bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis
Authors: Zhao Guanghui , Zhou Aihua , Lv Gang , Meng Min , Sun Min , Bai Yang , Han Yali , Wang Lin , Zhou Huaiyu , Cong Hua , Zhao Qunli , Zhu Xing-Quan , He Shenyi
Published: May 2013

Background

Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii.

Methods

Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines.

Results

TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection.

Conclusions

T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
Five years of malaria control in the continental region, Equatorial Guinea
Authors: Rehman Andrea M , Mann Andrea G , Schwabe Christopher , Reddy Michael R , Roncon Gomes Irina , Slotman Michel A , Yellott Lee , Matias Abrahan , Caccone Adalgisa , Nseng Nchama Gloria , Kleinschmidt Immo
Published: May 2013

Background

A successful malaria control programme began in 2004 on Bioko Island, Equatorial Guinea. From 2007, the same multiple malaria interventions, though reduced in scope for funding reasons, were introduced to the four mainland provinces of Equatorial Guinea (the continental region) aiming to recreate Bioko’s success. Two provinces received long-lasting insecticidal nets (LLINs) and two provinces received biannual indoor residual spraying (IRS). Enhanced case management and communications were introduced throughout.

Methods

Estimates of intervention coverage and indicators of malaria transmission for 2007 to 2011 were derived from annual malaria indicator surveys (MIS). Results were complemented by health information system (HIS) and entomological data. The personal protection offered by LLINs and IRS against Plasmodium falciparum infection was estimated with logistic regression.

Results

The estimated proportion of children aged 1–4 using either an LLIN the previous night or living in a house sprayed in the last six months was 23% in 2007 and 42% in 2011. The estimated prevalence of P. falciparum in children aged 1–4 was 68% (N=1,770; 95% confidence interval [CI]: 58-76%) in 2007 and 52% (N=1,602; 95% CI: 44-61%) in 2011. Children 1–4 years had lower prevalence if they used an LLIN the previous night (N=1,124, 56%; adjusted odds ratio [aOR] 0.64, 95% CI: 0.55-0.74) or if they lived in a sprayed house (N=1,150, 57%; aOR 0.80, 95% CI: 0.62-1.03) compared to children with neither intervention (N=4,131, 66%, reference group). The minority of children who both used an LLIN and lived in a sprayed house had the lowest prevalence of infection (N=171, 45%; aOR 0.52, 95% CI: 0.35-0.78). High site-level intervention coverage did not always correlate with lower site-level P. falciparum prevalence. The malaria season peaked in either June or July, not necessarily coinciding with MIS data collection.

Conclusions

Though moderate impact was achieved after five years of vector control, case management, and communications, prevalence remained high due to an inability to sufficiently scale-up coverage with either IRS or LLINs. Both LLINs and IRS provided individual protection, but greater protection was afforded to children who benefitted from both.
Expression of HPV16 E5 down-modulates the TGFbeta signaling pathway
Authors: French Deborah , Belleudi Francesca , Mauro Maria Vittoria , Mazzetta Francesca , Raffa Salvatore , Fabiano Vincenza , Frega Antonio , Torrisi Maria Rosaria
Published: May 2013

Background

Infection with high-risk human papillomavirus (HR-HPV) genotypes, mainly HPV16 and HPV18, is a major risk factor for cervical cancer and responsible for its progression. While the transforming role of the HPV E6 and E7 proteins is more characterized, the molecular mechanisms of the oncogenic activity of the E5 product are still only partially understood, but appear to involve deregulation of growth factor receptor expression. Since the signaling of the transforming growth factor beta (TGFbeta) is known to play crucial roles in the epithelial carcinogenesis, aim of this study was to investigate if HPV16 E5 would modulate the TGF-BRII expression and TGFbeta/Smad signaling.

Findings

The HPV16 E5 mRNA expression pattern was variable in low-grade squamous intraepithelial lesions (LSIL), while homogeneously reduced in high-grade lesions (HSIL). Parallel analysis of TGFBRII mRNA showed that the receptor transcript levels were also variable in LSILs and inversely related to those of the viral protein. In vitro quantitation of the TGFBRII mRNA and protein in human keratinocytes expressing 16E5 in a dose-dependent and time-dependent manner showed a progressive down-modulation of the receptor. Phosphorylation of Smad2 and nuclear translocation of Smad4 were also decreased in E5-expressing cells stimulated with TGFbeta1.

