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Severe acute respiratory syndrome (SARS) presents an unprecedented diagnostic and therapeutic challenge to clinicians. Despite recent progress in identifying and analyzing the coronavirus that is responsible for it, few reports have addressed the clinical complications of SARS. The present study was a two-center retrospective cohort study. All patients in the study had SARS, were managed in the two major Hong Kong hospitals (ie, Prince of Wales Hospital and United Christian Hospital), and had developed spontaneous pneumothorax during their hospitalization between March 10, 2003, and April 28, 2003. Spontaneous pneumothorax was reported in 6 of 356 SARS patients who were treated at the two hospitals during the period. This represents an incidence of 1.7%. None of the six patients had a history of smoking or pulmonary disease. The rate of admission to the ICU was 66.7% and the crude mortality rate was 33.3% in this group of patients. There was a trend for the mean neutrophil count in these patients to be higher than in previously reported cohorts of comparable SARS patients (14.5 x 10(9) vs 4.6 x 10(9) neutrophils per liter, respectively). Conservative measures like tube thoracostomy or observation alone offered satisfactory initial symptomatic management in five of six patients. Spontaneous pneumothorax is a specific and potentially life-threatening complication in SARS patients. Patients with extensive lung injury, as indicated by severe clinical courses, and in particular high neutrophil counts, appear to be most at risk. The benefits of surgical management must be balanced against the potential risks to health-care workers. [ABSTRACT FROM AUTHOR]

Melanoma poses a poor prognosis with high mortality rates upon metastasis. Exploring the molecular mechanisms governing melanoma progression paves the way for developing novel approaches to control melanoma metastasis and ultimately enhance patient survival rates. Extracellular galectin-3 (Gal-3) has emerged as a pleiotropic promoter of melanoma metastasis, exerting varying activities depending on its interacting partner. However, whether intracellular Gal-3 promotes melanoma aggressive behavior remains unknown. In this study, we explored Gal-3 expression in human melanoma tissues as well as in murine melanoma models to examine its causal role in metastatic behavior. We found that Gal-3 expression is downregulated in metastatic melanoma tissues compared with its levels in primary melanomas. Enforced silencing of Gal-3 in melanoma cells promoted migration, invasion, colony formation, in vivo xenograft growth, and metastasis and activated canonical oncogenic signaling pathways. Moreover, loss of Gal-3 in melanoma cells resulted in upregulated the expression of the prometastatic transcription factor NFAT1 and its downstream metastasis-associated proteins, matrix metalloproteinase 3, and IL-8. Overall, our findings implicate melanoma intracellular Gal-3 as a major determinant of its metastatic behavior and reveal a negative regulatory role for Gal-3 on the expression of NFAT1 in melanoma cells., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

International and national oncofertility networks, including the US-led Oncofertility Consortium, FertiProtekt, and the Danish Network, have played pivotal roles in advancing the discipline of oncofertility over the last decade. Many other countries lack a shared approach to pediatric oncofertility health service delivery. This study aims to describe baseline oncofertility practices at Australian New Zealand Children's Haematology/Oncology Group centers in 2019-2021, describe binational priorities for care, and propose a 5-year action plan for best practice to be implemented by the newly formed Australian New Zealand Consortium in Children, Adolescents, and Young Adults (CAYA) Oncofertility (ANZCO)., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Vascular cell adhesion is a complex orchestration of events that commonly feature lectin-ligand interactions between circulating cells, such as immune, stem, and tumor cells, and endothelial cells (ECs) lining post-capillary venules. Characteristically, circulating cell adherence to the vasculature endothelium is initiated through interactions between surface sialo-fucosylated glycoprotein ligands and lectins, specifically platelet (P)- or endothelial (E)-selectin on ECs or between leukocyte (L)-selectin on circulating leukocytes and L-selectin ligands on ECs, culminating in circulating cell extravasation. This lectin-ligand interplay enables the migration of immune cells into specific tissue sites to help maintain effective immunosurveillance and inflammation control, the homing of stem cells to bone marrow or tissues in need of repair, and, unfortunately, in some cases, the dissemination of circulating tumor cells (CTCs) to distant metastatic sites. Interestingly, there is a growing body of evidence showing that the family of β-galactoside-binding lectins, known as galectins, can also play pivotal roles in the adhesion of circulating cells to the vascular endothelium. In this review, we present contemporary knowledge on the significant roles of host- and/or tumor-derived galectin (Gal)-3, -8, and -9 in facilitating the adhesion of circulating cells to the vascular endothelium either directly by acting as bridging molecules or indirectly by triggering signaling pathways to express adhesion molecules on ECs. We also explore strategies for interfering with galectin-mediated adhesion to attenuate inflammation or hinder the metastatic seeding of CTCs, which are often rich in galectins and/or their glycan ligands., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Souchak, Mohammed, Lau and Dimitroff.)

