bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice
Authors: Zhou Ziqi , Lin Yanzhu , Zheng Hongyi , He Yuzhong , Xu Haohua , Zhang Siheng , Weng Wen , Li Wei , Zhu Linyan , Yang Haifeng
Published: May 2015

Phenytoin (PHT) is a commonly prescribed first‐line antiepileptic drug. However, long‐term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short‐/long‐term memory loss were observed in the PHT group, while the PHT + GD therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of NF‐κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT‐associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients.
Detecting metastatic prostate carcinoma in pelvic lymph nodes following neoadjuvant hormone therapy: the eyes have it!
Authors: Kehr Elizabeth , Masry Paul , Lis Rosina , Loda Massimo , Taplin Mary‐Ellen , Hirsch Michelle S
Published: May 2015

Aims

Residual cancer morphology in radical prostatectomies (RPs) after neoadjuvant hormone therapy includes inconspicuous cytology, and treated tumour cells can be difficult to identify in lymph nodes. The aim of this study was to evaluate the role of immunohistochemistry (IHC) in identifying occult lymph node metastases following neoadjuvant hormone treatment of prostate cancer.

Methods and results

One hundred and twenty‐eight lymph nodes from 24 patients treated with neoadjuvant hormone therapy, including abiraterone acetate alone or combined with leuprolide, were stained with antibodies against keratin AE1/AE3, prostate‐specific antigen (PSA), prostate‐specific acid phosphatase (PrAP), androgen receptor (AR), and NKX3.1. IHC slides were scored ‘blind’, and then retrospectively compared with haematoxylin and eosin (H&E)‐stained slides and pathology reports. IHC identified carcinoma in six lymph nodes from three patients. All metastases were positive for NKX3.1 and AR, five of six were positive for AE1/AE3, and three of six were positive for PSA; PrAP was negative in all metastatic foci. All six lymph node metastases had been identified by H&E staining at the time of RP.

Conclusions

These findings suggest that routine use of IHC on lymph nodes from neoadjuvant‐treated prostate carcinomas is not necessary. Nevertheless, for suspicious small foci of atypical cells in neoadjuvant‐treated lymph nodes, NKX3.1 and AR appear to have the greatest sensitivity.
Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases
Authors: Takahashi Naomi , Noda Shinji , Taniguchi Takashi , Adachi Makoto
Published: May 2015

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.
Comparison of postoperative estimated glomerular filtration rate between kidney donors and radical nephrectomy patients, and risk factors for postoperative chronic kidney disease
Authors: Lee Sang Hyub , Kim Dong Soo , Cho Seok , Kim Sang Jin , Kang Seok Ho , Park Jinsung , Park Sung Yul , Chang Sung‐Goo , Jeon Seung Hyun
Published: May 2015

Objectives

To compare post‐nephrectomy renal function between kidney donors and renal cell carcinoma patients, to evaluate trends in recovery, and to identify factors relevant to renal failure.

Methods

Patients who had radical or donor nephrectomy from four different institutions between 2003 and 2012 were reviewed. Propensity score matching was carried out and 79 patients were selected for each group. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula preoperatively and postoperatively at 1, 3, 6, 12, 24 and 36 months. Mean estimated glomerular filtration rate was compared, and the difference between preoperative values and each preceding date was calculated. A multivariate logistic regression was used to determine independent factors for a decrease in estimated glomerular filtration rate to <60 mL/min/1.73 m2.

Results

The donor nephrectomy group showed a trend of improved estimated glomerular filtration rate recovery at 24 months and 36 months compared with the radical nephrectomy group, which was statistically significant (P = 0.028, P = 0.012). Multivariate logistic regression showed that renal cell carcinoma (odds ratio 4.605, 95% confidence interval 1.626–13.040, P = 0.004), a baseline estimated glomerular filtration rate lower than 110 (odds ratio 4.477, 95% confidence interval 1.360–14.742, P = 0.014) and age older than 40 years (odds ratio 21.616, 95% confidence interval 2.761–169.222, P = 0.003) were predictive factors for a decrease in renal function.

Conclusions

Renal cell carcinoma is an independent risk factor for chronic kidney disease after nephrectomy. In addition, age older than 40 years and a baseline estimated glomerular filtration rate of 110 mL/min/1.73 m2 or less seem to represent risk factors associated with chronic kidney disease after nephrectomy.
Pressures toward Uniformity in Groups: A Dynamic Structural Equation Model
Authors: Anderson James G. , Triplett Mark
Published: May 2015

In this paper a dynamic structural equation model consisting of a set of difference equations has been constructed in order to examine the process by which groups generate pressures toward uniformity. The model is based on Festinger's hypotheses about communication resulting from such pressures.