Conclusions

Taken together our results indicate that HPV16 E5 expression is able to attenuate the TGFbeta1/Smad signaling and propose that this loss of signal transduction, leading to destabilization of the epithelial homeostasis at very early stages of viral infection, may represent a crucial mechanism of promotion of the HPV-mediated cervical carcinogenesis.
Signal transduction in primary human T lymphocytes in altered gravity – results of the MASER-12 suborbital space flight mission
Authors: Tauber Svantje , Hauschild Swantje , Crescio Claudia , Secchi Christian , Paulsen Katrin , Pantaleo Antonella , Saba Angela , Buttron Isabell , Thiel Cora Sandra , Cogoli Augusto , Pippia Proto , Ullrich Oliver
Published: May 2013

We investigated the influence of altered gravity on key proteins of T cell activation during the MASER-12 ballistic suborbital rocket mission of the European Space Agency (ESA) and the Swedish Space Cooperation (SSC) at ESRANGE Space Center (Kiruna, Sweden). We quantified components of the T cell receptor, the membrane proximal signaling, MAPK-signaling, IL-2R, histone modifications and the cytoskeleton in non-activated and in ConA/CD28-activated primary human T lymphocytes. The hypergravity phase during the launch resulted in a downregulation of the IL-2 and CD3 receptor and reduction of tyrosine phosphorylation, p44/42-MAPK phosphorylation and histone H3 acetylation, whereas LAT phosphorylation was increased. Compared to the baseline situation at the point of entry into the microgravity phase, CD3 and IL-2 receptor expression at the surface of non-activated T cells were reduced after 6 min microgravity. Importantly, p44/42-MAPK-phosphorylation was also reduced after 6 min microgravity compared to the 1g ground controls, but also in direct comparison between the in-flight μg and the 1g group. In activated T cells, the reduced CD3 and IL-2 receptor expression at the baseline situation recovered significantly during in-flight 1g conditions, but not during microgravity conditions. Beta-tubulin increased significantly after onset of microgravity until the end of the microgravity phase, but not in the in-flight 1g condition. This study suggests that key proteins of T cell signal modules are not severely disturbed in microgravity. Instead, it can be supposed that the strong T cell inhibiting signal occurs downstream from membrane proximal signaling, such as at the transcriptional level as described recently. However, the MASER-12 experiment could identify signal molecules, which are sensitive to altered gravity, and indicates that gravity is obviously not only a requirement for transcriptional processes as described before, but also for specific phosphorylation / dephosphorylation of signal molecules and surface receptor dynamics.
Self-reported sitting time is not associated with incidence of cardiovascular disease in a population-based cohort of mid-aged women
Authors: Herber-Gast Gerrie-Cor M , Jackson Caroline A , Mishra Gita D , Brown Wendy J
Published: May 2013

Background

In Westernised societies adults are increasingly spending many hours each day in sedentary, low energy expenditure activities such as sitting. Although there is growing evidence on the relationship between television/screen time and increased cardiovascular disease mortality, very little is known about the association between total sitting time (in different domains) and cardiovascular disease incidence. We investigated this in a population-based cohort of mid-aged women in Australia.

Findings

Data were from 6154 participants in the 1946–51 birth cohort of the Australian Longitudinal Study on Women’s Health who were free of cardiovascular disease at baseline. Survival analysis was used to determine the association between self-reported sitting time and cardiovascular disease incidence, determined through hospital diagnoses and cause of death data. During a mean (± SD) follow-up time of 9.9 ± 1.2 years, 177 cases of cardiovascular disease occurred. Mean sitting time (± SD) was 5.4 ± 2.6 hours a day. Sitting time was not associated with incident cardiovascular disease (adjusted hazard ratio 0.97, 95% CI 0.92 to 1.03). We found no interaction between physical activity and sitting time and cardiovascular disease.

Conclusions

In mid-aged women sitting time does not appear to be associated with cardiovascular disease incidence. These findings are contrary to expectations, given the growing evidence of a relationship between sitting time and cardiovascular disease mortality. Research in this area is scarce and additional studies are needed to confirm or refute these findings.
Expanding the applicability of Lavrentiev regularization methods for ill-posed problems
Authors: Argyros Ioannis K , Cho Yeol Je , George Santhosh
Published: May 2013

In this paper, we are concerned with the problem of approximating a solution of an ill-posed problem in a Hilbert space setting using the Lavrentiev regularization method and, in particular, expanding the applicability of this method by weakening the popular Lipschitz-type hypotheses considered in earlier studies such as (Bakushinskii and Smirnova in Numer. Funct. Anal. Optim. 26:35-48, 2005; Bakushinskii and Smirnova in Nonlinear Anal. 64:1255-1261, 2006; Bakushinskii and Smirnova in Numer. Funct. Anal. Optim. 28:13-25, 2007; Jin in Math. Comput. 69:1603-1623, 2000; Mahale and Nair in ANZIAM J. 51:191-217, 2009). Numerical examples are given to show that our convergence criteria are weaker and our error analysis tighter under less computational cost than the corresponding works given in (Bakushinskii and Smirnova in Numer. Funct. Anal. Optim. 26:35-48, 2005; Bakushinskii and Smirnova in Nonlinear Anal. 64:1255-1261, 2006; Bakushinskii and Smirnova in Numer. Funct. Anal. Optim. 28:13-25, 2007; Jin in Math. Comput. 69:1603-1623, 2000; Mahale and Nair in ANZIAM J. 51:191-217, 2009).