Background: This study aimed to assess the acceptability and attitudes of women towards human papillomavirus (HPV) self-sampling and compare the effectiveness of two delivery modes utilising face-to-face and online website for cervical cancer screening in Hong Kong., Methods: Women aged 30-65 years were invited to participate by distributing the study information pamphlets at the specialist clinics of a regional acute hospital. Those who were interested in participating were given the option to join directly face-to-face or through an online website. All participants provided informed consent and received self-sampling kits and acceptability questionnaires either immediately (face-to-face) or through the post after registering at the website (online). All participants were requested to collect their own vaginal samples using a swab which was then brushed on a DNA sample storage card and returned to the hospital either in person or by post. The self-collected samples were tested for high-risk HPV using the Sentis ™ HPV assay, a validated isothermal nucleic acid amplification real-time fluorescent detection assay. The primary outcome was the uptake rate of HPV self-sampling., Results: Of the 1998 women recruited (1200 face-to-face, 798 online), 1377 returned their samples, giving an overall uptake rate of 68.9%. The uptake rate was significantly greater in the face-to-face mode than in the online mode (74.6% vs. 60.4%, p < 0.001). The median age of the participants was 49 years, 43.7% were never or under-screened, and 7.1% had high-risk HPV detected. Overall, 82.1% of the participants reported self-sampling convenient, and 79.3% were not embarrassed when collecting self-samples. However, only 49.8% were confident that they had collected the self-samples correctly. Most (91.1%) of the participants expressed willingness to perform self-sampling again, mostly because it was simple (79.2%) and quick (56.3%)., Conclusions: HPV self-sampling can serve as an alternative primary screening method for cervical cancer in Hong Kong, especially for individuals who have not been adequately screened in the past. Both face-to-face and online website recruitment were associated with high acceptability, emphasising the potential benefits of utilising different platforms and strategies for reaching diverse populations., (© 2024. The Author(s).)

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.

The Sustainable Development Goal (SDG) 10 focuses on combating the climate change and its effects. The inclusion of this agenda in the Sustainable Development Goals by the United Nations has shown that worsened environmental degradation is currently a major threat facing humankind. The World Commission on Environment and Development 2015 has highlighted that income inequality is one of the major causes for environmental deterioration. Hence, reducing environmental degradation requires a look at the problem of unequal income distribution. Moreover, educational attainment plays a vital role in providing relevant knowledge and skills to people in handling environmental problems. Thus, the objective of the study is to investigate the relationship between income inequality, educational attainment, and CO 2 emissions by employing a panel data analysis for a group of 64 countries from 1990 to 2016.The study uses mainly dynamic common correlated effects (DCCE) estimator to take into account the issue of cross-section dependence which has been ignored by most of the previous studies. By tackling the problem of cross-section dependence, unbiased and reliable results could be produced in estimations. Our results portray that an inverted U-shaped environmental Kuznets curve (EKC) is found to be valid. Additionally, income inequality has a negative impact on environmental degradation. Likewise, educational attainment and CO 2 emissions are revealed to be negatively correlated. The findings of the study could provide a better understanding on the root causes of environmental degradation, and further suggest remedial actions to overcome the problem., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

