bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of CYP3A4-Inducing Capacity of Enzyme-Inducing Antiepileptic Drugs Using 4β-Hydroxycholesterol as Biomarker
Authors: Hole Kristine , Wollmann Birgit M. , Nguyen Camilla , Haslemo Tore , Molden Espen
Published: April 2018

Background:

Enzyme-inducing antiepileptic drugs (EIAEDs) are among the clinically most important inducers of cytochrome P450 (CYP) 3A4, but there is limited evidence regarding the comparative potency of each EIAED in raising CYP3A4 activity. The aim of this study was to estimate CYP3A4-inductive potency of EIAEDs by comparing CYP3A4 activity in patients treated with carbamazepine, phenobarbital, or phenytoin.

Methods:

Residual serum samples from patients treated with EIAEDs or levetiracetam were collected from a therapeutic drug monitoring service for analysis of 4β-hydroxycholesterol (4βOHC), which is an indicator of CYP3A4 activity. The samples were collected between January and September 2016 at Diakonhjemmet Hospital, Oslo, Norway. Concentration of 4βOHC, EIAEDs, and levetiracetam was measured by ultra-performance liquid chromatography tandem mass spectrometry. Kruskal–Wallis and Mann–Whitney tests were used for comparison of 4βOHC levels between the subgroups.

Results:

In total, 4βOHC measurements for 343 and 339 patients treated with EIAEDs and levetiracetam, respectively, were included in the study. Compared with levetiracetam-treated patients, the median 4βOHC concentration was 3.3-fold, 5.8-fold, and 6.9-fold higher in patients using phenobarbital, phenytoin, or carbamazepine, respectively (P < 0.0001). Phenytoin users (n = 65) and carbamazepine users (n = 225) had 1.8- and 2.1-fold higher median 4βOHC concentration than phenobarbital users (n = 28), respectively (P ≤ 0.0001).

Conclusions:

This study shows that phenytoin and carbamazepine have approximately twice the CYP3A4-inducing potency of phenobarbital. The results indicate that 2-fold higher doses of CYP3A4-metabolized drugs may generally be required during concurrent treatment with phenytoin or carbamazepine compared with phenobarbital.
Methadone Maintenance Treatment: A 15-year Retrospective Study in Split-Dalmatia County, Croatia
Authors: Sutlovic Davorka , Kljucevic Zeljko , Sliskovic Livia , Susnjar Helena , Viskovic Ivo , Definis-Gojanovic Marija
Published: April 2018

Background:

The aim of this retrospective study is to use existing epidemiological data on patients in methadone maintenance treatment in Split-Dalmatia County from 2001 to 2015 to evaluate the substitution treatment system and policy of opiate addicts treatment, the epidemiological trend, and risk of overdose mortality. In addition, we would like to highlight the problem of poor control of methadone therapy and thus the possibility of selling methadone. The result is a greater number of deaths caused by methadone in people who were not in methadone therapy.

Methods:

The research included data collected from 3189 patients who had been in the drug abuse treatment program in Split-Dalmatia County during 2001–2015 and data gathered from autopsy examinations of patients in Split-Dalmatia County with emphasis on data for 186 overdosed patients during research period.

Results:

The total number of patients in the methadone treatment program in Split-Dalmatia County during the research period, except in 2005 and 2006, has been stable, while the number of new opiate patients, being in first-time treatment, decreased by 62.5%. The number of addicts who were in a long-term maintenance program has increased by 198%, whereas the number of addicts who were in a short-term detoxification treatment has decreased by 96.4%. According to results obtained from performed autopsies, 186 death cases were determined as overdoses. Methadone was found in 56 of those cases and was declared as the cause of death in 39 cases (70%). Of the total number of autopsied patients with diagnosed methadone overdose, only 23 (59%) had been recorded to receive methadone therapy in Public Health Institute of Split-Dalmatia County database.

Conclusions:

The results of this study show the favorable epidemiological trend because of the decreasing number of new opiate patients in treatment. The retention of opiate patients in substitution therapy indicates the effectiveness of methadone maintenance programs. Our research did not determine any influence of methadone substitution therapy on an increasing risk of specific (overdose) mortality.
Effect of Inspiratory Muscle Training in the Management of Patients With Asthma
Authors: Duruturk Neslihan , Acar Manolya , Doğrul Mustafa Ilgaz
Published: April 2018

Purpose:

The aim of this study was to investigate the effects of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, dyspnea, fatigue, quality of life, and daily living activities of asthmatic patients.

Methods:

Thirty-eight asthmatic patients, between 18 and 65 years of age, were enrolled in the study and randomly divided into 2 groups; IMT (n = 20) or control (n = 18). Participants in the IMT group performed 30 breaths using a patient-specific threshold pressure device, twice daily for 6 wk at 50% maximal inspiratory pressure (MIP), in addition to “breathing training” during this period. Participants in the control group performed only the “breathing training” (sham or no threshold pressure device). Outcome measurements, performed before and after the intervention, included pulmonary function test, respiratory muscle strength, 6-min walk test, modified Medical Research Council dyspnea scale, St George's Respiratory Questionnaire, Fatigue Severity Scale, and London Chest Activity of Daily Living scale.