MSC:65F22, 65J15, 65J22, 65M30, 47A52.
Integrative analysis of congenital muscular torticollis: from gene expression to clinical significance
Authors: Yim Shin-Young , Yoon Dukyong , Park Myong Chul , Lee Il Jae , Kim Jang-Hee , Lee Myung Ae , Kwack Kyu-Sung , Lee Jan-Dee , Lee Jeong-Hun , Soh Euy-Young , Na Young-In , Park Rae Woong , Lee KiYoung , Jun Jae-Bum
Published: May 2013

Background

Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT.

Results

Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or imunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM.

Conclusions

We here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.
A semi-automated protocol for Archaea DNA extraction from stools
Authors: Khelaifia Saber , Ramonet Pierre-Yves , Bedotto Buffet Marielle , Drancourt Michel
Published: May 2013

Background

The PCR-based detection of archaea DNA in human specimens relies on efficient DNA extraction. We previously designed one such protocol involving only manual steps. In an effort to reduce the workload involved, we compared this manual protocol to semi-automated and automated protocols for archaea DNA extraction from human specimens.

Findings

We tested 110 human stool specimens using each protocol. An automated protocol using the EZ1 Advanced XL extractor with the V 1.066069118 Qiagen DNA bacteria card and the EZ1® DNA Tissue Kit (Qiagen, Courtaboeuf, France) yielded 35/110 (32%) positives for the real-time PCR detection of the Methanobrevibacter smithii 16S rRNA gene, with average Ct values of 36.1. A semi-automated protocol combining glass-powder crushing, overnight proteinase K digestion and lysis in the buffer from the EZ1 kit yielded 90/110 (82%) positive specimens (P = 0.001) with an average Ct value of 27.4 (P = 0.001). The manual protocol yielded 100/110 (91%) positive specimens (P = 0.001) with an average Ct value of 30.33 (P = 0.001). However, neither the number of positive specimens nor the Ct values were significantly different between the manual protocol and the semi-automated protocol (P > 0.1 and P > 0.1).

Conclusion

Proteinase K digestion and glass powder crushing dramatically increase the extraction yield of archaea DNA from human stools. The semi-automated protocol described here was more rapid than the manual protocol and yielded significantly more archaeal DNA. It could be applied for extracting total stool DNA for further PCR amplification.
Foot orthoses for the management of low back pain: a qualitative approach capturing the patient's perspective
Authors: Williams Anita E , Hill Lindsay A , Nester Christopher J
Published: May 2013

Background

The onset of non specific low back pain is associated with heavy lifting, age, female gender, and poor general health, with psychological factors being predictors of it becoming chronic. Additionally, it is thought that altered lower limb biomechanics are a contributory factor, with foot orthoses increasingly being considered as an appropriate intervention by physiotherapists and podiatrists. However, research into the effect of foot orthoses is inconclusive, primarily focusing on the biomechanical effect and not the symptomatic relief from the patient's perspective. The aim of this study was to explore the breadth of patients' experiences of being provided with foot orthoses and to evaluate any changes in their back pain following this experience.

Method

Following ethical approval, participants (n = 25) with non‐specific low back pain associated with altered lower limb biomechanics were provided with customised foot orthoses. At 16 weeks after being provided with the foot orthoses, conversational style interviews were carried out with each patient. An interpretivistic phenomenological approach was adopted for the data collection and analysis.

Results

For these participants, foot orthoses appeared to be effective. However, the main influence on this outcome was the consultation process and a patient focussed approach. The consultation was an opportunity for fostering mutual understanding, with verbal and visual explanation reassuring the patient and this influenced the patient's beliefs, their engagement with the foot orthoses (physical) and their experience of low back pain (psychological).

Conclusion

Clinicians need to adopt ‘psychologically informed practice’ in relation to the provision of foot orthoses. Likewise, researchers should consider all the influencing factors found in this study, both in relation to their study protocol and the outcomes they plan to measure.
The maintenance and monitoring of perioperative blood volume
Authors: Iijima Takehiko , Brandstrup Birgitte , Rodhe Peter , Andrijauskas Audrius , Svensen Christer H
Published: May 2013

The assessment and maintenance of perioperative blood volume is important because fluid therapy is a routine part of intraoperative care. In the past, patients undergoing major surgery were given large amounts of fluids because health-care providers were concerned about preoperative dehydration and intraoperative losses to a third space. In the last decade it has become clear that fluid therapy has to be more individualized. Because the exact determination of blood volume is not clinically possible at every timepoint, there have been different approaches to assess fluid requirements, such as goal-directed protocols guided by invasive and less invasive devices.