OECD countries have encountered the challenges of improving the environmental sustainability while maintaining economic growth by not impairing employment. This study attempts to reexamine the environmental Kuznets curve (EKC) hypothesis by using ecological footprint as an indicator of environmental degradation. Besides, our study aims to test the validity of environmental Phillips curve (EPC) and role of clean energy on ecological footprint. Our data cover a panel of 36 OECD countries from 1995 to 2015. We adopt the second-generation panel unit root and cointegration test to account for the presence of cross-section dependence (CSD). Moreover, the long-run relationship is estimated using Common Correlated Effect Mean Group (CCEMG) and Augmented Mean Group (AMG) that are robust to CSD. Our findings reveal that the EKC hypothesis is not valid while EPC is confirmed in OECD countries. Though there is a trade-off between unemployment and environmental degradation in OECD countries, the development of new technologies, especially in the clean energy sector, could be a key factor contributing to sustainable growth and better environmental quality. Thus, it is recommended that OECD countries should focus on the development of innovative green technologies and strengthen the initiatives that promote renewable energy consumption., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Galectins are a family of ß-galactoside-binding proteins that play a variety of roles in normal physiology. In cancer, their expression levels are typically elevated and often associated with poor prognosis. They are known to fuel a variety of cancer progression pathways through their glycan-binding interactions with cancer, stromal, and immune cell surfaces. Of the 15 galectins in mammals, galectin (Gal)-1, -3, and -9 are particularly notable for their critical roles in tumor immune escape. While these galectins play integral roles in promoting cancer progression, they are also instrumental in regulating the survival, differentiation, and function of anti-tumor T cells that compromise anti-tumor immunity and weaken novel immunotherapies. To this end, there has been a surge in the development of new strategies to inhibit their pro-malignancy characteristics, particularly in reversing tumor immunosuppression through galectin-glycan ligand-targeting methods. This review examines some new approaches to evading Gal-1, -3, and -9-ligand interactions to interfere with their tumor-promoting and immunoregulating activities. Whether using neutralizing antibodies, synthetic peptides, glyco-metabolic modifiers, competitive inhibitors, vaccines, gene editing, exo-glycan modification, or chimeric antigen receptor (CAR)-T cells, these methods offer new hope of synergizing their inhibitory effects with current immunotherapeutic methods and yielding highly effective, durable responses.

This study aims to explore the income-biodiversity loss nexus in South and Southeast Asian countries covering the period between 2013 and 2019. Negative Binomial regression models are used to deal with the count regressand variable with specific emphasis on different taxonomic groups of threatened species, namely, mammal, bird, reptile, amphibian, fish, mollusk, other invertebrate, plant, and total threatened species. We find strong support of an inverted U-shaped relationship between income and biodiversity loss in all taxonomic groups of threatened species examined. Additionally, agricultural land has a significant and positive effect on biodiversity loss. Control of corruption and biodiversity loss are found to be negatively associated. The inverted U-shaped EKC suggests that South and Southeast Asian countries are required to identify policy priority areas that could achieve robust economic growth while reducing biodiversity loss. Our findings also provide valuable policy insights to assist the policy makers to better cope with the problem of biodiversity loss via corruption control and agricultural land use., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V.)

Obesity is a worldwide concern as it leads to adverse effects on human health. This study uses a panel of 165 countries and annual data from 2000 to 2014 to examine the obesity Kuznets curve (OKC) hypothesis. By using tests and estimators that are robust to cross-section dependence (CSD), our results support the OKC hypothesis. This indicates that obesity increases at the initial stage of economic development and eventually would decrease once the threshold is reached. In addition, we find that the role of global warming on obesity is not significant. Food production is found to be a contributing factor to obesity. Besides, one-way and two-way causalities are identified between the variables. This study provides important insights particularly about the relationship between (i) economic growth and obesity and (ii) environmental degradation and obesity. Implication of the results and policy recommendations are also provided to policymakers and health personnel in finding solutions to the obesity epidemic around the world., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In metastatic melanoma, with a dismal survival rate and propensity for treatment resistance and recurrence, it is critical to establish biomarkers that better predict treatment response and disease severity. The melanoma glycome, composed of complex carbohydrates termed glycans, is an under-investigated area of research, although it is gaining momentum in the cancer biomarker and therapeutics field. Novel findings suggest that glycans play a major role in influencing melanoma progression and could be exploited for prognosticating metastatic activity and/or as therapeutic targets. In this review, we discuss the role of aberrant glycosylation, particularly the specialized function of β1,6 N-acetylglucosaminyltransferase 2 (GCNT2), in melanoma pathogenesis and summarize mechanisms of GCNT2 regulation to illuminate its potential as a predictive marker and therapeutic target., (© 2021 British Association of Dermatologists.)

