bluuebunny/crossref_metadata_2025 huggingface dataset:
Priapism as a Result of Chronic Myeloid Leukemia: Case Report, Pathology, and Review of the Literature
Authors: Shaeer Osama Kamal Zaki Mahmoud , Shaeer Kamal Zaki Mahmoud , AbdelRahman Islam Fathy Soliman , El-Haddad Mostafa Shawky , Selim Osama Mohamed
Published: January 2015

Introduction

Priapism is rare-presenting feature in male patients with chronic myeloid leukemia (CML). Several hypotheses for pathogenesis have been described. Management has been controversial; some authors described resolution following priapism-specific interventions, and others recommended addition of CML-specific therapy or even CML-specific therapy alone.

Aim

In this report, we describe presentation and management of a man with refractory priapism that was the first presenting manifestation of CML. We also report, for the first time, the pathology sections of the sinusoidal tissue in such cases. Literature is reviewed for similar cases and their outcome.

Methods

A 21-year-old male patient presented with painful priapism that started 6 days earlier and failed aspiration–irrigation. CBC revealed marked leucocytosis. Oncology care diagnosed CML, and treatment with Imatinib was commenced with prior semen cryopreservation. Following remission, a penile prosthesis was implanted, assisted by optical corporotomy. Sinusoidal tissue biopsy was stained by hematoxylin/eosin (H&E) and CD34.

Main Outcome Measures

Pathology sections of cavernous tissue following CML-induced priapism.

Results

The penile implant survived without complications. H&E examination of the sinusoidal tissue biopsy revealed leukemic infiltration associated with vascular endothelial damage. CD34 staining showed the mixed picture of leukemic infiltrates, intact vascular endothelium with lumena showing leukemic cells, alternating with destroyed vessels, and no vascular lumena and ruminants of endothelial cells.

Conclusion

Priapism can be the first manifestation of previously undetected CML. The pathological picture of sinusoidal tissue in such cases is presented. In the case at hand, a complete blood picture was helpful in early diagnosis of CML and early initiation of targeted chemotherapy along with the corporal irrigation/aspiration or shunt surgery. It is therefore recommended to have a CBC examined at presentation of any case of ischemic priapism of unknown etiology, early initiation of CML therapy along with aspiration/irrigation, preferably cryopreserving a semen sample before CML therapy.
Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE-Mediated Allergy to Semen
Authors: Jiang Nannan , Xi Guangpeng , Li Hongjun , Yin Jia
Published: January 2015

Introduction

Postorgasmic illness syndrome (POIS) is a rarely described syndrome characterized by transient flu-like symptoms and cognition disorders. Recent studies suggest that immunogenic reactivity to autologous semen is the underlying mechanism in POIS. However, there are no data published on immunoglobulin E (IgE)-mediated allergy to autologous semen in men without POIS.

Aim

The purpose of the current work was to characterize the first diagnosed POIS patient in China and to study the allergic response of autologous semen in the affected patient and in three healthy males.

Methods

Specific IgE was tested with seminal fluid and common perennial aeroallergens in vitro. Skin prick tests and intracutaneous tests with autologous diluted semen were performed in the patient and three healthy donors. The pattern of IgE reactivity to patient's semen was identified using immunoblotting and ELISA.

Main Outcome Measure

Clinical features of POIS, skin reactions with autologous diluted seminal fluid, and the IgE reactivity patterns of immunoblotting and ELISA in vitro.

Results

A patient was diagnosed with POIS. The patient complained of lifelong premature ejaculation symptoms and allergic rhinitis. Routine laboratory and hormonal assessments were generally within normal range. The patient had a positive skin test with his own semen. Three healthy donors also showed positive skin tests. No semen-specific IgE to autologous semen was detected in the serum of the affected patient or healthy males.

Conclusions

This is the first report of a man with POIS in China. He had positive skin reactions after injection of autologous seminal fluid but no detectable serum concentrations of specific IgE antibodies. IgE-mediated semen allergy in men may not be the potential mechanism of POIS.
Peyronie's Disease and Autoimmunity—A Real-Life Clinical Study and Comprehensive Review
Authors: Ventimiglia Eugenio , Capogrosso Paolo , Colicchia Michele , Boeri Luca , Serino Alessandro , La Croce Giovanni , Russo Andrea , Capitanio Umberto , Briganti Alberto , Cantiello Francesco , Mirone Vincenzo , Damiano Rocco , Montorsi Francesco , Salonia Andrea
Published: January 2015

Introduction

Although heavily investigated over the last decades, Peyronie's disease (PD) pathogenesis remains unclear.

Aim

We sought to investigate the association between PD and autoimmune diseases (ADs) in men seeking medical help for sexual dysfunction in the real-life setting.

Methods

Complete sociodemographic and clinical data from a homogenous cohort of 1,140 consecutive Caucasian–European men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index and ADs were stratified according to International Classification of Diseases, Ninth Revision classification.