This article focuses on laboratory volume determination, capillary dynamics, aspects of different fluids and how to clinically assess and monitor perioperative blood volume.
Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified?
Authors: Kibirige Davis , Mwebaze Raymond
Published: May 2013

Vitamin B12 is an essential micronutrient required for optimal hemopoetic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. This review article offers a current perspective on the physiological roles of vitamin B12, proposed pathophysiological mechanisms of vitamin B12 deficiency, screening for vitamin B12 deficiency and vitamin B12 supplementation among patients with diabetes mellitus.
Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor
Authors: Yardley Denise A. , Ismail-Khan Roohi R. , Melichar Bohuslav , Lichinitser Mikhail , Munster Pamela N. , Klein Pamela M. , Cruickshank Scott , Miller Kathy D. , Lee Min J. , Trepel Jane B
Published: May 2013

Purpose

Entinostat is an oral isoform selective histone deacetylase inhibitor that targets resistance to hormonal therapies in estrogen receptor–positive (ER+) breast cancer. This randomized, placebo-controlled, phase II study evaluated entinostat combined with the aromatase inhibitor exemestane versus exemestane alone.

Patients and Methods

Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor were randomly assigned to exemestane 25 mg daily plus entinostat 5 mg once per week (EE) or exemestane plus placebo (EP). The primary end point was progression-free survival (PFS). Blood was collected in a subset of patients for evaluation of protein lysine acetylation as a biomarker of entinostat activity.

Results

One hundred thirty patients were randomly assigned (EE group, n = 64; EP group, n = 66). Based on intent-to-treat analysis, treatment with EE improved median PFS to 4.3 months versus 2.3 months with EP (hazard ratio [HR], 0.73; 95% CI, 0.50 to 1.07; one-sided P = .055; two-sided P = .11 [predefined significance level of .10, one-sided]). Median overall survival was an exploratory end point and improved to 28.1 months with EE versus 19.8 months with EP (HR, 0.59; 95% CI, 0.36 to 0.97; P = .036). Fatigue and neutropenia were the most frequent grade 3/4 toxicities. Treatment discontinuation because of adverse events was higher in the EE group versus the EP group (11% v 2%). Protein lysine hyperacetylation in the EE biomarker subset was associated with prolonged PFS.

Conclusion

Entinostat added to exemestane is generally well tolerated and demonstrated activity in patients with ER+ advanced breast cancer in this signal-finding phase II study. Acetylation changes may provide an opportunity to maximize clinical benefit with entinostat. Plans for a confirmatory study are underway.
Evaluation of Tumor-Size Response Metrics to Predict Overall Survival in Western and Chinese Patients With First-Line Metastatic Colorectal Cancer
Authors: Claret Laurent , Gupta Manish , Han Kelong , Joshi Amita , Sarapa Nenad , He Jing , Powell Bob , Bruno René
Published: May 2013

Purpose

To assess new metrics of tumor-size response to predict overall survival (OS) in colorectal cancer (CRC) in Western and Chinese patients.

Patients and Methods

Various metrics of tumor-size response were estimated using longitudinal tumor size models and data from two phase III studies that compared bevacizumab plus chemotherapy versus chemotherapy as first-line therapy in Western (n = 923) and Chinese (n = 203) patients with CRC. Baseline prognostic factors and tumor-size metrics estimates were assessed in multivariate models to predict OS. Predictive performances of the models were assessed by simulating multiple replicas of the phase III studies.

Results

Time to tumor growth (TTG) was the best metric to predict OS. TTG fully captured bevacizumab effect. Chinese ethnicity had no impact on OS or on the TTG-OS relationships. The model correctly predicted OS distributions in each arm as well as bevacizumab hazard ratio (model prediction, 0.75 v 0.68 observed in Western patients; 95% prediction interval, 0.62 to 0.91).

Conclusion

TTG captured therapeutic benefit with bevacizumab in first-line CRC patients. Chinese ethnicity had no impact. Longitudinal tumor size data coupled with model-based approaches may offer a powerful alternative in the design and analysis of early clinical studies.
Ovarian Cancer Incidence Trends in Relation to Changing Patterns of Menopausal Hormone Therapy Use in the United States
Authors: Yang Hannah P. , Anderson William F. , Rosenberg Philip S. , Trabert Britton , Gierach Gretchen L. , Wentzensen Nicolas , Cronin Kathleen A. , Sherman Mark E.
Published: May 2013

Purpose

After a report from the Women's Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002.

Methods

Using the North American Association of Central Cancer Registries database (1995 to 2008; N = 171,142 incident ovarian cancers), we applied standard analytic approaches and age-period-cohort (APC) models to estimate ovarian cancer incidence rate changes before (1995 to 2002) and after (2003 to 2008) the WHI report.