Results:

Among the outcomes in the study, changes to key variables including MIP (P < .01); MIP, percent predicted (P < .01); maximal expiratory pressure (MEP), percent predicted (P < .01); 6-min walk test walking distance (P = .001); modified Medical Research Council scale (P =<.001); Fatigue Severity Scale (P = .03); St George's Respiratory Questionnaire symptoms (P = .03); London Chest Activity of Daily Living domestic (P = .03); and London Chest Activity of Daily Living leisure (P = .01) were significantly different in favor of IMT versus control.

Conclusion:

These findings suggest that IMT may be an effective modality to enhance respiratory muscle strength, exercise capacity, quality of life, daily living activities, reduced perception of dyspnea, and fatigue in asthmatic patients.
Nursing Sensitive Outcomes After Severe Traumatic Brain Injury: A Nationwide Study
Authors: Odgaard Lene , Aadal Lena , Eskildsen Marianne , Poulsen Ingrid
Published: April 2018

Background: Complications such as infections and conditions after immobilization are frequent after severe traumatic brain injury (TBI) due to compromised bodily functions. Traditionally, bodily functions are core elements in nursing, and therefore nurses in the rehabilitation departments are pivotal in the prevention of complications. Hence, the frequency of complications is an indicator of nursing care quality, which can be included in nursing-sensitive outcome indicators. To do so, it is necessary to know the frequency of the selected complications. Objective: The aim of this study was to quantify complications during the first year after severe TBI. Participants: This study included patients 15 years or older who received subacute neurorehabilitation after severe TBI from 2011 to 2015 (N = 469). Design: This is a register-based follow-up study using data from the Danish Head Trauma Database, a national clinical quality database aimed at monitoring and improving the quality of rehabilitation for patients with severe TBI. Main Measures: The following complications were assessed: urinary tract infection, pneumonia, pressure ulcers, joint contractures, and deep venous thrombosis. The prevalence of each complication was calculated at admission, discharge, and 1 year postinjury and for the period from admission and during subacute rehabilitation. In addition, the frequency of complications that certainly developed during subacute rehabilitation was calculated. Complications were compared between age-specific subgroups using multivariable binominal regression analyses. Results: Urinary tract infections (53%) and pneumonia (32%) were the most common complications in the period from admission and during subacute rehabilitation. Pressure ulcers (18%), joint contractures (18%), and deep venous thrombosis (4%) were less frequent. At discharge and 1 year postinjury, the prevalence was less than 4% for all complications, except for joint contractures (16% and 13% at discharge and 1 year postinjury, respectively). Conclusion: The prevalence of complications was high. The findings are important for future quality improvement of the rehabilitation trajectory and for further studies that explore the high frequency of complications.
Anorectal Manometry May Reduce the Number of Rectal Suction Biopsy Procedures Needed to Diagnose Hirschsprung Disease
Authors: Meinds Rob J. , Trzpis Monika , Broens Paul M.A.
Published: April 2018

Objectives:

The aim of the study was to evaluate whether anorectal manometry (ARM), which is used to test the rectoanal inhibitory reflex (RAIR), is a safe alternative for reducing the number of invasive rectal suction biopsy (RSB) procedures needed to diagnose Hirschsprung disease (HD).

Methods:

Between 2010 and 2017, we prospectively collected the ARM results of 105 patients suspected of having HD. Following the outcome, the patients either underwent additional tests to confirm HD or they were treated conservatively. Primary ARM‐based diagnoses were compared with the definitive diagnoses based on the pathology reports and/or clinical follow‐ups. Additionally, we analyzed whether modifications to our ARM protocol improved diagnostic accuracy.

Results:

The sensitivity of ARM and RSB was comparable (97% vs 97%). The specificity of ARM, performed according to our initial protocol, was significantly lower than that of RSB. After we modified the protocol the difference between the specificity of ARM and RSB was no longer statistically significant (74% vs 84%, respectively, P = 0.260). The negative predictive value of ARM was 100%, while their positive predictive value was significantly lower than that of RSB (56% vs 97%, P < 0.001).

Conclusions:

ARM is a viable screening tool for HD and, provided it is performed properly, it can be used to exclude HD with absolute certainty. By contrast, an absent rectoanal inhibitory reflex on ARM should always be followed by an RSB to confirm the diagnosis of HD. Using ARM as the diagnostic of first choice could reduce the number of invasive biopsies.
The effect of a single textured insole in gait rehabilitation of individuals with stroke
Authors: Aruin Alexander S. , Rao Noel
Published: April 2018