Purpose: Refugees and asylum seekers have unique and complex needs related to their experiences of forced displacement and resettlement. Cultural competence is widely recognized as important for the provision of effective and equitable services for refugee populations. However, the delivery of culturally appropriate services-including health care and social services-is often complicated by unclear definitions and operationalization of cultural competence. Further, the unique needs and priorities of people from refugee backgrounds are under-addressed in the cultural competence literature. This scoping review seeks to synthesize the peer-reviewed literature examining cultural competence in refugee service settings. Methods: A systematic search of four databases (EBSCO, Proquest, Scopus and Google Scholar) identified 26 relevant peer-reviewed studies for analysis. Results: A range of approaches to cultural competence were identified at the level of individual providers and organizations. Conclusion: We identified a need for greater refugee participation and perspectives in the practice of cultural competence, increased conceptual clarity and greater recognition of structural barriers. We call for further rigorous research that critically examines the concept of cultural competence and its meaning and relevance to refugee populations., Competing Interests: No competing financial interests exist., (© Ling San Lau and Graeme Rodgers 2021; Published by Mary Ann Liebert, Inc.)

Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7's cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell - EC interactions while delivering anergic signals to control B cell reactivity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Validity of the environmental Kuznets curve (EKC) hypothesis is consistently and widely debated among economists and environmentalists alike throughout time. In Malaysia, transport is one of the "dirtiest" sectors; it intensively consumes energy in powering engines by using fossil fuels and poses significant threats to environmental quality. Therefore, this study attempted an examination into the impact of corruption on transport carbon dioxide (CO 2 ) emissions. By adopting the fully modified ordinary least squares, canonical cointegrating regression, and dynamic ordinary least squares in performing long-run estimations, the results obtained based on the annual data spanning from 1990 to 2017 yielded various notable findings. First, more corruption would be attributable towards increased transport CO 2 emissions. Second, a monotonic increment of transport CO 2 emission was seen with higher economic growth and thus invalidated the presence of EKC. Overall, this study suggests that Malaysia has yet to reach the level of economic growth synonymous with transport CO 2 emission reduction due to the lack of high technology usage in the current system implemented. Therefore, this study could position policy recommendations of use to the Malaysian authorities in designing the appropriate economic and environmental policies, particularly for the transport sector.

In this paper, we revisit the environmental Kuznets curve (EKC) hypothesis by using estimations that account for cross-sectional dependency (CSD) and asymmetry effect in 76 countries for the period 1971-2014. Our results lend moderate support to the EKC hypothesis. The country-specific results unfold that a total of 16 out of 76 countries support the EKC hypothesis using CCEMG estimator. Results from AMG reveal that the EKC hypothesis holds in 24 out of 76 countries. It is worth highlighting that 11 countries (Australia, China, Congo Dem. Rep., Costa Rica, Gabon, Hong Kong, India, Korea, Myanmar, Turkey, and Uruguay) exhibit an inverted U-shaped curve regardless of whether CCEMG or AMG is used. The asymmetry analysis using PMG is also able to support the EKC hypothesis. We conclude that the EKC hypothesis does not fit all countries. Policy implication and recommendation in designing appropriate energy and economic policies are provided.

Genomic characterization has begun to redefine diagnostic classifications of cancers. However, it remains a challenge to infer disease phenotypes from genomic alterations alone. To help realize the promise of genomics, we have performed a quantitative proteomics investigation using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and 41 tissue samples spanning the 4 genomically based subgroups of medulloblastoma and control cerebellum. We have identified and quantitated thousands of proteins across these groups and find that we are able to recapitulate the genomic subgroups based upon subgroup restricted and differentially abundant proteins while also identifying subgroup specific protein isoforms. Integrating our proteomic measurements with genomic data, we calculate a poor correlation between mRNA and protein abundance. Using EPIC 850 k methylation array data on the same tissues, we also investigate the influence of copy number alterations and DNA methylation on the proteome in an attempt to characterize the impact of these genetic features on the proteome. Reciprocally, we are able to use the proteome to identify which genomic alterations result in altered protein abundance and thus are most likely to impact biology. Finally, we are able to assemble protein-based pathways yielding potential avenues for clinical intervention. From these, we validate the EIF4F cap-dependent translation pathway as a novel druggable pathway in medulloblastoma. Thus, quantitative proteomics complements genomic platforms to yield a more complete understanding of functional tumor biology and identify novel therapeutic targets for medulloblastoma.