Main Outcome Measures

Descriptive statistics and multivariate logistic regression models tested the association between ADs and PD.

Results

PD was diagnosed in 148 (13%) of the 1,140 men; of PD patients, 14 (9.5%) had a comorbid AD; conversely, the rate of ADs in non-PD patients was significantly lower (χ2 = 24.7; P < 0.01). Both patient age and AD comorbidity achieved multivariable independent predictor status for PD (odds ratio [OR]: 1.05; P < 0.01 and OR: 4.90; P < 0.01, respectively).

Conclusions

Our observational findings showed that ADs are highly comorbid with PD in a large cohort of same-race individuals seeking medical help for sexual dysfunction in the real-life setting.
The spectrum of the non‐rapid eye movement sleep electroencephalogram following total sleep deprivation is trait‐like
Authors: Tarokh Leila , Rusterholz Thomas , Achermann Peter , Van Dongen Hans P. A.
Published: January 2015

The sleep electroencephalogram (EEG) spectrum is unique to an individual and stable across multiple baseline recordings. The aim of this study was to examine whether the sleep EEG spectrum exhibits the same stable characteristics after acute total sleep deprivation. Polysomnography (PSG) was recorded in 20 healthy adults across consecutive sleep periods. Three nights of baseline sleep [12 h time in bed (TIB)] following 12 h of wakefulness were interleaved with three nights of recovery sleep (12 h TIB) following 36 h of sustained wakefulness. Spectral analysis of the non‐rapid eye movement (NREM) sleep EEG (C3LM derivation) was used to calculate power in 0.25 Hz frequency bins between 0.75 and 16.0 Hz. Intraclass correlation coefficients (ICCs) were calculated to assess stable individual differences for baseline and recovery night spectra separately and combined. ICCs were high across all frequencies for baseline and recovery and for baseline and recovery combined. These results show that the spectrum of the NREM sleep EEG is substantially different among individuals, highly stable within individuals and robust to an experimental challenge (i.e. sleep deprivation) known to have considerable impact on the NREM sleep EEG. These findings indicate that the NREM sleep EEG represents a trait.
Definition of an HBsAg to DNA international unit conversion factor by enrichment of circulating hepatitis B virus forms
Authors: Désiré N. , Ngo Y. , Franetich J.‐F. , Dembele L. , Mazier D. , Vaillant J.‐C. , Poynard T. , Thibault V.
Published: January 2015

Hepatitis B (HBV) virus infection is characterized by the overproduction of subviral particles (SVP) over infectious Dane particles (VP). Precise regulation of the ratio between these forms is unknown, but its fluctuation may have a clinical impact. An enrichment method was applied to assess the SVP/VP ratio in chronically infected patients (CHB) and to compare the sensitivity of HBs antigen (HBsAg) and DNA detection methods. Plasmas from 9 genotype A–D CHB patients were fractionated on Nycodenz® gradients, and both HBV DNA and HBsAg were quantified in each collected fraction using standardized techniques expressed in IU/mL. Infection of primary human hepatocytes (PHHs) was performed with crude or fractionated plasma. Independently of the genotype, all plasmas showed a similar rate‐zonal separation profile characterized by a bottom DNA‐enriched peak surmounted by HBsAg‐enriched fractions. Inoculation of PHH with plasma‐derived VP‐enriched fractions led to long‐lasting production of virus in cell supernatants with a SVP/VP ratio similar to that observed in patient plasmas. In the VP fraction, one IU of HBsAg corresponded to approximately 5 million IU of HBV DNA. Rate‐zonal gradient separation directly applied on patient plasma allows a better insight into the distribution of VP in HBeAg‐positive CHB carriers. This study highlights the sensitivity difference of the techniques classically used to monitor HBV infection and indicates that VP‐associated HBsAg contributes modestly to the overall amount of total circulating HBsAg in CHB. Such a fractionation approach should help to understand the fine regulation of HBsAg production over replication at different stages of CHB.
Effects of parental status on male body mass in the monogamous, biparental California mouse
Authors: Saltzman W. , Harris B. N. , de Jong T. R. , Nguyen P. P. , Cho J. T. , Hernandez M. , Perea‐Rodriguez J. P.
Published: January 2015

Studies of biparental mammals demonstrate that males may undergo systematic changes in body mass as a consequence of changes in reproductive status; however, these studies typically have not teased apart the effects of specific social and reproductive factors, such as cohabitation with a female per se, cohabitation with a breeding female specifically, and engagement in paternal care. We aimed to determine whether California mouse Peromyscus californicus fathers undergo systematic changes in body mass and if so, which specific social/reproductive factor(s) might contribute to these changes. We compared mean weekly body masses over a 5‐week period in (1) males housed with another male versus males housed with a non‐reproductive (tubally ligated) female; (2) males housed with a tubally ligated female versus males housed with a female that was undergoing her first pregnancy; (3) experienced fathers housed with versus without pups during their mate's subsequent pregnancy. Body mass did not differ between males housed with another male and those housed with a non‐reproductive female; however, males housed with a non‐reproductive female were significantly heavier than those housed with a primigravid female. Among experienced fathers, those housed with pups from their previous litter underwent significant increases in body mass across their mates' pregnancy, whereas fathers housed without pups did not. These results suggest that male body mass is reduced by cohabitation with a breeding (pregnant) female, but not by cohabitation with a non‐reproductive female, and that increases in body mass across the mate's pregnancy are associated with concurrent care of offspring rather than cohabitation with a pregnant female. Additional work is needed to determine the mechanisms and functional significance, if any, of these changes in male body mass with reproductive condition.
Assembling the components of the quorum sensing pathway in African trypanosomes
Authors: Mony Binny M. , Matthews Keith R.
Published: January 2015