Rehabilitation interventions designed to restore gait symmetry in individuals with stroke are not always effective. The goal was to evaluate the long-term effect of using a single textured insole in gait rehabilitation. Ten individuals with stroke who showed asymmetrical stance were randomly divided into two groups and participated in physical therapy. Individuals in the experimental group received a 6-week physical therapy while being provided with a textured insole in the shoe on the unaffected side. Individuals in the control group received a 6-week physical therapy only. Both groups underwent a battery of identical tests before the start of the rehabilitation intervention, following its completion, and 4 months after the end of therapy. After the intervention, weight bearing (WB) on the affected side and gait velocity increased in the experimental group (P<0.05) to a larger degree compared with the control group. Moreover, symmetry of gait was increased in the experimental group (P<0.05). Improvements in WB, gait velocity, and symmetry of gait were maintained in the experimental group after the end of 4-month retention period. The study outcome revealed that a 6-week intervention involving a single textured insole could result in a long-lasting improvement of gait velocity, symmetry of WB, and gait in individuals with stroke.
National Mortality Rates after Outpatient Cosmetic Surgery and Low Rates of Perioperative Deep Vein Thrombosis Screening and Prophylaxis
Authors: Bucknor Alexandra , Egeler Sabine A. , Chen Austin D. , Chattha Anmol , Kamali Parisa , Brownstein Gary , Reed Lawrence , Watts David , Lin Samuel J.
Published: April 2018

Background:

Concerns have arisen over reports of deaths occurring after certain outpatient plastic surgery procedures. Here, the authors present a national analysis, reporting on deaths occurring after outpatient cosmetic surgical procedures and venous thromboembolism screening.

Methods:

A retrospective analysis of the American Association for Accreditation of Ambulatory Surgical Facilities database was performed for the years 2012 to 2017. The authors retrieved data for all deaths occurring in association with cosmetic plastic surgery procedures. Patient demographics, procedural data, venous thromboembolism risk factor assessment, and cause of death were analyzed. Deidentified medical records, including coroner’s reports, were reviewed where available.

Results:

Data for 42 deaths were retrieved. Of these, 90.5 percent (n=38) were female, and 61.9 percent were Caucasian (n=26). Mean age was 51.6 years, while mean body mass index was 29.5 kg/m2. Overall, 54.8 percent of these deaths occurred after abdominoplasty: 42.9 percent in isolation, 9.5 percent in combination with breast surgery, and 2.4 percent with facial surgery. Of the causes of death, most (38.1 percent) were thromboembolic in origin. Notably, in 25 of 42 cases, venous thromboembolism risk factor assessment was incorrect or absent (59.5 percent).

Conclusions:

Accreditation agencies provide transparency and insight into outpatient surgical mortality on a national scale. Results suggest that adoption of venous thromboembolism screening techniques may not be universal despite an existing large body of published evidence. Optimization of thromboembolism prevention pathways remains vital, and consideration of anticoagulation in those undergoing abdominoplasty may be important in lowering outpatient mortality.
The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding
Authors: Pannucci Christopher J. , Fleming Kory I. , Agarwal Jayant , Rockwell W. Bradford , Prazak Ann Marie , Momeni Arash
Published: April 2018

Background:

Venous thromboembolism is a life- or limb-threatening complication that occurs in plastic surgery patients. At present, the optimal dose of enoxaparin that balances the risk of venous thromboembolism and the risk of medication-related adverse drug events—specifically, bleeding—remains unknown.

Methods:

This study compared pharmacodynamic and clinical outcomes, including 90-day venous thromboembolism and 90-day clinically relevant bleeding, between two prospectively performed clinical trials whose sole difference was postoperative anticoagulation strategy. Patients in trial 1 received enoxaparin 40 mg once daily for the duration of inpatient stay, and patients in trial 2 received enoxaparin 40 mg twice daily for the duration of inpatient stay. The study also examined the potential impact of a weight-based twice-daily prophylaxis strategy to achieve in-range anti–factor Xa levels.

Results:

The study compared 94 patients who received once-daily enoxaparin to 118 patients who received twice-daily enoxaparin. Twice-daily enoxaparin was associated with a significant decrease in 90-day acute venous thromboembolism (0 percent versus 5.3 percent; p = 0.012) and a nonsignificant increase in 90-day clinically relevant bleeding (6.8 percent versus 3.2 percent; p = 0.25). Twice-daily enoxaparin at 0.4 to 0.5 mg/kg may allow an increased proportion of patients to avoid both inadequate anticoagulation and overanticoagulation, based on anti–factor Xa levels.

Conclusions:

Twice-daily enoxaparin is superior to once-daily enoxaparin for 90-day acute venous thromboembolism risk reduction. Twice-daily enoxaparin may increase clinically relevant bleeding, although observed differences in this study were not significant. Weight-based twice-daily enoxaparin dosing may optimize the risks and benefits of prophylactic anticoagulation after plastic and reconstructive surgery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Asymptomatic Deep Vein Thrombosis during Free Flap: Concerns in Free Flap Surgery
Authors: Jung Jae-A , Park Bo Young , Kang So Ra , Kim Min Ji
Published: April 2018

Background:

Venous insufficiency is the most frequent cause of failure in free flap reconstruction of the lower extremity. When deep vein thrombosis is detected during preoperative assessment of the lower extremity, decisions regarding treatment plans become difficult, and no relevant guidelines regarding surgery and preoperative treatment of patients with deep vein thrombosis who need a free flap transfer are currently available.