We describe an MHC class II (I-A b )-restricted TCR transgenic mouse line that produces CD4 + T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4 + T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human ( Plasmodium falciparum ) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8 + T cell-mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4 + T cells and the previously described PbT-I CD8 + T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8 + DC (a subset of XCR1 + DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4 + T cell responses. Depletion of CD8 + DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4 + T cell immunity during malaria and provides evidence that CD4 + T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8 + DC., (Copyright © 2017 by The American Association of Immunologists, Inc.)

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8 + T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior.

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

Murine cerebral malaria is a complex disease caused by Plasmodium berghei ANKA infection. Several cell types, including CD8(+) T cells, are essential effectors of disease. Although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic T lymphocytes (CTL) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. Our studies show that there is a dramatic primary parasite-specific CTL response, akin to viral immunity, reaching approximately 30% of splenic CD8(+) T cells, with many producing interferon-γ and tumor necrosis factor-α. These cells express granzyme B and other markers of specific responders, are cytolytic, and respond to a broad array of major histocompatibility complex (MHC) I-restricted epitopes, 5 of which are identified here. Our studies indicate that vigorous CTL responses can be induced to pathogens even when they largely reside in red blood cells, which lack MHC I processing machinery.

Quality imaging may be described as "a timely access to and delivery of integrated and appropriate procedures, in a safe and responsive practice, and a prompt delivery of an accurately interpreted report by capable personnel in an efficient, effective, and sustainable manner." For this article, radiation safety is considered as one of the key quality elements. The stakeholders are the drivers of quality imaging. These include those that directly provide or use imaging procedures and others indirectly supporting the system. Imaging is indispensable in health care, and its use has greatly expanded worldwide. Globalization, consumer sophistication, communication and technological advances, corporatization, rationalization, service outsourcing, teleradiology, workflow modularization, and commoditization are reshaping practice. This article defines the emerging issues; an earlier article in the May 2011 issue described possible improvement actions. The issues that could threaten the quality use of imaging for all countries include workforce shortage; increased utilization, population radiation exposure, and cost; practice changes; and efficiency drive and budget constraints. In response to these issues, a range of quality improvement measures, strategies, and actions are used to maximize the benefits and minimize the risks. The 3 measures are procedure justification, optimization of image quality and radiation protection, and error prevention. The development and successful implementation of such improvement actions require leadership, collaboration, and the active participation of all stakeholders to achieve the best outcomes that we all advocate., (Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Workforce shortage, workload increase, workplace changes, and budget challenges are emerging issues around the world, which could place quality imaging at risk. It is important for imaging stakeholders to collaborate, ensure patient safety, improve the quality of care, and address these issues. There is no single panacea. A range of improvement measures, strategies, and actions are required. Examples of improvement actions supporting the 3 quality measures are described under 5 strategies: conducting research, promoting awareness, providing education and training, strengthening infrastructure, and implementing policies. The challenge is to develop long-term, cost-effective, system-based improvement actions that will bring better outcomes and underpin a sustainable future for quality imaging. In an imaging practice, these actions will result in selecting the right procedure (justification), using the right dose (optimization), and preventing errors along the patient journey. To realize this vision and implement these improvement actions, a range of expertise and adequate resources are required. Stakeholders should collaborate and work together. In today's globalized environment, collaboration is strength and provides synergy to achieve better outcomes and greater success., (Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC(50)) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies.

As part of a sleep monitoring project, we used actigraphy based on body-worn accelerometer sensors to remotely monitor and study the sleep-wake cycle of elderly staying at nursing homes. We have conducted a fifteen patient trial of a sleep activity pattern monitoring (SAPM) system at a local nursing home. The data was collected and stored in our server and the processing of the data was done offline after sleep diaries used for validation and ground truth were updated into the system. The processing algorithm matches and annotates the sensor data with manual sleep diary information and is processed asynchronously on the grid/cloud back end. In this paper we outline the mapping of the system for grid / cloud processing, and initial results that show expected near-linear performance for scaling the number of users.

