosis in colorectal cancer. However the protein-protein interaction network associated with TNF-DAPK signaling still remains unclear. We identified HSF1 as a new DAPK phosphorylation target in response to low concentration of TNF and verified a physical interaction between DAPK and HSF1 both in vitro and in vivo. We show that HSF1 binds to the DAPK promoter. Transient over-expression of HSF1 protein led to an increase in DAPK mRNA level and consequently to an enforcement of apoptosis. In contrast, treatment with a DAPK specific inhibitor as well as DAPKsh knockdown abolished the activation of HSF1 at Ser230. Furthermore, translational studies demonstrated a positive correlation between DAPK and pHSF1S230 protein expression in human colorectal carcinoma tissues. Together, our data define a novel link between DAPK and HSF1 and highlight a positive feedback loop in DAPK regulation under mild inflammatory stress in colorectal tumors. For the first time we show that under TNF the pro-survival HSF1 protein can be redirected to a pro-apoptotic program.
EFR3s are palmitoylated plasma membrane proteins that control responsiveness to G protein-coupled receptors
Authors: Bojjireddy Naveen , Guzman-Hernandez Maria Luisa , Reinhard Nathalie Renée , Jovic Marko , Balla Tamas
Published: November 2014

The yeast Efr3p protein is a major regulator of the Stt4p phosphatidylinositol 4-kinase at ER-PM contact sites. Its mutant fly homologue, Rbo displays diminishing light responses attributed to progressively impaired PLC signaling. Here we find that Efr3s play a role in maintaining responsiveness to angiotensin II (AngII) receptors. RNAi-mediated depletion of EFR3A and EFR3B impaired the sustained phase of cytosolic Ca2+ response to high concentration of AngII in HEK293 cells expressing the wild type but not a truncated AT1a receptor, missing the phosphorylation sites. Efr3 depletion had minimal effect on the recovery of plasma membrane phosphoinositides during stimulation, and AT1 receptors still underwent ligand-induced internalization. A higher level of basal receptor phosphorylation and a larger response was observed after stimulation. Moreover, Gq activation more rapidly desensitized after AngII stimulation in Efr3 downregulated cells. Similar but smaller effect of EFR3 depletion was observed on the desensitization of the cAMP response after isoproterenol stimulation. These data suggest that mammalian Efr3s contribute to the control of the phosphorylation state and hence desensitization of AT1a receptors and could affect GPCR responsiveness in higher eukaryotes.
Meeting the complex needs of individuals living with HIV: a case study approach
Authors: Paparello Joel , Zeller Irene , While Alison
Published: November 2014

This article critically discusses the nursing care and management of a person living with the human immunodeficiency virus (HIV) infection as a long-term condition, requiring highly complex HIV care. Complex HIV care is managed in the secondary care setting. However, recent legislation has motivated shifts in HIV care to the community care setting. This article aims to enhance health professionals' understanding in order to equip practice and district nurses to deliver HIV care provision. Antiretroviral adherence is a prerequisite for disease survival as well as an essential component of complete HIV self-care management. It is therefore imperative that nurses tailor adherence strategies according to each patient's requirements. Case management strategies such as the use of cognitive behavioural therapy to alleviate depressive symptoms will be considered. Furthermore, the use of motivational interviewing for antiretroviral adherence is highlighted as a potential intervention to help patients overcome the physical, psychological and physiological challenges of living with HIV-associated comorbidities. The delivery of integrated HIV care is pivotal for the management of the person living with HIV, as is the facilitation of a self-caring behaviour.
Community-dwelling women's knowledge of urinary incontinence
Authors: Day Mary Rose , Patricia Leahy-Warren , Loughran Sarah , O'Sullivan Elaine
Published: November 2014

As the population ages, the risk and prevalence of urinary incontinence (UI) will increase. Although this is the case, many women do not seek help or treatment. It is therefore important to investigate women's knowledge of UI. This pilot study aimed to describe community-dwelling women's knowledge of UI. A convenience sample method was used to recruit 50 community-dwelling women aged 50 and over. Some 36 participants completed a demographic questionnaire and the Urinary Incontinence Knowledge Scale (UIKS)—a response rate of 72%. The findings indicated that participants had poor knowledge of UI, principally in relation to risk, prevention, treatment and management factors. Fewer than 20% of participants indicated they had been given information on bladder and bowel health issues. The findings suggested that women had unmet educational needs relating to UI. Community nurses have a key role to play in promoting targeted awareness and continence education advice regarding UI to community-dwelling women.
Anticipatory prescribing at the end of life in Lothian care homes
Authors: Finucane Anne M , Stevenson Barbara , Gardner Hilary , McArthur Dorothy , Murray Scott A
Published: November 2014