Parameters of the model have been estimated from a consideration of one of the equilibrium conditions of the model. Hypothetical time paths that describe the dynamic behaviour of the system have been generated by a series of computer simulation runs. These graphs describe the process by which group cohesiveness and discrepancy in opinions among group members adjust to each other over time.

The model has lead to a number of major insights into this dynamic process. The results of the simulation indicate the existence of multiple equilibrium points for the system and that the relevance of the issue for the group's functioning is a critical factor in determining the rate at which a new equilibrium is reached once the initial equilibrium is disturbed.

Groups can and do attempt to influence members in order to achieve uniformity of opinions, beliefs, values and behaviour (Asch, 1951; Deutsch and Gerard, 1955; Scott 1965). Cartwrght and Zander (1968) in reviewing the theoretical explanations of why groups attempt to achieve uniformity point out four functions that such pressure serves; namely goal attainment (Festinger, 1950), group maintenance (Stock, Whitman and Lieberman, 1958), the development of social reality through consensus (Festinger, 1954; Schachter, 1959), and achievement of consensus concerning group relations with its social surroundings (Burns, 1955; Cohen, 1955; Yinger, 1950).

As a result discrepancies in opinions, beliefs, values and behaviour, give rise to pressures on members to communicate with one another. Festinger (1950) in his investigations of informal social communications has enumerated a set of hypotheses concerning such communication that results from group pressures to achieve uniformity. Several of his hypotheses are concerned with members of the group as a whole and form the basis of one model by Simon and Guetzkow (1955) involving a set of differential equations.

In the following section of this paper Festinger's verbal theory will be recast as a causal model (Blalock, 1969). A dynamic structural equation model will be developed consisting of a set of difference equations. This structural model will form the basis of a computer simulation model which will be validated with data from studies by Festinger, Schachter and Back (1950), Festinger and Thibaut (1951) and Back (1951).
Analysis of Changing Group Inequalities in a Changing Occupational Structure
Authors: Reitz Jeffrey G.
Published: May 2015

This paper proposes an index of group (racial, ethnic, sexual, etc.) occupational inequalities which can be computed from standard group-by-group occupational distributions, and which can be interpreted substantively as the relative likelihood that a group member will respond successfully to a new high status job opportunity, given that such opportunities are encountered at random throughout society. That is, the index summarises group differences in occupational aspirations and in all forms of discrimination encountered in the job market, in terms of conditional probabilities. Numerical values of the index have this same interpretation regardless of the occupational opportunity structure underlying observed occupational distributions. Thus the index can be used to compare group inequalities at different points in time, regardless of how the overall occupational distribution changes (and also regardless of changes in the relative sizes of groups). The index is applied to the analysis of changing occupational inequalities among Canadian ethnic groups between 1951 and 1961, and also to changing unemployment rates among blacks and whites in the United States between 1961 and 1969.
On the Social Production of Visual Difference
Authors: Bud Robert
Published: May 2015

A curator explores the process of construction of a major new Chemical Industry Gallery at London's Science Museum. The Museum is found to have acted as a broker bringing together diverse interests no one of which had an overwhelming significance. The paper follows the negotiations involved in selecting objects, text and physical environment and the translation of goals during the process. An exhibit is seen as a combination of mythic form and machine, and the paper concludes that the qualities of the machine exert an ever greater demand at the expense of the myth, during the course of construction.
On the Art of Representation: Notes on the Politics of Visualisation
Authors: Law John , Whittaker John
Published: May 2015

This paper considers how technologies of representation are used by writers about acid rain research to re-present that research to non-scientists. The processes by which such technologies suppress what they purport to represent and replace it with novel and more docile elements which are often visual is described. Visual technologies for combining and further simplifying these elements are considered. Finally, the analogy between political and visual representation is drawn out, though the specificity of visual technologies is emphasised.
Perspectives of US Direct Care Workers on the Grief Process of Persons with Intellectual and Developmental Disabilities: Implications for Practice
Authors: Gray Jennifer A. , Abendroth Maryann
Published: May 2015

Background

The study explored the grief process of persons with intellectual and developmental disabilities (PWIDDs) as perceived by direct care workers (DCWs) and how such workers can guide and support PWIDDs experiencing grief.

Materials and Methods

A thematic analysis approach was used to examine data from nine focus groups with 60 DCWs from five community‐based organizations.

Results

Findings were supported in the context of seminal grief and bereavement theories. Three themes (i.e. reactions to loss, processing the loss and incorporating the loss) and related subthemes emerged from the data.