Methods:

To find a relevant guideline in decision-making regarding surgery and preoperative treatment of patients with deep vein thrombosis who require free flap reconstruction, a systematic literature review was conducted searching MEDLINE, PubMed Central, Cochrane, and Embase databases for articles published between 1996 and 2015. In addition, the authors introduced six of their cases of deep vein thrombosis diagnosed before free flap surgery in which the flap survived.

Results:

The literature review identified two articles that discussed intraoperative deep vein thrombosis diagnosed in three patients, including the reported cases. Analyses included epidemiology, cause, and management strategy. A consensus for the management of asymptomatic deep vein thrombosis before free flap surgery is still lacking. In the authors’ cases, successful flap transfer was possible by proceeding with an appropriate preoperative evaluation, intensive anticoagulation treatment, intraoperative reperfusion procedure, and postoperative care.

Conclusion:

Preoperatively detected asymptomatic deep vein thrombosis is not a contraindication for free flap reconstruction, and a flap transfer can be successfully performed with suitable planning and management.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
In Search of Mobile Applications for Urogynecology Providers
Authors: Wallace Shannon L. , Mehta Shailja , Farag Sara , Kelley Robert S. , Chen Katherine T.
Published: April 2018

Introduction

Thousands of medical applications (apps) are available for mobile devices. Finding accurate, health care provider–centered apps may be time consuming and frustrating for urogynecologists. The objective of this study was to identify and evaluate urogynecology (urogyn) apps using a modified APPLICATIONS scoring system.

Materials and Methods

Urogyn apps were identified from the Apple iTunes and Google Play Stores using the following 10 MeSH terms: urogynecology, incontinence, prolapse, urinary tract infection, pelvic surgery, fecal incontinence, defecation disorder, voiding disorder, urethral diverticulum, and fistula. Patient-centered and inaccurate apps were excluded. The remaining apps were evaluated with a modified APPLICATIONS scoring system, which included both objective and subjective criteria to determine each app’s ability to aid in clinical decision making and to provide informational data. Objective rating components were price, paid subscription, literature referenced, in-app purchases, Internet connectivity, advertisements, text search field, interplatform compatibility and incorporated images, figures, videos, and special features. Subjective rating components were ease of navigation and presentation.

Results

Our search yielded 133 and 235 apps in the Apple iTunes and Google Play Stores, respectively. Only 8 apps (4 of which were in both stores) were determined to be accurate and useful; these were evaluated using the modified APPLICATIONS scoring system. The top-rated app was Practical Urology.

Conclusion

Few accurate clinical decision-making and informational apps exist for urogynecologists. Apps varied by comprehensiveness and quality. This study highlights the importance of systematically reviewing and rating medical apps. It also emphasizes the need for developing accurate apps for urogynecologists that improve health care provider performance and patient outcomes.
The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease
Authors: Kosack Lindsay , Wingelhofer Bettina , Popa Alexandra , Vilagos Bojan , Orlova Anna , Majek Peter , Parapatics Katja , Lercher Alexander , Agerer Benedikt , Ringler Anna , Klughammer Johanna , Smyth Mark , Khamina Kseniya , Baazim Hatoon , Rosa David A. , Park Jisung , Gunning Patrick T. , Bock Christoph , Siddle Hannah V. , Kubicek Stefan , Murchison Elizabeth P. , Bennett Keiryn L. , Moriggl Richard , Bergthaler Andreas
Published: April 2018

The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of DFTD, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC class I gene expression. This link between the hyperactive ERBB-STAT3 axis and MHC class I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and led us to the proposition of a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.
A transmissible RNA pathway in honey bees
Authors: Maori Eyal , Garbian Yael , Kunik Vered , Mozes-Koch Rita , Malka Osnat , Kalev Haim , Sabath Niv , Sela Ilan , Shafir Sharoni
Published: April 2018

One of the characteristics of RNA interference (RNAi) is systemic spread of the silencing signal among cells and tissues throughout the organism. Systemic RNAi, initiated by double-stranded RNA (dsRNA) ingestion, has been reported in diverse invertebrates, including honey bees, demonstrating environmental RNA uptake that undermines homologous gene expression. However, the question why any organism would take up RNA from the environment has remained largely unanswered. Here, we report on horizontal RNA flow among honey bees mediated by secretion and ingestion of worker and royal jelly diets. We show that ingested dsRNA spreads through the bee’s hemolymph associated with a protein complex. The systemic dsRNA is secreted with the jelly and delivered to larvae via ingestion. Furthermore, we demonstrate that transmission of jelly-secreted dsRNA to larvae is biologically active and triggers gene knockdown that lasts into adulthood. Finally, RNA extracted from worker and royal jellies harbor differential naturally occurring RNA populations. Some of these RNAs corresponded to honey bee protein coding genes, transposable elements, non-coding RNA as well as bacteria, fungi and viruses. These results reveal an inherent property of honey bees to share RNA among individuals and generations. Thus, our findings suggest a transmissible RNA pathway, playing a role in social immunity and epigenetic signaling between honey bees and potentially among other closely interacting organisms.