Suppressor of cytokine signaling (SOCS)-1 is a critical inhibitor of IFN-gamma signal transduction in vivo, but the precise biochemical mechanism of action of SOCS-1 is unclear. Studies in vitro have shown that SOCS-1 binds to Jaks and inhibits their catalytic activity, but recent studies indicate SOCS-1 may act in a similar manner to SOCS-3 by firstly interacting with cytokine receptors and then inhibiting Jak activity. Here, we have generated mice, termed Ifngr1(441F), in which a putative SOCS-1 binding site, tyrosine 441 (Y441), on the IFN-gamma receptor subunit 1 (IFNGR1) is mutated. We confirm that SOCS-1 binds to IFNGR1 in wild-type but not mutant cells. Mutation of Y441 results in impaired negative regulation of IFN-gamma signaling. IFN-gamma-induced STAT1 activation is prolonged in Ifngr1(441F) cells, but not to the extent seen in cells completely lacking SOCS-1, suggesting that SOCS-1 maintains activity to modulate IFN-gamma signaling via other mechanisms. Despite this, we show that hypersensitivity to IFN-gamma results in enhanced innate tumor protection in Ifngr1(441F) mice in vivo, and unregulated expression of an IFN-gamma-dependent chemokine, monokine-induced by IFN-gamma. Collectively, these data indicate that Y441 contributes to the regulation of signaling through IFNGR1 via the recruitment of SOCS-1 to the receptor.

Paxillin, a major focal-adhesion complex component belongs to the subfamily of LIM domain proteins and participates in cell adhesion-mediated signal transduction. It is implicated in cell-motility responses upon activation of cell-surface receptors and can recruit, among others, the GIT1 [GRK (G-protein-coupled-receptor kinase)-interacting ARF (ADP-ribosylation factor) GAP (GTPase-activating protein)]-PIX [PAK (p21-activated kinase)-interacting exchange factor]-PAK1 complex. Several adhesion proteins including zyxin, Hic5 and Trip6 are also nuclear and can exert transcriptional effects. In the present study we show that endogenous paxillin shuttles between the cytoplasm and nucleus, and we have used a variety of tagged paxillin constructs to map the nuclear export signal. This region overlaps an important LD(4) motif that binds GIT1 and FAK1 (focal-adhesion kinase 1). We provide evidence that phosphorylation of Ser(272) within LD(4) blocks nuclear export, and we show that this modification also reduces GIT1, but not FAK1, binding; however, Ser(272) phosphorylation does not appear to be mediated by PAK1 as previously suggested. Expression of nuclear-localized paxillin LIM domains stimulate DNA synthesis and cell proliferation. By real-time PCR analysis we have established that overexpression of either full-length paxillin or a truncated nuclear form suppresses expression of the parental imprinted gene H19, and modulation of this locus probably affects the rate of NIH-3T3 cell proliferation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.

Although CD8(+) T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8(+) T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8(+) T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8(+) and CD4(+) T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8alpha(+) subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.

The aim of the study was to compare the standard technique of cardiac output determination by pulmonary artery catheter thermodilution (PAC-TD) with a noninvasive ultrasound Doppler monitor (USCOM Pty., Ltd., Coffs Harbour, Australia) in surgery for liver transplantation. We wished to determine if the degree of accuracy would allow the ultrasound cardiac output monitor (USCOM) to be used as an alternative monitor in a clinical setting in which wide fluctuations in cardiac output could be expected. This was a prospective method comparison study, with 71 paired measurements obtained in 12 patients undergoing liver transplantation in a university teaching hospital. Bland-Altman analysis of the 2 techniques showed a bias of 0.39 L/minute, with the USCOM cardiac output lower compared with that of PAC-TD. The bias was small and did not vary with the magnitude of the cardiac output. The 95% limits of agreement were -1.47 and 2.25 L/minute. There was good repeatability for USCOM measurements, with a repeatability coefficient of 0.43 for USCOM versus 0.77 for PAC-TD. We conclude that USCOM is acceptable for the clinical determination of noninvasive cardiac output, particularly in situations in which tracking changes over time is more important than knowing the precise value. However, the utility of USCOM is limited by its inability to measure pulmonary artery pressure.