Results

Among women age ≥ 50 years, age-standardized ovarian cancer incidence declined by 0.8% per year (95% CI, −1.8% to −0.5% per year) before the WHI announcement; after the WHI report, the rate declined by 2.4% per year (95% CI, −2.5% to −2.2% per year). APC models confirmed an accelerated decline in ovarian cancer incidence after the WHI report, adjusted for age and birth cohort effects. This sudden change was notable among women most likely to have used MHT (ie, women age 50 to 69 years, white women, and residents of regions with highest MHT prescription frequency). The largest changes were found for the endometrioid histologic subtype.

Conclusion

After a marked reduction in MHT use around 2002, ovarian cancer incidence rates demonstrated an accelerated decline, with the largest changes for endometrioid carcinomas. This strong temporal association, although not proving a causal role of hormones in ovarian carcinogenesis, suggests that future analytic research supporting cancer control efforts should clarify the role of hormonal exposures on the development and behavior of subtypes of ovarian cancer.
Trajectories of Psychological Distress in Adolescent and Young Adult Patients With Cancer: A 1-Year Longitudinal Study
Authors: Kwak Minyoung , Zebrack Brad J. , Meeske Kathleen A. , Embry Leanne , Aguilar Christine , Block Rebecca , Hayes-Lattin Brandon , Li Yun , Butler Melissa , Cole Steven
Published: May 2013

Purpose

To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and clinical predictors of changes in distress were examined.

Patients and Methods

In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18).

Results

Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress.

Conclusion

Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.
Randomized Selection Design Trial Evaluating CD8+-Enriched Versus Unselected Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy for Patients With Melanoma
Authors: Dudley Mark E. , Gross Colin A. , Somerville Robert P.T. , Hong Young , Schaub Nicholas P. , Rosati Shannon F. , White Donald E. , Nathan Debbie , Restifo Nicholas P. , Steinberg Seth M. , Wunderlich John R. , Kammula Udai S. , Sherry Richard M. , Yang James C. , Phan Giao Q. , Hughes Marybeth S. , Laurencot Carolyn M. , Rosenberg Steven A.
Published: May 2013

Purpose

Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown.

Patients and Methods

Patients with metastatic melanoma were prospectively assigned to receive unselected young TILs versus CD8+-enriched TILs. All patients received lymphodepleting chemotherapy and high-dose IL-2 therapy and were assessed for response, toxicity, survival, and immunologic end points.

Results

Thirty-four patients received unselected young TILs with a median of 8.0% CD4+lymphocytes, and 35 patients received CD8+-enriched TILs with a median of 0.3% CD4+lymphocytes. One month after TIL infusion, patients who received CD8+-enriched TILs had significantly fewer CD4+peripheral blood lymphocytes (P = .01). Twelve patients responded to therapy with unselected young TILs (according to Response Evaluation Criteria in Solid Tumors [RECIST]), and seven patients responded to CD8+-enriched TILs (35% v 20%; not significant). Retrospective studies showed a significant association between response to treatment and interferon gamma secretion by the infused TILs in response to autologous tumor (P = .04), and in the subgroup of patients who received TILs from subcutaneous tumors, eight of 15 patients receiving unselected young TILs responded but none of eight patients receiving CD8+-enriched TILs responded.

Conclusion

A randomized selection design trial was feasible for improving individualized TIL therapy. Since the evidence indicates that CD8+-enriched TILs are not more potent therapeutically and they are more laborious to prepare, future studies should focus on unselected young TILs.
The Dialectics of Parody
Authors: Renfrew Alastair
Published: May 2013

Iurii Tynianov’s characterization of the relationship between Fyodor Dostoevsky and Nikolai Gogol as parodic, which he later develops into a broader concern with the mechanics of literary evolution, also provokes a concern with the specifically dialectical nature of the change of historical forms. Rather than viewing this interest in dialectics as a tactically convenient phase in the accommodation of Formalism to the ideological requirements of the Soviet 1920s, the present article interprets Tynianov as the author of a particular “literary-historical” dialectic: it pre-dates the reifying tendencies of “official” Soviet dialectical materialism and is intimately related to the key Formalist category of “estrangement.” This dialectic proceeds from textual relationships (hence the initial focus on parody) as opposed to relationships between “base concepts.” It can usefully be related to Fredric Jameson’s recent attempt to reconnect dialectical thought with the rise and fall of various strands of twentieth-century theory (structuralism and deconstruction chief among them). Jameson’s revisionism is then extended to a consideration of a personalized, “dialogic” dialectic in the work of Mikhail Bakhtin.
Mimesis and Motivation: The Two Faces of Fictional Coherence
Authors: Sternberg Meir
Published: May 2013

This paper deals with “motivation” as fiction’s twofold logic of patterning and relates it to other concepts or lines of sense-making (e.g., integration, naturalization). The argument is best summarized through the paper’s headings.