Conclusions

PWIDDs are susceptible to traumatic grief, and DCWs are often key witnesses to such experiences. DCWs’ perspectives can guide the development of grief and bereavement training which can lead to more tailored support systems.
A genomewide association mapping study using ultrasound‐scanned information identifies potential genomic regions and candidate genes affecting carcass traits in Nellore cattle
Authors: Santana M.H.A. , Ventura R.V. , Utsunomiya Y.T. , Neves H.H.R. , Alexandre P.A. , Oliveira Junior G.A. , Gomes R.C. , Bonin M.N. , Coutinho L.L. , Garcia J.F. , Silva S.L. , Fukumasu H. , Leme P.R. , Ferraz J.B.S.
Published: May 2015

The aim of this study was to identify candidate genes and genomic regions associated with ultrasound‐derived measurements of the rib‐eye area (REA), backfat thickness (BFT) and rumpfat thickness (RFT) in Nellore cattle. Data from 640 Nellore steers and young bulls with genotypes for 290 863 single nucleotide polymorphisms (SNPs) were used for genomewide association mapping. Significant SNP associations were explored to find possible candidate genes related to physiological processes. Several of the significant markers detected were mapped onto functional candidate genes including ARFGAP3, CLSTN2 and DPYD for REA; OSBPL3 and SUDS3 for BFT; and RARRES1 and VEPH1 for RFT. The physiological pathway related to lipid metabolism (CLSTN2, OSBPL3, RARRES1 and VEPH1) was identified. The significant markers within previously reported QTLs reinforce the importance of the genomic regions, and the other loci offer candidate genes that have not been related to carcass traits in previous investigations.
Sonographic features of congenital infantile fibrosarcoma that appeared as a sacrococcygeal teratoma during pregnancy
Authors: Suzuki Takashi , Murakoshi Takeshi , Tanaka Kei , Ogasawara Aiko , Torii Yuichi
Published: May 2015

We experienced an extremely rare case of congenital infantile fibrosarcoma originating from the fetal sacrococcygeal region in pregnancy. At first, we suspected fetal sacrococcygeal teratoma; however, the following ultrasonography findings of the tumor complicated this diagnosis: (i) laterality; (ii) no cystic component; (iii) hypervascularity, with the feeding vessels not derived from the middle sacral artery; and (iv) a skin covering. The pathological findings indicated that the tumor was an infantile fibrosarcoma, not a teratoma. Thus, we believe that these sonographic features may aid the prenatal diagnosis of congenital infantile fibrosarcoma, which, in turn, may contribute to a better prognosis and may be useful for parental counseling.
Exploring the compatibility of mental health nursing, recovery‐focused practice and the welfare state
Authors: Conlon M. M. M. , Bush C. J. , Ariyaratnam M. I. , Brennan G. K. , Owtram R.
Published: May 2015

Accessible summary

Mental health nurses are expected to adhere to a range of professional values.

The values of social integration that mental health nurses practise are somewhat at odds with the values of the British welfare state.

Alternative systems of welfare support are demonstrated in other countries.

Mental health nurses must consider models of practice, such as that described by Clifton et al. (2013b), to manage the disconnection between what is expected and what can be achieved.

This discussion paper considers the implications for mental health nursing practice when working alongside individuals in receipt of state benefits. There is arguably a profound impact on an individual's recovery from mental ill health when that individual is also dependent on financial support from the government. Access to welfare benefits can have a significant impact on the recovery journey of that individual. This discussion paper will consider the practice implications for mental health nurses whose professional values include maxims such as ‘challenging inequality’ and ‘respecting diversity’, and will seek to examine the implications for practice when such values are divergent from those demonstrated in government policy. The paper will make comparisons with international welfare systems to demonstrate the way in which alternative configurations of state welfare can promote a system of social justice that is in greater equilibrium with the professional values of mental health nurses. Finally, the discussion will focus on the options for mental health nurses to either subscribe to government policy or to find compromise solutions that enable attention to remain focused and active on a strong value base of social justice and recovery‐focused practice.
Increased Pygo2 expression in liver of patients with hepatitis B virus‐related fibrosis
Authors: Li Wenting , Zhu Chuanlong , Wu Yuanbo , Wang Zheng , Zhu Chuanwu
Published: May 2015

Background & Aims

It has been reported that Wnt/β‐catenin signalling pathway played a key role in liver fibrosis and that Pygo2 was an important mediator in β‐catenin induced pathway. However, the role of Pygo2 in liver fibrogenesis was unknown. Our study was to investigate the expression of Pygo2 and its diagnostic value in patients with HBV‐related liver fibrosis.