SIGNIFICANCE

Honey bees are eusocial insects, living in a colony that is often described as a superorganism. RNA mobility among cells of an organism has been documented in plants and animals. Here we show that RNA spreads further in honey bees, and is horizontally transferred between individuals and across generations. We found that honey bees share biologically active RNA through secretion and ingestion of worker and royal jellies. Such RNA initiates RNA interference, which is a known defense mechanism against viral infection. Furthermore, we characterized diverse RNA profiles of worker and royal jelly, including fragmented viral RNA. Our findings demonstrate a transmissible RNA pathway with potential roles in social immunity and epigenetic signaling among members of the hive.
Modulation of mitochondrial Hsp90 (TRAP1) ATPase activity by calcium and magnesium
Authors: Elnatan Daniel , Agard David A.
Published: April 2018

The Hsp90 protein family are ATP-dependent molecular chaperones that maintain protein homeostasis and regulate many essential cellular processes. Higher eukaryotic cells have organelle-specific Hsp90 paralogs that are adapted to each unique sub-cellular environment. The mitochondrial Hsp90, TRAP1, supports the folding and activity of electron transport components and is increasingly being appreciated as a critical player in mitochondrial signaling. It is well known that calcium plays an important regulatory role in mitochondria and can even accumulate to much higher concentrations than in the cytoplasm. Surprisingly, we find that calcium can replace the requirement for magnesium to support TRAP1 ATPase activity. Using anomalous x-ray diffraction, we reveal a novel calcium-binding site within the TRAP1 nucleotide-binding pocket located near the ATP α-phosphate and completely distinct from the magnesium site adjacent to the β and γ-phosphates. In the presence of magnesium, ATP hydrolysis by TRAP1, as with other Hsp90s, is non-cooperative, whereas calcium binding results in cooperative ATP hydrolysis by the two protomers within the Hsp90 dimer. The structural data suggest a mechanism for the cooperative behavior. Owing to the cooperativity, at high ATP concentrations, ATPase activity is higher with calcium, whereas the converse is true at low ATP concentrations. Integrating these observations, we propose a model where the divalent cations choice can control switching between non-cooperative and cooperative TRAP1 ATPase mechanisms in response ATP concentrations. This may facilitate coordination between cellular energetics, mitochondrial signaling, and protein homeostasis via alterations in the TRAP1 ATP-driven cycle.
Real-time visualization and quantification of human Cytomegalovirus replication in living cells using the ANCHOR DNA labeling technology
Authors: Mariamé Bernard , Kappler-Gratias Sandrine , Kappler Martin , Balor Stéphanie , Gallardo Franck , Bystricky Kerstin
Published: April 2018

Human cytomegalovirus (HCMV) induces latent life-long infections in all human populations. Depending on geographic area and socio-economic conditions between 30 to nearly 100% of individuals are affected. The biology of this virus is difficult to explore due to its extreme sophistication and the lack of pertinent animal model. Here we present the first application of the ANCHOR DNA labeling system to a herpes virus, allowing real time imaging and direct monitoring of HCMV infection and replication in human living cells. The ANCHOR system is composed of a protein (OR) which specifically binds to a short, non-repetitive DNA target sequence (ANCH) and spreads onto neighboring sequences due to protein oligomerization. If OR protein is fused to GFP, this accumulation results in a site specific fluorescent focus. We have created a recombinant ANCHOR-HCMV harboring an ANCH target sequence and the gene encoding the cognate OR-GFP fusion protein. Infection of permissive cells with ANCHOR-HCMV enables visualization of the nearly complete viral cycle until cell fragmentation and death. Quantitative analysis of infection kinetics and of viral DNA replication revealed cell-type specific behavior of HCMV and sensitivity to inhibitors. Our results show that the ANCHOR technology is a very efficient tool for the study of complex DNA viruses and new highly promising biotechnology applications.

IMPORTANCE

The ANCHOR technology is to date the most powerful tool to follow and quantify the replication of HCMV in living cells and to gain new insights into its biology. This technology is applicable to virtually any DNA virus or virus presenting a dsDNA phase, paving the way to infection imaging in various cell lines or even in animal models and opening fascinating fundamental and applied prospects. Associated to high content automated microscopy, this technology permitted rapid, robust and precise determination of Ganciclovir IC50 and IC90 on HCMV replication, with minimal hands-on investment. To search for new antiviral activities, the experiment is easy to up-grade towards efficient and cost-effective screening of large chemical libraries. The simple infection of permissive cells with ANCHOR-viruses in the presence of a compound of interest may even provide a first estimation about the stage of the viral cycle this molecule is acting upon.
Ectopic expression ofHoxb1induces cardiac and craniofacial malformations
Authors: Zaffran Stéphane , Odelin Gaёlle , Stefanovic Sonia , Lescroart Fabienne , Etchevers Heather C.
Published: April 2018