1. Why Is the Discourse Like That? Motivation as Twofold Reason-Giving

2. Reality, Artifice, and Motivation: Doctrinal Biases, Variable Products, Universal Modes; 2.1 Aristotle’s Mimesis of Nature by Art; or, Why Plot above Character?; 2.2 Viktor Shklovsky and Mimesis Fallen below Art

3. How the Extremes Compare: Toward an Alternative Theory

4. Conceptualizing Motivation: Basic Requirements

5. Motivation and Integration: The Concept of Functional Mediacy; 5.1 Motivation in Tomashevsky’s “Thematics”: The Shift from Cover to Coherence; 5.2 From Polarity to Threefold: The Typology of Motivation; 5.3 Motivating and Integrating Distinguished in Face of Persistent Mix-Up; 5.4 Naturalization

6. Integral and Differential Motivation: The Mimetic Function

7. Motivation and Communicative Structure: Point of View as Sense-Making Construct; 7.1 Who Motivates, and from Whose Standpoint?; 7.2 Motivating Fictional as against Factual Discourse: The Difference Made by Quotation; 7.3 Appeal to Existence or to Perspective? Unrealistic World and/or Unreliable Subject?; 7.4 Fictional Motivation under the Proteus Principle; 7.5 Sibling Rivalry and Contingent Resolution within the Family of Mimesis

I am an art theoretician.... I know what motivation is!

Viktor Shklovsky, A Sentimental Journey
Internet-delivered eye movement desensitization and reprocessing (iEMDR): an open trial
Authors: Spence Jay , Titov Nickolai , Johnston Luke , Dear Blake F , Wootton Bethany , Terides Matthew , Zou Judy
Published: May 2013

Recent research indicates internet-delivered cognitive behavioural therapy (iCBT) can reduce symptoms of post traumatic stress disorder (PTSD). This study examined the efficacy of an internet-delivered treatment protocol that combined iCBT and internet-delivered eye movement desensitization and reprocessing (iEMDR), in an uncontrolled trial. Eleven of the 15 participants completed post-treatment questionnaires. Large effect sizes were found from pre-treatment to 3-month follow-up (d = 1.03 – 1.61) on clinician-assessed and self-reported measures of PTSD, anxiety and distress, with moderate effect sizes (d = 0.59 – 0.70) found on measures of depression and disability. At post-treatment, 55% of the participants no longer met criteria for PTSD and this was sustained at follow-up. Symptom worsening occurred in 3 of 15 (20%) of the sample from pre- to post-treatment; however, these participants reported overall symptom improvement by follow-up. Future research directions for iEMDR are discussed.
Belief-Free Communication Equilibria in Repeated Games
Authors: Tomala Tristan
Published: May 2013

This paper considers a general model of repeated games with incomplete information and imperfect monitoring. We study belief-free communication equilibria (BFCE) defined as follows. Players communicate with a mediator who receives types and signals and recommends actions. A BFCE is a communication device such that all players have an incentive to play faithfully, irrespectively of their belief about the state. We characterize BFCE payoffs for any repeated game with incomplete information in terms of one-shot payoff functions, information, and signaling structure.
Stabilization of Stochastic Iterative Methods for Singular and Nearly Singular Linear Systems
Authors: Wang Mengdi , Bertsekas Dimitri P.
Published: May 2013

We consider linear systems of equations, Ax = b, with an emphasis on the case where A is singular. Under certain conditions, necessary as well as sufficient, linear deterministic iterative methods generate sequences {xk} that converge to a solution as long as there exists at least one solution. This convergence property can be impaired when these methods are implemented with stochastic simulation, as is often done in important classes of large-scale problems. We introduce additional conditions and novel algorithmic stabilization schemes under which {xk} converges to a solution when A is singular and may also be used with substantial benefit when A is nearly singular.
A case report of an intracaval extrathoracic solitary fibrous tumour
Authors: Koh SZ , Tiong HY , Wang S , Madhavan K
Published: May 2013

Solitary fibrous tumours are infrequent neoplasms based in the pleura that are predominantly benign with malignant pathology and behaviour described in 10–36% of cases. Extrathoracic solitary fibrous tumours (ESFTs) have been considered separately to their intrathoracic counterparts and comprise a third of all solitary fibrous tumours. The extrathoracic location was identified as an adverse prognostic factor for local recurrence but not for metastatic disease. So far, there have not been any reports of solitary fibrous tumours demonstrating caval infiltration. We present a case of a benign ESFT infiltrating into the perirenal inferior vena cava. Together with extrauterine leiomyomas, ESFTs should also be considered as a differential diagnosis for the rare benign lesions invading the inferior vena cava.
Novel xylan-controlled delivery of therapeutic proteins to inflamed colon by the human anaerobic commensal bacterium
Authors: Hamady ZZR
Published: May 2013