Methods

Hundred and sixty‐four patients with HBV infection underwent liver biopsy and liver stiffness measurement (LSM) by transient elastography (Fibroscan®; Echosens). Liver function was tested by routine biochemical examinations. Liver condition was assessed by haematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Pygo2 in liver tissue was measured by Real‐time PCR and immunohistochemistry, respectively, while the serum levels of Pygo2 were detected by ELISA. The relationship between degree of liver fibrosis and Pygo2 expression was assessed by correlation analysis. Receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of serum Pygo2, LSM and their combination.

Results

The mRNA and protein levels of Pygo2 in HBV‐infected patients were all higher than in normal persons (P < 0.05 respectively). Moreover, Pygo2 expression increased along with the progression of liver fibrosis (P < 0.05 respectively). The trend of serum Pygo2 agreed with its expression in liver tissue. The combination of serum Pygo2 and LSM had a significantly higher area under the curve than Pygo2 or LSM alone (P < 0.05 respectively).

Conclusions

This study suggested that Pygo2 was involved in HBV‐induced liver fibrogenesis. Pygo2 is a valuable biomarker for the evaluation of fibrosis in HBV‐infected patients.
The Impact of Lumbosacral Transitional Vertebrae on Therapeutic Outcomes of Transforaminal Epidural Injection in Patients with Lumbar Disc Herniation
Authors: Son Kang‐Min , Lee Sun‐Mi , Lee Gun Woo , Ahn Myun‐Hwan , Son Jung‐Hwan
Published: May 2015

Background

Although some studies have evaluated the clinical impact of lumbosacral transitional vertebrae (LSTV), few have attempted to determine an effective conservative treatment method for lumbar disc herniation (LDH) presenting concurrently with LSTV.

Methods

We prospectively enrolled 291 consecutive patients who were followed‐up for at least one year after transforaminal epidural injection (TFEI) for LDH. We confirmed the presence of LSTV with Paik et al.'s method, the Castellvi classification, and the Southworth and Bersack method. Clinical outcomes were evaluated with a visual analogue scale (VAS) for pain intensity and the Oswestry Disability Index (ODI) for functional status.

Results

Of the 291 patients, 47 (16.2%) had LSTV, including 33 with sacralization and 14 with lumbarization, while 244 (83.8%) did not have LSTV. Patients in both groups improved significantly after TFEI in terms of the VAS (P < 0.001) and ODI (P < 0.001) scores. However, LDH patients with LSTV had a worse clinical outcome after six months of TFEI than did those without LSTV, with a significant difference between groups for both the VAS (P < 0.01) and ODI (P = 0.01) scores. LDH patients with sacralization had worse post‐treatment clinical outcomes than LDH patients with lumbarization (P < 0.001) or LDH patients without LSTV (P < 0.001).

Conclusions

Sacralization can reduce the improvement after TFEI among LDH patients, while lumbarization appears to have no direct effect on TFEI outcomes. The presence of sacralization should be identified before TFEI, and if present, patients should be informed that the outcomes of TFEI may not be as good as they would be if sacralization was not present.
OsWS1 involved in cuticular wax biosynthesis is regulated by osa‐miR1848
Authors: Xia Kuaifei , Ou Xiaojin , Gao Chunzhi , Tang Huadan , Jia Yongxia , Deng Rufang , Xu Xinlan , Zhang Mingyong
Published: May 2015

Cuticular wax forms a hydrophobic layer covering aerial plant organs and acting as a protective barrier against biotic and abiotic stresses. Compared with well‐known wax biosynthetic pathway, molecular regulation of wax biosynthesis is less known. Here, we show that rice OsWS1, a member of the membrane‐bound O‐acyl transferase gene family, involved in wax biosynthesis and was regulated by an osa‐miR1848. OsWS1‐tagged green fluorescent protein localized to the endoplasmic reticulum (ER). Compared with wild‐type rice, OsWS1 overexpression plants displayed a 3% increase in total wax, especially a 35% increase in very long‐chain fatty acids, denser wax papillae around the stoma, more cuticular wax crystals formed on leaf and stem surfaces, pollen coats were thicker and more seedlings survived after water‐deficit treatment. In contrast, OsWS1‐RNAi and osa‐miR1848 overexpression plants exhibited opposing changes. Gene expression analysis showed that overexpression of osa‐miR1848 down‐regulated OsWS1 transcripts; furthermore, expression profiles of OsWS1 and osa‐miR1848 were inversely correlated in the leaf, panicle and stem, and upon water‐deficit treatment. These results suggest that OsWS1 is regulated by osa‐miR1848 and participates in cuticular wax formation.
Hydrogen isotope response to changing salinity and rainfall in Australian mangroves
Authors: Ladd S. Nemiah , Sachs Julian P.
Published: May 2015