African trypanosomes, parasites that cause human sleeping sickness, undergo a density‐dependent differentiation in the bloodstream of their mammalian hosts. This process is driven by a released parasite‐derived factor that causes parasites to accumulate in G1 and become quiescent. This is accompanied by morphological transformation to ‘stumpy’ forms that are adapted to survival and further development when taken up in the blood meal of tsetse flies, the vector for trypanosomiasis. Although the soluble signal driving differentiation to stumpy forms is unidentified, a recent genome‐wide RNAi screen identified many of the intracellular signalling and effector molecules required for the response to this signal. These resemble components of nutritional starvation and quiescence pathways in other eukaryotes, suggesting that parasite development shares similarities with the adaptive quiescence of organisms such as yeasts and Dictyostelium in response to nutritional starvation and stress. Here, the trypanosome signalling pathway is discussed in the context of these conserved pathways and the possible contributions of opposing ‘slender retainer’ and ‘stumpy inducer’ arms described. As evolutionarily highly divergent eukaryotes, the organisation and conservation of this developmental pathway can provide insight into the developmental cycle of other protozoan parasites, as well as the adaptive and programmed developmental responses of all eukaryotic cells.
Isolation of haemolytic bacilli from field‐collected Culicoides oxystoma and Culicoides peregrinus: potential vectors of bluetongue virus in West Bengal, India
Authors: HARSHA R. , PAN B. , GHOSH K. , MAZUMDAR A.
Published: January 2015

Two haemolytic bacterial strains of Bacillus pumilus (CU1A, CU1B) and one blood‐utilizing strain of Bacillus licheniformis (CU2B) were isolated from relatively low numbers of field‐collected females of Culicoides oxystoma and Culicoides peregrinus (Diptera: Ceratopogonidae). A total of 36 females, including 18 of each of C. oxystoma and C. peregrinus (consisting of one and a pool of eight blood‐engorged specimens, and one and a pool of eight non‐engorged specimens for each species), were tested. In C. oxystoma, all three strains of bacteria were isolated from the one non‐engorged, the pool of non‐engorged and the pool of blood‐engorged females tested, but CU1A and CU2B were not found in the one blood‐engorged female tested. In C. peregrinus, all three strains were present in the pool of blood‐engorged females. However, the strain CU2B was not found in the pool of non‐engorged females. In the one blood‐engorged and one non‐engorged female tested, CU1A and CU2B were detected. The bacterial strains were identified based on Gram staining, enzyme activity (amylase and protease) and alignment of the 16S rRNA partial gene sequence to that available in the National Center for Biotechnology Information (NCBI) database GenBank. The functional role and significance of these haemolytic and blood‐digesting bacteria within the genus Culicoides remain to be determined.
A new species of Tunga perforating the osteoderms of its armadillo host in Argentina and redescription of the male of Tunga terasma
Authors: EZQUIAGA M. C. , LINARDI P. M. , DE AVELAR D. M. , LARESCHI M.
Published: January 2015

A new species of Tunga (Siphonaptera: Tungidae) collected from armadillos in Argentina is described. The new species is characterized by large and pigmented eyes, the presence of two bristles on antennal segment II, two bristles at the base of the maxilla, and a discoid neosome compressed anteroposteriorly. The gravid female is located in the carapace of the host, perforating the osteoderms. The new species resembles Tunga penetrans and Tunga terasma in general appearance. However, it differs by the greater anteroposterior compression of the neosome, a more angular head, and a manubrium with a pointed proximal end and convex ventral margin (the proximal end of the manubrium is rounded or slightly pointed in T. terasma, and the ventral margin is straight in both T. penetrans and T. terasma). In addition, specimens of T. penetrans have more bristles in antennal segments II and III, and lack bristles in the posterior tibia. This is the first report of a species of Tunga perforating the osteoderms of its host and thereby showing a high degree of specialization. Tunga terasma is recorded for the first time in Argentina; the male is described again and the characteristics of the species amended. This information may be useful in epidemiological studies of diseases caused by species of Tunga.
Nitrergic neuro‐muscular transmission is up‐regulated in patients with diverticulosis
Authors: Espín F. , Rofes L. , Ortega O. , Clavé P. , Gallego D.
Published: January 2015

Background

Neuro‐transmission impairment could be associated to motility changes observed in patients with diverticular disease. Therefore, the objective was to characterize the inhibitory neuro‐muscular transmission and gene expression changes of the enteric inhibitory pathways in patients with diverticulosis (DS).