Members of the large family of Hox transcription factors are encoded by genes whose tightly regulated expression in development and in space within different embryonic tissues confer positional identity from the neck to the tips of the limbs. Many structures of the face, head and heart develop from cell populations expressing few or noHoxgenes.Hoxb1is the member of its chromosomal cluster expressed in the most rostral domain during vertebrate development, but never by the multipotent neural crest cell population anterior to the cerebellum. We have developed a novel floxed transgenic mouse line,CAG-Hoxb1,-EGFP (CAG-Hoxb1), which upon recombination by Cre recombinase conditionally induces robustHoxb1andeGFPover-expression. When induced within the neural crest lineage, pups die at birth. A variable phenotype develops from E11.5 on, associating frontonasal hypoplasia/aplasia, micrognathia/agnathia, major ocular and forebrain anomalies, and cardiovascular malformations. Neural crest derivatives in the body appear unaffected. Transcription of effectors of developmental signaling pathways (Bmp, Shh, Vegfa) and transcription factors (Pax3, Sox9) is altered in mutants. These outcomes emphasize that repression ofHoxb1, along with other paralog group 1 and 2Hoxgenes, is strictly necessary in anterior cephalic NC for craniofacial, visual, auditory and cardiovascular development.
Varieties of the plant Ctenante oppenheimiana: A colorful enigma of evolution
Authors: Filho Humberto A. , Bruno Odemir M.
Published: April 2018

The plant Ctenante oppenheimiana presents an interesting contrast of colors in the abaxial epidermis. A striking feature is that the stomata are green and cover a purple pavement where the pavement cells have green cellular walls. These characteristics have been used in studies about ecophysiology and phenotypic plasticity. However, the existence of a second tricolor variety of the plant make these characteristics even more heterogeneous and introduce new paradigms of the physiological role underlying this morphology. In this work we show by optical microscopy images the striking differences between the varieties bicolor and tricolor of the plant Ctenante oppenheimiana
Genomic resources forGoniozus legneri,Aleochara bilineataandPaykullia maculata, representing three independent origins of the parasitoid lifestyle in insects
Authors: Kraaijeveld Ken , Neleman Peter , Mariën Janine , de Meijer Emile , Ellers Jacintha
Published: April 2018

Parasitoid insects are important model systems for a multitude of biological research topics and widely used as biological control agents against insect pests. While the parasitoid lifestyle has evolved numerous times in different insect groups, research has focused almost exclusively on Hymenoptera from the parasitica clade. The genomes of several members of this group have been sequenced, but no genomic resources are available from any of the other, independent evolutionary origins of the parasitoid lifestyle. Our aim here was to develop genomic resources for three parasitoid insects outside the parasitica. We present draft genome assemblies forGoniozus legneri, a parasitoid Hymenopteran more closely related to the non-parasitoid wasps and bees than to the parasitica wasps, the Coleopteran parasitoidAleochara bilineataand the Dipteran parasitoidPaykullia maculata.The genome assemblies are fragmented, but complete in terms of gene content. We also provide preliminary structural annotations. We anticipate that these genomic resources will be valuable for testing the generality of findings obtained from parasitica wasps in future comparative studies.

Data availability

The Whole Genome Shotgun projects have been deposited at DDBJ/ENA/GenBank under the accessions NCVS00000000 (G. legneri), NBZA00000000 (A. bilineata) and NDXZ00000000 (P. maculata).The versions described in this paper are versions NCVS01000000, NBZA01000000 and NDXZ01000000, respectively. Mapped reads and genome annotations are available throughhttp://parasitoids.labs.vu.nl/parasitoids/. This website also includes genome browsers and viroblast instances for each genome.
Hackathons as a means of accelerating scientific discoveries and knowledge transfer
Authors: Ghouila Amel , Siwo Geoffrey Henry , Entfellner Jean-Baka Domelevo , Panji Sumir , Button-Simons Katrina A. , Davis Sage Zenon , Fadlelmola Faisal M. ,   The DREAM of Malaria Hackathon Participants, Ferdig Michael T. , Mulder Nicola
Published: April 2018

Scientific research plays a key role in the advancement of human knowledge and pursuit of solutions to important societal challenges. Typically, research occurs within specific institutions where data are generated and subsequently analyzed. Although collaborative science bringing together multiple institutions is now common, in such collaborations the analytical processing of the data is often performed by individual researchers within the team, with only limited internal oversight and critical analysis of the workflow prior to publication. Here, we show how hackathons can be a means of enhancing collaborative science by enabling peer review before results of analyses are published by cross-validating the design of studies or underlying data sets and by driving reproducibility of scientific analyses. Traditionally, in data analysis processes, data generators and bioinformaticians are divided and do not collaborate on analyzing the data. Hackathons are a good strategy to build bridges over the traditional divide and are potentially a great agile extension to the more structured collaborations between multiple investigators and institutions.
Crystal structure and Hirshfeld surface analysis of 4′-(2-chlorophenyl)-1′-methyl-3′′-phenyl-7′′,8′′-dihydro-5′′H-dispiro[indoline-3,2′-pyrrolidine-3′,6′′-isoquinoline]-2,5′′-dione
Authors: Vishnupriya R. , Selva Meenatchi C. , Suresh J. , Sumesh R. V. , Kumar R. Ranjith , Lakshman P. L. Nilantha
Published: April 2018