Hydrogen isotope ratios (2H/1H, δ2H) of leaf waxes covary with those in precipitation and are therefore a useful paleohydrologic proxy. Mangroves are an exception to this relationship because their δ2H values are also influenced by salinity. The mechanisms underlying this response were investigated by measuring leaf lipid δ2H and leaf and xylem water δ2H and δ18O values from three mangrove species over 9.5 months in a subtropical Australian estuary. Net 2H/1H fractionation between surface water and leaf lipids decreased by 0.5–1.0‰ ppt−1 for n‐alkanes and 0.4–0.8‰ ppt−1 for isoprenoids. Xylem water was 2H depleted relative to surface water, reflecting 2H discrimination of 4–10‰ during water uptake at all salinities and opportunistic uptake of freshwater at high salinity. However, leaf water 2H enrichment relative to estuary water was insensitive to salinity and identical for all species. Therefore, variations in leaf and xylem water δ2H values cannot explain the salinity‐dependent 2H depletion in leaf lipids, nor the 30‰ range in leaf lipid δ2H values among species. Biochemical changes in direct response to salt stress, such as increased compatible solute production or preferential use of stored carbohydrates, and/or the timing of lipid production and subsequent turnover rates, are more likely causes.
Extracorporeal cardiopulmonary resuscitation for breath‐holding spells followed by cardiac arrest due to left main coronary artery stenosis
Authors: Ozyilmaz Isa , Altin Husnu Fırat , Yildiz Okan , Erek Ersin , Ergul Yakup , Guzeltas Alper
Published: May 2015

Non‐syndromic congenital supravalvular aortic stenosis (SVAS) leads to ventricular hypertrophy and increased oxygen consumption, and when combined with other factors reduces coronary blood flow, potentially resulting in myocardial ischemia and sudden cardiac death. While the anatomic obstruction of coronary circulation is as common in non‐syndromic SVAS as in Williams syndrome, it often remains unacknowledged. Extracorporeal membrane oxygenation (ECMO) is an elective procedure that can be used to support patients with cardiac arrest during diagnosis as a way to reduce cardiopulmonary load in preparation for surgery or further treatment. In this report, we describe the rare case of an infant with severe SVAS and mild valvular pulmonary and left main coronary artery stenosis, as well as breath‐holding spells. After multiple cardiac arrests, the infant underwent diagnostic catheter angiography on ECMO and had the pathology surgically corrected.
Genetic analysis of Grapevine leafroll‐associated virus 3 population from Galicia, Spain
Authors: Pesqueira A. M. , Cabaleiro C. , Velasco L.
Published: May 2015

Grapevine leafroll‐associated virus 3 (GLRaV‐3; Ampelovirus, Closteroviridae) isolates from Galicia in northwestern Spain were selected to characterize their genetic diversity according to different factors (age, origin, location, variety, etc.). The vines belonged either to local white and red varieties autochthonous to Galicia or to varieties from other Spanish regions but widely used in Galicia. These GLRaV‐3 isolates came from different vineyards in Galicia located in coastal or inner areas. Multiplex RT‐PCR allowed the detection of isolates belonging to groups I, II, III–V and VI. Two genomic regions were studied in the isolates, the HSP70h and the capsid protein, using specific primers that allow the detection of variants from groups I to V. Some possible recombinants could be detected; however, multiple infections with different variants indicated that they were not genuine recombinants. No differences were found in the population structure considering variety or geographical factors. Isolates belonging to four groups were found in the distinct areas surveyed: groups I and II were the most common, followed by groups VI and III, as is the case in the rest of the world. In the same surveys, the presence of insect vectors for GLRaV‐3 was investigated and found lacking in inland areas but present in those with milder climate. Genetic analysis did not support isolation of the GLRaV‐3 isolates in Galicia, suggesting that the uncontrolled exchange of infected vines and/or rootstocks has been a major agent of virus spread.
Mother–Child Interaction as a Cradle of Theory of Mind: The Role of Maternal Emotional Availability
Authors: Licata Maria , Kristen Susanne , Sodian Beate
Published: May 2015

The present longitudinal study investigated the relative importance of emotional availability (EA) in 56 mother–child dyads when the child was 7 months and four‐year old as predictors of child's Theory of Mind at 4 years while controlling for early maternal mind‐mindedness (MM). Dyadic EA at 7 months predicted the child's Theory of Mind, even when controlling for child temperamental and cognitive characteristics as well as dyadic EA at 4 years and early maternal MM. Results indicate the specific importance of high emotional connectedness between mothers and infants for preschoolers' Theory of Mind development.
Bedside teaching: specialists versus non‐specialists
Authors: Woodley Niall , McKelvie Karen , Kellett Catherine
Published: May 2015

Background

Bedside teaching (BT) is a valuable learning experience for medical students. In 2010, the BT curriculum at the University of Dundee was revised so that clinical specialist doctors facilitated these sessions. The aim of this study was to compare student opinion of BT delivered by specialist and non‐specialist doctors.