Methods

Circular muscle strips from sigmoid colon of patients with DS and controls were studied using the organ bath technique to evaluate spontaneous contractility and enteric motor neurons stimulated by electrical field and qRT‐PCR to assess the expression of nNOS, iNOS, P2Y1R and PGP9.5.

Key Results

Patients with DS presented decreased spontaneous rhythmic contractions (SRC) that were significantly enhanced after incubation with L‐NNA (1 mM) and TTX (1 μM), and unaffected by the P2Y1 antagonist MRS2500 (1 μM). Stimulation on enteric motor neurons caused an increased duration of the latency of OFF‐contractions in DS group (p < 0.001), antagonized by L‐NNA and slightly affected by MRS2500 (1 μM). No differences in the IC50 between controls and DS patients were observed on inhibition of SRC for the NO‐donor sodium nitroprusside (SNP) and the preferential P2Y agonist ADPβS. Moreover, nNOS relative expression was also up‐regulated 2.3‐fold in the DS group (p < 0.05) whereas there was no significant difference in relative expression of iNOS, P2Y1R and the neuronal marker PGP9.5 between groups.

Conclusions & Inferences

Patients with DS presented an over‐expression of nNOS with increased endogenously NO‐mediated responses suggesting enhanced NO‐release. Up‐regulation in the nitrergic pathway in early stages of the disease might play a role in colonic motor disorders associated to diverticular disease.
THEORIZING HYBRIDITY: INSTITUTIONAL LOGICS, COMPLEX ORGANIZATIONS, AND ACTOR IDENTITIES: THE CASE OF NONPROFITS
Authors: SKELCHER CHRIS , SMITH STEVEN RATHGEB
Published: January 2015

We propose a novel approach to theorizing hybridity in public and nonprofit organizations. The concept of hybridity is widely used to describe organizational responses to changes in governance, but the literature seldom explains how hybrids arise or what forms they take. Transaction cost and organizational design literatures offer some solutions, but lack a theory of agency. We use the institutional logics approach to theorize hybrids as entities that face a plurality of normative frames. Logics provide symbolic and material elements that structure organizational legitimacy and actor identities. Contradictions between institutional logics offer space for them to be elaborated and creatively reconstructed by situated agents. We propose five types of organizational hybridity – segmented, segregated, assimilated, blended, and blocked. Each type is theoretically derived from empirically observed variations in organizational responses to institutional plurality. We develop propositions to show how our approach to hybridity adds value to academic and policy‐maker audiences.
UNDERSTANDING HYBRID ROLES: THE ROLE OF IDENTITY PROCESSES AMONGST PHYSICIANS
Authors: SPYRIDONIDIS DIMITRIOS , HENDY JANE , BARLOW JAMES
Published: January 2015

Increasing attention has been paid in both public administration and organizational theory to understanding how physicians assume a ‘hybrid’ role as they take on managerial responsibilities. Limited theoretical attention has been devoted to the processes involved in negotiating, developing, and maintaining such a role. We draw on identity theory, using a qualitative, five‐year longitudinal case study, to explore how hybrid physician–managers in the English National Health Service and the organizations they are situated in achieve this. We highlight the importance of saliency – how central an identity is to an individual's values and beliefs – in managing new identities. We found three differing responses to taking on a hybrid physician–manager role, with identity emerging as a mitigating factor for negotiating potentially conflicting roles. We discuss the implications for existing theory and practice in the management of public organizations and identify an agenda for further research.
Psychological distress following marital separation interacts with a polymorphism in the serotonin transporter gene to predict cardiac vagal control in the laboratory
Authors: Hasselmo Karen , Sbarra David A. , O'Connor Mary‐Frances , Moreno Francisco A.
Published: January 2015

Marital separation is linked to negative mental and physical health; however, the strength of this link may vary across people. This study examined changes in respiratory sinus arrhythmia (RSA), used to assess cardiac vagal control, in recently separated adults (N = 79; M time since separation = 3.5 months). When reflecting on the separation, self‐reported psychological distress following the separation interacted with a polymorphism in the serotonin transporter gene (5‐HTTLPR) and a relevant single nucleotide polymorphism (SNP), rs25531, to predict RSA. Among people reporting emotional difficulties after the separation, those who were homozygous for the short allele had lower RSA levels while reflecting on their relationship than other genotypes. The findings, although limited by the relatively small sample size, are discussed in terms of how higher‐sensitivity genotypes may interact with psychological responses to stress to alter physiology.
Updating and validating a new framework for restoring and analyzing latency‐variable ERP components from single trials with residue iteration decomposition (RIDE)
Authors: Ouyang Guang , Sommer Werner , Zhou Changsong
Published: January 2015