Common symptoms at the end of life include pain, breathlessness, anxiety, respiratory secretions and nausea. National end-of-life care strategies advocate anticipatory prescribing for timely management of these symptoms to enhance patient care by preventing unnecessary distress. This study investigated the extent to which residents in eight Lothian care homes had anticipatory medications prescribed prior to death. Data were collected as part of a service development project to improve palliative care in nursing care homes in Edinburgh. Of the 77 residents who died in the care homes, 54% had anticipatory medicines prescribed. Only 15% had prescriptions for all four nationally recommended anticipatory medications. Many care home residents do not have the recommended anticipatory medications in place in the last days of life and thus may experience inadequate symptom control. Interventions that increase the availability of anticipatory medicines to manage common symptoms at the end of life for care home residents are required.
Change management in diabetes care
Authors: Mendes Aysha
Published: November 2014

Aysha Mendes argues that a cultural shift is required from health professionals as well as patients if the trend in diabetes prevalence is to be reversed
Using a silicone-based dressing as a primary wound contact layer
Authors: Derbyshire Adam
Published: November 2014

The use of silicone-based dressings as a primary contact layer for wound care can prevent epithelial stripping, pain and sensitivity and have been widely available for nearly 20 years. Cuticell Contact from BSN medical is the latest silicone-based dressing to add to the armoury of the wound care clinician. Using documented case studies the author explores the reasoning behind why clinicians should consider re-examining the use of silicone dressings.
Using no-rinse skin wipes to treat incontinence-associated dermatitis
Authors: Baadjies Ruth , Karrouze Irene , Rajpaul Kumal
Published: November 2014

Individuals who suffer with incontinence, especially in relation to faeces, will often be at risk of skin breakdown and develop incontinence-associated dermatitis (IAD) which, if left untreated, can lead to pressure ulcer formation ( Gray, 2004 ). IAD is caused by increased, unrelieved moisture against the skin, usually from liquid faeces and urine, which can then weaken the skin integrity. The integrity of the skin in this area is also at risk of pressure ulcers caused by shear or friction ( Beeckman et al, 2010a ). Treatment and prevention of IAD lesions involves a three-step process used in post-incontinence episodes, which includes cleansing, moisturisation and protection of the skin ( Beeckman et al, 2011a ). Using a wipe covers all of these steps immediately following incontinence episodes ( Rönner et al, 2010 ). This reduces the need to gather a number of different items required for post-incontinence skin care, which usually includes a dry wipe to be soaked in soapy water to wash the skin, a moisturiser to replace lost moisture and a skin protectant to prevent moisture from direct contact with the skin ( Foxley and Baadjies, 2009 ). This article will give some examples of the use of a particular continence and cleansing wipe in clinical practice.
Elevation devices for the prevention of heel pressure ulcers: a review
Authors: Clegg Rosie , Palfreyman Simon
Published: November 2014

Aim: The objective of this systematic literature review was to gain insight into the effectiveness of off-loading devices to prevent heel pressure ulcers within the acute hospital setting.

Background: Heels have been identified as the second most common site for pressure ulcers. Devices which off-load pressure can include pillows, wedges and boots. It is unclear as to which method or device is best at preventing pressure ulcers.

Design and methods: A systematic review was carried out through the search of electronic databases and bibliographies of relevant publications. Randomised controlled trials (RCTs) and systematic reviews that compared devices which off-load heels to prevent pressure ulcers were identified.

Results: A total of five studies were included in the review. The methodological quality of the studies was generally poor. The studies reported that heel-boot elevation devices appeared more beneficial. However, poor compliance with wearing the devices was identified, as well as a perceived increased risk of falls. There were little data on cost-effectiveness.

Conclusions: There is little high-quality trial evidence to support the routine use of heel devices to prevent pressure ulcers. However, they may have a role to play within a multifaceted programme of pressure-ulcer prevention.
A topical haemoglobin spray for oxygenating chronic venous leg ulcers: a pilot study
Authors: Norris Ray
Published: November 2014

Acute wounds will generally heal independently of any interventions, whereas chronic wounds are chronic for a reason and are unlikely to successfully heal without intervention.

In the treatment of venous leg ulcers, the gold standard will always be compression therapy. However, many wounds still do not heal despite best practice. Therefore, the use of adjunct therapies alongside standard care become the priority for healing.

This article describes a small evaluation, involving 17 patients with chronic venous leg ulcers, that set out to determine the effect of a topical oxygen therapy on wound size. The therapy comprises a canister that sprays pure haemoglobin in a water solution into the wound. The haemoglobin spray needs to be used at least once every 3 days, and no training is required on its use. Results showed the device helped promote wound healing in 14 out of 17 wounds treated for more than 2 weeks. These patients had previously been shown to be non-healing during a 4-week run-in period where they received standard care, including compression therapy.
Aberrant Expression of Osteopontin and E-Cadherin Indicates Radiation Resistance and Poor Prognosis for Patients with Cervical Carcinoma
Authors: Huang Xinqiong , Qian Yujie , Wu Hainan , Xie Xiaoxue , Zhou Qin , Wang Ying , Kuang Weilu , Shen Lin , Li Kai , Su Juan , Shen Liangfang , Chen Xiang
Published: November 2014

Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group ( p<0.001). These patients also had a lower 5-year PFS rate ( p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001).