Methods

A retrospective survey was sent to two medical student year groups who received teaching delivered by either specialist or non‐specialist doctors during year 2.

Results

The response rate was 24.5 per cent, of which 49.4 per cent were taught by specialists. Responses indicated that specialist doctors improved communication skills (p = 0.034), were less intimidating (p = 0.01) and gave greater opportunity to ask questions (p = 0.028) than their non‐specialist counterparts. Overall, students taught by specialty doctors rated BT as more valuable (p < 0.001). A positive correlation was noted between the frequency of patient interaction and the overall value of BT (p < 0.0121); however, there was no significant association between the main teaching location and the overall value of BT.

Discussion

Findings indicate that specialist doctors provide students with a better understanding of disease processes. Several students from the specialist group noted that their tutors linked theory to practice. No significant difference was found between the two groups regarding whether teaching was at an appropriate level. Specialist doctors therefore allow a number of improvements over the use of non‐specialist doctors for BT.

Overall, students taught by specialty doctors rated bedside teaching as more valuable
Interleukin‐6 enhances the activity of in vivo long‐term reconstituting hematopoietic stem cells in “hypoxic‐like” expansion cultures ex vivo
Authors: Duchez Pascale , Rodriguez Laura , Chevaleyre Jean , Lapostolle Veronique , Vlaski Marija , Brunet de la Grange Philippe , Ivanovic Zoran
Published: May 2015

BACKGROUND

Since interleukin (IL)‐6 synergizes with the physiologically relevant O2 concentration in the maintenance of primitive hematopoietic stem cell (HSC) subpopulations, we hypothesized that its addition to our hypoxic response mimicking cultures (HRMCs), composed of an antioxidant‐supplied serum‐free xeno‐free medium supplemented with the cytokines stabilizing hypoxia‐inducible factor‐1α and balancing HSC self‐renewal and commitment, will result in a similar effect even if they are exposed to 20% O2.

STUDY DESIGN AND METHODS

HRMCs were exposed to 20 and 5% O2 with and without IL‐6. Functional committed progenitors (colony‐forming cells [CFCs]: CFU‐GM, BFU‐E, CFU‐Mix, and CFU‐Mk) were evaluated as well as the short‐ and long‐term repopulating HSCs using in vivo NSG mice model (primary and secondary recipients, respectively).

RESULTS

The addition of IL‐6 to HRMCs exposed to 20% O2 did not significantly impact either the CFCs or in vivo short‐term repopulating cells. However, it enhanced both the frequency and the individual proliferative capacity of the most primitive long‐term repopulating cell population evidenced by the generation of human CFCs in the marrow of secondary recipient mice. The exposure of HRMCs to 5% O2 negatively affected the amplification of CFCs, which was not changed by the addition of IL‐6 and exhibited a partial enhancing effect on the long‐term repopulating cells.

CONCLUSION

The addition of IL‐6 to the cytokine cocktail further improves our expansion procedure based on atmospheric O2 concentration‐exposed HRMCs by enhancing the maintenance of the most primitive HSCs without a negative impact on the less primitive HSC populations and CFCs.
Bimodal distribution of Trypanosoma cruzi antibody levels in blood donors from a highly endemic area of Argentina: what is the significance of low‐reactive samples?
Authors: Remesar Mirta , Sabino Ester C. , del Pozo Ana , Mayer Allen , Busch Michael P. , Custer Brian
Published: May 2015

BACKGROUND

Low‐level seroreactive donor samples that are inconsistently detected by different Trypanosoma cruzi immunoassays are common, but the population distribution has not been reported in an endemic region. The objective was to understand the distribution of low‐level reactive samples using highly sensitive immunoassays and the relationship with epidemiologic evidence of exposure to T. cruzi.

STUDY DESIGN AND METHODS

Blood donors (BDs) were recruited in two blood banks located in Chaco province, in northeastern Argentina, from June 2006 to March 2007. Donors completed a Chagas exposure questionnaire and provided blood samples. All samples were tested in parallel with five contemporary and commercially available enzyme immunoassays for T. cruzi and a subgroup by a chemiluminescent assay.

RESULTS

Of the 1423 enrolled donors, 304 (21.4%) tested positive on all assays while 93 (6.5%) were reactive on at least one assay (inconclusive). Epidemiologic evidence of exposure to T. cruzi was significantly higher among positive and inconclusive donors compared to seronegative BD (p values range from 0.01 to <0.001 depending on the exposure). Histograms of the signal‐to‐cutoff values from all positive samples showed clear bimodal distributions for the whole parasite lysate assays, but not for the one recombinant antigen‐based assay. Low antibody level responses were present in 30% to 40% of the reactives, depending on the assay.