Introduction

Growth factors such as keratinocyte growth factor-2 (KGF-2) and transforming growth factor-beta (TGF-β) are important immunoregulatory and epithelial growth factors. They are also potential therapeutic proteins for inflammatory bowel disease. However, owing to protein instability in the upper gastrointestinal tract, it is difficult to achieve therapeutic levels of these proteins in the injured colon when given orally. Furthermore, the short half-life necessitates repeated dosage with large amounts of the growth factor, which may have dangerous side effects, hence the importance of temporal and spatial control of growth factor delivery.

Methods

The human commensal gut bacterium, Bacteroides ovatus, was genetically engineered to produce human KGF-2 or TGF-β 1 (BO-KGF or BO-TGF) in a regulated manner in response to the dietary polysaccharide, xylan. The successful application of BO-KGF or BO-TGF in the prevention of dextran sodium sulphate induced murine colitis is presented here.

Results

This novel drug delivery system had a significant prophylactic effect, limiting the development of intestinal inflammation both clinically and histopathologically. The ability to regulate heterologous protein production by B ovatus using xylan is both unique and an important safety feature of this drug delivery system.

Conclusions

The use of genetically engineered B ovatus for the controlled and localised delivery of epithelial growth promoting and immunomodulatory proteins has potential clinical applications for the treatment of various diseases targeting the colon.
Operative and non-operative management of endoscopic retrograde cholangiopancreatography-associated duodenal injuries
Authors: Rabie M Ezzedien , Mir NH , Skaini MS Al , Hakeem I El , Hadad A , Ageely H , Shaban AN , Obaid M , Hummadi AM
Published: May 2013

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is indispensable in everyday surgical practice. Despite this, as an invasive procedure, it has its own mortality and morbidity, the most feared of which is periduodenal perforations. Our experience with ERCP related periduodenal perforations and its treatment strategies are presented. Additionally, a rarely encountered subtype is highlighted.

Methods

Patients who underwent ERCP and sustained a periduodenal perforation between August 2008 and October 2011 were reviewed.

Results

During the period from August 2008 to October 2011, 597 ERCP procedures were performed in our hospital. Ten of these patients (3 male, 7 female) had a perforation. The mean patient age was 56.6 years. During the procedure, injury was suspected in four patients; it passed unnoticed in the remaining six. The decision to operate or follow a conservative policy was based on a combination of clinical and radiological findings. Operative intervention was required in three patients, with one mortality, while conservative treatment was followed in the remaining seven. A laparotomy was performed early in two patients whereas it was performed after an initial period of conservative treatment in one. The presence of periduodenal fluid collection, contrast extravasation or free intraperitoneal air were decisive factors for performing laparotomy.

Conclusions

ERCP-related periduodenal perforations include different categories. Certain types require operative repair while others should be treated conservatively. The choice of the management approach should be individualised, depending on the clinical picture and radiological findings. Although rare, these are potentially serious complications that may end fatally. Early recognition and appropriate intervention is the only way to avert a fatal outcome.
Telaprevir-Related Dermatitis; Neuroleptic Malignant Syndrome with Risperidone Long-Acting Injection; Tigecycline-Related Pancreatitis; Venlafaxine-Related Psychosis; Neurologic Adverse Effects of Ranolazine
Authors: Mancano Michael A.
Published: May 2013

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Melatonin: Delirium (Postsurgical)
Authors: Generali Joyce A , Cada Dennis J
Published: May 2013

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Preventing Large-Scale Controlled Substance Diversion from within the Pharmacy
Authors: Martin Emory S. , Dzierba Steven H. , Jones David M.
Published: May 2013

Large-scale diversion of controlled substances (CS) from within a hospital or heath system pharmacy is a rare but growing problem. It is the responsibility of pharmacy leadership to scrutinize control processes to expose weaknesses. This article reviews examples of large-scale diversion incidents and diversion techniques and provides practical strategies to stimulate enhanced CS security within the pharmacy staff. Large-scale diversion from within a pharmacy department can be averted by a pharmacist-in-charge who is informed and proactive in taking effective countermeasures.
Johann Philipp Kirnberger and Authorship
Authors: Jerold Beverly
Published: May 2013

It has long been known that Johann Philipp Kirnberger received writing assistance from others (notably Johann Abraham Peter Schulz) in preparing his publications, but examination reveals it to have been more extensive than previously thought. While Kirnberger has been granted credit for all the music articles in the first volume of Johann Georg Sulzer’s Allgemeine Theorie der schönen Künste , major contradictions with Kirnberger’s professed views appear in some articles, and others reflect an expertise in practical music that Kirnberger lacked. Some contemporaries credited Johann Friedrich Agricola with many of the music articles in Sulzer’s first volume. This article examines the question, as well as the role that Schulz and others played in Kirnberger’s own publications.
test
Authors: Moten Fred
Published: May 2013