In the title dispiro compound, C32H26ClN3O2, the cyclohexanone ring of the isoquinoline unit has a distorted envelope conformation, with the methylene C atom adjacent to the spiro C atom as the flap. The central 1-methylpyrrolidine ring has an envelope conformation with the N atom as the flap. The mean planes of the indolin-2-one ring system, the chlorobenzene ring and the isoquinoline ring system are inclined to the mean plane of the central 1-methylpyrrolidine ring by 87.95 (11), 71.01 (12) and 88.81 (10)°, respectively. There are two short C—H...O intramolecular contacts present. In the crystal, molecules are linked via C—H... O hydrogen bonds, forming chains along the a-axis direction. The NH H atom is involved in a weak N—H...O hydrogen bond with the same carbonyl O atom. There are no further significant intermolecular contacts present. The largest contribution to the overall Hirshfeld surface of 52.3% is due to H—H contacts.
The formation of a cross-selling initiative climate and its interplay with service climate
Authors: Yu Ting , de Ruyter Ko , Patterson Paul , Chen Ching-Fu
Published: April 2018

Purpose

This study aims to explore the formation and consequences of a cross-selling initiative climate, as well as how a service climate, which provides an important boundary condition, affects both its formation and its ultimate impact on service-sales performance. This article identifies two important predictors of a cross-selling initiative climate: frontline employees’ perceptions of supervisors’ bottom-line mentality and their own sense of accountability.

Design/methodology/approach

The multilevel data set includes 180 frontline staff and supervisors (team leaders) from 31 teams employed by a spa/beauty salon chain. Hierarchical linear modelling and partial least squares methods serve to analyse the data.

Findings

Supervisors’ bottom-line mentality disrupts a cross-selling initiative climate. A sense of accountability exerts a positive impact at both individual and team levels. A service climate at the team level weakens the impact of a sense of accountability on a cross-selling initiative climate. A cross-selling initiative climate has a positive effect on team-level service-sales performance, but this effect is weakened by the service climate.

Originality/value

This study conceptualises an important frontline work unit attribute as a climate. It offers an initial argument that a cross-selling initiative climate is a central factor driving a work unit’s service-sales performance, which can increase firms’ productivity and competitive advantages. With this initial attempt to explore the antecedents and consequences of a cross-selling initiative climate, the study also offers novel insights into the interplay between a service and a cross-selling initiative climate.
CSR types and the moderating role of corporate competence
Authors: Chen Xiaoye , Huang Rong , Yang Zhiyong , Dube Laurette
Published: April 2018

Purpose

This paper aims to investigate the impact of different types of corporate social responsibility (CSR; i.e. value-creating CSR, promotional CSR and philanthropic CSR) on consumer responses and the moderating role of corporate competence.

Design/methodology/approach

The authors tested the hypotheses by using two empirical studies – a survey and an experimental study. The evidence is generated based on generalized linear model repeated-measures ANOVAs for the survey study and two-way factorial ANOVAs for the experimental study.

Findings

The findings show that in general, consumers respond to value-creating CSR more favorably than to philanthropic CSR or promotional CSR. In addition, corporate competence moderates consumers’ responses to different types of CSR in such a way that promotional CSR is more likely to have the desired effects when carried out by low-competency rather than by high-competency firms, whereas value-creating CSR is more effective for high-competency firms than for low-competency ones. Philanthropic CSR works equally in both types of firms.

Research limitations/implications

This research answers a long-term call to study the differential consumer effects of various CSR types. It also identifies perceived corporate competence, an important consumer-based corporate factor, as a potential moderator of consumers’ response to CSR types.

Practical implications

Armed with the findings, companies can choose CSR practices that fit with their company characteristics. This research offers important and specific managerial implications to firms with different company profiles on their CSR choices.

Originality/value

Given that today’s managers are faced with the challenge of selecting desirable CSR activities from a group of options, the authors answered the call by studying the differential effects of a wide array of CSR choices and provide important practical guidance to managers. For the first time in the literature, the study also investigates the potential interactive effects between specific CSR types and corporate competence on consumer reactions. This inquiry bears significant relevance to the ongoing discussions concerning whether and how company characteristics generate influences on the outcomes of CSR strategies.
Maintenance of high-rise residential buildings
Authors: Chua Shirley Jin Lin , Zubbir Najilah Bt , Ali Azlan Shah , Au-Yong Cheong Peng
Published: April 2018

Purpose

Preventive maintenance is an effective maintenance strategy to ensure the constant and efficient usage of building systems and their components. The reactive-based maintenance as the main strategy in high-rise residential buildings is a concern as the maintenance output resulting from the strategy could not achieve the standard level of performance. The purpose of this paper is to identify the characteristics of preventive maintenance and establish the relationship with maintenance performance in high-rise residential buildings.

Design/methodology/approach

The characteristics of preventive maintenance and maintenance performance parameters were identified through the literature review. A quantitative approach was adopted, where a questionnaire was distributed to the maintenance personnel of high-rise residential buildings. Then, ranking analysis and correlation were conducted to produce findings that help to achieve the research objectives.