CONCLUSION

The population of individuals exposed to T. cruzi in highly endemic regions has a bimodal distribution of antibody response to the parasite. Although the clinical significance of low‐level reactivity is not fully established, these results may reflect evolving seroreversions after spontaneously resolved infections.
Effects of Various Cognitive Video Stimulations on the Measured Stamina of Runners
Authors: Gonzales Benoît R. , Hagin Vincent , Dowrick Peter W. , Groslambert Alain
Published: May 2015

This study assessed whether cognitive stimulations could improve running performance. Nine trained men (22.6 ± 2.1 years old) performed four tests of stamina i) a control test (CT) at 100% of maximal aerobic velocity without any specific attention instructions, ii) a video self modeling test filmed from behind (VB), where runners attended to a video-loop of themselves, iii) a video self modeling test filmed from the front (VF), and iv) a video of landscapes (VL) with music. The results revealed a significant increase (p = .004) of stamina in all video conditions: VB (235 ± 59 s); VF (229 ± 53 s); VL (242 ± 57 s), compared with CT (182 ± 33 s). The results showed that the oxygen consumption was significantly lower (p = .02) in VB. Two distinct processes could explain these results including the active role of mirror neurons and the influence of music.
Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria
Authors: Bassat Quique , Ogutu Bernhards , Djimde Abdoulaye , Stricker Kirstin , Hamed Kamal
Published: May 2015

Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated
Plasmodium falciparum
malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.
RX-P873, a Novel Protein Synthesis Inhibitor, Accumulates in Human THP-1 Monocytes and Is Active against Intracellular Infections by Gram-Positive (Staphylococcus aureus) and Gram-Negative (Pseudomonas aeruginosa) Bacteria
Authors: Buyck Julien M. , Peyrusson Frédéric , Tulkens Paul M. , Van Bambeke Françoise
Published: May 2015

The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by
Staphylococcus aureus
and
Pseudomonas aeruginosa
, using a pharmacodynamic approach allowing the determination of maximal relative efficacies (
E
max
values) and bacteriostatic concentrations (

C
s

values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter (
S. aureus
) and 2 to 8 mg/liter (
P. aeruginosa
), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains.
E
max
values (expressed as the decrease in the number of CFU from that in the initial inoculum) against
S. aureus
and
P. aeruginosa
reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h.

C
s

values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for
S. aureus
; ciprofloxacin and ceftazidime for
P. aeruginosa
). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against
P. aeruginosa
than against
S. aureus
. Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species.
Open-Label Study To Evaluate the Single-Dose Pharmacokinetics, Safety, and Tolerability of Doripenem in Infants Less than 12 Weeks in Chronological Age
Authors: Cirillo Iolanda , Vaccaro Nicole , Castaneda-Ruiz Bibiana , Redman Rebecca , Cossey Veerle , Bradley John S. , Allegaert Karel
Published: May 2015

Doripenem, a parenteral carbapenem with broad-spectrum activity against aerobic Gram-negative and Gram-positive and anaerobic pathogens, is currently approved for use in adults in the United States and European Union. Single-dose doripenem pharmacokinetics in 52 infants <12 weeks in chronological age were investigated in this phase 1 study. Hospitalized, medically stable infants <12 weeks in chronological age were stratified into 6 groups based on chronological and gestational age designed to reflect increasing renal maturation and decreasing volume of distribution (
V

z

) for β-lactam antimicrobials during the first 3 months of life. Subjects received single-dose doripenem (5 mg/kg of body weight for <8 weeks and 8 mg/kg for ≥8 weeks in chronological age) administered intravenously over 1 h. Plasma samples were obtained immediately before the end of the infusion and 1.5, 3, and 7 h after the start of the infusion. Urine was obtained by indwelling catheter during the 8 h following infusion. Doripenem showed linear pharmacokinetics across the 6 age groups. Neonates (<4 weeks in chronological age) had increased mean exposure (area under the plasma concentration-time curve from time zero to infinite time [AUC
∞
], 45.7 versus 32.4 μg · h/ml), longer elimination half-life (2.98 versus 1.79 h), and lower clearance (2.03 versus 3.03 ml/min/kg) compared with infants >4 weeks. Mean
V

z

was highest in subjects with the earliest gestational age (<32 weeks): 0.564 liter/kg for neonates and 0.548 liter/kg for infants. Single-dose pharmacokinetics of doripenem administered as a 1-hour infusion in term and preterm infants <12 weeks in chronological age were similar to what has been observed in neonates and very young infants with other carbapenems. Single-dose doripenem was generally safe and well tolerated. (This study has been registered with ClinicalTrials.gov under registration no. NCT01381848 and with EudraCT under registration no. 2009-014387-20.)
Comparative Evaluation of Colistin Susceptibility Testing Methods among Carbapenem-Nonsusceptible Klebsiella pneumoniae and Acinetobacter baumannii Clinical Isolates
Authors: Dafopoulou Konstantina , Zarkotou Olympia , Dimitroulia Evangelia , Hadjichristodoulou Christos , Gennimata Vasiliki , Pournaras Spyros , Tsakris Athanasios
Published: May 2015