The poet Major Jackson (Holding Company, Hoops) compiles this eclectic Spring issue, which includes the work of several distinguished writers and newcomers. Featuring poetry by writers like Mark Doty, Martin Espada, Tony Hoagland, Laura Kasischke, Sharon Olds, Carl Phillips, and Tracy K. Smith, the issue is a dazzling tour of the modern poetic landscape in America. There is also a wide variety of fiction, from the story of a high school girl in the South and her relationship with a white teacher ("What Happens Next," by Emily Bernard) to a New York doorman dying of cancer ("The Rubber Game," by Sherri Phillips). The issue also features a Plan B essay by Floyd Skloot ("The Great Dream"), about the mostly thwarted ambitions of the members of his family, and an appreciation of the British writer Barbara Pym ("Patron Saint of Quiet Lives," by Raina Lipsitz).
Dance Dance Dance
Authors: Lemon Alex
Published: May 2013

The poet Major Jackson (Holding Company, Hoops) compiles this eclectic Spring issue, which includes the work of several distinguished writers and newcomers. Featuring poetry by writers like Mark Doty, Martin Espada, Tony Hoagland, Laura Kasischke, Sharon Olds, Carl Phillips, and Tracy K. Smith, the issue is a dazzling tour of the modern poetic landscape in America. There is also a wide variety of fiction, from the story of a high school girl in the South and her relationship with a white teacher ("What Happens Next," by Emily Bernard) to a New York doorman dying of cancer ("The Rubber Game," by Sherri Phillips). The issue also features a Plan B essay by Floyd Skloot ("The Great Dream"), about the mostly thwarted ambitions of the members of his family, and an appreciation of the British writer Barbara Pym ("Patron Saint of Quiet Lives," by Raina Lipsitz).
The Visions of Sane Persons
Authors: Seaton Maureen
Published: May 2013

The poet Major Jackson (Holding Company, Hoops) compiles this eclectic Spring issue, which includes the work of several distinguished writers and newcomers. Featuring poetry by writers like Mark Doty, Martin Espada, Tony Hoagland, Laura Kasischke, Sharon Olds, Carl Phillips, and Tracy K. Smith, the issue is a dazzling tour of the modern poetic landscape in America. There is also a wide variety of fiction, from the story of a high school girl in the South and her relationship with a white teacher ("What Happens Next," by Emily Bernard) to a New York doorman dying of cancer ("The Rubber Game," by Sherri Phillips). The issue also features a Plan B essay by Floyd Skloot ("The Great Dream"), about the mostly thwarted ambitions of the members of his family, and an appreciation of the British writer Barbara Pym ("Patron Saint of Quiet Lives," by Raina Lipsitz).
The Length of the Field
Authors: Phillips Carl
Published: May 2013

The poet Major Jackson (Holding Company, Hoops) compiles this eclectic Spring issue, which includes the work of several distinguished writers and newcomers. Featuring poetry by writers like Mark Doty, Martin Espada, Tony Hoagland, Laura Kasischke, Sharon Olds, Carl Phillips, and Tracy K. Smith, the issue is a dazzling tour of the modern poetic landscape in America. There is also a wide variety of fiction, from the story of a high school girl in the South and her relationship with a white teacher ("What Happens Next," by Emily Bernard) to a New York doorman dying of cancer ("The Rubber Game," by Sherri Phillips). The issue also features a Plan B essay by Floyd Skloot ("The Great Dream"), about the mostly thwarted ambitions of the members of his family, and an appreciation of the British writer Barbara Pym ("Patron Saint of Quiet Lives," by Raina Lipsitz).
Middle Distance
Authors: Wiese Anne Pierson
Published: May 2013

The poet Major Jackson (Holding Company, Hoops) compiles this eclectic Spring issue, which includes the work of several distinguished writers and newcomers. Featuring poetry by writers like Mark Doty, Martin Espada, Tony Hoagland, Laura Kasischke, Sharon Olds, Carl Phillips, and Tracy K. Smith, the issue is a dazzling tour of the modern poetic landscape in America. There is also a wide variety of fiction, from the story of a high school girl in the South and her relationship with a white teacher ("What Happens Next," by Emily Bernard) to a New York doorman dying of cancer ("The Rubber Game," by Sherri Phillips). The issue also features a Plan B essay by Floyd Skloot ("The Great Dream"), about the mostly thwarted ambitions of the members of his family, and an appreciation of the British writer Barbara Pym ("Patron Saint of Quiet Lives," by Raina Lipsitz).