Trial‐to‐trial latency variability pervades cognitive EEG responses and may mix and smear ERP components but is usually ignored in conventional ERP averaging. Existing attempts to decompose temporally overlapping and latency‐variable ERP components show major limitations. Here, we propose a theoretical framework and model of ERPs consisting of temporally overlapping components locked to different external events or varying in latency from trial to trial. Based on this model, a new ERP decomposition and reconstruction method was developed: residue iteration decomposition (RIDE). Here, we describe an update of the method and compare it to other decomposition methods in simulated and real datasets. The updated RIDE method solves the divergence problem inherent to previous latency‐based decomposition methods. By implementing the model of ERPs as consisting of time‐variable and invariable single‐trial component clusters, RIDE obtains latency‐corrected ERP waveforms and topographies of the components, and yields dynamic information about single trials.
Empowering leadership in R&D teams: a closer look at its components, process, and outcomes
Authors: Zhu Yu‐Qian , Chen Houn‐Gee
Published: January 2015

Empowering leadership in R&D teams has gained increasing popularity as it provides a balance between autonomy and control, encourages member participation and self‐leadership, and benefits creativity and innovation. This research examined the unique influences of two behavior components of empowering leadership: group‐focused empowering leadership and differentiated individual‐focused empowering leadership on R&D team's processes and team effectiveness. Using data from 54 R&D teams, we found that group‐focused empowering leadership is strongly related to intra‐team collaboration, which in turn is positively related to both team innovativeness and performance. Differentiated individual‐focused empowering leadership, however, is positively related to intra‐team competition.
Analysis of the Formation of the Structure of Social Networks by Using Latent Space Models for Ranked Dynamic Networks
Authors: Sewell Daniel K. , Chen Yuguo
Published: January 2015

The formation of social networks and the evolution of their structures have been of interest to researchers for many decades. We wish to answer questions about network stability, group formation and popularity effects. We propose a latent space model for ranked dynamic networks that can be used to frame and answer these questions intuitively. The well-known data collected by Newcomb in the 1950s are very well suited to analyse the formation of a social network. We applied our model to these data to investigate the network stability, what groupings emerge and when they emerge, and how individual popularity is associated with individual stability.
A Novel Ermakov–Painlevé II System: ‐Dimensional Coupled NLS and Elastodynamic Reductions
Authors: Rogers Colin
Published: January 2015

Wave packet ansätze are introduced into an ‐dimensional Manakov‐type system and key invariants are isolated. Reduction is made to a novel coupled Ermakov–Painlevé II system and an algorithm presented for the derivation of wave packet representations via the classical Ermakov nonlinear superposition principle. Application of the procedure in the context of certain transverse wave motions in a generalized Mooney–Rivlin hyperelastic material is likewise shown to lead an Ermakov–Painlevé II reduction.
Moderate Deviation Principles for Empirical Covariance in the Neighbourhood of the Unit Root
Authors: Miao Yu , Wang Yanling , Yang Guangyu
Published: January 2015

In this paper, we consider the linear autoregressive model with varying coefficients θn∈[0,1). When θn tending to the unit root, the moderate deviation principle for empirical covariance is discussed, and as statistical applications, we provide the moderate deviation estimates of the least square and the Yule–Walker estimators of the parameter θn.
Identification of the novel HLA‐DQB1*03:03:02:04 allele in a Spanish individual
Authors: Cervera I. , Herraiz M. A. , Vidart J. , Ortega S. , Martinez‐Laso J.
Published: January 2015

HLA‐DQB1*03:03:02:04 and DQB1*03:03:02:02 alleles differ by a single point mutation in intron 2.
Effect of diabetes on tuberculosis presentation and outcomes in Kiribati
Authors: Cavanaugh J. , Viney K. , Kienene T. , Harley D. , Kelly P. M. , Sleigh A. , O'Connor J. , Mase S.
Published: January 2015

Objectives

To determine the association between diabetes and the clinical features and treatment outcomes of TB in Kiribati.

Methods

We enrolled consecutive patients with TB who presented from August 2010 to February 2012 and compared clinical features and TB treatment outcomes for patients with and without diabetes, as measured by haemoglobin A1c assay. Poor outcome was defined as death, default or treatment failure, and good outcome as treatment success or cure.

Results

Two hundred and seventy‐five eligible persons with TB disease were enrolled; 101 (37%) had diabetes. TB patients with diabetes were more likely to have acid‐fast bacilli (AFB) seen on sputum smear microscopy (RR: 1.3; 95% CI: 1.03–1.62). The risk of poor outcome did not differ between patients with or without diabetes (RR: 1.1; 95% CI: 0.5–2.7).