We compared six colistin susceptibility testing (ST) methods on 61 carbapenem-nonsusceptible
Klebsiella pneumoniae
(
n
= 41) and
Acinetobacter baumannii
(
n
= 20) clinical isolates with provisionally elevated colistin MICs by routine ST. Colistin MICs were determined by broth microdilution (BMD), BMD with 0.002% polysorbate 80 (P80) (BMD-P80), agar dilution (AD), Etest, Vitek2, and MIC test strip (MTS). BMD was used as the reference method for comparison. The EUCAST-recommended susceptible and resistant breakpoints of ≤2 and >2 μg/ml, respectively, were applied for both
K. pneumoniae
and
A. baumannii
. The proportions of colistin-resistant strains were 95.1, 77, 96.7, 57.4, 65.6, and 98.4% by BMD, BMD-P80, AD, Etest, MTS, and Vitek2, respectively. The Etest and MTS methods produced excessive rates of very major errors (VMEs) (39.3 and 31.1%, respectively), while BMD-P80 produced 18% VMEs, AD produced 3.3% VMEs, and Vitek2 produced no VMEs. Major errors (MEs) were rather limited by all tested methods. These data show that gradient diffusion methods may lead to inappropriate colistin therapy. Clinical laboratories should consider the use of automated systems, such as Vitek2, or dilution methods for colistin ST.
IgG Antibodies to Endothelial Protein C Receptor-Binding Cysteine-Rich Interdomain Region Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 Are Acquired Early in Life in Individuals Exposed to Malaria
Authors: Turner Louise , Lavstsen Thomas , Mmbando Bruno P. , Wang Christian W. , Magistrado Pamela A. , Vestergaard Lasse S. , Ishengoma Deus S. , Minja Daniel T. R. , Lusingu John P. , Theander Thor G.
Published: May 2015

Severe malaria syndromes are precipitated by
Plasmodium falciparum
parasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variant
P. falciparum
erythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of PfEMP1 proteins associated with severe malaria and found that the receptor for these PfEMP1 variants is endothelial protein C receptor (EPCR). The binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDR) of the subtypes α1.1 and α1.4 to α1.8. In this study, we investigated the acquisition of anti-CIDR antibodies using plasma samples collected in four study villages with different malaria transmission intensities in northeastern Tanzania during a period with a decline in malaria transmission. We show that individuals exposed to high levels of malaria transmission acquire antibodies to EPCR-binding CIDR domains early in life and that these antibodies are acquired more rapidly than antibodies to other CIDR domains. The rate by which antibodies to EPCR-binding CIDR domains are acquired in populations in areas where malaria is endemic is determined by the malaria transmission intensity, and on a population level, the antibodies are rapidly lost if transmission is interrupted. This indicates that sustained exposure is required to maintain the production of the antibodies.
Micropatterned Macrophage Analysis Reveals Global Cytoskeleton Constraints Induced by Bacillus anthracis Edema Toxin
Authors: Trescos Yannick , Tessier Emilie , Rougeaux Clémence , Goossens Pierre L. , Tournier Jean-Nicolas
Published: May 2015

Bacillus anthracis
secretes the edema toxin (ET) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. The effects of ET on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. In this study, we have developed different adhesive micropatterned surfaces (L and crossbow) to control the shape of bone marrow-derived macrophages (BMDMs) and primary peritoneal macrophages. We found that macrophage F-actin cytoskeleton adopts a specific polar organization slightly different from classical human HeLa cells on the micropatterns. Moreover, ET induced a major quantitative reorganization of F-actin within 16 h with a collapse at the nonadhesive side of BMDMs along the nucleus. There was an increase in size and deformation into a kidney-like shape, followed by a decrease in size that correlates with a global cellular collapse. The collapse of F-actin was correlated with a release of focal adhesion on the patterns and decreased cell size. Finally, the cell nucleus was affected by actin reorganization. By using this technology, we could describe many previously unknown macrophage cellular dysfunctions induced by ET. This novel tool could be used to analyze more broadly the effects of toxins and other virulence factors that target the cytoskeleton.