Findings

The research findings indicate that there are seven maintenance characteristics significantly correlated with maintenance performance indicators (maintenance costs deviation, time variance of maintenance work, customer service and downtime rate). It is recommended that these characteristics are considered during the execution of preventive maintenance as they have a significant effect on the maintenance performance.

Originality/value

The extensive literature suggests the relationship between the characteristics of preventive maintenance and maintenance performance, but is still questionable. Thus, this research investigates the relationship between preventive maintenance characteristic and maintenance performance for high-rise residential buildings in Malaysia. The findings of the research can act as a guide for maintenance personnel to optimise maintenance performance by focusing on the highlighted preventive maintenance characteristics.
Synergizing climate change mitigation and adaptation in Cameroon
Authors: Ngum Faith , Alemagi Dieudonne , Duguma Lalisa , Minang Peter A. , Kehbila Anderson , Tchoundjeu Zac
Published: April 2018

Purpose

This paper aims to examine the policy environments, institutional arrangements and practical implementation of some initiatives undertaken by the Government of Cameroon, together with some relevant stakeholders, in addressing climate change mitigation and adaptation at various levels in the country, which are prerequisites to promote synergistic ways of addressing climate change mitigation and adaptation.

Design/methodology/approach

Using a qualitative approach to data collection, the paper draws upon information collected from relevant literature and interviews with 18 key country resource personnel.

Findings

Results revealed that most reviewed policies/programs/strategies do not mention “climate change” explicitly but propose some activities which indirectly address it. Interaction is fair within the government ministries but weak between these ministries and other institutions. Inadequate financial resources are being opined as the most important challenge stakeholders are (and would continue) facing as a result of adopting integrated approaches to climate change. Other challenges include inadequate coordination, insufficient sensitization and capacity building, ineffective implementation, inadequate compliance, lack of proper transparency and inadequate public participation. To redress the aforementioned constraints and challenges, the paper concludes by outlining a number of recommendations for policy design.

Originality/value

The following recommendations were made: create a national technical committee to oversee and provide scientific guidance to the government on synergistic approaches; promote private sector investment and sponsorship on synergistic approaches; create local awareness, etc. It is important to underscore that minimal studies have been conducted to analyze multi-stakeholder perspectives on synergies between climate change mitigation and adaptation in Cameroon. This study attempts to bridge this major gap.
Current state and perspective of water management policy in terms of climate change
Authors: Stojkovic Zlatanovic Sanja , Stojkovic Milan , Mitkovic Mihailo
Published: April 2018

Purpose

The purpose of this paper is to set out the policy guidelines and recommendations to harmonise the Serbian water legislation with European Union standards in the area of water system management as impacted by climate change.

Design/methodology/approach

The EU Water Framework Directive is analysed in the context of implementation of the integrated water management policy presented in the Serbian Water Law (2010), as well as the National Water Management Strategy (2016). It has been found that the water management legislation that deals with the impact of climate change on water resources is incomplete. Although there are numerous challenges related to research of climate change and water systems, water policy and legal aspects cannot be neglected. The so-called soft law instruments represented in a form of strategy documents could be a valuable response in terms of an adaptive and integrated water policy approach.

Findings

The research is applied to a case study of the Velika Morava River Basin, at Ljubicevski Most hydrological station. Long-term projections suggest a decrease in annual precipitation levels and annual flows up to the year 2100 for climatic scenarios A1B and A2, accompanied by a rapid increase in air temperatures.

Originality/value

This study proposes a water management policy and provides recommendations for the Velika Morava River Basin as impacted by climate change, according to the European Union legislation.
Does sin matter in corporate governance issues in the United States
Authors: Ezzine Hanene , Olivero Bernard
Published: April 2018

Purpose

The authors provide evidence for the effects of social norms on corporate governance risk by studying “sin” stocks publicly traded companies involved in producing alcohol, firearms, biotechnology, gambling, military, nuclear power and tobacco. There is a societal norm against funding operations that promote vice and expropriation by controlling shareholders.

Design/methodology/approach

The sample is representative of S&P 500 firms in 2014. The authors use Datastream to obtain a sample of sin stocks. The authors’ descriptive analysis is completed by four variations of the basic ordinary least squares regression model according to dependent variable corporate governance risk score.

Findings

The authors find that non-financial incentives alone do not explain corporate governance risk. The authors provide strong empirical support for an alignment of financial and non-financial incentives. The authors show that when sin firm’s current performance is good, suggesting that the market holds a positive belief in firm’s future profitability, managers will likely have more incentive to expropriate shareholders.

Research limitations/implications

Belonging of firm to a sin industry does not reflect the acceptance level of social norms. The evolution of social norms towards sin stocks overcomes the drawback of assuming a constant social norms level over time. Therefore, researchers are encouraged to use the changes in consumption of sin products as a proxy for the evolution of social norms and examine does sin matter in corporate governance issue in other countries.

Practical implications

Well-planned and well-managed philanthropy sin industries to creating education programmes for the disadvantaged to protecting the environment, in the name of corporate social responsibility has become a necessary ingredient in virtually every large corporation’s business plan.

Originality/value

This paper fulfils an identified need to study does sin matter issue in corporate governance issue.