Conclusion

TB patients with diabetes are more likely than those without to have sputum with AFB on microscopy. This could increase transmission in the community. Early detection of TB by screening patients with diabetes, and the converse, could be important public health interventions where diabetes and TB are prevalent.
A registry of HLA‐typed donors for production of virus‐specific CD4 and CD8 T lymphocytes for adoptive reconstitution of immune‐compromised patients
Authors: Li Pira Giuseppina , Ivaldi Federico , Starc Nadia , Landi Fabiola , Rutella Sergio , Locatelli Franco , Sacchi Nicoletta , Tripodi Gino , Manca Fabrizio
Published: January 2015

Background

Virus‐specific CD4 and CD8 T lymphocytes from HLA‐matched donors are effective for treatment and prophylaxis of viral infections in immune‐compromised recipients of hematopoietic stem cell transplant recipients. Adoptive immune reconstitution is based on selection of specific T cells or on generation of specific T‐cell lines from the graft donor. Unfortunately, the graft donor is not always immune to the relevant pathogen or the graft donor may not be available (registry‐derived or cord blood donors).

Study Design and Methods

Since the possibility of using T cells from a third‐party subject is now established, we screened potential donors for T‐cell responses against cytomegalovirus (CMV), Epstein‐Barr virus (EBV), and adenovirus, the viruses most frequently targeted by adoptive immune reconstitution. Specific T‐cell responses against viral antigens were analyzed in 111 donors using a miniaturized interferon‐γ release assay.

Results

Responders to CMV were 64%, to EBV 40%, and to adenovirus 51%. Simultaneous responders to the three viruses were 49%. CMV‐specific CD4 and CD8 T‐cell lines could be generated from 11 of 12 donors defined as positive responders according to the T‐cell assay.

Conclusions

These data demonstrate that a large fraction of volunteers can be recruited in a donor registry for selection or expansion of virus specific T cells and that our T‐cell assay predicts the donors' ability to give rise to established T‐cell lines endowed with proliferative potential and effector function for adoptive immune reconstitution.
Converting fluid‐based cytologic specimens to histologic specimens for immunohistochemistry
Authors: Wallace Koranda A. , Goldschmidt Michael H. , Patel Reema T.
Published: January 2015

Background

Cavitary effusions are often evaluated cytologically to determine if there is an underlying neoplastic cause. Differentiation of neoplastic epithelial from mesothelial populations within effusions can be difficult using routine cytology. In addition, cytology alone cannot provide information on the immunophenotype of round cell populations. Gel foam techniques can be used to convert effusions into cell blocks for immunohistochemical (IHC) staining which can then be used to differentiate mesothelial from epithelial cell populations, and also allow immunophenotyping of round cell populations within effusions.

Objectives

The aim of this study was to evaluate a gel foam cell block technique for converting potential neoplastic cells in cavitary effusions into cell blocks to characterize these further by IHC.

Results

Thirteen canine and 7 feline samples with cohesive cell populations were evaluated using gel foam cell blocks and IHC. Samples evaluated by routine cytology were categorized as (1) epithelial cells, (2) cohesive cell population without cytologic distinction between mesothelial and epithelial cells, and (3) mesothelial cells with signs of atypia. Antibody‐mediated staining of vimentin and cytokeratin of the effusion cell blocks yielded further classification of cohesive cell populations. In addition, a total of 4 effusions with malignant round cells were evaluated; they were immunophenotyped as either B‐ or T‐cell lymphoma.

Conclusion

The use of cytokeratin and vimentin IHC on gel foam cell blocks from cavitary effusions provided robust staining and allowed characterization of cohesive cells as mesothelial or epithelial and immunophenotyping of lymphoid cell populations. In addition, this method is cost and time effective.
Involvement of the δ‐opioid receptor in exercise‐induced cardioprotection
Authors: Miller Lindsey E. , McGinnis Graham R. , Peters Bridget A. , Ballmann Christopher G. , Nanayakkara Gayani , Amin Rajesh , Quindry John C.
Published: January 2015

New Findings

What is the central question of this study?

Does the δ‐opioid receptor trigger exercise‐induced cardioprotection against ischaemia–reperfusion injury?

What is the main finding and its importance?

In exercised hearts, the δ‐opioid receptor appears to trigger cardioprotection against ischaemia–reperfusion‐induced tissue necrosis but not apoptosis.

Endogenous opioids mediate exercise‐induced cardioprotection against ischaemia–reperfusion (IR) injury, although the opioid receptor subtype mediating this effect is unknown. We investigated whether the δ‐opioid receptor mediates exercise‐induced cardioprotection against IR injury. Endogenous opioids are produced in various tissues, including the heart and skeletal muscle; therefore, we also sought to identify the effect of exercise on circulating endogenous opioid as well as transcript, protein and receptor expression in heart and skeletal muscle. Male Sprague–Dawley rats (n = 73) were assigned randomly to treadmill exercise or sedentary treatments. Cardiac tissue and serum were harvested 0, 20 and 120 min following exercise and from sedentary animals (n = 32) to quantify effects on proenkephalin and δ‐opioid receptor mRNA and protein levels, as well as serum enkephalin. Skeletal muscle (soleus) was harvested at identical time points for determination of proenkephalin protein and mRNA. A separate group of rats (n = 41) were randomly assigned to sham operation (Sham; surgical control), sedentary (Sed), exercise (Ex) or exercise + δ‐opioid receptor antagonist (ExD; naltrindole, 5 mg kg−1
i.p.) and received IR by left anterior descending coronary artery ligation in vivo. After IR, tissues were harvested to quantify treatment effects on necrosis and apoptosis. Cardiac proenkephalin mRNA expression increased following exercise (0 min, P = 0.03; 120 min, P = 0.021), while soleus expression was unaffected. Exercise‐induced changes in serum enkephalin were undetectable. After IR, tissue necrosis was elevated in Sed and ExD hearts (P < 0.001 and P = 0.003, respectively) compared with the Sham group, while the Ex group was partly protected. After IR, apoptosis was evident in Sed hearts (P = 0.016), while Ex and ExD hearts were protected. Data suggest that cardioprotective opioids are produced by the heart, but not by the soleus. After IR, the δ‐opioid receptor may mediate, in part, cardioprotection against necrosis but not apoptosis.
The impact of arterial load on left ventricular performance: an invasive haemodynamic study in severe mitral stenosis
Authors: Venkateshvaran Ashwin , Sola Srikanth , Govind Satish Chandra , Dash Pravat Kumar , Barooah Banajit , Shahgaldi Kambiz , Sahlén Anders , Lund Lars , Winter Reidar , Nagy Anikó Ilona , Manouras Aristomenis
Published: January 2015

Key points

A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading.

As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results.

The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways.

Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness.

Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS.

Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load‐independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm2) and 40 age‐matched controls. MS subjects underwent simultaneous bi‐ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single‐beat LV elastance (Ees) was employed for LV contractility measurements. Effective arterial elastance (Ea) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea: 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml−1; P < 0.001) and LV contractility (Ees: 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml−1; P < 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm2) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P < 0.001) and indexed LV end‐diastolic volume (LVEDVindex: 57 ± 16 to 64 ± 16 ml m−2; P < 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.
Pannexin 1 channels mediate the release of ATP into the lumen of the rat urinary bladder
Authors: Beckel Jonathan M. , Daugherty Stephanie L. , Tyagi Pradeep , Wolf‐Johnston Amanda S. , Birder Lori A. , Mitchell Claire H. , de Groat William C.
Published: January 2015

Key points

ATP is released through pannexin channels into the lumen of the rat urinary bladder in response to distension or stimulation with bacterial endotoxins.

Luminal ATP plays a physiological role in the control of micturition because intravesical perfusion of apyrase or the ecto‐ATPase inhibitor ARL67156 altered reflex bladder activity in the anaesthetized rat.

The release of ATP from the apical and basolateral surfaces of the urothelium appears to be mediated by separate mechanisms because intravesical administration of the pannexin channel antagonist Brilliant Blue FCF increased bladder capacity, whereas i.v. administration did not.

Intravesical instillation of small interfering RNA‐containing liposomes decreased pannexin 1 expression in the rat urothelium in vivo and increased bladder capacity.

These data indicate a role for pannexin‐mediated luminal ATP release in both the physiological and pathophysiological control of micturition and suggest that urothelial pannexin may be a viable target for the treatment of overactive bladder disorders.

ATP is released from the bladder epithelium, also termed the urothelium, in response to mechanical or chemical stimuli. Although numerous studies have described the contribution of this release to the development of various bladder disorders, little information exists regarding the mechanisms of release. In the present study, we examined the role of pannexin channels in mechanically‐induced ATP release from the urothelium. PCR confirmed the presence of pannexin 1 and 2 mRNA in rat urothelial tissue, whereas immunofluorescence experiments localized pannexin 1 to all three layers of the urothelium. During continuous bladder cystometry in anaesthetized rats, inhibition of pannexin 1 channels using carbenoxolone (CBX) or Brilliant Blue FCF (BB‐FCF) (1–100 μm, intravesically), or by using intravesical small interfering RNA, increased the interval between voiding contractions. Intravenous administration of BB‐FCF (1–100 μg kg−1) did not alter bladder activity. CBX or BB‐FCF (100 μm intravesically) also decreased basal ATP concentrations in the perfusate from non‐distended bladders and inhibited increases in ATP concentrations in response to bladder distension (15 and 30 cmH2O pressure). Intravesical perfusion of the ATP diphosphohydrolase apyrase (2 U ml−1), or the ATPase inhibitor ARL67156 (10 μm) increased or decreased reflex bladder activity, respectively. Intravesical instillation of bacterial lipopolysaccharides (LPS) (Escherichia coli 055:B5, 100 μg ml−1) increased ATP concentrations in the bladder perfusate, and also increased voiding frequency; these effects were suppressed by BB‐FCF. These data indicate that pannexin channels contribute to distension‐ or LPS‐evoked ATP release into the lumen of the bladder and that luminal release can modulate voiding function.
Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing
Authors: Wagenmakers Anton J. M. , Strauss Juliette A. , Shepherd Sam O. , Keske Michelle A. , Cocks Matthew
Published: January 2015

This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF‐A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age‐related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF‐B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.
Suitability of poroelastic and viscoelastic mechanical models for high and low frequency MR elastography
Authors: McGarry M. D. J. , Johnson C. L. , Sutton B. P. , Georgiadis J. G. , Van Houten E. E. W. , Pattison A. J. , Weaver J. B. , Paulsen K. D.
Published: January 2015

Purpose:

Descriptions of the structure of brain tissue as a porous cellular matrix support application of a poroelastic (PE) mechanical model which includes both solid and fluid phases. However, the majority of brain magnetic resonance elastography (MRE) studies use a single phase viscoelastic (VE) model to describe brain tissue behavior, in part due to availability of relatively simple direct inversion strategies for mechanical property estimation. A notable exception is low frequency intrinsic actuation MRE, where PE mechanical properties are imaged with a nonlinear inversion algorithm.

Methods:

This paper investigates the effect of model choice at each end of the spectrum of in vivo human brain actuation frequencies. Repeat MRE examinations of the brains of healthy volunteers were used to compare image quality and repeatability for each inversion model for both 50 Hz externally produced motion and ≈1 Hz intrinsic motions. Additionally, realistic simulated MRE data were generated with both VE and PE finite element solvers to investigate the effect of inappropriate model choice for ideal VE and PE materials.

Results:

In vivo, MRE data revealed that VE inversions appear more representative of anatomical structure and quantitatively repeatable for 50 Hz induced motions, whereas PE inversion produces better results at 1 Hz. Reasonable VE approximations of PE materials can be derived by equating the equivalent wave velocities for the two models, provided that the timescale of fluid equilibration is not similar to the period of actuation. An approximation of the equilibration time for human brain reveals that this condition is violated at 1 Hz but not at 50 Hz. Additionally, simulation experiments when using the “wrong” model for the inversion demonstrated reasonable shear modulus reconstructions at 50 Hz, whereas cross‐model inversions at 1 Hz were poor quality. Attenuation parameters were sensitive to changes in the forward model at both frequencies, however, no spatial information was recovered because the mechanisms of VE and PE attenuation are different.

Conclusions:

VE inversions are simpler with fewer unknown properties and may be sufficient to capture the mechanical behavior of PE brain tissue at higher actuation frequencies. However, accurate modeling of the fluid phase is required to produce useful mechanical property images at the lower frequencies of intrinsic brain motions.
In vivo demonstration of magnetic guidewire steerability in a MRI system with additional gradient coils
Authors: Lalande Viviane , Gosselin Frederick P. , Vonthron Manuel , Conan Benjamin , Tremblay Charles , Beaudoin Gilles , Soulez Gilles , Martel Sylvain
Published: January 2015

Purpose:

To assess the ability to control the steering of a modified guidewire actuated by the magnetic force of a magnetic resonance imaging system with additional gradient coils for selective arterial catheterization in rabbits.

Methods:

Selective catheterizations of the right renal artery, left renal artery, superior mesenteric artery, and iliac artery were performed on two rabbits. A 3D magnetic force was applied onto a magnetic bead placed at the tip of a guidewire. The ability of the guidewire to advance in the aorta without entering the side branches when the magnetic force was not applied was also evaluated. Steering of the guidewire was combined with a dedicated tracking system and its position was registered on the 3D model of a magnetic resonance angiography (MRA).

Results:

The magnetic catheterization of the renal arteries was successful and showed reproducibility. Superior mesenteric artery and iliac artery showed that the catheterization was feasible. These two arteries were difficult to visualize on MRA, making catheterization and setting the direction of the force more difficult. There was no inadvertent catheterization of side vessels when the guidewire was advanced with magnetic steering despite the hook shape at the tip of the guidewire caused by the alignment of the bead anisotropy with the permanent magnetic field.

Conclusions:

This first evaluation of selective catheterization of aortic branches with a magnetic guidewire provided a successful steering in the less angled side branches and this modified guidewire was advanced in the aorta without inadvertent selective catheterization when manipulated without magnetic actuation.
Informing Coaches’ Practices: Toward an Application of Foucault’s Ethics
Authors: Denison Jim , Pringle Richard , Cassidy Tania , Hessian Paul
Published: January 2015

Progress and improvement in sport is often the result of some type of change. However, change for change sake is not always beneficial. Therefore, to be an effective ‘change agent’ a coach must be able to problematize his or her actions and assess why or why not a change might be needed. Accordingly, helping coaches become active problematizers is vital to the change process. Toward this end, we present in this paper our reflections as coach developers and coaches who considered how to apply Michel Foucault’s understanding of ethics to make self-change a positive force for enhancing athletes’ experiences. We then conclude by suggesting how coach developers might begin to incorporate Foucault’s work into the development of coaches capable of producing change that matters.